Klaus Lieb

Borderline personality disorder is characterised by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. Clinical signs of the disorder include emotional dysregulation, impulsive aggression, repeated self-injury, and chronic suicidal tendencies, which make these patients frequent users of mental-health resources. Causal factors are only partly known, but genetic factors and adverse events during childhood, such as physical and sexual abuse, contribute to the development of the disorder. Dialectical behaviour therapy and psychodynamic partial hospital programmes are effective treatments for out-of-control patients, and drug therapy can reduce depression, anxiety, and impulsive aggression. More research is needed for the understanding and management of this disabling clinical condition. Current strategies are focusing on the neurobiological underpinnings of the disorder and the development and dissemination of better and more cost-effective treatments to clinicians.

Consistent failure over the past few decades to reduce the high prevalence of stress-related disorders has motivated a search for alternative research strategies. Resilience refers to the phenomenon of many people maintaining mental health despite exposure to psychological or physical adversity. Instead of aiming to understand the pathophysiology of stress-related disorders, resilience research focuses on protective mechanisms that shield people against the development of such disorders and tries to exploit its insights to improve treatment and, in particular, disease prevention. To fully harness the potential of resilience research, a critical appraisal of the current state of the art — in terms of basic concepts and key methods — is needed. We highlight challenges to resilience research and make concrete conceptual and methodological proposals to improve resilience research. Most importantly, we propose to focus research on the dynamic processes of successful adaptation to stressors in prospective longitudinal studies.

Dialectical Behavioral Therapy (DBT) was initially developed and evaluated as an outpatient treatment program for chronically suicidal individuals meeting criteria for borderline personality disorder (BPD). Within the last few years, several adaptations to specific settings have been developed. This study aims to evaluate a three-month DBT inpatient treatment program. Clinical outcomes, including changes on measures of psychopathology and frequency of self-mutilating acts, were assessed for 50 female patients meeting criteria for BPD. Thirty-one patients had participated in a DBT inpatient program, and 19 patients had been placed on a waiting list and received treatment as usual in the community. Post-testing was conducted four months after the initial assessment (i.e. four weeks after discharge for the DBT group). Pre-post-comparison showed significant changes for the DBT group on 10 of 11 psychopathological variables and significant reductions in self-injurious behavior. The waiting list group did not show any significant changes at the four-months point. The DBT group improved significantly more than participants on the waiting list on seven of the nine variables analyzed, including depression, anxiety, interpersonal functioning, social adjustment, global psychopathology and self-mutilation. Analyses based on Jacobson's criteria for clinically relevant change indicated that 42% of those receiving DBT had clinically recovered on a general measure of psychopathology. The data suggest that three months of inpatient DBT treatment is significantly superior to non-specific outpatient treatment. Within a relatively short time frame, improvement was found across a broad range of psychopathological features. Stability of the recovery after one month following discharge, however, was not evaluated and requires further study.

Psychological resilience refers to the phenomenon that many people are able to adapt to the challenges of life and maintain mental health despite exposure to adversity. This has stimulated research on training programs to foster psychological resilience. We evaluated concepts, methods and designs of 43 randomized controlled trials published between 1979 and 2014 which assessed the efficacy of such training programs and propose standards for future intervention research based on recent developments in the field. We found that concepts, methods and designs in current resilience intervention studies are of limited use to properly assess efficacy of interventions to foster resilience. Major problems are the use of definitions of resilience as trait or a composite of resilience factors, the use of unsuited assessment instruments, and inappropriate study designs. To overcome these challenges, we propose 1) an outcome-oriented definition of resilience, 2) an outcome-oriented assessment of resilience as change in mental health in relation to stressor load, and 3) methodological standards for suitable study designs of future intervention studies. Our proposals may contribute to an improved quality of resilience intervention studies and may stimulate further progress in this growing research field.

Many patients with borderline personality disorder receive pharmacological treatment, but there is uncertainty about the usefulness of such therapies.To evaluate the evidence of effectiveness of pharmacotherapy in treating different facets of the psychopathology of borderline personality disorder.A Cochrane Collaboration systematic review and meta-analysis of randomised comparisons of drug v. placebo, drug v. drug, or single drug v. combined drug treatment in adult patients with borderline personality disorder was conducted. Primary outcomes were overall disorder severity as well as specific core symptoms. Secondary outcomes comprised associated psychiatric pathology and drug tolerability.Twenty-seven trials were included in which first- and second-generation antipsychotics, mood stabilisers, antidepressants and omega-3 fatty acids were tested. Most beneficial effects were found for the mood stabilisers topiramate, lamotrigine and valproate semisodium, and the second-generation antipsychotics aripiprazole and olanzapine. However, the robustness of findings is low, since they are based mostly on single, small studies. Selective serotonin reuptake inhibitors so far lack high-level evidence of effectiveness.The current evidence from randomised controlled trials suggests that drug treatment, especially with mood stabilisers and second-generation antipsychotics, may be effective for treating a number of core symptoms and associated psychopathology, but the evidence does not currently support effectiveness for overall severity of borderline personality disorder. Pharmacotherapy should therefore be targeted at specific symptoms.

Dual frontolimbic brain pathology has been suggested as a possible correlate of impulsivity and aggressive behavior. One previous study reported volume loss of the hippocampus and the amygdala in patients with borderline personality disorder. We measured limbic and prefrontal brain volumes to test the hypothesis that frontolimbic brain pathology might be associated with borderline personality disorder.Eight unmedicated female patients with borderline personality disorder and eight matched healthy controls were studied. The volumes of the hippocampus, amygdala, and orbitofrontal, dorsolateral prefrontal, and anterior cingulate cortex were measured in the patients using magnetic resonance imaging volumetry and compared to those obtained in the controls.We found a significant reduction of hippocampal and amygdala volumes in borderline personality disorder. There was a significant 24% reduction of the left orbitofrontal and a 26% reduction of the right anterior cingulate cortex in borderline personality disorder. Only left orbitofrontal volumes correlated significantly with amygdala volumes.While volume loss of a single brain structure like the hippocampus is quite an unspecific finding in neuropsychiatry, the patterns of volume loss of the amygdala, hippocampus, and left orbitofrontal and right anterior cingulate cortex might differentiate borderline personality disorder from other neuropsychiatric conditions.

Gamma ray yield functions of (p, αγ) and (p, γ) resonance reactions on semi-thick 19F, 23Na, 24,26Mg and 27Al targets were measured and used to calibrate the accelerating voltage and energy resolution of the new 500 kV heavy ion implanter at Göttingen. The energy spread of the proton beam was found to vary linearly with the accelerating voltage from ΔE(200 keV) = 55 eV fwhm to ΔE(500 keV) = 105 eV; it is made up by a 0.012% high voltage ripple and the Doppler broadening of the resonances due to the thermal motion of the target nuclei. A long term stability of the proton energy of < 5 eV/h at 300 keV was achieved with new resistors in the voltage regulating system. Applications of the accelerator for the remeasurement of some resonance energies and widths and for depth profiling of light implanted ions in metals by the resonance broadening method will be briefly discussed.

Background Over the decades, a variety of psychological interventions for borderline personality disorder (BPD) have been developed. This review updates and replaces an earlier review (Stoffers‐Winterling 2012). Objectives To assess the beneficial and harmful effects of psychological therapies for people with BPD. Search methods In March 2019, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication. Selection criteria Randomised controlled trials comparing different psychotherapeutic interventions with treatment‐as‐usual (TAU; which included various kinds of psychotherapy), waiting list, no treatment or active treatments in samples of all ages, in any setting, with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self‐harm, suicide‐related outcomes, and psychosocial functioning. There were 11 secondary outcomes, including individual BPD symptoms, as well as attrition and adverse effects. Data collection and analysis At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's 'Risk of bias' tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis. Main results We included 75 randomised controlled trials (4507 participants), predominantly involving females with mean ages ranging from 14.8 to 45.7 years. More than 16 different kinds of psychotherapy were included, mostly dialectical behaviour therapy (DBT) and mentalisation‐based treatment (MBT). The comparator interventions included treatment‐as‐usual (TAU), waiting list, and other active treatments. Treatment duration ranged from one to 36 months. Psychotherapy versus TAU Psychotherapy reduced BPD symptom severity, compared to TAU; standardised mean difference (SMD) −0.52, 95% confidence interval (CI) −0.70 to −0.33; 22 trials, 1244 participants; moderate‐quality evidence. This corresponds to a mean difference (MD) of −3.6 (95% CI −4.4 to −2.08) on the Zanarini Rating Scale for BPD (range 0 to 36), a clinically relevant reduction in BPD symptom severity (minimal clinical relevant difference (MIREDIF) on this scale is −3.0 points). Psychotherapy may be more effective at reducing self‐harm compared to TAU (SMD −0.32, 95% CI −0.49 to −0.14; 13 trials, 616 participants; low‐quality evidence), corresponding to a MD of −0.82 (95% CI −1.25 to 0.35) on the Deliberate Self‐Harm Inventory Scale (range 0 to 34). The MIREDIF of −1.25 points was not reached. Suicide‐related outcomes improved compared to TAU (SMD −0.34, 95% CI −0.57 to −0.11; 13 trials, 666 participants; low‐quality evidence), corresponding to a MD of −0.11 (95% CI −0.19 to −0.034) on the Suicidal Attempt Self Injury Interview. The MIREDIF of −0.17 points was not reached. Compared to TAU, psychotherapy may result in an improvement in psychosocial functioning (SMD −0.45, 95% CI −0.68 to −0.22; 22 trials, 1314 participants; low‐quality evidence), corresponding to a MD of −2.8 (95% CI −4.25 to −1.38), on the Global Assessment of Functioning Scale (range 0 to 100). The MIREDIF of −4.0 points was not reached. Our additional Trial Sequential Analysis on all primary outcomes reaching significance found that the required information size was reached in all cases. A subgroup analysis comparing the different types of psychotherapy compared to TAU showed no clear evidence of a difference for BPD severity and psychosocial functioning. Psychotherapy may reduce depressive symptoms compared to TAU but the evidence is very uncertain (SMD −0.39, 95% CI −0.61 to −0.17; 22 trials, 1568 participants; very low‐quality evidence), corresponding to a MD of −2.45 points on the Hamilton Depression Scale (range 0 to 50). The MIREDIF of −3.0 points was not reached. BPD‐specific psychotherapy did not reduce attrition compared with TAU. Adverse effects were unclear due to too few data. Psychotherapy versus waiting list or no treatment Greater improvements in BPD symptom severity (SMD −0.49, 95% CI −0.93 to −0.05; 3 trials, 161 participants), psychosocial functioning (SMD −0.56, 95% CI −1.01 to −0.11; 5 trials, 219 participants), and depression (SMD −1.28, 95% CI −2.21 to −0.34, 6 trials, 239 participants) were observed in participants receiving psychotherapy versus waiting list or no treatment (all low‐quality evidence). No evidence of a difference was found for self‐harm and suicide‐related outcomes. Individual treatment approaches DBT and MBT have the highest numbers of primary trials, with DBT as subject of one‐third of all included trials, followed by MBT with seven RCTs. Compared to TAU, DBT was more effective at reducing BPD severity (SMD −0.60, 95% CI −1.05 to −0.14; 3 trials, 149 participants), self‐harm (SMD −0.28, 95% CI −0.48 to −0.07; 7 trials, 376 participants) and improving psychosocial functioning (SMD −0.36, 95% CI −0.69 to −0.03; 6 trials, 225 participants). MBT appears to be more effective than TAU at reducing self‐harm (RR 0.62, 95% CI 0.49 to 0.80; 3 trials, 252 participants), suicidality (RR 0.10, 95% CI 0.04, 0.30, 3 trials, 218 participants) and depression (SMD −0.58, 95% CI −1.22 to 0.05, 4 trials, 333 participants). All findings are based on low‐quality evidence. For secondary outcomes see review text. Authors' conclusions Our assessments showed beneficial effects on all primary outcomes in favour of BPD‐tailored psychotherapy compared with TAU. However, only the outcome of BPD severity reached the MIREDIF‐defined cut‐off for a clinically meaningful improvement. Subgroup analyses found no evidence of a difference in effect estimates between the different types of therapies (compared to TAU) . The pooled analysis of psychotherapy versus waiting list or no treatment found significant improvement on BPD severity, psychosocial functioning and depression at end of treatment, but these findings were based on low‐quality evidence, and the true magnitude of these effects is uncertain. No clear evidence of difference was found for self‐harm and suicide‐related outcomes. However, compared to TAU, we observed effects in favour of DBT for BPD severity, self‐harm and psychosocial functioning and, for MBT, on self‐harm and suicidality at end of treatment, but these were all based on low‐quality evidence. Therefore, we are unsure whether these effects would alter with the addition of more data.

Acting in accord with long-term goals requires control of interfering impulses, the success of which depends on several different processes. Using a structural-equation modeling approach, we investigated 5 behavioral components of impulsivity: the control of stimulus interference, proactive interference, and response interference, as well as decisional and motivational impulsivity. Results support the existence of 5 correlated but separable components of impulsive behavior. The present study is the 1st to demonstrate the separability of stimulus and response interference. It also supports the notion that control of response-related interference is not a unitary construct: Response-selection demands were separable from those of withholding or stopping. Relations between behavioral impulsivity components and self-report measures of impulsivity were largely absent. We conclude that as the construct of impulsivity has been extended to describe an increasingly diverse set of phenomena and processes, it has become too broad to be helpful in guiding future research.

Exposure to ambient air pollution is a well-established determinant of health and disease. The Lancet Commission on pollution and health concludes that air pollution is the leading environmental cause of global disease and premature death. Indeed, there is a growing body of evidence that links air pollution not only to adverse cardiorespiratory effects but also to increased risk of cerebrovascular and neuropsychiatric disorders. Despite being a relatively new area of investigation, overall, there is mounting recent evidence showing that exposure to multiple air pollutants, in particular to fine particles, may affect the central nervous system (CNS) and brain health, thereby contributing to increased risk of stroke, dementia, Parkinson’s disease, cognitive dysfunction, neurodevelopmental disorders, depression and other related conditions. The underlying molecular mechanisms of susceptibility and disease remain largely elusive. However, emerging evidence suggests inflammation and oxidative stress to be crucial factors in the pathogenesis of air pollution-induced disorders, driven by the enhanced production of proinflammatory mediators and reactive oxygen species in response to exposure to various air pollutants. From a public health perspective, mitigation measures are urgent to reduce the burden of disease and premature mortality from ambient air pollution.

Background Resilience can be defined as the maintenance or quick recovery of mental health during or after periods of stressor exposure, which may result from a potentially traumatising event, challenging life circumstances, a critical life transition phase, or physical illness. Healthcare professionals, such as nurses, physicians, psychologists and social workers, are exposed to various work‐related stressors (e.g. patient care, time pressure, administration) and are at increased risk of developing mental disorders. This population may benefit from resilience‐promoting training programmes. Objectives To assess the effects of interventions to foster resilience in healthcare professionals, that is, healthcare staff delivering direct medical care (e.g. nurses, physicians, hospital personnel) and allied healthcare staff (e.g. social workers, psychologists). Search methods We searched CENTRAL, MEDLINE, Embase, 11 other databases and three trial registries from 1990 to June 2019. We checked reference lists and contacted researchers in the field. We updated this search in four key databases in June 2020, but we have not yet incorporated these results. Selection criteria Randomised controlled trials (RCTs) in adults aged 18 years and older who are employed as healthcare professionals, comparing any form of psychological intervention to foster resilience, hardiness or post‐traumatic growth versus no intervention, wait‐list, usual care, active or attention control. Primary outcomes were resilience, anxiety, depression, stress or stress perception and well‐being or quality of life. Secondary outcomes were resilience factors. Data collection and analysis Two review authors independently selected studies, extracted data, assessed risks of bias, and rated the certainty of the evidence using the GRADE approach (at post‐test only). Main results We included 44 RCTs (high‐income countries: 36). Thirty‐nine studies solely focused on healthcare professionals (6892 participants), including both healthcare staff delivering direct medical care and allied healthcare staff. Four studies investigated mixed samples (1000 participants) with healthcare professionals and participants working outside of the healthcare sector, and one study evaluated training for emergency personnel in general population volunteers (82 participants). The included studies were mainly conducted in a hospital setting and included physicians, nurses and different hospital personnel (37/44 studies). Participants mainly included women (68%) from young to middle adulthood (mean age range: 27 to 52.4 years). Most studies investigated group interventions (30 studies) of high training intensity (18 studies; > 12 hours/sessions), that were delivered face‐to‐face (29 studies). Of the included studies, 19 compared a resilience training based on combined theoretical foundation (e.g. mindfulness and cognitive‐behavioural therapy) versus unspecific comparators (e.g. wait‐list). The studies were funded by different sources (e.g. hospitals, universities), or a combination of different sources. Fifteen studies did not specify the source of their funding, and one study received no funding support. Risk of bias was high or unclear for most studies in performance, detection, and attrition bias domains. At post‐intervention, very‐low certainty evidence indicated that, compared to controls, healthcare professionals receiving resilience training may report higher levels of resilience (standardised mean difference (SMD) 0.45, 95% confidence interval (CI) 0.25 to 0.65; 12 studies, 690 participants), lower levels of depression (SMD −0.29, 95% CI −0.50 to −0.09; 14 studies, 788 participants), and lower levels of stress or stress perception (SMD −0.61, 95% CI −1.07 to −0.15; 17 studies, 997 participants). There was little or no evidence of any effect of resilience training on anxiety (SMD −0.06, 95% CI −0.35 to 0.23; 5 studies, 231 participants; very‐low certainty evidence) or well‐being or quality of life (SMD 0.14, 95% CI −0.01 to 0.30; 13 studies, 1494 participants; very‐low certainty evidence). Effect sizes were small except for resilience and stress reduction (moderate). Data on adverse effects were available for three studies, with none reporting any adverse effects occurring during the study (very‐low certainty evidence). Authors' conclusions For healthcare professionals, there is very‐low certainty evidence that, compared to control, resilience training may result in higher levels of resilience, lower levels of depression, stress or stress perception, and higher levels of certain resilience factors at post‐intervention. The paucity of medium‐ or long‐term data, heterogeneous interventions and restricted geographical distribution limit the generalisability of our results. Conclusions should therefore be drawn cautiously. The findings suggest positive effects of resilience training for healthcare professionals, but the evidence is very uncertain. There is a clear need for high‐quality replications and improved study designs.

The Miniball germanium detector array has been operational at the REX (Radioactive ion beam EXperiment) post accelerator at the Isotope Separator On-Line facility ISOLDE at CERN since 2001. During the last decade, a series of successful Coulomb excitation and transfer reaction studies have been performed with this array, utilizing the unique and high-quality radioactive ion beams which are available at ISOLDE. In this article, an overview is given of the technical details of the full Miniball setup, including a description of the $\gamma$ -ray and particle detectors, beam monitoring devices and methods to deal with beam contamination. The specific timing properties of the REX-ISOLDE facility are highlighted to indicate the sensitivity that can be achieved with the full Miniball setup. The article is finalized with a summary of some physics highlights at REX-ISOLDE and the utilization of the Miniball germanium detectors at other facilities.

Mental burden due to the SARS-CoV-2 pandemic has been widely reported for the general public and specific risk groups like healthcare workers and different patient populations. We aimed to assess its impact on mental health during the early phase by comparing pandemic with prepandemic data and to identify potential risk and protective factors.For this systematic review and meta-analyses, we systematically searched PubMed, PsycINFO, and Web of Science from January 1, 2019 to May 29, 2020, and screened reference lists of included studies. In addition, we searched PubMed and PsycINFO for prepandemic comparative data. Survey studies assessing mental burden by the SARS-CoV-2 pandemic in the general population, healthcare workers, or any patients (eg, COVID-19 patients), with a broad range of eligible mental health outcomes, and matching studies evaluating prepandemic comparative data in the same population (if available) were included. We used multilevel meta-analyses for main, subgroup, and sensitivity analyses, focusing on (perceived) stress, symptoms of anxiety and depression, and sleep-related symptoms as primary outcomes.Of 2429 records retrieved, 104 were included in the review (n = 208,261 participants), 43 in the meta-analysis (n = 71,613 participants). While symptoms of anxiety (standardized mean difference [SMD] 0.40; 95% CI 0.15-0.65) and depression (SMD 0.67; 95% CI 0.07-1.27) were increased in the general population during the early phase of the pandemic compared with prepandemic conditions, mental burden was not increased in patients as well as healthcare workers, irrespective of COVID-19 patient contact. Specific outcome measures (eg, Patient Health Questionnaire) and older comparative data (published ≥5 years ago) were associated with increased mental burden. Across the three population groups, existing mental disorders, female sex, and concerns about getting infected were repeatedly reported as risk factors, while older age, a good economic situation, and education were protective.This meta-analysis paints a more differentiated picture of the mental health consequences in pandemic situations than previous reviews. High-quality, representative surveys, high granular longitudinal studies, and more research on protective factors are required to better understand the psychological impacts of the SARS-CoV-2 pandemic and to help design effective preventive measures and interventions that are tailored to the needs of specific population groups.

Abstract The SARS-CoV-2 pandemic is not only a threat to physical health but is also having severe impacts on mental health. Although increases in stress-related symptomatology and other adverse psycho-social outcomes, as well as their most important risk factors have been described, hardly anything is known about potential protective factors. Resilience refers to the maintenance of mental health despite adversity. To gain mechanistic insights about the relationship between described psycho-social resilience factors and resilience specifically in the current crisis, we assessed resilience factors, exposure to Corona crisis-specific and general stressors, as well as internalizing symptoms in a cross-sectional online survey conducted in 24 languages during the most intense phase of the lockdown in Europe (22 March to 19 April) in a convenience sample of N = 15,970 adults. Resilience, as an outcome, was conceptualized as good mental health despite stressor exposure and measured as the inverse residual between actual and predicted symptom total score. Preregistered hypotheses (osf.io/r6btn) were tested with multiple regression models and mediation analyses. Results confirmed our primary hypothesis that positive appraisal style (PAS) is positively associated with resilience ( p &lt; 0.0001). The resilience factor PAS also partly mediated the positive association between perceived social support and resilience, and its association with resilience was in turn partly mediated by the ability to easily recover from stress (both p &lt; 0.0001). In comparison with other resilience factors, good stress response recovery and positive appraisal specifically of the consequences of the Corona crisis were the strongest factors. Preregistered exploratory subgroup analyses (osf.io/thka9) showed that all tested resilience factors generalize across major socio-demographic categories. This research identifies modifiable protective factors that can be targeted by public mental health efforts in this and in future pandemics.

Smith and colleagues developed the Brief Resilience Scale (BRS) to assess the individual ability to recover from stress despite significant adversity. This study aimed to validate the German version of the BRS. We used data from a population-based (sample 1: n = 1.481) and a representative (sample 2: n = 1.128) sample of participants from the German general population (age ≥ 18) to assess reliability and validity. Confirmatory factor analyses (CFA) were conducted to compare one- and two-factorial models from previous studies with a method-factor model which especially accounts for the wording of the items. Reliability was analyzed. Convergent validity was measured by correlating BRS scores with mental health measures, coping, social support, and optimism. Reliability was good (α = .85, ω = .85 for both samples). The method-factor model showed excellent model fit (sample 1: χ2/df = 7.544; RMSEA = .07; CFI = .99; SRMR = .02; sample 2: χ2/df = 1.166; RMSEA = .01; CFI = 1.00; SRMR = .01) which was significantly better than the one-factor model (Δχ2(4) = 172.71, p < .001) or the two-factor model (Δχ2(3) = 31.16, p < .001). The BRS was positively correlated with well-being, social support, optimism, and the coping strategies active coping, positive reframing, acceptance, and humor. It was negatively correlated with somatic symptoms, anxiety and insomnia, social dysfunction, depression, and the coping strategies religion, denial, venting, substance use, and self-blame. To conclude, our results provide evidence for the reliability and validity of the German adaptation of the BRS as well as the unidimensional structure of the scale once method effects are accounted for.

Borderline personality disorder (BPD) is a mental disorder with a high burden on patients, family members, and health-care systems. The condition was previously regarded as untreatable, but progress in understanding and management has resulted in earlier diagnosis and better treatment outcomes. A coherent syndrome of BPD typically onsets during adolescence (after age 12 years). BPD is often preceded by or co-develops with symptoms of internalising disorders (depression and anxiety), externalising disorders (conduct problems, hyperactivity, and substance use), or both. BPD is associated with various poor outcomes, including low occupational and educational attainment, lack of long-term relationships, increased partner conflict, sexual risk-taking, low levels of social support, low life satisfaction, and increased service use. Psychotherapy is the main treatment for BPD; drug treatment is only indicated for comorbid conditions that require medication, or during a crisis if psychosocial interventions are insufficient. Awareness of BPD by non-specialists, as well as specialists, is key to appropriate early intervention.

Psychological responses to potentially traumatic events tend to be heterogeneous, with some individuals displaying resilience. Longitudinal associations between resilience and mental distress during the COVID-19 pandemic, however, are poorly understood. The objective of this study was to examine the association between resilience and trajectories of mental distress during the COVID-19 pandemic.Participants were 6,008 adults from the Understanding America Study, a probability-based Internet-panel representative of the US adult population. Baseline data were collected between March 10 and March 31, 2020, with nine follow-up waves conducted between April 1 and August 4. Mixed-effects logistic regression was used to examine the association between date and mental distress, stratified by resilience level (low, normal, or high).In contrast to the high resilience group, participants in the low and normal resilience groups experienced increases in mental distress in the early months of the pandemic (low: OR=2.94, 95% CI=1.93-4.46; normal: OR=1.91, 95% CI=1.55-2.35). Men, middle-aged and older adults, Black adults, and adults with a graduate degree were more likely to report high resilience, whereas adults living below the poverty line were less likely to report high resilience.These associations should not be interpreted as causal, and resilience was measured at only one time-point.Trajectories of mental distress varied markedly by resilience level during the early months of the COVID-19 pandemic, with low-resilience adults reporting the largest increases in mental distress during this crisis. Activities that foster resilience should be included in broader strategies to support mental health throughout the pandemic.

The World Health Organization declared COVID-19 outbreak a global pandemic on March 11, 2020. Following the rapid and uncontrollable course of the pandemic, many governments decided to massively restrict public and private life to prevent further spread of the virus. Especially the measures to enforce “physical distancing” during the “lockdown” can be seen as a global macro-stressor affecting a major part of mankind in an unprecedented manner. Lockdown can have manifold psychosocial consequences, including unemployment and precarious economic situations, marital and familial discord, and domestic violence. Subsequent psychological responses, such as feelings of loneliness, anger or preoccupation about the future, are likely. This was picked up by mass media as well as expertse.g., 1, warning the public about possible negative effects of the lockdown on mental health. While many speculations and hypothetical considerations arose, there is a paucity of empirical real-world data. Initial ad-hoc studies have been conducted quickly, reporting high incidence of negative mental health outcomes, such as depression and anxietye.g., 2. Thereby, reports inferred detrimental consequences for the mental state of the general population. However, those studies have several shortcomings. Most of them applied cross-sectional designs, which may capture very transient symptoms rather than long-lasting fluctuations in men­tal states, and do not allow comparison with pre-lockdown mea­sures. Also, the questionnaires that were used are often only screening tools rather than in-depth assessment instruments. In contrast, more meaningful insights can be gathered from longitudinal studies built on continuous, detailed assessments of mental health before and during the lockdown. We present here extensive data on behavioral and mental health changes in relation to the lockdown of public life in Germany. We capitalize on a population-based, prospective, longitudinal cohort study termed LORA (Longitudinal Resilience Assessment3), conducted in the Rhine-Main region since 2017. Its main aim is investigating resilience – i.e., the ability to maintain mental health despite difficult life circumstances – in initially healthy adults (assessed by the Mini International Neuropsychiatric Interview4). After an extensive baseline evaluation, major life events, micro-stressors in the form of daily hassles, and mental health status (primary outcome, assessed by the German version of the General Health Questionnaire, GHQ-285) are recorded every three months using an online monitoring system. The pandemic and the lockdown during the ongoing study provided a unique natural experiment for investigating how initially mentally healthy subjects respond to a major macro-stressor. Lockdown started in Germany on March 22 and was gradually relaxed from May 6 onwards. We immediately increased the sampling rate of our LORA study to once per week, the first assessment taking place on March 31. Ethical approval was obtained from the ethical review boards of the University Hospitals of Mainz and Frankfurt. Data presented here are from the first eight weeks of the weekly assessments, compared to the last measurement time point in LORA prior to lockdown. Almost half of the overall sample (N=523) contributed data; this sample was not significantly different from the complete initial one. The sample consisted of 69% females, and had a mean age of 31.5±8.4 years. Among participants, 47.8% were cohabitating with a partner and 22.8% had children under 18 years; 40.9% were working full-time and another 34.8% were studying or undergoing a professional training. Six participants were positively tested for SARS-CoV-2 since mid-March, and 57 had to undergo strict quarantine. As much as 362 participants worked and studied from home during lockdown. Overall, the number of daily hassles per week decreased from an average of 60.0±27.2 prior to the lockdown to 41.2±22.3 at week 8. This decrease was significant when comparing pre-lockdown values to those at weeks 1-4 (t508=13.5, p<0.001) and weeks 5-8 (t475=17.7, p<0.001). Parallel to this, mental health status significantly improved over the entire post-lockdown period, indicated by a decrease of GHQ-28 mean values from 20.5±9.7 before lockdown to 16.8±7.6 averaged across weeks 1-4 (t508=7.8, p<0.001), and to 16.2±7.1 averaged across weeks 5-8 (t474=8.8, p<0.001). A quadratic latent growth mixture model revealed the existence of three subpopulations among the study sample, with distinct mental health trajectories from pre-lockdown through week 8 of the assessment. Group 1 (8.3% of the sample, mean age 28.0±5.9 years, 86.8% female) showed high initial mental dysfunction values, that increased until week 3 and then decreased, returning to the baseline level by week 6 of the assessment. Group 2 (83.6% of the sample, mean age 31.7±8.5, 66.7% female) maintained or improved their mental health during the entire assessment period. Group 3 (8.1% of the sample, mean age 32.7±9.2, 73.7% female) significantly deteriorated in mental health from week 3 onwards. The overall reduced amount of daily hassles and increase of mental health scores is, at first sight, counterintuitive. However, our analyses revealed subpopulations differentially affected by the pandemic. For Groups 1 and 2, the lockdown measures resulted in reduced mundane stress-inducing factors, such as less commuting or reduced workload. Thus, these groups experienced a short-term reduction of micro-stressors. However, in our sample of initially mentally healthy participants, we identified a susceptible group, whose mental health deteriorated over the course of the assessment. The existence of this “vulnerable group” may explain the rise in mental disorders seen in some cross-sectional studies: while the majority of people cope well with the consequences of the pandemic (at least if the economic impact is buffered against), a subgroup of individuals is susceptible to adversities and develops mental health problems. Vulnerability towards such lockdown effects might be higher in people already suffering from psychiatric disorders, or in elderly populations with impoverished social networks. Indeed, Group 1 of our study had significantly younger participants than the other two (F2,520=4.0, p=0.02). Further, it is likely that socioeconomic challenges and risk factors such as unemployment or poverty, less powerful in Germany than in many other countries, will have later negative influences. Our results indicate that unspecific, general interventions may not be the optimal response to lockdown measures. Resources should rather be allocated to early identification and support of particularly vulnerable individuals in times of crisis. Future studies should quantify risk and especially protective factors playing a role in coping with the stressors of the current pandemic, followed by tailored interventions targeting the identified factors in susceptible individuals to prevent the manifestation of mental disorders. In sum, we refute the undifferentiated view that lockdown per se has a negative effect on mental health. Rather, it affects a vulnerable group of individuals, while the vast majority of people remain healthy or even improve their mental well-being, as everyday stressors are reduced.

The COVID-19 pandemic and resulting measures can be regarded as a global stressor. Cross-sectional studies showed rather negative impacts on people's mental health, while longitudinal studies considering pre-lockdown data are still scarce. The present study investigated the impact of COVID-19 related lockdown measures in a longitudinal German sample, assessed since 2017. During lockdown, 523 participants completed additional weekly online questionnaires on e.g., mental health, COVID-19-related and general stressor exposure. Predictors for and distinct trajectories of mental health outcomes were determined, using multilevel models and latent growth mixture models, respectively. Positive pandemic appraisal, social support, and adaptive cognitive emotion regulation were positively, whereas perceived stress, daily hassles, and feeling lonely negatively related to mental health outcomes in the entire sample. Three subgroups ("recovered," 9.0%; "resilient," 82.6%; "delayed dysfunction," 8.4%) with different mental health responses to initial lockdown measures were identified. Subgroups differed in perceived stress and COVID-19-specific positive appraisal. Although most participants remained mentally healthy, as observed in the resilient group, we also observed inter-individual differences. Participants' psychological state deteriorated over time in the delayed dysfunction group, putting them at risk for mental disorder development. Consequently, health services should especially identify and allocate resources to vulnerable individuals.

Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures.This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses.Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors.This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

A characteristic feature of borderline personality disorder (BPD) is self-injurious behavior in conjunction with stress-induced reduction of pain perception. Reduced pain sensitivity has been experimentally confirmed in patients with BPD, but the neural correlates of antinociceptive mechanisms in BPD are unknown. We predicted that heat stimuli in patients with BPD would activate brain areas concerned with cognitive and emotional evaluation of pain.To assess the psychophysical properties and neural correlates of altered pain processing in patients with BPD.Case-control study.A university hospital.Twelve women with BPD and self-injurious behavior and 12 age-matched control subjects.Psychophysical assessment and blood oxygen level-dependent functional magnetic resonance imaging during heat stimulation with fixed-temperature heat stimuli and individual-temperature stimuli adjusted for equal subjective pain in all the participants.Blood oxygen level-dependent functional magnetic resonance imaging signal changes during heat pain stimulation.Patients with BPD had higher pain thresholds and smaller overall volumes of activity than controls in response to identical heat stimuli. When the stimulus temperature was individually adjusted for equal subjective pain level, overall volumes of activity were similar, although regional patterns differed significantly. Patient response was greater in the dorsolateral prefrontal cortex and smaller in the posterior parietal cortex. Pain also produced neural deactivation in the perigenual anterior cingulate gyrus and the amygdala in patients with BPD.The interaction between increased pain-induced response in the dorsolateral prefrontal cortex and deactivation in the anterior cingulate and the amygdala is associated with an antinociceptive mechanism in patients with BPD.

Self-mutilation occurs in 70-80% of patients who meet DSM-IV criteria for borderline personality disorder. Approximately 60% of these patients report that they do not feel pain during acts of self-mutilation such as cutting or burning. Findings of recent studies measuring pain perception in patients with BPD are difficult to interpret since variables such as distress, dissociation or relevant psychotropic medication have not been controlled. The Cold Pressor Test (CPT) and the Tourniquet Pain Test (TPT) were administered to 12 female patients with BPD who reported analgesia during self-mutilation and 19 age-matched healthy female control subjects. All subjects were free of psychotropic medication. The patients were studied on two occasions: during self-reported calmness and during intensive distress (strong urge to cut or burn themselves). Even during self-reported calmness, patients with BPD showed a significantly reduced perception of pain compared to healthy control subjects in both tests. During distress, pain perception in BPD patients was further significantly reduced as compared with self-reported calmness. The present findings show that self-mutilating patients with BPD who experience analgesia during self-injury show an increased threshold for pain perception even in the absence of distress. This may reflect a state-independent increased pain threshold which is further elevated during stress. Interpretation of these findings is limited by their reliance upon self-reports.

Increased levels of prostanoids have been implicated in various neuropathological diseases, although little is known about their cellular sources inside the brain. In this study, we analyzed the expression of cyclooxygenase-2 (COX-2), a key enzyme in arachidonic acid metabolism, in rat microglia. COX-2 mRNA and protein as well as prostaglandin E2 formation were almost undetectable in unstimulated microglial cultures but were found to be strongly upregulated in response to lipopolysaccharide. However, in contrast to most peripheral cells, proinflammatory cytokines such as tumor necrosis factor alpha, interleukin-1 beta or interleukin-6 failed to markedly induce COX-2 expression. Similar effects were observed by analyzing transcription nuclear factor-kappa B (NF-kappa B) which was strongly activated in microglia by lipopolysaccharide but not by incubation with cytokines. Moreover, known inhibitors of NF-kappa B activation, such as dexamethasone and the antioxidant pyrrolidine dithiocarbamate, as well as the protein kinase C (PKC) inhibitor Gö6976, strongly reduced lipopolysaccharide-induced COX-2 transcription, indicating the involvement of NF-kappa B and PKC in COX-2 expression. Our results suggest that microglia may represent an important source of prostanoids in the brain, thus reinforcing their prominent role in cerebral inflammatory processes.

Although affective instability is an essential criterion for borderline personality disorder (BPD), it has rarely been reported as an outcome criterion. To date, most of the studies assessing state affective instability in BPD using paper-pencil diaries did not find indications of this characteristic, whereas in others studies, the findings were conflicting. Furthermore, the pattern of instability that characterizes BPD has not yet been identified.We assessed the affective states of 50 female patients with BPD and 50 female healthy controls (HC) during 24 hours of their everyday life using electronic diaries.In contrast to previous paper-and-pencil diary studies, heightened affective instability for both emotional valence and distress was clearly exhibited in the BPD group but not in the HC group. Inconsistencies in previous papers can be explained by the methods used to calculate instability (see Appendix). In additional, we were able to identify a group-specific pattern of instability in the BPD group characterized by sudden large decreases from positive mood states. Furthermore, 48% of the declines from a very positive mood state in BPD were so large that they reached a negative mood state. This was the case in only 9% of the HC group, suggesting that BPD patients, on average, take less time to fluctuate from a very positive mood state to a negative mood state.Future ambulatory monitoring studies will be useful in clarifying which events lead to the reported, sudden decrease in positive mood in BPD patients.

Shame is considered to be a central emotion in borderline personality disorder and to be related to self-injurious behavior, chronic suicidality, and anger-hostility. However, its level and impact on people with borderline personality disorder are largely unknown. The authors examined levels of self-reported shame, guilt, anxiety, and implicit shame-related self-concept in women with borderline personality disorder and assessed the association of shame with self-esteem, quality of life, and anger-hostility.Sixty women with borderline personality disorder completed self-report measures of shame- and guilt-proneness, state shame, anxiety, depression, self-esteem, quality of life, and clinical symptoms. Comparison groups consisted of 30 women with social phobia and 60 healthy women. Implicit shame-related self-concept (relative to anxiety) was assessed by the Implicit Association Test.Women with borderline personality disorder reported higher levels of shame- and guilt-proneness, state shame, and anxiety than women with social phobia and healthy comparison subjects. The implicit self-concept in women with borderline personality disorder was more shame-prone (relative to anxiety-prone) than in women in the comparison groups. After depression was controlled for, shame-proneness was negatively correlated with self-esteem and quality of life and positively correlated with anger-hostility.Shame, an emotion that is prominent in women with borderline personality disorder, is associated with the implicit self-concept as well as with poorer quality of life and self-esteem and greater anger-hostility. Psychotherapeutic approaches to borderline personality disorder need to address explicit and implicit aspects of shame.

The aim of this study was to assess for the first time the prevalence and factors associated with stimulant use exclusively for cognitive enhancement among pupils and university students in Germany.A sample of 1 035 pupils (vocational and grammar schools) in small and big cities and 512 university students of 3 Departments (Medicine, Pharmacy, Economics) completed a questionnaire regarding knowledge and use of stimulants for cognitive enhancement and factors associated with their use.Lifetime prevalence for use of prescription stimulants (methylphenidate, amphetamines) for cognitive enhancement in pupils was 1.55% and in students 0.78%. Last-year and last-month prevalence rates were significantly lower. 2.42% of pupils and 2.93% of students reported lifetime illicit use of stimulants (amphetamines, cocaine, ecstasy) for cognitive enhancement with lower last-year and last-month rates. Prevalence was higher in male pupils, pupils from vocational schools and pupils with bad marks.The illicit use of stimulants for cognitive enhancement is significantly higher than non-medical use of prescription stimulants among pupils and students. Stimulant use is determined by gender, school type, and school marks. The potential risks associated with stimulant use require early awareness and intervention strategies.

We investigated the regulation of COX-2 expression and activity by adenosine receptors in rat microglial cells. The selective adenosine A2a-receptor agonist CGS21680 and the non-selective adenosine A1- and A2-receptor agonist 5'-N-ethylcarboxiamidoadenosine (NECA) induced an increase in COX-2 mRNA levels and the synthesis of prostaglandin E2 (PGE2). The adenosine A1-receptor agonist cyclopentyladenosine (CPA) was less potent, and the adenosine A1-receptor-specific agonist N6-2-(-aminophenylo)ethyladenosine (APNEA) showed only marginal effects. Microglia expressed adenosine A1-, A2a-, and A3-, but not A2b-receptor mRNAs, whereas astroglial cells expressed adenosine A2b- but not A2a-receptor mRNA. The adenosine A2a-receptor selective antagonist (E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine (KF17837) inhibited both CGS21680-induced COX-2 expression and PGE2 release. CGS21680-increased PGE2 levels were inhibited by dexamethasone, by the nonsteroidal antiinflammatory drug meloxicam, and by the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ22536). CGS21680 and NECA both increased intracellular cAMP levels in microglial cells. Dibutyryl cAMP as well as forskolin induced the release of PGE2. The results strongly suggest that adenosine A2a-receptor-induced intracellular signaling events cause an up-regulation of the COX-2 gene and the release of PGE2. Apparently, the cAMP second messenger system plays a crucial role in COX-2 gene regulation in rat microglial cells. The results are discussed with respect to neurodegenerative disorders of the CNS such as Alzheimer's disease, in which activated microglia are critically involved and COX inhibitors may be of therapeutic benefit.

Background Drugs are widely used in borderline personality disorder (BPD) treatment, chosen because of properties known from other psychiatric disorders ("off‐label use"), mostly targeting affective or impulsive symptom clusters. Objectives To assess the effects of drug treatment in BPD patients. Search methods We searched bibliographic databases according to the Cochrane Developmental, Psychosocial and Learning Problems Group strategy up to September 2009, reference lists of articles, and contacted researchers in the field. Selection criteria Randomised studies comparing drug versus placebo, or drug versus drug(s) in BPD patients. Outcomes included total BPD severity, distinct BPD symptom facets according to DSM‐IV criteria, associated psychopathology not specific to BPD, attrition and adverse effects. Data collection and analysis Two authors selected trials, assessed quality and extracted data, independently. Main results Twenty‐eight trials involving a total of 1742 trial participants were included. First‐generation antipsychotics (flupenthixol decanoate, haloperidol, thiothixene); second‐generation antipsychotics (aripirazole, olanzapine, ziprasidone), mood stabilisers (carbamazepine, valproate semisodium, lamotrigine, topiramate), antidepressants (amitriptyline, fluoxetine, fluvoxamine, phenelzine sulfate, mianserin), and dietary supplementation (omega‐3 fatty acid) were tested. First‐generation antipsychotics were subject to older trials, whereas recent studies focussed on second‐generation antipsychotics and mood stabilisers. Data were sparse for individual comparisons, indicating marginal effects for first‐generation antipsychotics and antidepressants. The findings were suggestive in supporting the use of second‐generation antipsychotics, mood stabilisers, and omega‐3 fatty acids, but require replication, since most effect estimates were based on single studies. The long‐term use of these drugs has not been assessed. Adverse event data were scarce, except for olanzapine. There was a possible increase in self‐harming behaviour, significant weight gain, sedation and changes in haemogram parameters with olanzapine. A significant decrease in body weight was observed with topiramate treatment. All drugs were well tolerated in terms of attrition. Direct drug comparisons comprised two first‐generation antipsychotics (loxapine versus chlorpromazine), first‐generation antipsychotic against antidepressant (haloperidol versus amitriptyline; haloperidol versus phenelzine sulfate), and second‐generation antipsychotic against antidepressant (olanzapine versus fluoxetine). Data indicated better outcomes for phenelzine sulfate but no significant differences in the other comparisons, except olanzapine which showed more weight gain and sedation than fluoxetine. The only trial testing single versus combined drug treatment (olanzapine versus olanzapine plus fluoxetine; fluoxetine versus fluoxetine plus olanzapine) yielded no significant differences in outcomes. Authors' conclusions The available evidence indicates some beneficial effects with second‐generation antipsychotics, mood stabilisers, and dietary supplementation by omega‐3 fatty acids. However, these are mostly based on single study effect estimates. Antidepressants are not widely supported for BPD treatment, but may be helpful in the presence of comorbid conditions. Total BPD severity was not significantly influenced by any drug. No promising results are available for the core BPD symptoms of chronic feelings of emptiness, identity disturbance and abandonment. Conclusions have to be drawn carefully in the light of several limitations of the RCT evidence that constrain applicability to everyday clinical settings (among others, patients' characteristics and duration of interventions and observation periods).

Clinical experience suggests that people with borderline personality disorder often meet criteria for attention-deficit hyperactivity disorder (ADHD). However, empirical data are sparse.To establish the prevalence of childhood and adult ADHD in a group of women with borderline personality disorder and to investigate the psychopathology and childhood experiences of those with and without ADHD.We assessed women seeking treatment for borderline personality disorder (n=118) for childhood and adult ADHD, co-occurring Axis I and Axis II disorders, severity of borderline symptomatology and traumatic childhood experiences.Childhood (41.5%) and adult (16.1%) ADHD prevalence was high. Childhood ADHD was associated with emotional abuse in childhood and greater severity of adult borderline symptoms. Adult ADHD was associated with greater risk for co-occurring Axis I and II disorders.Adults with severe borderline personality disorder frequently show a history of childhood ADHD symptomatology. Persisting ADHD correlates with frequency of co-occurring Axis I and II disorders. Severity of borderline symptomatology in adulthood is associated with emotional abuse in childhood. Further studies are needed to differentiate any potential causal relationship between ADHD and borderline personality disorder.

Interferon alpha (IFNalpha) is used for the treatment of several disorders, such as chronic hepatitis or malignant melanoma. During the therapy, IFNalpha may cause severe neuropsychiatric syndromes including depression with suicidal ideation, paranoid psychoses, or confusional states. The reasons and management of these side effects are widely unknown. Our aim is to review research evidence for the contribution of IFNalpha for the etiopathology of psychiatric syndromes. Therefore, research findings of neuropsychiatric syndromes induced by IFNalpha treatment, the putative mechanisms underlying those syndromes, and their treatment are-reviewed. Furthermore, neuropsychiatric syndromes in diseases with high IFNalpha levels such as systemic lupus erythematosus (SLE) are discussed. Finally, the question is addressed whether IFNalpha may contribute to the etiopathology of endogenous psychiatric disorders. IFNalpha may cause psychiatric syndromes in a subset of treated patients. The underlying pathogenetic mechanisms include various effects on neuroendocrine, cytokine, and neurotransmitter systems. Research data on the role of IFNalpha in the pathogenesis of endogenous psychiatric disorders are conflicting. Future research should improve our understanding of the role of IFNalpha for the etiopathology of psychiatric syndromes and has an impact on treatment of IFNalpha-induced psychiatric syndromes.

The neuropeptide substance P is a major mediator of neurogenic inflammation and immunomodulatory activities within the central and peripheral nervous system. In several cell types, substance P induces the expression of proinflammatory cytokines that have been implicated in the pathogenesis of different neuropathologies. Substance P preferentially binds to NK-1, a receptor of the neurokinin family, but how the receptor-elicited signal is translated into inflammatory gene expression is not yet understood. In this work, we describe that in U373 MG astrocytoma cells, nanomolar concentrations of substance P potently triggered activation of NF-kappa B, a transcription factor involved in the control of cytokine expression and apoptosis. Substance P-induced NF-kappa B activation was associated with the increased mRNA expression and secretion of IL-8, an NF-kappa B-controlled target gene. The stimulatory effect of substance P was specific, since an NK-1-selective receptor antagonist completely prevented NF-kappa B activation in response to substance P, but not IL-1 beta. In addition, we show that the activity of substance P required mobilization of intracellular calcium and formation of reactive oxygen intermediates as second messengers. Our results suggest that NF-kappa B may be an important component controlling neurogenic inflammation within the peripheral and central nervous system.

The aim of the present study was to investigate whether there is a difference in evening/nocturnal interleukin-6 (IL-6) serum excretion in patients with primary insomnia compared to controls. We hypothesized that in insomniac patients, the excretion of evening/nocturnal IL-6 is enhanced, like observed in aged adults and after sleep deprivation in healthy subjects. We studied IL-6 serum concentrations in 11 patients (two males and nine females) with primary insomnia and 11 age and gender-matched healthy controls. Sleep was monitored polysomnographically for three consecutive nights. The measurement of IL-6 (from 19:00 h to 09:00 h) in 2-h intervals were performed prior to and during the last laboratory night. Polysomnographically determined sleep parameters and subjective ratings of sleep demonstrated clear-cut impairments of sleep in the insomniac group. Nocturnal IL-6 secretion was significantly increased (p<.05) in insomniac patients for the whole measurement period (mean area under the curve+/-SD: 27.94+/-14.15 pg/ml x 2h) compared to controls (16.70+/-7.64 pg/ml x 2h). Total IL-6 secretion correlated inversely with subjectively perceived sleep quality and amount of slow wave sleep in the insomniac patients. Amount of Wake Time correlated positively with IL-6 excretion in insomniacs. The results of the present study demonstrate significantly increased nocturnal IL-6 secretion in insomniacs. It might be speculated that chronic primary insomnia with polysomnographically documented sleep impairments activates the production of IL-6 analogous to sleep deprivation studies in healthy subjects. This might also implicate a higher risk for inflammatory and cardiovascular diseases in patients with chronic insomnia.

Subtle prefrontal and limbic structural abnormalities have been reported in borderline personality disorder (BPD). In order to further validate the previously reported findings and to more precisely describe the nature of the structural change we performed a voxel-based morphometric (VBM) study in patients with BPD. Twenty female patients with BPD and 21 female healthy controls were investigated. High-resolution 3-D datasets were acquired and analyzed following an optimized protocol of VBM in the framework of statistical parametric mapping (SPM99). Gray matter volume loss was found in the left amygdala. No other differences in gray or white matter volume or density were found anywhere else in the brain. Our findings support the hypothesis that temporolimbic abnormalities play a role in the pathophysiology of BPD. Prefrontal structural alterations in BPD were not observed in this study.

Affective dysregulation and dissociation are currently discussed as core features of borderline personality disorder (BPD). Affective dysregulation is hypothesized to be correlated with increased amygdala functioning and dissociation is linked to inhibited processing on the amygdala and dampened autonomic output, according to the corticolimbic disconnection model of dissociation from Sierra and Berrios [Biological Psychiatry 44 (1998) 898]. We assessed startle response, which is mainly mediated by the amygdala, to investigate the relationship between affective dysregulation and dissociation. We hypothesized that patients with BPD would reveal enhanced responses to startling tones, but that these would be lessened by the presence of state dissociative experiences. 21 unmedicated female patients with BPD and 21 healthy female controls listened to 15 startling tones (95-dB, 500-ms, 1000-Hz) while heart rate, skin conductance and orbicularis oculi electromyogram responses were measured. Covariance analysis showed that the BPD group had a significantly higher startle response in the electromyogram as compared to controls. Furthermore, present-state dissociative experiences significantly influenced the startle response. Patients with low dissociative experiences revealed enhanced startle responses whereas patients with high dissociative experiences showed reduced responses. Our data support affective dysregulation in BPD as well as the corticolimbic disconnection model of dissociation, at least for EMG. Furthermore, it highlights the importance of assessing present-state dissociation in basic research as well as psychotherapy.

Study Objective To estimate the 12‐month prevalence of cognitive‐enhancing drug use. Design Paper‐and‐pencil questionnaire that used the randomized response technique. Setting University in Mainz, Germany. Participants A total of 2569 university students who completed the questionnaire. Measurements and Main Results An anonymous, specialized questionnaire that used the randomized response technique was distributed to students at the beginning of classes and was collected afterward. From the responses, we calculated the prevalence of students taking drugs only to improve their cognitive performance and not to treat underlying mental disorders such as attention‐deficit–hyperactivity disorder, depression, and sleep disorders. The estimated 12‐month prevalence of using cognitive‐enhancing drugs was 20%. Prevalence varied by sex (male 23.7%, female 17.0%), field of study (highest in students studying sports‐related fields, 25.4%), and semester (first semester 24.3%, beyond first semester 16.7%). To our knowledge, this is the first time that the randomized response technique has been used to survey students about cognitive‐enhancing drug use. Conclusion Using the randomized response technique, our questionnaire provided data that showed a high 12‐month prevalence of cognitive‐enhancing drug use in German university students. Our study suggests that other direct survey techniques have underestimated the use of these drugs. Drug prevention programs need to be established at universities to address this issue.

The processing of verbal fluency tasks relies on the coordinated activity of a number of brain areas, particularly in the frontal and temporal lobes of the left hemisphere. Recent studies using functional magnetic resonance imaging (fMRI) to study the neural networks subserving verbal fluency functions have yielded divergent results especially with respect to a parcellation of the inferior frontal gyrus for phonemic and semantic verbal fluency. We conducted a coordinate-based activation likelihood estimation (ALE) meta-analysis on brain activation during the processing of phonemic and semantic verbal fluency tasks involving 28 individual studies with 490 healthy volunteers. For phonemic as well as for semantic verbal fluency, the most prominent clusters of brain activation were found in the left inferior/middle frontal gyrus (LIFG/MIFG) and the anterior cingulate gyrus. BA 44 was only involved in the processing of phonemic verbal fluency tasks, BA 45 and 47 in the processing of phonemic and semantic fluency tasks. Our comparison of brain activation during the execution of either phonemic or semantic verbal fluency tasks revealed evidence for spatially different activation in BA 44, but not other regions of the LIFG/LMFG (BA 9, 45, 47) during phonemic and semantic verbal fluency processing.

OBJECTIVE: The study sought to better understand why some people with mental illness self-stigmatize and develop low self-esteem while others remain indifferent to stigma or respond with a sense of empowerment. The authors hypothesized that a high level of perceived discrimination, little sense of identification with the group of people with mental illness, and a high level of perceived legitimacy of discrimination lead to self-stigma. METHODS: Sixty women with borderline personality disorder and 30 women with social phobia, who were recruited at three centers in Germany and Switzerland, completed stigma-related questionnaires. RESULTS: After depression and index diagnosis were controlled for, a low level of perceived discrimination and of the legitimacy of discrimination predicted high self-esteem and high empowerment. Identification with the group of people with mental illness did not predict self-esteem or empowerment. CONCLUSIONS: Perceived legitimacy of discrimination may be a crucial determinant of a person's response to stigma.

Methylation of the promoter of brain-derived neurotrophic factor exon IV and antidepressant response in major depression

Wagner S, Doering B, Helmreich I, Lieb K, Tadić A. A meta‐analysis of executive dysfunctions in unipolar major depressive disorder without psychotic symptoms and their changes during antidepressant treatment. Objective: Empirical evidence supports the existence of significant executive deficits in patients with major depressive disorder (MDD) as compared to non‐depressed controls. Nevertheless, the effect size of executive dysfunctions in unipolar, non‐psychotic MDD as well as their relationship to antidepressant treatment is ambiguous. Method: Meta‐analytic methods were used to assess the severity of executive dysfunctions in unipolar, non‐psychotic MDD as compared to healthy controls and to investigate their course during antidepressant treatment. Results: Fifteen studies comparing the executive functions of 375 patients with DSM‐IV MDD and 481 healthy controls were analysed. Furthermore, in three studies, including 122 patients with MDD, the Stroop test performance was examined before and after antidepressant treatment. Patients with MDD performed 0.439 up to 1.18 ( P &lt; 0.0001) standard mean differences worse than healthy controls. The Stroop performance improved during the course of treatment ( P = 0.0001). Conclusion: We revealed significant executive dysfunctions in patients with unipolar, non‐psychotic MDD compared with healthy controls and an improvement of the Stroop performance during the course of treatment. Future studies with different test procedures are needed to further investigate the influence of antidepressant treatment on executive functions.

Antisocial personality disorder (AsPD) is associated with a wide range of disturbance including persistent rule-breaking, criminality, substance use, unemployment, homelessness and relationship difficulties.To evaluate the potential beneficial and adverse effects of psychological interventions for people with AsPD.Our search included CENTRAL Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsycINFO, ASSIA, BIOSIS and COPAC.Prospective, controlled trials in which participants with AsPD were randomly allocated to a psychological intervention and a control condition (either treatment as usual, waiting list or no treatment).Three authors independently selected studies. Two authors independently extracted data. We calculated mean differences, with odds ratios for dichotomous data.Eleven studies involving 471 participants with AsPD met the inclusion criteria, although data were available from only five studies involving 276 participants with AsPD. Only two studies focused solely on an AsPD sample. Eleven different psychological interventions were examined. Only two studies reported on reconviction, and only one on aggression. Compared to the control condition, cognitive behaviour therapy (CBT) plus standard maintenance was superior for outpatients with cocaine dependence in one study, but CBT plus treatment as usual was not superior for male outpatients with recent verbal/physical violence in another. Contingency management plus standard maintenance was superior for drug misuse for outpatients with cocaine dependence in one study but not in another, possibly because of differences in the behavioural intervention. However, contingency management was superior in social functioning and counselling session attendance in the latter. A multi-component intervention utilising motivational interviewing principles, the 'Driving Whilst Intoxicated program', plus incarceration was superior to incarceration alone for imprisoned drink-driving offenders.Results suggest that there is insufficient trial evidence to justify using any psychological intervention for adults with AsPD. Disappointingly few of the included studies addressed the primary outcomes defined in this review (aggression, reconviction, global functioning, social functioning, adverse effects). Three interventions (contingency management with standard maintenance; CBT with standard maintenance; 'Driving Whilst Intoxicated program' with incarceration) appeared effective, compared to the control condition, in terms of improvement in at least one outcome in at least one study. Each of these interventions had been originally developed for people with substance misuse problems. Significant improvements were mainly confined to outcomes related to substance misuse. No study reported significant change in any specific antisocial behaviour. Further research is urgently needed for this prevalent and costly condition.

Little is known about how women with borderline personality disorder (BPD) and women with social phobia react to mental illness stigma. The goal of this study was to assess empirically self-stigma and its correlates in these groups. Self-stigma and related constructs were measured by self-report questionnaires among 60 women with BPD and 30 women with social phobia. Self-stigma was inversely related to self-esteem, self-efficacy, and quality of life and predicted low self-esteem after controlling for depression and shame-proneness. Stereotype awareness was not significantly correlated with self-esteem or quality of life. While there was no difference in stereotype awareness between women with BPD and women with social phobia, women with BPD showed higher self-stigma than women with social phobia. Self-stigma is associated with low self-esteem and other indices of poor psychological well-being. In comparison to women with social phobia, women with BPD suffer from more self-stigma. This may reflect intense labeling processes as being mentally ill due to repeated hospitalizations, frequent interpersonal difficulties, and visible scars.

Response inhibition is disturbed in several disorders sharing impulse control deficits as a core symptom. Since response inhibition is a cognitively and neurally multifaceted function which has been shown to rely on differing neural subprocesses and neurotransmitter systems, further differentiation to define neurophysiological endophenotypes is essential. Response inhibition may involve at least three separable cognitive subcomponents, i.e. interference inhibition, action withholding, and action cancelation. Here, we introduce a novel paradigm – the Hybrid Response Inhibition task – to disentangle interference inhibition, action withholding and action cancelation and their neural subprocesses within one task setting during functional magnetic resonance imaging (fMRI). To validate the novel task, results were compared to a battery of separate, standard response inhibition tasks independently capturing these subcomponents and subprocesses. Across all subcomponents, mutual activation was present in the right inferior frontal cortex (rIFC), pre-supplementary motor area (pre-SMA) and parietal regions. Interference inhibition revealed stronger activation in pre-motor and parietal regions. Action cancelation resulted in stronger activation in fronto-striatal regions. Our results show that all subcomponents share a common neural network and thus all constitute different subprocesses of response inhibition. Subprocesses, however, differ to the degree of regional involvement: interference inhibition relies more pronouncedly on a fronto-parietal–pre-motor network suggesting its close relation to response selection processes. Action cancelation, in turn, is more strongly associated with the fronto-striatal pathway implicating it as a late subcomponent of response inhibition. The new paradigm reliably captures three putatively subsequent subprocesses of response inhibition and might be a promising tool to differentially assess disturbed neural networks in disorders showing impulse control deficits.

In addition to reduced pain perception, patients with borderline personality disorder (BPD) show higher pain thresholds under subjective stress conditions as compared with non-stress conditions. However, the correlation between symptoms of stress and pain thresholds has not been investigated so far. Using a new and convenient methodology, electric stimulation, we expected higher pain and detection thresholds in patients with BPD than in to healthy controls as well as a positive correlation between pain thresholds and symptoms of stress (aversive arousal and dissociation) in BPD patients. Twelve female patients with BPD and twelve healthy controls were included in the study. Electric stimulation was applied on the right index finger, and detection and pain thresholds were assessed by gradually intensifying the stimuli. We found significantly elevated pain thresholds in patients with BPD as compared with healthy controls, but no difference between patients and controls in detection thresholds. In patients, a significant positive correlation was revealed between pain thresholds and dissociation as well as between pain thresholds and aversive arousal. Besides demonstrating a close correlation between pain thresholds and symptoms of stress in patients with BPD, this study replicated earlier findings of reduced pain perception in patients with BPD. Measuring electric pain thresholds is a valid and reasonable method for larger studies.

These practical guidelines for the biological treatment of personality disorders in primary care settings were developed by an international Task Force of the World Federation of Societies of Biological Psychiatry (WFSBP). They embody the results of a systematic review of all available clinical and scientific evidence pertaining to the biological treatment of three specific personality disorders, namely borderline, schizotypal and anxious/avoidant personality disorder in addition to some general recommendations for the whole field. The guidelines cover disease definition, classification, epidemiology, course and current knowledge on biological underpinnings, and provide a detailed overview on the state of the art of clinical management. They deal primarily with biological treatment (including antidepressants, neuroleptics, mood stabilizers and some further pharmacological agents) and discuss the relative significance of medication within the spectrum of treatment strategies that have been tested for patients with personality disorders, up to now. The recommendations should help the clinician to evaluate the efficacy spectrum of psychotropic drugs and therefore to select the drug best suited to the specific psychopathology of an individual patient diagnosed for a personality disorder.

Surgeons are usually exposed to high workloads leading to fatigue and stress. This not only increases the likelihood of mistakes during surgery but also puts pressure on surgeons to use drugs to counteract fatigue, distress, concentration deficits, burnout or symptoms of depression. The prevalence of surgeons taking pharmacological cognitive enhancement (CE) or mood enhancement (ME) drugs has not been systematically assessed so far.Surgeons who attended five international conferences in 2011 were surveyed with an anonymous self-report questionnaire (AQ) regarding the use of prescription or illicit drugs for CE and ME and factors associated with their use. The Randomized Response Technique (RRT) was used in addition. The RRT guarantees a high degree of anonymity and confidentiality when a person is asked about stigmatizing issues, such as drug abuse.A total of 3,306 questionnaires were distributed and 1,145 entered statistical analysis (response rate: 36.4%). According to the AQ, 8.9% of all surveyed surgeons confessed to having used a prescription or illicit drug exclusively for CE at least once during lifetime. As one would expect, the prevalence rate assessed by RRT was approximately 2.5-fold higher than that of the AQ (19.9%; 95% confidence interval (CI), 15.9% to 23.9%, N = 1,105). An even larger discrepancy between the RRT and AQ was observed for the use of antidepressants with a 6-fold higher prevalence (15.1%; 95% CI, 11.3% to 19.0%, N = 1,099) as compared to 2.4% with the AQ. Finally, logistic regression analysis revealed that pressure to perform at work (odds ratio (OR): 1.290; 95% CI, 1.000 to 1.666; P = 0.05) or in private life (OR: 1.266; 95% CI, 1.038 to 1.543; P = 0.02), and gross income (OR: 1.337; 95% CI, 1.091 to 1.640; P = 0.005), were positively associated with the use of drugs for CE or ME.The use of illicit and prescription drugs for CE or ME is an underestimated phenomenon among surgeons which is generally attributable to high workload, perceived workload, and private stress. Such intake of drugs is associated with attempts to counteract fatigue and loss of concentration. However, drug use for CE may lead to addiction and to overestimation of one's own capabilities, which can put patients at risk. Coping strategies should be taught during medical education.

Disorders such as borderline personality disorder (BPD) or attention-deficit/hyperactivity disorder (ADHD) are characterized by impulsive behaviors. Impulsivity as used in clinical terms is very broadly defined and entails different categories including personality traits as well as different cognitive functions such as emotion regulation or interference resolution and impulse control. Impulse control as an executive function, however, is neither cognitively nor neurobehaviorally a unitary function. Recent findings from behavioral and cognitive neuroscience studies suggest related but dissociable components of impulse control along functional domains like selective attention, response selection, motivational control, and behavioral inhibition. In addition, behavioral and neural dissociations are seen for proactive vs. reactive inhibitory motor control. The prefrontal cortex with its sub-regions is the central structure in executing these impulse control functions. Based on these concepts of impulse control, neurobehavioral findings of studies in BPD and ADHD were reviewed and systematically compared. Overall, patients with BPD exhibited prefrontal dysfunctions across impulse control components rather in orbitofrontal, dorsomedial, and dorsolateral prefrontal regions, whereas patients with ADHD displayed disturbed activity mainly in ventrolateral and medial prefrontal regions. Prefrontal dysfunctions, however, varied depending on the impulse control component and from disorder to disorder. This suggests a dissociation of impulse control related frontal dysfunctions in BPD and ADHD, although only few studies are hitherto available to assess frontal dysfunctions along different impulse control components in direct comparison of these disorders. Yet, these findings might serve as a hypothesis for the future systematic assessment of impulse control components to understand differences and commonalities of prefrontal cortex dysfunction in impulsive disorders.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the effects of resilience‐enhancing interventions in clinical and non‐clinical populations.

The majority of patients with Major Depressive Disorder (MDD) suffer from significant executive dysfunctions. To investigate the time course of executive functions during antidepressant treatment, repeated measures of executive functions are necessary. In order to avoid practice effects, the assessment of alternate forms is suggested. The aim of this study was to compare the processing times of four alternate versions of the Trail Making Test (TMT) A and B in patients with MDD. Fifty-five subjects with DSM-IV MDD were included in the study. We analyzed mean processing times and retest reliability of the four versions of TMT A and B. Mean processing times did not differ between the four tested versions of TMT A and B. Retest reliability of TMT A and B was between 0.76 and 0.89 and between 0.86 and 0.94, respectively. Because of their identical difficulty and high reliability, the herein described versions of the TMT A and B are suitable for sequential testing of executive functioning.

<h3>Objective:</h3> We investigated induction of α-secretase A disintegrin and metalloprotease 10 (ADAM10) by the synthetic retinoid acitretin (Neotigason; Actavis, München-Riem, Germany) in patients with mild to moderate Alzheimer disease (AD) via measurement of CSF content of α-secretase–derived amyloid precursor protein (APPs-α). <h3>Methods:</h3> Twenty-one patients clinically diagnosed with mild to moderate AD received acitretin (30 mg per day) or placebo in a 4-week double-blind study. Primary endpoint was the difference of CSF APPs-α ratios calculated from the APPs-α levels after treatment and at baseline. We monitored safety and tolerability of the treatment. In addition, we assessed biomarkers such as β-amyloid 42 (Aβ₄₂) under treatment conditions. <h3>Results:</h3> The acitretin group showed a significant increase in CSF APPs-α levels compared with the placebo group (difference 0.38, 95% confidence interval 0.03–0.72, <i>p</i> = 0.035) within this rather short treatment period. The synthetic retinoid acitretin was overall safe and well tolerated. <h3>Conclusions:</h3> Our pilot study highlights that acitretin is able to enhance the nonamyloidogenic APP processing in human patients. Clinical consequences of this regulation should be investigated in larger and longer trials in patients with AD to evaluate acitretin9s potential to serve as a novel therapeutic drug. <h3>Classification of evidence:</h3> This study provides Class III evidence that in patients with AD, oral acitretin increases CSF APPs-α levels.

The prescribing behaviour of doctors is influenced by the pharmaceutical industry. This study investigated the extent to which contacts with pharmaceutical sales representatives (PSR) and the perception of these contacts influence prescribing habits.An online questionnaire regarding contact with PSRs and perceptions of this contact was sent to 1,388 doctors, 11.5% (n = 160) of whom completed the survey. Individual prescribing data over a year (number of prescriptions, expenditure, and daily doses) for all on-patent branded, off-patent branded, and generic drugs were obtained from the Bavarian Association of Statutory Health Insurance Physicians.84% of the doctors saw PSR at least once a week, and 14% daily. 69% accepted drug samples, 39% accepted stationery and 37% took part in sponsored continuing medical education (CME) frequently. 5 physicians (3%) accepted no benefits at all. 43% of doctors believed that they received adequate and accurate information from PSRs frequently or always and 42% believed that their prescribing habits were influenced by PSR visits occasionally or frequently. Practices that saw PSRs frequently had significantly higher total prescriptions and total daily doses (but not expenditure) than practices that were less frequently visited. Doctors who believed that they received accurate information from PSRs showed higher expenditures on off-patent branded drugs (thus available as generics) and a lower proportion of generics. The eschewal of sponsored CME was associated with a lower proportion of on patent-branded drug prescriptions, lower expenditure on off-patent branded drug prescriptions and a higher proportion of generics. Acceptance of office stationery was associated with higher daily doses.Avoidance of industry-sponsored CME is associated with more rational prescribing habits. Furthermore, gift acceptance and the belief that one is receiving adequate information from a PSR are associated with changed prescribing habits. Further studies with larger sample sizes are needed.

Inhibitory deficits contribute to cognitive decline in the aging brain. Separating subcomponents of response inhibition may help to resolve contradictions in the existing literature. A total of 49 healthy participants underwent functional magnetic resonance imaging (fMRI) while performing a Go/no-go-, a Simon-, and a Stop-signal task. Regression analyses were conducted to identify correlations of age and activation patterns. Imaging results revealed a differential effect of age on subcomponents of response inhibition. In a simple Go/no-go task (no spatial discrimination), aging was associated with increased activation of the core inhibitory network and parietal areas. In the Simon task, which required spatial discrimination, increased activation in additional inhibitory control regions was present. However, in the Stop-signal task, the most demanding of the three tasks, aging was associated with decreased activation. This suggests that older adults increasingly recruit the inhibitory network and, with increasing load, additional inhibitory regions. However, if inhibitory load exceeds compensatory capacity, performance declines in concert with decreasing activation. Thus, the present findings may refine current theories of cognitive aging.

Background Resilience can be defined as maintaining or regaining mental health during or after significant adversities such as a potentially traumatising event, challenging life circumstances, a critical life transition or physical illness. Healthcare students, such as medical, nursing, psychology and social work students, are exposed to various study‐ and work‐related stressors, the latter particularly during later phases of health professional education. They are at increased risk of developing symptoms of burnout or mental disorders. This population may benefit from resilience‐promoting training programmes. Objectives To assess the effects of interventions to foster resilience in healthcare students, that is, students in training for health professions delivering direct medical care (e.g. medical, nursing, midwifery or paramedic students), and those in training for allied health professions, as distinct from medical care (e.g. psychology, physical therapy or social work students). Search methods We searched CENTRAL, MEDLINE, Embase, 11 other databases and three trial registries from 1990 to June 2019. We checked reference lists and contacted researchers in the field. We updated this search in four key databases in June 2020, but we have not yet incorporated these results. Selection criteria Randomised controlled trials (RCTs) comparing any form of psychological intervention to foster resilience, hardiness or post‐traumatic growth versus no intervention, waiting list, usual care, and active or attention control, in adults (18 years and older), who are healthcare students. Primary outcomes were resilience, anxiety, depression, stress or stress perception, and well‐being or quality of life. Secondary outcomes were resilience factors. Data collection and analysis Two review authors independently selected studies, extracted data, assessed risks of bias, and rated the certainty of the evidence using the GRADE approach (at post‐test only). Main results We included 30 RCTs, of which 24 were set in high‐income countries and six in (upper‐ to lower‐) middle‐income countries. Twenty‐two studies focused solely on healthcare students (1315 participants; number randomised not specified for two studies), including both students in health professions delivering direct medical care and those in allied health professions, such as psychology and physical therapy. Half of the studies were conducted in a university or school setting, including nursing/midwifery students or medical students. Eight studies investigated mixed samples (1365 participants), with healthcare students and participants outside of a health professional study field. Participants mainly included women (63.3% to 67.3% in mixed samples) from young adulthood (mean age range, if reported: 19.5 to 26.83 years; 19.35 to 38.14 years in mixed samples). Seventeen of the studies investigated group interventions of high training intensity (11 studies; > 12 hours/sessions), that were delivered face‐to‐face (17 studies). Of the included studies, eight compared a resilience training based on mindfulness versus unspecific comparators (e.g. wait‐list). The studies were funded by different sources (e.g. universities, foundations), or a combination of various sources (four studies). Seven studies did not specify a potential funder, and three studies received no funding support. Risk of bias was high or unclear, with main flaws in performance, detection, attrition and reporting bias domains. At post‐intervention, very‐low certainty evidence indicated that, compared to controls, healthcare students receiving resilience training may report higher levels of resilience (standardised mean difference (SMD) 0.43, 95% confidence interval (CI) 0.07 to 0.78; 9 studies, 561 participants), lower levels of anxiety (SMD −0.45, 95% CI −0.84 to −0.06; 7 studies, 362 participants), and lower levels of stress or stress perception (SMD −0.28, 95% CI −0.48 to −0.09; 7 studies, 420 participants). Effect sizes varied between small and moderate. There was little or no evidence of any effect of resilience training on depression (SMD −0.20, 95% CI −0.52 to 0.11; 6 studies, 332 participants; very‐low certainty evidence) or well‐being or quality of life (SMD 0.15, 95% CI −0.14 to 0.43; 4 studies, 251 participants; very‐low certainty evidence). Adverse effects were measured in four studies, but data were only reported for three of them. None of the three studies reported any adverse events occurring during the study (very‐low certainty of evidence). Authors' conclusions For healthcare students, there is very‐low certainty evidence for the effect of resilience training on resilience, anxiety, and stress or stress perception at post‐intervention. The heterogeneous interventions, the paucity of short‐, medium‐ or long‐term data, and the geographical distribution restricted to high‐income countries limit the generalisability of results. Conclusions should therefore be drawn cautiously. Since the findings suggest positive effects of resilience training for healthcare students with very‐low certainty evidence, high‐quality replications and improved study designs (e.g. a consensus on the definition of resilience, the assessment of individual stressor exposure, more attention controls, and longer follow‐up periods) are clearly needed.

The SARS-CoV-2 pandemic has caused mental stress in a number of ways: overstrain of the health care system, lockdown of the economy, restricted opportunities for interpersonal contact and excursions outside the home and workplace, and quarantine measures where necessary. In this article, we provide an overview of psychological distress in the current pandemic, identifying protective factors and risk factors.The PubMed, PsycINFO, and Web of Science databases were systematically searched for relevant publications (1 January 2019 - 16 April 2020). This study was registered in OSF Registries (osf.io/34j8g). Data on mental stress and resilience in Germany were obtained from three surveys carried out on more than 1000 participants each in the framework of the COSMO study (24 March, 31 March, and 21 April 2020).18 studies from China and India, with a total of 79 664 participants, revealed increased stress in the general population, with manifestations of depression and anxiety, post-traumatic stress, and sleep disturbances. Stress was more marked among persons working in the health care sector. Risk factors for stress included patient contact, female sex, impaired health status, worry about family members and significant others, and poor sleep quality. Protective factors included being informed about the increasing number of persons who have recovered from COVID, social support, and a lower perceived infectious risk. The COSMO study, though based on an insufficiently representative population sample because of a low questionnaire return rate (<20%), revealed increased rates of despondency, loneliness, and hopelessness in the German population as compared to norm data, with no change in estimated resilience.Stress factors associated with the current pandemic probably increase stress by causing anxiety and depression. Once the protective factors and risk factors have been identified, these can be used to develop psychosocial interventions. The informativeness of the results reported here is limited by the wide variety of instruments used to acquire data and by the insufficiently representative nature of the population samples.

Motor inhibitory control implemented as response inhibition is an essential cognitive function required to dynamically adapt to rapidly changing environments. Despite over a decade of research on the neural mechanisms of response inhibition, it remains unclear, how exactly response inhibition is initiated and implemented. Using a multimodal MEG/fMRI approach in 59 subjects, our results reliably reveal that response inhibition is initiated by the right inferior frontal gyrus (rIFG) as a form of attention-independent top-down control that involves the modulation of beta-band activity. Furthermore, stopping performance was predicted by beta-band power, and beta-band connectivity was directed from rIFG to pre-supplementary motor area (pre-SMA), indicating rIFG's dominance over pre-SMA. Thus, these results strongly support the hypothesis that rIFG initiates stopping, implemented by beta-band oscillations with potential to open up new ways of spatially localized oscillation-based interventions.

Resilience has been defined as the maintenance or quick recovery of mental health during and after times of adversity. How to operationalize resilience and to determine the factors and processes that lead to good long-term mental health outcomes in stressor-exposed individuals is a matter of ongoing debate and of critical importance for the advancement of the field. One of the biggest challenges for implementing an outcome-based definition of resilience in longitudinal observational study designs lies in the fact that real-life adversity is usually unpredictable and that its substantial qualitative as well as temporal variability between subjects often precludes defining circumscribed time windows of inter-individually comparable stressor exposure relative to which the maintenance or recovery of mental health can be determined. To address this pertinent issue, we propose to frequently and regularly monitor stressor exposure (E) and mental health problems (P) throughout a study's observation period [Frequent Stressor and Mental Health Monitoring (FRESHMO)-paradigm]. On this basis, a subject's deviation at any single monitoring time point from the study sample's normative E–P relationship (the regression residual) can be used to calculate that subject's current mental health reactivity to stressor exposure (“stressor reactivity,” SR). The SR score takes into account the individual extent of experienced adversity and is comparable between and within subjects. Individual SR time courses across monitoring time points reflect intra-individual temporal variability in SR, where periods of under-reactivity (negative SR score) are associated with accumulation of fewer mental health problems than is normal for the sample. If FRESHMO is accompanied by regular measurement of potential resilience factors, temporal changes in resilience factors can be used to predict SR time courses. An increase in a resilience factor measurement explaining a lagged decrease in SR can then be considered to index a process of adaptation to stressor exposure that promotes a resilient outcome (an allostatic resilience process). This design principle allows resilience research to move beyond merely determining baseline predictors of resilience outcomes, which cannot inform about how individuals successfully adjust and adapt when confronted with adversity. Hence, FRESHMO plus regular resilience factor monitoring incorporates a dynamic-systems perspective into resilience research.

The aim of this study was to identify interventions targeting children and their caregivers to reduce psychosocial problems in the course of the COVID-19 pandemic and comparable outbreaks. The review was performed using systematic literature searches in MEDLINE, Embase, PsycINFO and COVID-19-specific databases, including the CDC COVID-19 Research Database, the World Health Organisation (WHO) Global Database on COVID-19 Research and the Cochrane COVID-19 Study Register, ClinicalTrials.gov, the EU Clinical Trials Register and the German Clinical Trials Register (DRKS) up to 25th September 2020. The search yielded 6657 unique citations. After title/abstract and full text screening, 11 study protocols reporting on trials planned in China, the US, Canada, the UK, and Hungary during the COVID-19 pandemic were included. Four interventions targeted children ≥10 years directly, seven system-based interventions targeted the parents and caregivers of younger children and adolescents. Outcome measures encompassed mainly anxiety and depressive symptoms, different dimensions of stress or psychosocial well-being, and quality of supportive relationships. In conclusion, this systematic review revealed a paucity of studies on psychosocial interventions for children during the COVID-19 pandemic. Further research should be encouraged in light of the expected demand for child mental health management.

A recently updated Cochrane review supports the efficacy of psychotherapy for borderline personality disorder (BPD).To evaluate the effects of standalone and add-on psychotherapeutic treatments more concisely.We applied the same methods as the 2020 Cochrane review, but focused on adult samples and comparisons of active treatments and unspecific control conditions. Standalone treatments (i.e. necessarily including individual psychotherapy as either the sole or one of several treatment components) and add-on interventions (i.e. complementing any ongoing individual BPD treatment) were analysed separately. Primary outcomes were BPD severity, self-harm, suicide-related outcomes and psychosocial functioning. Secondary outcomes were remaining BPD diagnostic criteria, depression and attrition.Thirty-one randomised controlled trials totalling 1870 participants were identified. Among standalone treatments, statistically significant effects of low overall certainty were observed for dialectical behaviour therapy (self-harm: standardised mean difference (SMD) -0.54, P = 0.006; psychosocial functioning: SMD -0.51, P = 0.01) and mentalisation-based treatment (self-harm: risk ratio 0.51, P < 0.0007; suicide-related outcomes: risk ratio 0.10, P < 0.0001). For adjunctive interventions, moderate-quality evidence of beneficial effects was observed for DBT skills training (BPD severity: SMD -0.66, P = 0.002; psychosocial functioning: SMD -0.45, P = 0.002), and statistically significant low-certainty evidence was observed for the emotion regulation group (BPD severity: mean difference -8.49, P < 0.00001), manual-assisted cognitive therapy (self-harm: mean difference -3.03, P = 0.03; suicide-related outcomes: SMD -0.96, P = 0.005) and the systems training for emotional predictability and problem-solving (BPD severity: SMD -0.48, P = 0.002).There is reasonable evidence to conclude that psychotherapeutic interventions are helpful for individuals with BPD. Replication studies are needed to enhance the certainty of findings.

Background Among people with a diagnosis of borderline personality disorder (BPD) who are engaged in clinical care, prescription rates of psychotropic medications are high, despite the fact that medication use is off‐label as a treatment for BPD. Nevertheless, people with BPD often receive several psychotropic drugs at a time for sustained periods. Objectives To assess the effects of pharmacological treatment for people with BPD. Search methods For this update, we searched CENTRAL, MEDLINE, Embase, 14 other databases and four trials registers up to February 2022. We contacted researchers working in the field to ask for additional data from published and unpublished trials, and handsearched relevant journals. We did not restrict the search by year of publication, language or type of publication. Selection criteria Randomised controlled trials comparing pharmacological treatment to placebo, other pharmacologic treatments or a combination of pharmacologic treatments in people of all ages with a formal diagnosis of BPD. The primary outcomes were BPD symptom severity, self‐harm, suicide‐related outcomes, and psychosocial functioning. Secondary outcomes were individual BPD symptoms, depression, attrition and adverse events. Data collection and analysis At least two review authors independently selected trials, extracted data, assessed risk of bias using Cochrane's risk of bias tool and assessed the certainty of the evidence using the GRADE approach. We performed data analysis using Review Manager 5 and quantified the statistical reliability of the data using Trial Sequential Analysis. Main results We included 46 randomised controlled trials (2769 participants) in this review, 45 of which were eligible for quantitative analysis and comprised 2752 participants with BPD in total. This is 18 more trials than the 2010 review on this topic. Participants were predominantly female except for one trial that included men only. The mean age ranged from 16.2 to 39.7 years across the included trials. Twenty‐nine different types of medications compared to placebo or other medications were included in the analyses. Seventeen trials were funded or partially funded by the pharmaceutical industry, 10 were funded by universities or research foundations, eight received no funding, and 11 had unclear funding. For all reported effect sizes, negative effect estimates indicate beneficial effects by active medication. Compared with placebo, no difference in effects were observed on any of the primary outcomes at the end of treatment for any medication. Compared with placebo, medication may have little to no effect on BPD symptom severity, although the evidence is of very low certainty (antipsychotics: SMD ‐0.18, 95% confidence interval (CI) ‐0.45 to 0.08; 8 trials, 951 participants; antidepressants: SMD −0.27, 95% CI −0.65 to 1.18; 2 trials, 87 participants; mood stabilisers: SMD −0.07, 95% CI −0.43 to 0.57; 4 trials, 265 participants). The evidence is very uncertain about the effect of medication compared with placebo on self‐harm, indicating little to no effect (antipsychotics: RR 0.66, 95% CI 0.15 to 2.84; 2 trials, 76 participants; antidepressants: MD 0.45 points on the Overt Aggression Scale‐Modified‐Self‐Injury item (0‐5 points), 95% CI −10.55 to 11.45; 1 trial, 20 participants; mood stabilisers: RR 1.08, 95% CI 0.79 to 1.48; 1 trial, 276 participants). The evidence is also very uncertain about the effect of medication compared with placebo on suicide‐related outcomes, with little to no effect (antipsychotics: SMD 0.05, 95 % CI −0.18 to 0.29; 7 trials, 854 participants; antidepressants: SMD −0.26, 95% CI −1.62 to 1.09; 2 trials, 45 participants; mood stabilisers: SMD −0.36, 95% CI −1.96 to 1.25; 2 trials, 44 participants). Very low‐certainty evidence shows little to no difference between medication and placebo on psychosocial functioning (antipsychotics: SMD −0.16, 95% CI −0.33 to 0.00; 7 trials, 904 participants; antidepressants: SMD −0.25, 95% CI ‐0.57 to 0.06; 4 trials, 161 participants; mood stabilisers: SMD −0.01, 95% CI ‐0.28 to 0.26; 2 trials, 214 participants). Low‐certainty evidence suggests that antipsychotics may slightly reduce interpersonal problems (SMD −0.21, 95% CI −0.34 to ‐0.08; 8 trials, 907 participants), and that mood stabilisers may result in a reduction in this outcome (SMD −0.58, 95% CI ‐1.14 to ‐0.02; 4 trials, 300 participants). Antidepressants may have little to no effect on interpersonal problems, but the corresponding evidence is very uncertain (SMD −0.07, 95% CI ‐0.69 to 0.55; 2 trials, 119 participants). The evidence is very uncertain about dropout rates compared with placebo by antipsychotics (RR 1.11, 95% CI 0.89 to 1.38; 13 trials, 1216 participants). Low‐certainty evidence suggests there may be no difference in dropout rates between antidepressants (RR 1.07, 95% CI 0.65 to 1.76; 6 trials, 289 participants) and mood stabilisers (RR 0.89, 95% CI 0.69 to 1.15; 9 trials, 530 participants), compared to placebo. Reporting on adverse events was poor and mostly non‐standardised. The available evidence on non‐serious adverse events was of very low certainty for antipsychotics (RR 1.07, 95% CI 0.90 to 1.29; 5 trials, 814 participants) and mood stabilisers (RR 0.84, 95% CI 0.70 to 1.01; 1 trial, 276 participants). For antidepressants, no data on adverse events were identified. Authors' conclusions This review included 18 more trials than the 2010 version, so larger meta‐analyses with more statistical power were feasible. We found mostly very low‐certainty evidence that medication may result in no difference in any primary outcome. The rest of the secondary outcomes were inconclusive. Very limited data were available for serious adverse events. The review supports the continued understanding that no pharmacological therapy seems effective in specifically treating BPD pathology. More research is needed to understand the underlying pathophysiologic mechanisms of BPD better. Also, more trials including comorbidities such as trauma‐related disorders, major depression, substance use disorders, or eating disorders are needed. Additionally, more focus should be put on male and adolescent samples.

Plain language summaries (PLSs) have been introduced to communicate research in an understandable way to a nonexpert audience. Guidelines for writing PLSs have been developed and empirical research on PLSs has been conducted, but terminology and research approaches in this comparatively young field vary considerably. This prompted us to review the current state of the art of the theoretical and empirical literature on PLSs. The two main objectives of this review were to develop a conceptual framework for PLS theory, and to synthesize empirical evidence on PLS criteria. We began by searching Web of Science, PubMed, PsycInfo and PSYNDEX (last search 07/2021). In our review, we included empirical investigations of PLSs, reports on PLS development, PLS guidelines, and theoretical articles referring to PLSs. A conceptual framework was developed through content analysis. Empirical studies investigating effects of PLS criteria on defined outcomes were narratively synthesized. We identified 7,714 records, of which 90 articles met the inclusion criteria. All articles were used to develop a conceptual framework for PLSs which comprises 12 categories: six of PLS aims and six of PLS characteristics. Thirty-three articles empirically investigated effects of PLSs on several outcomes, but study designs were too heterogeneous to identify definite criteria for high-quality PLSs. Few studies identified effects of various criteria on accessibility, understanding, knowledge, communication of research, and empowerment. We did not find empirical evidence to support most of the criteria we identified in the PLS writing guidelines. We conclude that although considerable work on establishing and investigating PLSs is available, empirical evidence on criteria for high-quality PLSs remains scarce. The conceptual framework developed in this review may provide a valuable starting point for future guideline developers and PLS researchers.

Given the chronic work-related stressors experienced by nursing staff in today's healthcare systems, international evidence suggests an elevated risk of developing stress-related mental symptoms. Therefore, identifying effective methods to foster resilience (i.e., maintenance or fast recovery of mental health despite stressor exposure) seems crucial. To date, little is known about the efficacy of these interventions in nurses.This systematic review aimed at summarizing the evidence on the pre-pandemic efficacy of psychological interventions to foster resilience, to improve mental symptoms and well-being as well as to promote resilience factors in nurses. Based on training programs with evidence for positive effects on resilience and mental health in meta-analyses, we aimed at identifying important and helpful intervention techniques.Systematic review and meta-analyses based on a Cochrane review on pre-pandemic resilience interventions in healthcare professionals.MEDLINE, Embase, CENTRAL and 11 other databases were searched until June 2020 to identify eligible randomized controlled trials. Trial registers, reference lists and contact with authors were additional sources.Two reviewers independently assessed study eligibility and extracted data. The Cochrane risk of bias assessment tool was used to evaluate the risk of bias of included studies. We conducted random-effects pairwise meta-analyses for five primary outcomes, including resilience. The intervention contents and techniques were narratively synthesized.Of 39,794 records retrieved, 24 studies were included in the review (N = 1879 randomized participants), 17 in meta-analyses (n = 1020 participants). At post-intervention, we found very-low certainty evidence of moderate effects in favor of resilience training for resilience (standardized mean difference [SMD] 0.39; 95% CI [confidence interval] 0.12-0.66) and well-being (SMD 0.44; 95% CI 0.15-0.72), while there was no evidence of effects on symptoms of anxiety, depression and stress. The improvement of well-being was sustained in the short-term (≤3 months), with additional delayed benefits for anxiety and stress. There was no evidence of effects at later follow-ups, with the caveat of only three available studies. Among nine programs with evidence of positive moderate effect sizes, intervention contents included mindfulness and relaxation, psychoeducation, emotion regulation, cognitive strategies, problem-solving and the strengthening of internal and external resources.Given the chronic stressor exposure in nursing staff, our findings may guide both the design and implementation of nurse-directed resilience interventions. To improve the certainty of evidence, more rigorous high-quality research using improved study designs (e.g., larger sample sizes, longer follow-up periods) is urgently needed.PROSPERO 2017 CRD42017082827.

Many societies have been recently exposed to humanitarian and health emergencies, which have resulted in a large number of people experiencing significant distress and being at risk to develop mental disorders such as depression, anxiety and post‐traumatic stress disorder. The World Health Organization has released a series of scalable psychosocial interventions for people impaired by distress in communities exposed to adversities. Prominent among these is a low‐intensity transdiagnostic psychosocial intervention, Problem Management Plus (PM+), and its digital adaptation Step‐by‐Step (SbS). This systematic review is the first to summarize the available evidence on the effects of PM+ and SbS. Up to March 8, 2023, five databases were searched for randomized controlled trials examining the effects of PM+ or SbS on distress indicators (i.e., general distress; anxiety, depressive or post‐traumatic stress disorder symptoms; functional impairment, self‐identified problems) and positive mental health outcomes (i.e., well‐being, quality of life, social support/relationships). We performed random‐effects multilevel meta‐analyses on standardized mean differences (SMDs) at post‐intervention and short‐term follow‐up assessments. Our search yielded 23 eligible studies, including 5,298 participants. We found a small to medium favorable effect on distress indicators (SMD=–0.45, 95% CI: –0.56 to –0.34) and a small beneficial effect on positive mental health outcomes (SMD=0.31, 95% CI: 0.14‐0.47), which both remained significant at follow‐up assessment and were robust in sensitivity analyses. However, our analyses pointed to substantial between‐study heterogeneity, which was only partially explained by moderators, and the certainty of evidence was very low across all outcomes. These results provide evidence for the effectiveness of PM+ and SbS in reducing distress indicators and promoting positive mental health in populations exposed to adversities, but a larger high‐quality evidence base is needed, as well as research on participant‐level moderators of the effects of these interventions, their suitability for stepped‐care programs, and their cost‐effectiveness.

In view of disease-related threats, containment measures, and disrupted healthcare, individuals with pre-existing mental illness might be vulnerable to adverse effects of the COVID-19 pandemic. Previous reviews indicated increased mental distress, with limited information on peri-pandemic changes. In this systematic review, we aimed to identify longitudinal research investigating pre- to peri-pandemic and/or peri-pandemic changes of mental health in patients, focusing on the early phase and considering specific diagnoses. PsycINFO, Web of Science, the WHO Global literature on coronavirus disease database, and the Cochrane COVID-19 Study Register weresearched through 31 May 2021. Studies were synthesized using vote counting based on effect direction. We included 40 studies mostly from Western, high-income countries. Findings were heterogeneous, with improving and deteriorating mental health observed compared to pre-pandemic data, partly depending on underlying diagnoses. For peri-pandemic changes, evidence was limited, with some suggestion of recovery of mental distress. Study quality was heterogeneous; only few studies investigated potential moderators (e.g., chronicity of mental illness). Mental health effects on people with pre-existing conditions are heterogeneous within and across diagnoses for pre- to peri-pandemic and peri-pandemic comparisons. To improve mental health services amid future global crises, forthcoming research should understand medium- and long-term effects, controlling for containment measures.

Dedicated Ge-detector arrays are being developed for the investigation of rare γ decays with low γ-ray multiplicity at the upcoming radioactive ion beam facilities. These arrays are optimized for the high full-energy peak efficiency and angular resolution of the γ-ray detection needed for a proper Doppler correction of the γ-rays emitted by fast recoiling nuclei. MINIBALL will consist of 40 six-fold segmented, encapsulated Ge detectors which are clustered in eight cryostats with three detectors each and four cryostats with four detectors, respectively. The individual components - the six-fold segmented Ge detector, the cryostats, the fast preamplifier, the digital pulse-processing electronics and the mechanical frame - and their properties are described. The results of test measurements with the first MINIBALL cluster detector using a 137Cs source and the in-beam reaction D(37Cl, n) 38Ar are presented. It is shown that from pulse-shape analysis of the events within a detector segment the effective granularity of the MINIBALL array can be enhanced from 240 to ∼ 4000. The specifications of MINIBALL are compiled on the basis of experimental data. First results with a 12-fold segmented, encapsulated detector are discussed with respect to the feasibility of future γ-ray tracking arrays.

Approximately 70–80% of women meeting criteria for borderline personality disorder (BPD) report attenuated pain perception or analgesia during non-suicidal, intentional self-mutilation. The aim of this study was to use laser-evoked potentials (LEPs) and psychophysical methods to differentiate the factors that may underlie this analgesic state. Ten unmedicated female patients with BPD (according to DSM-IV) and 14 healthy female control subjects were investigated using brief radiant heat pulses generated by a thulium laser and five-channel LEP recording. Heat pulses were applied as part of a spatial discrimination task (two levels of difficulty) and during a mental arithmetic task. BPD patients had significantly higher heat pain thresholds (23%) and lower pain ratings (67%) than control subjects. Nevertheless, LEP amplitudes were either normal (N1, P2, P3) or moderately enhanced in BPD patients (N2). LEP latencies and task performance did not differ between patients and control subjects. The P3 amplitudes, the vertex potential (N2–P2), and the N1, which is generated near the secondary somatosensory cortex, were significantly reduced during distraction by mental arithmetic in both groups. In addition, P3 amplitudes reflected task difficulty. This study confirms previous findings of attenuated pain perception in BPD. Normal nociceptive discrimination task performance, normal LEPs, and normal P3 potentials indicate that this attenuation is neither related to a general impairment of the sensory-discriminative component of pain, nor to hyperactive descending inhibition, nor to attention deficits. These findings suggest that hypoalgesia in BPD may primarily be due to altered intracortical processing similar to certain meditative states.

The pathology of Borderline personality disorder (BPD) is poorly understood and its biological basis remains largely unknown. One functional brain imaging study using [(18)F]Deoxyglucose-PET previously reported frontal and prefrontal hypometabolism. We studied brain metabolism at baseline in 12 medication-free female patients with BPD without current substance abuse or depression and 12 healthy female controls by [(18)F]Deoxyglucose-PET and statistical parametric mapping. We found significant frontal and prefrontal hypermetabolism in patients with BPD relative to controls as well as significant hypometabolism in the hippocampus and cuneus. This study demonstrated limbic and prefrontal dysfunction under resting conditions in patients with BPD by FDG-PET. Dysfunction in this network of brain regions, which has been implicated in the regulation of emotion, may underlie symptoms of BPD.

Abstract Microglia are the major cell type involved in neuroinflammatory events in brain diseases such as encephalitis, stroke, and neurodegenerative disorders, and contribute significantly to the release of prostaglandins (PGs) during neuronal insults. In this report, we studied the immediate‐early intracellular signalling pathways in microglia, following bacterial lipopolysaccharide (LPS) stimulation, leading to the synthesis and release of PGE 2 . Here we show that LPS induces cyclooxygenase (COX) 2 by activating sphingomyelinases leading to the release of ceramides, which in turn, activate the p38 mitogen‐activated protein kinases (MAPK), but not the p42/44 MAPK. We further show that exogenously added ceramide analogue (C 2 ‐ceramide) also induce PGE 2 synthesis through a p38 MAPK‐dependent pathway. This potential nature of ceramides in activating microglia suggests that endogenously produced ceramides during neuronal apoptosis in ischemia or neurodegenerative diseases could also contribute to the amplification of neuroinflammatory events. In contrast to protein kinase C (PKC) and phosphocholine‐specific phospholipase C (PC‐PLC), which transcriptionally regulate LPS‐induced COX‐2 synthesis, inhibition of phospholipase A 2 (PLA 2 ) has no effect on COX‐2 transcription, although it inhibits the release of PGE 2 . Transcriptional regulation of LPS‐induced COX‐2 by PKC is further proved by the ability of the PKC inhibitor, Gö 6976, to inhibit LPS‐induced 8‐isoprostane synthesis, but not affecting LPS‐induced COX‐2 activity. Our data with 8‐isoprostane also indicates that COX‐2 plays a major role in ROS production in LPS‐activated microglia. This detailed view of the intracellular signaling pathway in microglial activation and COX‐2 expression opens a new therapeutic window in the search for new and more effective central anti‐inflammatory agents. © 2005 Wiley‐Liss, Inc.

Substance P (SP), a member of the tachykinin peptide family, is a major mediator of neuroimmunomodulatory activities and neurogenic inflammation within the central and peripheral nervous system. SP has been shown to induce the expression of proinflammatory cytokines such as IL-6, which might be implicated in the etiopathology of several human brain disorders. We showed in a previous study that nanomolar concentrations of SP triggered activation of NF-kappaB, a transcription factor involved in the control of cytokine expression. However, activation of NF-kappaB was not involved in SP-induced expression of IL-6. Here, we describe p38 mitogen-activated protein kinase (p38 MAPK) as a signal transduction component that operates independently from NF-kappaB activation and that mediates SP-induced IL-6 expression in the human astrocytoma cell line U373 MG. SP induced the phosphorylation of p38 MAPK within 10 min, and this activation persisted up to 30 min and was independent from p42/44 MAPKs and protein kinase C activation, which all are induced after stimulation with SP. As shown by EMSA, p38 MAPK was not involved in SP-induced activation of NF-kappaB. p38 MAPK, however, mediated SP-induced IL-6 expression as shown by the use of specific inhibitors of this kinase. Our results suggest that activation of p38 MAPK is an important component controlling neurogenic inflammation within the CNS independently from NF-kappaB. Drugs targeting this MAPK may therefore interfere with SP-correlated neuropsychiatric disorders and may represent a therapeutic approach in these disorders.

Objective: The purpose of this article was to determine the relative efficacy of a psychotherapy program when combined with pharmacotherapy versus medication and clinical management in more severely depressed patients. Method: A randomized controlled trial was conducted in 124 hospitalized patients with DSM-IV major depressive disorder that compared 5 weeks of interpersonal psychotherapy modified for depressed inpatients (15 individual and eight group sessions) plus pharmacotherapy with a regimen that involved medication plus intensive clinical management. The study included a prospective, naturalistic follow-up 3 and 12 months after acute treatment in 97 of 105 treatment completers. The 17-item version of the Hamilton Depression Rating Scale (HAM-D) was the primary outcome measure. Results: For the intent-to-treat cohort (N=124), analysis of covariance (ANCOVA) showed that patients treated with interpersonal psychotherapy had a significantly greater reduction of depressive symptoms at week 5. Response rates differed significantly between the two treatment conditions, favoring the group that received adjuvant interpersonal psychotherapy (70%) versus clinical management (51%). Remission rates also tended to be higher for patients in the interpersonal psychotherapy group (49% versus 34%). Patients who initially responded to interpersonal psychotherapy exhibited greater treatment gains at the 3-month follow-up evaluation, since only 3% of these subjects relapsed, compared with 25% of the clinical management subjects. Nine months later, this difference lost statistical significance. Conclusions: An inpatient treatment program with both brief and intensive psychotherapy plus pharmacotherapy is superior to standard treatment. The results, which add to a growing body of evidence, suggest that this combination treatment may offer an advantage over treatment with medication and clinical management for more severely depressed patients.

Quantitative assessment of shame and guilt using self-report questionnaires can help to understand the role of these emotions in various mental disorders. However, shame and guilt measures have predominantly been tested among healthy subjects that usually show low levels of guilt and shame. Thus, little is known about the comparative validity of different shame and guilt questionnaires in a population of shame- and guilt-prone persons with mental illness as compared to healthy subjects. This study used the Test of Self-Conscious Affect (TOSCA-3), the Personal Feelings Questionnaire (PFQ-2) and the Experiential Shame Scale (ESS) among 60 women with borderline personality disorder (BPD) and 60 healthy women. Intercorrelations of shame-proneness, guilt-proneness and state shame as well as their correlations with self-efficacy, empowerment, state and trait-anxiety, experiential avoidance, depression, and general psychopathology were assessed. In both groups, shame-proneness was moderately related to guilt-proneness, both as assessed by the TOSCA-3 and the PFQ-2. For the TOSCA-3, among healthy subjects shame-proneness was significantly correlated with other constructs while guilt-proneness was not. This difference turned largely insignificant among women with BPD. For the PFQ-2, shame- and guilt-proneness showed similar correlational patterns with other constructs in both groups. The guilt-proneness scale of the TOSCA-3 showed poor internal consistency. State shame (ESS) was strongly related to state anxiety in both groups, and its correlations with other constructs were similar to state anxiety. The discriminant validity of the TOSCA-3 to distinguish between shame- and guilt-proneness may be diminished in clinical samples. The measure of state shame (ESS) showed a large overlap with state anxiety.

Statistical comparisons of [18F]FDG PET scans between healthy subjects and patients with Alzheimer's disease (AD) or amnestic mild cognitive impairment (aMCI) using Statistical Parametric Mapping (SPM) usually require normalization of regional tracer uptake via ROIs defined using additional software. Here, we validate a simple SPM-based method for count normalization. FDG PET scans of 21 mild, 15 very mild AD, 11 aMCI patients and 15 age-matched controls were analyzed. First, we obtained relative increases in the whole patient sample compared to controls (i.e. areas relatively preserved in patients) with proportional scaling to the cerebral global mean (CGM). Next, average absolute counts within the cluster with the highest t-value were extracted. Statistical comparisons of controls versus three patients groups were then performed using count normalization to CGM, sensorimotor cortex (SMC) as standard, and to the cluster-derived counts. Compared to controls, relative metabolism in aMCI patients was reduced by 15%, 20%, and 23% after normalization to CGM, SMC, and cluster-derived counts, respectively, and 11%, 21%, and 25% in mild AD patients. Logistic regression analyses based on normalized values extracted from AD-typical regions showed that the metabolic values obtained using CGM, SMC, and cluster normalization correctly classified 81%, 89% and 92% of aMCI and controls; classification accuracies for AD groups (very mild and mild) were 91%, 97%, and 100%. The proposed algorithm of fully SPM-based count normalization allows for a substantial increase of statistical power in detecting very early AD-associated hypometabolism, and very high accuracy in discriminating mild AD and aMCI from healthy aging.

Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability in affect regulation, impulse control, interpersonal relationships, and self-image. In previous studies, we have used portable mini-computers to assess the severity of recurrent states of aversive emotional distress and dissociation during ambulatory conditions. Here, we used this approach for the assessment of the hypothalamic-pituitary-adrenal (HPA) axis in patients with BPD. We studied 23 unmedicated female patients with BPD and 24 matched healthy controls. Salivary cortisol was collected from all participants during ambulatory conditions in response to reminders provided by portable mini-computers on 3 consecutive days every 2 h for 14 h after awakening. In addition, cortisol in response to awakening was determined in four 15 min intervals on days 1 and 2. After the last collection of cortisol on the second day, 0.5 mg dexamethasone was administered in order to achieve cortisol suppression on day 3 (low-dose dexamethasone suppression test, DST). Patients with BPD displayed significantly higher salivary cortisol levels than healthy controls as demonstrated by higher total cortisol in response to awakening and higher total daily cortisol levels. There were significantly more non-suppressors of cortisol in the low-dose DST in the patient group when compared to the control group. The ambulatory assessment of saliva cortisol is a suitable approach to study basic parameters of the HPA-axis in patients with BPD. Increased adrenal activity and lowered feedback sensitivity of the HPA-axis may characterise BPD. Further studies have to reveal reasons of heightened adrenal activity in these patients.

Deep brain stimulation is the stereotaxic placement of unilateral or bilateral electrodes connected to a permanently implanted neurostimulator. Although the mode of action is unknown, the hypothesis is that chronic high frequency (130–185 Hz) stimulation reduces neural transmission through inactivation of voltage-dependent ion channels. 1 Breit S Schulz JB Benabid AL Deep brain stimulation. Cell Tissue Res. 2004; 318: 275-288 Crossref PubMed Scopus (207) Google Scholar Deep brain stimulation is widely used for severe tremor in Parkinson's disease, an indication in which it is highly effective in reducing the severe motor complications (mainly tremor) associated with the disease, whereas the overall process of degeneration cannot be slowed down, as shown in a recent study by R Hilker and colleagues. 2 Hilker R Portman AT Voges J et al. Disease progression continues in patients with advanced Parkinson's disease and effective subthalamic nucleus stimulation. J Neurol Neurosurg Psychiatry. 2005; 76: 1217-1221 Crossref PubMed Scopus (142) Google Scholar Further clinical indications include essential tremor and primary dystonia. Use of the technique is also being investigated in treatment-resistant cluster headache (stimulation of the ipsilateral ventro posterior hypothalamus), 3 Schoenen J Di Clemente L Vandenheede M et al. Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action. Brain. 2005; 128: 940-947 Crossref PubMed Scopus (320) Google Scholar treatment-refractory obsessive-compulsive disorder (stimulation of the anterior limb of the capsula interna), and treatment-refractory major depression (stimulation of a subgenual cingulate region and other regions; figure). 4 Nuttin BJ Gabriels LA Cosyns PR et al. Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder. Neurosurgery. 2003; 52: 1263-1272 Crossref PubMed Scopus (39) Google Scholar

The γ-ray spectrum emitted after thermal neutron capture in 35Cl has been studied by use of the crystal and pair spectrometers installed at the ILL high flux reactor. We identified about 400 transitions in this reaction 326 of which were placed into the 36C1 level scheme; several new states were found. The level energies up to 3.5 MeV were measured with a precision of 5–20 eV relative to the 412 keV 198Au standard, those above 3.5 MeV with a precision of 10ppm. The neutron binding energy was determined to be EB = 8579.68(9) keV.

Impulsivity is a core feature of borderline personality disorder (BPD). However, previous clinical and experimental studies investigating impulsivity in BPD rendered mixed results. In this study, impulsivity was assessed by self-report scales and behavioral inhibition tasks to compare different data levels.Fifteen women with BPD and 15 matched healthy control subjects (HC) completed the Barratt Impulsiveness Scale, Eysenck's Impulsivity Questionnaire and the UPPS (Urgency, Lack of Perseverance, Lack of Premeditation and Sensation Seeking) scale, and participated in a Stroop task, an antisaccade task and a stop signal task.Patients with BPD scored significantly higher on self-report measures as compared to HC, but not in behavioral tests. In BPD patients, but not in HC, behavioral inhibition errors were correlated with more intense emotional state.We found a discrepancy between self-report and behavioral data. Further studies need to assess additional possible mechanisms underlying increased impulsivity, their relation to emotional instability, and their neurobiological underpinnings.

Inferior frontal white matter circuits are likely to be relevant to dysfunctional affect regulation, aggression, dissociative symptoms, neuropsychological functioning and psychopathology in women with borderline personality disorder (BPD) and comorbid attention-deficit hyperactivity disorder (ADHD). 20 women with BPD and comorbid ADHD and 20 healthy women were investigated, and groups were matched for age, education and premorbid intelligence. Mean diffusivity and fractional anisotropy were measured bilaterally in the inferior frontal white matter by diffusion tensor imaging (DTI). Conflict resolution was assessed by the Attention Network Test, sustained vigilance by the Degraded-Stimulus Continuous Performance Test. Among women with BPD and comorbid ADHD, increased mean diffusivity in inferior frontal white matter was associated with higher levels of dysfunctional affect regulation, anger–hostility, dissociative symptoms, and general psychopathology (p < .05, uncorrected). Poor conflict resolution during the attention task was positively associated with anger–hostility, psychopathology, dissociation and the number of ADHD-symptoms, but not related to DTI variables. Both groups did not differ significantly with respect to DTI variables or neuropsychological performance. In the BPD group, a lifetime history of major depression or a current eating disorder were associated with impaired inferior frontal white matter integrity, while a history of sexual abuse or a current posttraumatic stress disorder were not. Inferior frontal white matter microstructural abnormalities may be linked to key aspects of psychopathology in women with BPD and comorbid ADHD and add to alterations in orbitofrontal and limbic areas. The relationship between neuropsychological functioning and white matter structure remains unclear.

Differences in the clinical presentation of men and women with borderline personality disorder (BPD) are of potential interest for investigations into the neurobiology, genetics, natural history, and treatment response of BPD. The purpose of this study was to investigate gender differences in axis I and axis II comorbidity and in diagnostic criteria in BPD patients.110 women and 49 men with BPD were assessed with the computer-based version of the Munich-Composite International Diagnostic Interview and the Structured Clinical Interview for DSM-IV Personality Disorders. Gender differences were investigated for the following outcomes: (a) lifetime, 12-month and 4-week prevalence of axis I disorders; (b) axis II disorders, and (c) DSM-IV BPD diagnostic criteria.With regard to lifetime prevalence of axis I disorders, men more often displayed a substance use disorder, in particular alcohol dependency (65 vs. 43%); on the other hand, women more frequently had an affective (94 vs. 82%), anxiety (92 vs. 80%) or eating disorder (35 vs. 18%), in particular anorexia nervosa (21 vs. 4%). Regarding the 12-month prevalence, we found significantly more women suffering from anorexia nervosa (13 vs. 0%). Considering the 4-week prevalence, there were no significant gender differences. With regard to axis II disorders, men had a higher frequency of antisocial personality disorder (57 vs. 26%). Regarding the BPD diagnostic criteria, men more often displayed 'intensive anger' (74 vs. 49%), whereas women more frequently showed 'affective instability' (94 vs. 82%).In this German study, we could replicate and extend the findings from previous US studies, where men and women with BPD showed important differences in their pattern of psychiatric comorbidity. The implications for clinicians and researchers are discussed.

Inpatient dialectical behavior therapy (DBT) is an effective treatment for borderline personality disorder (BPD), but often treatment is ended prematurely and predictors of dropout are poorly understood. We, therefore, studied predictors of dropout among 60 women with BPD during inpatient DBT. Non-completers had higher experiential avoidance and trait anxiety at baseline, but fewer life-time suicide attempts than completers. There was a trend for more anger–hostility and perceived stigma among non-completers. Experiential avoidance and anxiety may be associated with dropout in inpatient DBT. Low life-time suicidality and high anger could reflect a subtype at risk for discontinuation of inpatient treatment.

Objectives. Affective dysregulation is a clinical hallmark of borderline personality disorder (BPD). This study used an instructed fear task combined with functional MRI (fMRI) and skin conductance response (SCR) to test hypotheses about mechanisms of disturbed fronto-limbic neural circuitry underlying dysfunctional emotional processing in BPD. Methods. Female BPD patients and matched control subjects were exposed to two visual stimuli during fMRI scanning and SCR recording. Subjects were instructed shortly before scanning that one stimulus (Threat) potentially represents an aversive event whereas another stimulus (Safe) represents safety. The aversive event (electrodermal stimulation) itself was only experienced before this instruction and never occurred during fMRI scanning. Results. Both groups showed stronger SCR to Threat compared to Safe indicating differential fear response which habituated over time. BPD compared to control subjects did not show fMRI signal decrease of amygdala activity or relative ventromedial prefrontal cortex (vmPFC) activity increase over time. Moreover, BPD patients showed increased connectivity of the amygdala with vmPFC but decreased connectivity of subgenual ACC with dorsal ACC compared to control subjects. Conclusions. Prolonged amygdala response and a functional disconnection between ventral and dorsal mPFC regions may be part of the neural mechanisms underlying emotional dysregulation in BPD patients.

Pharmacological cognitive enhancement (CE) is a topic of increasing public awareness. In the scientific literature on student use of CE as a study aid for academic performance enhancement, there are high prevalence rates regarding the use of caffeinated substances (coffee, caffeinated drinks, caffeine tablets) but remarkably lower prevalence rates regarding the use of illicit/prescription stimulants such as amphetamines or methylphenidate. While the literature considers the reasons and mechanisms for these different prevalence rates from a theoretical standpoint, it lacks empirical data to account for healthy students who use both, caffeine and illicit/prescription stimulants, exclusively for the purpose of CE. Therefore, we extensively interviewed a sample of 18 healthy university students reporting non-medical use of caffeine as well as illicit/prescription stimulants for the purpose of CE in a face-to-face setting about their opinions regarding differences in general and morally-relevant differences between caffeine and stimulant use for CE. 44% of all participants answered that there is a general difference between the use of caffeine and illicit/prescription stimulants for CE, 28% did not differentiate, 28% could not decide. Furthermore, 39% stated that there is a moral difference, 56% answered that there is no moral difference and one participant was not able to comment on moral aspects. Participants came to their judgements by applying three dimensions: medical, ethical and legal. Weighing the medical, ethical and legal aspects corresponded to the students' individual preferences of substances used for CE. However, their views only partly depicted evidence-based medical aspects and the ethical issues involved. This result shows the need for well-directed and differentiated information to prevent the potentially harmful use of illicit or prescription stimulants for CE.

Both emotion regulation and impulsivity are core aspects of borderline personality disorder (BPD) pathology. Although both problems may be combined specifically in BPD, few studies to date have investigated the emotional modulation of impulsivity in BPD.Women with BPD and matched healthy controls performed go/no-go tasks after induction of anger, joy or a neutral mood by vocally presented short stories. Dependent variables were the behavioural results and functional magnetic resonance imaging data.We included 17 women with BPD and 18 controls in our study. No behavioural group differences were found. However, patients with BPD showed stronger activation of the left amygdala and weaker activation of the subgenual anterior cingulate during anger induction than controls. Inhibition in the go/no-go task after anger induction increased activity in the left inferior frontal cortex in controls, but not in women with BPD, who, in turn, showed increased activation in the subthalamic nucleus.Findings cannot be generalized to men, and 4 patients were taking antidepressant medication (selective serotonin reuptake inhibitors). In addition, no patient control group was investigated, thus we do not know whether findings are specific to BPD compared with other disorders.Our findings are consistent with the view that a disturbed amygdala-prefrontal network in patients with BPD is compensated by a subcortical loop involving the subthalamic nucleus, leading to normal behavioural inhibition in these patients.

Attention-Deficit/Hyperactivity Disorder (ADHD) is marked by inhibitory and attentional deficits which can persist into adulthood. Those deficits have been associated with dysfunctional fronto-striatal and fronto-parietal circuits. The present study sought to delineate neural correlates of component specific inhibitory deficits in adult ADHD using functional magnetic resonance imaging (fMRI). 20 adult ADHD patients and 24 matched healthy controls were included. Brain activation was assessed during three stages of behavioral inhibition, i.e. interference inhibition (Simon task), action withholding (Go/no-go task) and action cancelation (Stop-signal task). Behaviorally, ADHD patients were affected in all tasks. Impaired interference inhibition was associated with hypoactivation in parietal and medial frontal regions. During action withholding and cancelation ADHD patients displayed hypoactivation in a fronto-striatal network. These findings support the notion of at least two disturbed neural circuits in ADHD differentially associated with deficits in separate inhibitory subcomponents. Thereby, deficits in inhibitory subcomponents which are closely connected to response interference were related to hypofunction in more attention related circuits, while stopping related deficits were rather associated with hypofunction in inhibitory circuits.

The right inferior frontal cortex (rIFC) is frequently activated during executive control tasks. Whereas the function of the dorsal portion of rIFC, more precisely the inferior frontal junction (rIFJ), is convergingly assigned to the attention system, the functional key role of the ventral portion, i.e., the inferior frontal gyrus (rIFG), is hitherto controversially debated. Here, we used a two-step methodical approach to clarify the differential function of rIFJ and rIFG. First, we used event-related functional magnetic resonance imaging (fMRI) during a modified stop signal task with an attentional capture condition (acSST) to delineate attentional from inhibitory motor processes (step 1). Then, we applied coordinate-based meta-analytic connectivity modeling (MACM) to assess functional connectivity profiles of rIFJ and rIFG across various paradigm classes (step 2). As hypothesized, rIFJ activity was associated with the detection of salient stimuli, and was functionally connected to areas of the ventral and dorsal attention network. RIFG was activated during successful response inhibition even when controlling for attentional capture and revealed the highest functional connectivity with core motor areas. Thereby, rIFJ and rIFG delineated largely independent brain networks for attention and motor control. MACM results attributed a more specific attentional function to rIFJ, suggesting an integrative role between stimulus-driven ventral and goal-directed dorsal attention processes. In contrast, rIFG was disclosed as a region of the motor control but not attention system, being essential for response inhibition. The current study provides decisive evidence regarding a more precise functional characterization of rIFC subregions in attention and inhibition.

Borderline personality disorder (BPD) affects 2.7% of adults. About 78% of adults with BPD also develop a substance-related disorder or addiction at some time in their lives. These persons are more impulsive and clinically less stable than BPD patients without substance dependency. They display suicidal behavior to a greater extent, drop out of treatment more often, and have shorter abstinence phases. The combination of borderline personality disorder with addiction requires a special therapeutic approach.This review is based on a selective literature search about the treatment of patients with BPD and addiction, with particular attention to Cochrane Reviews and randomized controlled trials (RCT).The available evidence is scant. In two RCTs, Dialectical Behavior Therapy for Substance Use Disorders (DBT-SUD) was found to improve patients' overall functional level (standardized mean difference, 1.07-1.78) and to increase the number of abstinence days (effect strength [ES], 1.03) and negative urine samples (ES, 0.75). Dual focus schema therapy (DFST) was evaluated in three RCTs. Because of methodological problems, however, no useful quantitative comparison across trials is possible. In one RCT, dynamic deconstructive psychotherapy (DDP) was found to have only a moderate, statistically insignificant effect. Only a single study provides data about potentially helpful drug therapy over the intermediate term.Patients with borderline personality disorder and comorbid addiction should be treated as early as possible for both conditions in a thematically hierarchical manner. There is no evidence for any restriction on drug therapy to prevent recurrent addiction in these patients. The psychotherapeutic techniques that can be used (despite the currently inadequate evidence base) include DBT-SUD, DFST, and DDP. These patients need qualified expert counseling in choosing a suitable type of psychotherapy. Specific treatment is available in only a few places, and the relevant treatment networks in Germany are just beginning to be constructed.

Early improvement of depressive symptoms during the first two weeks of antidepressant treatment has been discussed to be a resilience signal predicting a later positive treatment outcome in patients with Major Depressive Disorder (MDD). However, the predictive value of early improvement varies between studies, and the use of different antidepressants may explain heterogeneous results. The objective of this review was to assess the predictive value of early improvement on later response and remission and to identify antidepressants with the highest chance of early improvement. We included 17 randomized controlled trials investigating early improvement in 14,779 adult patients with MDD comparing monotherapy with an antidepressant against placebo or another antidepressant drug. 62% (range: 35-85%) of patients treated with an antidepressant and 47% (range: 21-69%) with placebo were early improver, defined as a >20%/25% symptom reduction after two weeks of treatment. Early improvement predicted response and remission after 5-12 weeks of treatment with high sensitivity (85%; 95%-CI: 84.3 to 85.7) and low to moderate specificity (54%; 95%-CI: 53.1 to 54.9). Early improver had a 8.37 fold (6.97-10.05) higher likelihood to become responder and a 6.38 fold (5.07-8.02) higher likelihood to be remitter at endpoint than non-improver. The highest early improver rates were achieved in patients treated with mirtazapine or a tricyclic antidepressant. This finding of a high predictive value of early improvement on treatment outcome may be important for treatment decisions in the early course of antidepressant treatment. Further studies should test the efficacy of such early treatment decisions.

Academic performance enhancement or cognitive enhancement (CE) via stimulant drug use has received increasing attention. The question remains, however, whether CE solely represents the use of drugs for achieving better academic or workplace results or whether CE also serves various other purposes. The aim of this study was to put the phenomenon of pharmacological academic performance enhancement via prescription and illicit (psycho-) stimulant use (Amphetamines, Methylphenidate) among university students into a broader context. Specifically, we wanted to further understand students' experiences, the effects of use on students and other factors, such as pressure to perform in their academic and private lives.A sample of 18 healthy university students reporting the non-medical use of prescription and illicit stimulants for academic performance enhancement was interviewed in a face-to-face setting. The leading questions were related to the situations and context in which the students considered the non-medical use of stimulants.Based on the resultant transcript, two independent raters identified six categories relating to the life context of stimulant use for academic performance enhancement: Context of stimulant use beyond academic performance enhancement, Subjective experience of enhancement, Timing of consumption, Objective academic results, Side effects, Pressure to perform.The answers reveal that academic performance enhancement through the use of stimulants is not an isolated phenomenon that solely aims at enhancing cognition to achieve better academic results but that the multifaceted life context in which it is embedded is of crucial relevance. The participants not only considered the stimulants advantageous for enhancing academic performance, but also for leading an active life with a suitable balance between studying and time off. The most common reasons given for stimulant use were to maximize time, to increase motivation and to cope with memorizing. According to the interviews, there is a considerable discrepancy between subjective experiences and objective academic results achieved.

Stimulants and caffeine have been proposed for cognitive enhancement by healthy subjects. This study investigated whether performance in chess – a competitive mind game requiring highly complex cognitive skills – can be enhanced by methylphenidate, modafinil or caffeine. In a phase IV, randomized, double-blind, placebo-controlled trial, 39 male chess players received 2×200 mg modafinil, 2×20 mg methylphenidate, and 2×200 mg caffeine or placebo in a 4×4 crossover design. They played twenty 15-minute games during two sessions against a chess program (Fritz 12; adapted to players’ strength) and completed several neuropsychological tests. Marked substance effects were observed since all three substances significantly increased average reflection time per game compared to placebo resulting in a significantly increased number of games lost on time with all three treatments. Treatment effects on chess performance were not seen if all games (n=3059) were analysed. Only when controlling for game duration as well as when excluding those games lost on time, both modafinil and methylphenidate enhanced chess performance as demonstrated by significantly higher scores in the remaining 2876 games compared to placebo. In conjunction with results from neuropsychological testing we conclude that modifying effects of stimulants on complex cognitive tasks may in particular result from more reflective decision making processes. When not under time pressure, such effects may result in enhanced performance. Yet, under time constraints more reflective decision making may not improve or even have detrimental effects on complex task performance.

Resilience is the ability to maintain or rapidly regain mental health during or after stressful life experiences. Cancer is a major risk factor for stress- associated mental illness. In this review, we attempt to identify effective resilience- promoting interventions in adults with cancer.The analysis was restricted to randomized, controlled trials of resilience- promoting interventions in adults with cancer in which training was provided for at least one psychosocial resilience factor. A selective search, with systematic compo- nents, for relevant publications was carried out in the PubMed and CENTRAL data- bases. Effect sizes (Hedges' g) were calculated wherever a fully reported dataset for resilience or post-traumatic growth was available.Twenty-two trials with a total of 2,912 patients were included in the analy- sis; the intervention was provided in an individual setting in five trials and in group format in 17. Beneficial effects on resilience and post-traumatic growth, some of them large, were observed in patients who were acutely ill with cancer and after in- terventions that were provided in more than 12 sessions. The effect size ranged from g = 0.33 to g = 1.45. Largely beneficial effects were achieved by interventions based on the concepts of positive psychology, supportive-expressive group therapy, behavioral therapy, or mindfulness, with considerable variation in individual effect sizes.Interventions that promote resilience should be made available to inter- ested and motivated cancer patients. These interventions should be provided, in as soon as the diagnosis is made and should ex- tend over more than 12 sessions whenever possible.

Abstract. The Brief Resilience Scale (BRS) measures the ability to recover from stress. To provide further evidence for construct validity of the German BRS and to determine population-based norms, a large sample (N = 1,128) representative of the German adult population completed a survey including the BRS and instruments measuring perceived stress and the resilience factors optimism, self-efficacy, and locus of control. Confirmatory factor analyses showed best model fit for a five-factor model differentiating the ability to recover from stress from the three resilience factors. On the basis of latent and manifest correlations, convergent and discriminant validity of the BRS were fair to good. Female sex, older age, lower weekly working time, higher perceived stress, lower optimism, and self-efficacy as well as higher external locus of control predicted lower BRS scores, that is, lower ability to recover from stress.

Abstract Purpose of the Review We aim to identify the most recent evidence of randomised controlled trials evaluating continued drug treatments in people with a diagnosis of BPD, review the most recent findings, highlight trends in terms of currently ongoing studies and comment on the overall body of evidence. Recent Findings We identified seven new RCTs, plus newly available data for an older RCT. Only three of these RCTs have been published in full text, while we found study data posted at trial registry platforms for the others. Summary The new findings do not support fluoxetine as a treatment option for suicide and self-harm prevention. A large effectiveness study did not detect beneficial effects of lamotrigine in routine care. The prevalent use of medications in BPD is still not reflected or supported by the current evidence. More research is needed regarding the most commonly used substances and substance classes, i.e. SSRIs, and quetiapine, but also with respect to people presenting with distinct comorbid conditions.

Delirium is a common neurobehavioral complication in hospitalized patients with a high prevalence in various clinical settings. Prevention of delirium is critical due to its common occurrence and associated poor outcomes. Our objective was to evaluate the efficacy of multicomponent interventions in preventing incident delirium in hospitalized patients at risk.Systematic review and meta-analysis.Hospital.We included a study if it was a randomized controlled trial and was evaluating effects of coordinated non-pharmacologic multicomponent interventions in the prevention of delirium.We performed a systematic literature search in PubMed and CENTRAL (PROSPERO: CRD42019138981; last update May 24, 2019). We assessed the quality of included studies by using the criteria established by the Cochrane Collaboration. We extracted the measured outcomes for delirium incidence, duration of delirium, length of hospital stay, falls during hospital stay, discharge to institutional care, and inpatient mortality.In total, we screened 1,027 eligible records and included eight studies with 2,105 patients in the review. We found evidence of an effect (ie, reduction) of multicomponent interventions on the incidence of delirium (risk ratio = .53; 95% confidence interval = .41-.69; I2 = 0). We detected no clear evidence of an effect for delirium duration, length of hospital stay, accidental falls, and mortality. Subgroup analyses did not result in findings of substantial effect modifiers, which can be explained by the high homogeneity within studies.Our findings confirm the current guidelines that multicomponent interventions are effective in preventing delirium. Data are still lacking to reach evidence-based conclusions concerning potential benefits for hard outcomes such as length of hospital stay, return to independent living, and mortality. J Am Geriatr Soc 68:1864-1871, 2020.

Background Many existing scales for microstressor assessment do not differentiate between objective (ie, observable) stressor events and stressful cognitions or concerns. They often mix items assessing objective stressor events with items measuring other aspects of stress, such as perceived stressor severity, the evoked stress reaction, or further consequences on health, which may result in spurious associations in studies that include other questionnaires that measure such constructs. Most scales were developed several decades ago; therefore, modern life stressors may not be represented. Ecological momentary assessment (EMA) allows for sampling of current behaviors and experiences in real time and in the natural habitat, thereby maximizing the generalization of the findings to real-life situations (ie, ecological validity) and minimizing recall bias. However, it has not been used for the validation of microstressor questionnaires so far. Objective The aim is to develop a questionnaire that (1) allows for retrospective assessment of microstressors over one week, (2) focuses on objective (ie, observable) microstressors, (3) includes stressors of modern life, and (4) separates stressor occurrence from perceived stressor severity. Methods Cross-sectional (N=108) and longitudinal studies (N=10 and N=70) were conducted to evaluate the Mainz Inventory of Microstressors (MIMIS). In the longitudinal studies, EMA was used to compare stressor data, which was collected five times per day for 7 or 30 days with retrospective reports (end-of-day, end-of-week). Pearson correlations and multilevel modeling were used in the analyses. Results High correlations were found between end-of-week, end-of-day, and EMA data for microstressor occurrence (counts) (r≥.69 for comparisons per week, r≥.83 for cumulated data) and for mean perceived microstressor severity (r≥.74 for comparisons per week, r≥.85 for cumulated data). The end-of-week questionnaire predicted the EMA assessments sufficiently (counts: beta=.03, 95% CI .02-.03, P&lt;.001; severity: beta=.73, 95% CI .59-.88, P&lt;.001) and the association did not change significantly over four subsequent weeks. Conclusions Our results provide evidence for the ecological validity of the MIMIS questionnaire.

Acute disease outbreaks such as the COVID-19 pandemic cause a high burden of psychological distress in people worldwide. Interventions to enable people to better cope with such distress should be based on the best available evidence. We therefore performed a scoping review to systematically identify and summarize the available literature of interventions that target the distress of people in the face of highly contagious disease outbreaks.MEDLINE, Cochrane CENTRAL, Web of Science (January 2000 to May 7, 2020), and reference lists were systematically searched and screened by two independent reviewers. Quantitative and qualitative studies investigating the effects of psychological interventions before, during, and after outbreaks of highly contagious emerging infectious diseases, such as SARS, MERS, Ebola, or COVID-19 were included. Study effects were grouped (e.g. for healthcare professionals, community members, people at risk) and intervention contents at the individual and organizational level summarized. We assessed the level of evidence using a modified scheme from the Oxford Centre for Evidence-based Medicine and the Australian National Health and Medical Research Council.Of 4030 records found, 19 studies were included (two RCTs). Most interventions were delivered during-exposure and face-to-face, focused on healthcare workers and crisis personnel, and combined psychoeducation with training of coping strategies. Based on two high-quality studies, beneficial effects were reported for resilience factors (e.g. positive cognitive appraisal) and professional attitudes of healthcare workers, with mixed findings for mental health (e.g. depression). Across all studies, there was positive qualitative feedback from participants and facilitators. We identified seven ongoing studies mostly using online- and mobile-based deliveries.There is preliminary evidence for beneficial effects of interventions to enable people to better cope with the distress of highly contagious emerging disease outbreaks. Besides the need for more high-quality studies, the summarized evidence may inform decision makers to plan interventions during the current pandemic and to develop pandemic preparedness plans.

Sensory neuropeptides modulate the mucosal response to inflammation in experimental colitis. Because nerve growth factor (NGF) regulates the expression of neuropeptides such as substance P and calcitonin gene-related peptide (CGRP) and is implicated as a link between the nervous system and the immune system in the inflammatory process, we investigated the functional role of NGF and neurotrophin-3 during experimental colitis.Immunoneutralizing antibodies specific for NGF and neurotrophin (NT)-3 were used to block their endogenous activity. Mild trinitrobenzene sulfonic acid (TNBS) colitis was induced, and damage scores were assessed after 1 week. Neuropeptide content in the colon and NT messenger RNA (mRNA) expression were determined.The pretreatment with anti-NGF or anti-NT-3 caused a significant 2-3-fold increase in the severity of the experimental inflammation as assessed by a macroscopic damage score, histologic ulceration score, and myeloperoxidase activity in the tissue. CGRP, but not substance P, contents in the colon were significantly reduced by NGF immunoneutralization. NGF mRNA was slightly up-regulated after NGF immunoneutralization, but NT-3 mRNA was unchanged by NT-3 immunoneutralization. CGRP mRNA was not significantly changed after 1 week of colitis by NGF or NT-3 immunoneutralization, whereas beta-preprotachykinin mRNA was up-regulated after immunoneutralization.These findings suggest a regulatory role for NGF and NT-3 in experimental inflammation of the gut. This effect may be partly caused by the reduction of mucosal CGRP content caused by the NGF blockade.

The neurokinin-1 receptor (NK-1R) and its ligand substance P (SP) are involved in the pathogenesis of certain neural tumors. Because nerves are significantly altered in pancreatic cancer, evidence for alteration of this pathway in human pancreatic cancer was sought. Expression of NK-1R was analyzed by real-time quantitative RT-PCR, in situ hybridization, immunohistochemistry, and Western blot analysis in normal human pancreatic and pancreatic cancer tissue samples and in pancreatic cancer cell lines. Furthermore, the influence of SP analogs and of the NK-1R antagonist MEN 11467 on pancreatic cancer cell growth was analyzed by sulforhodamine B (SRB) assay. By real-time quantitative RT-PCR, NK-1R mRNA was increased 36.7-fold (p < 0.001) in human pancreatic cancer samples compared with normal controls. Enhanced NK-1R expression levels were not related to tumor grade but were associated with advanced tumor stage and poorer prognosis. By in situ hybridization and immunohistochemistry, NK-1R mRNA and immunoreactivity were only occasionally weakly present in acinar and ductal cells in the normal pancreas. In contrast, moderate to strong NK-1R mRNA signals and immunoreactivity were present in most cancer cells. By Western blot analysis, NK-1R was increased 26-fold (p < 0.01) in pancreatic cancer samples in comparison to normal controls. NK-1R mRNA was detected in five pancreatic cancer cell lines by real-time quantitative RT-PCR, with the highest levels in CAPAN-1 cells and the lowest in ASPC-1 cells. SP analogs stimulated pancreatic cancer cell growth, depending on the NK-1R expression level, and this effect could be blocked by a selective NK-1R antagonist. These findings illustrate that the NK-1R pathway is activated in human pancreatic cancer and has the potential to contribute to cancer cell growth, thus suggesting the existence of a neuro-cancer cell interaction in vivo.

Previous studies in children with attention-deficit/hyperactivity disorder and attention deficit disorder (ADHD/ADD) have shown impaired sleep quality with increased nocturnal motor activity. However, polysomnographic findings are not unequivocal. Up to now, in adults with ADHD, only 1 case-control polysomnographic study with small sample size has been performed. We investigated objective and subjective sleep quality in adult ADHD, including an electroencephalogram spectral power analysis. Single-blind comparative study. University medical center. Twenty adult unmedicated ADHD patients without current comorbid major depression, drug abuse, or comorbid axis-II disorder and 20 sex- and age-matched control subjects. N/A. Conventional polysomnographic parameters and sleep electroencephalogram spectral power analysis was calculated for the 2 laboratory nights. Subjective sleep parameters were estimated by sleep questionnaires to assess the relationship between objective and subjective sleep measurements. Adult ADHD patients showed increased nocturnal motor activity (as indicated by heightened indexes of periodic leg movements in sleep), which was significantly inversely correlated with subjective total sleep time. Although ADHD patients displayed significantly increased objective total sleep time, the subjective ratings documented impaired sleep quality in those with ADHD. Other polysomnographic sleep patterns and spectral electroencephalogram parameters did not differ between ADHD patients and normal controls. Similar to children, adults with ADHD show increased nocturnal motor activity. Otherwise, sleep does not seem to be impaired in ADHD patients. However, the dissociation between objective and subjective sleep parameters points to a misinterpretation of sleep quality in patients with ADHD.