Two Sides of Theory of Mind: Mental State Attribution to Moving Shapes in Paranoid Schizophrenia Is Independent of the Severity of Positive Symptoms.

BACKGROUND: Theory of Mind (ToM) impairment has repeatedly been found in paranoid schizophrenia. The current study aims at investigating whether this is related to a deficit in ToM (undermentalizing) or an increased ToM ability to hyperattribute others' mental states (overmentalizing). METHODS: Mental state attribution was examined in 24 patients diagnosed with schizophrenia (12 acute paranoid (APS) and 12 post-acute paranoid (PPS)) with regard to positive symptoms as well as matched healthy persons using a moving shapes paradigm. We used 3-T-functional magnetic resonance imaging (fMRI) to provide insights into the neural underpinnings of ToM due to attributional processes in different states of paranoid schizophrenia. RESULTS: In the condition that makes demands on theory of mind skills (ToM condition), in patients with diagnosed schizophrenia less appropriate mental state descriptions have been used, and they attributed mental states less often to the moving shapes than healthy persons. On a neural level, patients suffering from schizophrenia exhibited within the ToM network hypoactivity in the medial prefrontal cortex (MPFC) and hyperactivity in the temporo-parietal junction (TPJ) as compared to the healthy sample. CONCLUSIONS: Our results indicate both undermentalizing and hypoactivity in the MPFC and increased overattribution related to hyperactivity in the TPJ in paranoid schizophrenia, providing new implications for understanding ToM in paranoid schizophrenia.

Who is at risk for weight gain after weight-gain associated treatment with antipsychotics, antidepressants, and mood stabilizers: A machine learning approach.

BACKGROUND: Weight gain is a common side effect in psychopharmacology; however, targeted therapeutic interventions and prevention strategies are currently absent in day-to-day clinical practice. To promote the development of such strategies, the identification of factors indicative of patients at risk is essential. METHODS: In this study, we developed a transdiagnostic model using and comparing decision tree classifiers, logistic regression, XGboost, and a support vector machine to predict weight gain of ≥5% of body weight during the first 4 weeks of treatment with psychotropic drugs associated with weight gain in 103 psychiatric inpatients. We included established variables from the literature as well as an extended set with additional clinical variables and questionnaires. RESULTS: Baseline BMI, premorbid BMI, and age are known risk factors and were confirmed by our models. Additionally, waist circumference has emerged as a new and significant risk factor. Eating behavior next to blood glucose were found as additional potential predictor that may underlie therapeutic interventions and could be used for preventive strategies in a cohort at risk for psychotropics induced weight gain (PIWG). CONCLUSION: Our models validate existing findings and further uncover previously unknown modifiable factors, such as eating behavior and blood glucose, which can be used as targets for preventive strategies. These findings underscore the imperative for continued research in this domain to establish effective preventive measures for individuals undergoing psychotropic drug treatments.

Borderline personality disorder and sexuality: causes and consequences of dissociative symptoms.

BACKGROUND: Sexual risk behavior in patients diagnosed with borderline personality disorder (BPD) is supposed to be associated with traumatic experiences and dissociative symptoms. Nevertheless, scientific research thereon is scarce which might be due to the high prevalence of sexual trauma and fear of overwhelming patients with explicit sexual content. METHODS: We investigated a clinical sample of patients diagnosed with BPD (n = 114) and compared them to a sample of matched healthy controls (HC) (n = 114) concerning the dissociative symptoms derealization, depersonalization, and conversion in sexual situations. In a subgroup of patients with BPD (n = 41) and matched HC (n = 40) dissociative symptoms after exposure to an acoustically presented erotic narrative were assessed in the lab. Regression analyses were used to examine the associations between sexual trauma, post-traumatic stress disorder (PTSD), dissociation in sexual situations, and risky sexual behavior. RESULTS: Patients diagnosed with BPD endorsed higher dissociative symptoms in sexual situations retrospectively and in the lab compared to HC. Regression analyses revealed that depersonalization and conversion symptoms in sexual situations were explained by severity of BPD, while derealization was explained by PTSD symptomatology. Impulsive and sexual behavior with an uncommitted partner were higher in the BPD group and explained by derealization, while conversion showed an inverse association. CONCLUSION: Our findings highlight the importance of addressing distinct dissociative symptoms in sexual situations when counselling and treating women with BPD. In the long term, this could contribute to a reduction in sexual risk behavior in patients with BPD. TRIAL REGISTRATION: This analysis is part of a larger ongoing study and was registered prior to accessing the data (Registration trial DRKS00029716).

The Effect of Nabiximols on Driving Ability in Adults with Chronic Tic Disorders: Results of a Substudy Analysis of the Double-Blind, Randomized, Placebo-Controlled CANNA-TICS Trial.

Background: The multicenter, randomized, double-blind, parallel-group, phase IIIb CANNA-TICS (CANNAbinoids in the treatment of TICS) trial showed clear trends for improvement of tics, depression, and quality of life with nabiximols versus placebo in adult patients with Gilles de la Tourette syndrome and other chronic tic disorders. Although in general nabiximols was well tolerated, it is unclear whether treatment using this cannabis extract influences driving skills in patients with chronic tic disorders. Methods: Here we report results of the "Fitness to Drive" substudy of the CANNA-TICS trial. The key endpoint was fitness to drive as a binary criterion with a computerized assessment at baseline and after 9 weeks of stable treatment (week 13) with nabiximols or placebo. A patient was considered unfit to drive according to the German Federal Highway Research Institute guidelines. Results: In the substudy, a total of 64 patients (76.6% men, mean±standard deviation of age: 36.8±13.9) were recruited at two study sites. The number of patients who were fit to drive increased from 24 (55.8%) at baseline to 28 (71.8%) at week 13 among 43 patients treated with nabiximols, and decreased from 14 (66.7%) to 10 (52.6%) among 21 patients who received placebo. The risk difference (nabiximols - placebo) was 0.17 (95% confidence interval=-0.08 to 0.43) in favor of nabiximols. Specifically, only 2 of 24 (8.3%) patients in the nabiximols, but 4 of 14 (28.6%) patients in the placebo group changed for the worse from fit (at baseline) to unfit (at week 13) to drive, whereas 8 of 19 (42.1%) patients in the nabiximols, and only 2 of 7 (28.6%) patients in the placebo group improved from unfit to fit. Conclusion: Treatment with nabiximols does not impair skills relevant to driving in those patients with tic disorders who were fit to drive at baseline and even improved fitness to drive in a subset of patients who were unfit to drive before start of treatment. EudraCT number: 2016-000564-42.

Association of clinical parameters and polygenic risk scores for body mass index, schizophrenia, and diabetes with antipsychotic-induced weight gain.

Antipsychotic-induced weight gain (AIWG) is a common adverse event in schizophrenia. Genome-wide association studies (GWAS) and polygenic risk scores (PRS) for other diseases or traits are recent approaches to disentangling the genetic architecture of AIWG. 200 patients with schizophrenia treated monotherapeutically with antipsychotics were included in this study. A multiple linear regression analysis with ten-fold crossvalidation was performed to predict the percentage weight change after five weeks of treatment. Independent variables were sex, age, body mass index (BMI) at baseline, medication-associated risk, and PRSs (BMI, schizophrenia, diabetes, and metabolic syndrome). An explorative GWAS analysis was performed on the same subjects and traits. PRSs for BMI (ß = 3.78; p = 0.0041), schizophrenia (ß = 5.38; p = 0.021) and diabetes type 2 (ß = 13.4; p = 0.046) were significantly associated with AIWG. Other significant factors were sex, baseline BMI and medication. Compared to the model without genetic factors, the addition of PRSs for BMI, schizophrenia, and diabetes type 2 increased the goodness of fit by 6.5 %. The GWAS identified the association of three variants (rs10668573, rs10249381 and rs1988834) with AIWG at a genome-wide level of p < 1 · 10-6. Using PRS for schizophrenia, BMI, and diabetes type 2 increased the explained variation of predicted weight gain, compared to a model without PRSs. For more precise results, PRSs derived from other traits (ideally AIWG) should be investigated. Potential risk variants identified in our GWAS need to be further investigated and replicated in independent samples.

Deconstructing depression by machine learning: the POKAL-PSY study.

Unipolar depression is a prevalent and disabling condition, often left untreated. In the outpatient setting, general practitioners fail to recognize depression in about 50% of cases mainly due to somatic comorbidities. Given the significant economic, social, and interpersonal impact of depression and its increasing prevalence, there is a need to improve its diagnosis and treatment in outpatient care. Various efforts have been made to isolate individual biological markers for depression to streamline diagnostic and therapeutic approaches. However, the intricate and dynamic interplay between neuroinflammation, metabolic abnormalities, and relevant neurobiological correlates of depression is not yet fully understood. To address this issue, we propose a naturalistic prospective study involving outpatients with unipolar depression, individuals without depression or comorbidities, and healthy controls. In addition to clinical assessments, cardiovascular parameters, metabolic factors, and inflammatory parameters are collected. For analysis we will use conventional statistics as well as machine learning algorithms. We aim to detect relevant participant subgroups by data-driven cluster algorithms and their impact on the subjects' long-term prognosis. The POKAL-PSY study is a subproject of the research network POKAL (Predictors and Clinical Outcomes in Depressive Disorders; GRK 2621).

Loneliness Is Associated With Lower Self- and Clinician-Rated Levels of Personality Functioning.

Personality disorders (PDs) are associated with interpersonal dysfunction, loneliness, and reduced social embeddedness. This study investigates loneliness and social network size in association with self- and clinician-rated personality functioning regarding the DSM-5's Alternative Model for Personality Disorders (AMPD). Eighty psychiatric inpatients including participants with and without PDs completed the Semi-structured Interview for Personality Functioning, the Level of Personality Functioning Scale - Brief Form, the UCLA Loneliness Scale, and the Social Network Index. Patients with PDs reported more loneliness and personality dysfunctioning than patients without PDs. Social network size did not differ between patient groups and showed lower correlations with personality functioning compared to loneliness. Loneliness was further associated with deficits in personality functioning. Deficits in distinct AMPD domains and loneliness may constitute transdiagnostically relevant factors that are related and mutually reinforcing. This could be important for identifying patients beyond PD diagnoses who are at risk of poor psychosocial functioning and require tailored psychotherapy.

Suicidal behaviors and adverse childhood experiences: A cross-diagnostic study in persistent depressive disorder and borderline personality disorder.

Adverse childhood experiences (ACE) constitute a known risk factor for suicidality. There is a research gap regarding differential patterns of associations between variants of suicidal ideations and behaviors (SIB) and characteristics of ACE in severe mental disorders. This cross-diagnostic study investigates whether SIB are related to ACE subtypes in two high-risk conditions, i.e., persistent depressive disorder (PDD) and borderline personality disorder (BPD). Inpatients with PDD (n = 117; age 40.2 years ± 12.3) and BPD (n = 74; age 26.2 ± 7.9) were assessed with the Columbia-Suicide Severity Rating Scale for suicidal ideations (SI), suicidal behaviors (SB) and actual suicide attempts (SA); ACE were recorded with the Childhood Trauma Questionnaire. In PDD, SI and SA were associated with childhood physical abuse (ORs 7.2 and 2.3, respectively). In BPD, SA were associated with severe experiences of physical abuse (OR 6.5). Weaker yet significant associations were found for childhood emotional abuse in PDD with SB (including SA), and in BPD with SA. Recall of childhood physical abuse may be clinically relevant information for identifying particular risks of SIB. Future studies should investigate these differential patterns in more depth and in terms of causality.

Altered amygdalar emotion space in borderline personality disorder normalizes following dialectical behaviour therapy.

BACKGROUND: Borderline personality disorder (BPD) is a mental health condition characterized by an inability to regulate emotions or accurately process the emotional states of others. Previous neuroimaging studies using classical univariate analyses have tied such emotion dysregulation to aberrant activity levels in the amygdala of patients with BPD. However, multivariate analyses have not yet been used to investigate how representational spaces of emotion information may be systematically altered in patients with BPD. METHODS: Patients with BPD performed an emotional face matching task while undergoing MRI before and after a 10-week inpatient program of dialectical behavioural therapy. Representational similarity analysis (RSA) was applied to activity patterns (evoked by angry, fearful, neutral and surprised faces) in the amygdala and temporo-occipital fusiform gyrus of patients with BPD and in the amygdala of healthy controls. RESULTS: We recruited 15 patients with BPD (8 females, 6 males, 1 transgender male) to participate in the study, and we obtained a neuroimaging data set for 25 healthy controls for a comparative analysis. The RSA of the amygdala revealed a negative bias in the underlying affective space (in that activity patterns evoked by angry, fearful and neutral faces were more similar to each other than to patterns evoked by surprised faces), which normalized after therapy. This bias-to-normalization effect was present neither in activity patterns of the temporo-occipital fusiform gyrus of patients nor in amygdalar activity patterns of healthy controls. LIMITATIONS: Larger samples and additional questionnaires would help to better characterize the association between specific aspects of therapy and changes in the neural representational space. CONCLUSION: Our findings suggest a more refined role for the amygdala in the pathological processing of perceived emotions and may provide new diagnostic and prognostic imaging-based markers of emotion dysregulation and personality disorders.Clinical trial registration: DRKS00019821, German Clinical Trials Register (Deutsches Register Klinischer Studien).

Effects of resilience and timing of adverse and adaptive experiences on interpersonal behavior: a transdiagnostic study in a clinical sample.

Adverse childhood experiences (ACE) have been linked to less prosocial behavior during social exclusion in vulnerable groups. However, little is known about the impact of the timing of ACE and the roles of protective factors. Therefore, this study investigated the association of the behavioral response to experimental partial social exclusion with adverse and adaptive experiences across age groups and resilience in clinical groups with persistent depressive disorder and borderline personality disorder, i.e., groups with high ACE, and in healthy controls (HC) (N = 140). Adverse and adaptive experiences during childhood, youth, and adulthood were assessed with the Traumatic Antecedents Questionnaire, and resilience was measured with the Connor Davidson Resilience Scale. A modified version of the Cyberball paradigm was used to assess the direct behavioral response to partial social exclusion. In patients, adverse events during youth (B = - 0.12, p = 0.016) and adulthood (B = - 0.14, p = 0.013) were negatively associated with prosocial behavior, whereas in the HC sample, adaptive experiences during youth were positively associated with prosocial behavior (B = 0.25, p = 0.041). Resilience did not mediate these effects. The findings indicate that critical events during youth may be particularly relevant for interpersonal dysfunction in adulthood.

Transdiagnostic analysis of adverse childhood experiences and their association with psychopathology-A TRANS-D conform study.

Transdiagnostic approaches challenge traditional psychiatric classification systems. Adverse childhood experiences (ACE) represent a transdiagnostic risk factor for psychopathology with dose dependency. As different qualities of ACE typically co-occur, we identified ACE patterns to assess their power for predicting psychopathology compared to traditional diagnoses. Following TRANS-D guidelines, we categorized participants (N=360) with persistent depressive disorder (PDD), borderline personality disorder (BPD), or healthy control status (HC) into subcategories defined by ACE pattern, using the Childhood Trauma Questionnaire (CTQ). Improvement of the transdiagnostic vs. diagnostic approach in predicting psychopathology was evaluated in a cross-validated predictive modeling framework focusing on the clinical sample of PDD and BPD patients. Results were externally validated in another transdiagnostic sample (N=138). Seven pattern-based subcategories with distinct ACE profiles were identified in the primary sample and replicated in the validation sample. Patterns cut across diagnostic groups. Predictive modeling showed that diagnoses could not predict depressive symptoms and loneliness. Transdiagnostic constructs systematically predicted all measures. This study showcases ACE as a promising construct for transdiagnostic research. Our data-driven framework identified robust ACE subcategories mapping onto general and interpersonal psychopathology. Patterns of CTQ-based information may provide an approach to integrating information on co-occurring ACE to inform diagnostics and treatment.

A factor analytic comparison of three commonly used depression scales (HAMD, MADRS, BDI) in a large sample of depressed inpatients.

BACKGROUND: Quantifying depression mainly relies on the use of depression scales, and understanding their factor structure is crucial for evaluating their validity. METHODS: This post-hoc analysis utilized prospectively collected data from a naturalistic study of 1014 inpatients with major depression. Confirmatory and exploratory factor analyses were performed to test the psychometric abilities of the Hamilton Depression Rating Scale, the Montgomery Asberg Depression Rating Scale, and the self-rated Beck Depression Inventory. A combined factor analysis was also conducted including all items of all scales. RESULTS: All three scales showed good to very good internal consistency. The HAMD-17 had four factors: an "anxiety" factor, a "depression" factor, an "insomnia" factor, and a "somatic" factor. The MADRS also had four factors: a "sadness" factor, a neurovegetative factor, a "detachment" factor and a "negative thoughts" factor, while the BDI had three factors: a "negative attitude towards self" factor, a "performance impairment" factor, and a "somatic" factor. The combined factor analysis suggested that self-ratings might reflect a distinct illness dimension within major depression. CONCLUSIONS: The factors obtained in this study are comparable to those found in previous research. Self and clinician ratings are complementary and not redundant, highlighting the importance of using multiple measures to quantify depression.

CANNA-TICS: Efficacy and safety of oral treatment with nabiximols in adults with chronic tic disorders - Results of a prospective, multicenter, randomized, double-blind, placebo controlled, phase IIIb superiority study.

Preliminary data suggest that cannabis-based medicines might be a promising new treatment for patients with Tourette syndrome (TS)/chronic tic disorders (CTD) resulting in an improvement of tics, comorbidities, and quality of life. This randomized, multicenter, placebo-controlled, phase IIIb study aimed to examine efficacy and safety of the cannabis extract nabiximols in adults with TS/CTD (n = 97, randomized 2:1 to nabiximols:placebo). The primary efficacy endpoint was defined as a tic reduction of ≥ 25% according to the Total Tic Score of the Yale Global Tic Severity Scale after 13 weeks of treatment. Although a much larger number of patients in the nabiximols compared to the placebo group (14/64 (21·9%) vs. 3/33 (9·1%)) met the responder criterion, superiority of nabiximols could formally not be demonstrated. In secondary analyses, substantial trends for improvements of tics, depression, and quality of life were observed. Additionally exploratory subgroup analyses revealed an improvement of tics in particular in males, patients with more severe tics, and patients with comorbid attention deficit/hyperactivity disorder suggesting that these subgroups may benefit better from treatment with cannabis-based medication. There were no relevant safety issues. Our data further support the role of cannabinoids in the treatment of patients with chronic tic disorders.

Premature T cell aging in major depression: A double hit by the state of disease and cytomegalovirus infection.

Introduction: Previous research indicates that premature T cell senescence is a characteristic of major depressive disorder (MDD). However, known senescence inducing factors like cytomegalovirus (CMV) infection or, probably, childhood adversity (CA) have not been taken into consideration so far. Objective: Differentiation and senescent characteristics of T cells of MDD patients were investigated in relation to healthy controls (HC), taking the CMV seropositivity and CA into account. Methods: 127 MDD and 113 HC of the EU-MOODSTRATIFICATION cohort were analyzed. Fluorescence activated cell sorting (FACS) analysis was performed to determine B, NK, and T cell frequencies. In a second FACS analysis, naïve, effector memory (Tem), central memory (Tcm), effector memory cells re-expressing RA (TEMRA), as well as CD28+ and CD27+ memory populations, were determined of the CD4+ and CD8+ T cell populations in a subsample (N = 35 MDD and N = 36 HC). CMV-antibody state was measured by IgG ELISA and CA by the Childhood Trauma Questionnaire. Results: We detected a CMV-antibody positivity in 40% of MDD patients (35% HC, n. s.) with seropositive MDD cases showing a higher total childhood trauma score. Second, a higher inflation of memory CD4+ T helper cells in CMV seronegative patients as compared to seronegative HC and reduced numbers of naïve CD4+ T helper cells in CMV seropositive patients (not in CMV seropositive HC) were found. Third, a higher inflation of memory CD8+ T cytotoxic cells in CMV seropositive cases as compared to CMV seropositive HC, particularly of the TEMRA cells, became apparent. Higher percentages of CD4+ TEMRA and late stage CD27-CD28- TEMRA cells were similar in both HC and MDD with CMV seropositivity. Overall, apportioning of T cell subpopulations did not differ between CA positive vs negative cases. Conclusions: MDD patients show several signs of a CMV independent "MDD specific" premature T cell aging, such as a CMV independent increase in CD4+ T memory cells and a latent naïve CD4 T-cell reduction and a latent CD8+ T-cell increase. However, these two latent T cell senescence abnormalities only become evident with CMV infection (double hit).

Lifestyle behaviors, metabolic disturbances, and weight gain in psychiatric inpatients treated with weight gain-associated medication.

Many psychiatric patients suffer from overweight/obesity and subsequent metabolic disturbances, where psychotropic medication is one of the main contributors. However, the magnitude of weight gain ranges individually, which leads to questioning the role of other contributors like lifestyle factors. The present study investigated several lifestyle factors among psychiatric inpatients, their relation to biological factors, and their predictive capability for weight gain during treatment. Using a naturalistic observational study design, psychiatric inpatients of all diagnoses were followed for 4 weeks from the start of treatment with weight gain-associated medication. N = 163 participants entered the study. Lifestyle factors were assessed by patient self-report questionnaires. Body weight change over time was calculated relative to baseline body weight. Our study provides three main findings: (1) Obesity and/or metabolic syndrome (metSy) were associated with emotional eating (disinhibition), craving for fast food and sweets, and weight cycling. (2) Patients without metSy and normal BMI experienced increased sweets craving (also for women), a more positive attitude towards drugs, and an improvement of affect (also for men). (3) Sex, presence of metSy and/or drug dosage interacted with disinhibition change, sweets craving change (trend), and fast food craving change to predict weight change over time. Furthermore, drug attitude change interacted with BMI, drug dosage, and presence of metSy to predict weight change. Lifestyle factors, especially eating behaviors, are related to metabolic disturbances and predict weight gain in interaction with clinical parameters.

Association between the behavioral response during social exclusion and recalled childhood maltreatment.

Social exclusion is a critical event for mental health. Patients with interpersonal dysfunction, e.g., with borderline personality disorder (BPD) or persistent depressive disorder (PDD), are particularly vulnerable, often based on their experiences of early adversity in life. The etiological pathways from childhood maltreatment (CM) to current behavior during social exclusion are still underexplored. This cross-diagnostic study investigated the relationship between self-reported CM and behavioral reaction to social exclusion in an experimental paradigm (Cyberball). Data from 140 subjects including patients with BPD and PDD as well as healthy controls were analyzed. The effect of CM (Childhood Trauma Questionnaire, CTQ) on behavior to social exclusion during Cyberball (ball tossing behavior) was analyzed including rejection sensitivity (RS) as a mediator. In the whole sample, the CTQ score (B = -.004, p < .05) as well as the emotional neglect subscore (B = -.016, p < .01) were associated with a reduced ball tossing behavior towards the excluder. There were no significant indirect effects involving RS. These current findings support the relationship between CM and an altered interpersonal response in critical interpersonal situations. Larger cohorts with multidimensional data in social domains are warranted to further investigate the link between CM and current interpersonal dysfunction.

Association of loneliness and social network size in adulthood with childhood maltreatment: Analyses of a population-based and a clinical sample.

BACKGROUND: Perceived loneliness and objective social network size are related but distinct factors, which negatively affect mental health and are prevalent in patients who have experienced childhood maltreatment (CM), for example, patients with persistent depressive disorder (PDD) and borderline personality disorder (BPD). This cross-diagnostic study investigated whether loneliness, social network size, or both are associated with self-reported CM. METHODS: Loneliness and social network size were assessed in a population-based sample at two time points (Study 1, N = 509), and a clinical group of patients with PDD or BPD (Study 2, N = 190) using the UCLA Loneliness Scale and the Social Network Index. Further measures were the Childhood Trauma Questionnaire, and standard depression rating scales. Linear regression analyses were applied to compare associations of loneliness or social network size with CM. Multiple mediation analyses were used to test the relative importance of loneliness and social network size in the relationship between CM and depressive symptoms. RESULTS: In both studies, loneliness showed a stronger association than social network size with CM. This was particularly marked for emotional neglect and emotional abuse. Loneliness but not social network size mediated the relationship between CM and depressive symptoms. CONCLUSIONS: Loneliness is particularly associated with self-reported CM, and in this respect distinct from the social network size. Our results underline the importance of differentiating both psychosocial constructs and suggest focusing on perceived loneliness and its etiological underpinnings by mechanism-based psychosocial interventions.

Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration.

Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice.

Biobanking in everyday clinical practice in psychiatry-The Munich Mental Health Biobank.

Translational research on complex, multifactorial mental health disorders, such as bipolar disorder, major depressive disorder, schizophrenia, and substance use disorders requires databases with large-scale, harmonized, and integrated real-world and research data. The Munich Mental Health Biobank (MMHB) is a mental health-specific biobank that was established in 2019 to collect, store, connect, and supply such high-quality phenotypic data and biosamples from patients and study participants, including healthy controls, recruited at the Department of Psychiatry and Psychotherapy (DPP) and the Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital of the Ludwig-Maximilians-University (LMU), Munich, Germany. Participants are asked to complete a questionnaire that assesses sociodemographic and cross-diagnostic clinical information, provide blood samples, and grant access to their existing medical records. The generated data and biosamples are available to both academic and industry researchers. In this manuscript, we outline the workflow and infrastructure of the MMHB, describe the clinical characteristics and representativeness of the sample collected so far, and reveal future plans for expansion and application. As of 31 October 2021, the MMHB contains a continuously growing set of data from 578 patients and 104 healthy controls (46.37% women; median age, 38.31 years). The five most common mental health diagnoses in the MMHB are recurrent depressive disorder (38.78%; ICD-10: F33), alcohol-related disorders (19.88%; ICD-10: F10), schizophrenia (19.69%; ICD-10: F20), depressive episode (15.94%; ICD-10: F32), and personality disorders (13.78%; ICD-10: F60). Compared with the average patient treated at the recruiting hospitals, MMHB participants have significantly more mental health-related contacts, less severe symptoms, and a higher level of functioning. The distribution of diagnoses is also markedly different in MMHB participants compared with individuals who did not participate in the biobank. After establishing the necessary infrastructure and initiating recruitment, the major tasks for the next phase of the MMHB project are to improve the pace of participant enrollment, diversify the sociodemographic and diagnostic characteristics of the sample, and improve the utilization of real-world data generated in routine clinical practice.

Loneliness is associated with maladaptive schema modes in patients with persistent depressive disorder.

OBJECTIVES: Though loneliness represents a public health concern, this complex unpleasant feeling is commonly neglected in psychiatric care and may constitute a new treatment target in clinical groups particularly prone to feeling lonely and socially isolated, e.g., persistent depressive disorder (PDD). Schema modes encompass a set of distinct cognitive-affective patterns that may contribute to loneliness and social isolation. Aim of this study was to examine the interplay between subjective loneliness and objective social network size with schema modes in patients with PDD as well as healthy controls (HC). METHOD: Sixty-two PDD patients (DSM-5; 35 female, Mage = 40.5, SD = 12.4) and 71 HC (60 female, Mage = 28.1, SD = 10.1) were assessed cross-sectionally using the following self-report measures: UCLA Loneliness Scale, Social Network Index (SNI), and Schema-Mode-Inventory, revised version (SMI-r). Correlational and multiple linear regression analyses were performed. RESULTS: PDD patients reported significantly higher scores of loneliness and maladaptive schema modes and a smaller social network than HC. Loneliness was significantly positively associated with the modes Vulnerable Child, Detached Protector, Bully and Attack, and Punitive Parent, and negatively with Contented Child and Healthy Adult in both groups. In contrast, social network size was only positively associated with the Contented Child mode. CONCLUSION: Loneliness is highly prevalent in PDD and in contrast to social network size associated with maladaptive schema modes. Therapeutically addressing these schema modes with specific techniques may represent a mechanism-based intervention for patients suffering from loneliness and should be investigated in clinical trials.