Perspectives on physician-assisted suicide in mental healthcare: results of a survey of physicians and medical students.

BACKGROUND: Physician-assisted suicide (PAS) is typically associated with serious physical illnesses that are prevalent in palliative care. However, individuals with mental illnesses may also experience such severity that life becomes intolerable. In February 2020, the previous German law prohibiting PAS was repealed. Patients with severe mental illnesses are increasingly likely to approach physicians with requests for PAS. AIMS: To explore the ethical and moral perspectives of medical students and physicians when making individual decisions regarding PAS. METHOD: An anonymised digital survey was conducted among medical students and physicians in Germany. Participants were presented with a case vignette of a chronically depressed patient requesting PAS. Participants decided on PAS provision and assessed theoretical arguments. We employed generalised ordinal regression and qualitative analysis for data interpretation. RESULTS: A total of N = 1478 participants completed the survey. Of these, n = 470 (32%) stated that they would refuse the request, whereas n = 582 (39%) would probably refuse, n = 375 (25%) would probably agree and n = 57 (4%) would definitely agree. Patient-centred arguments such as the right to self-determination increased the likelihood of consent. Concerns that PAS for chronically depressed patients might erode trust in the medical profession resulted in a decreased willingness to provide PAS. CONCLUSIONS: Participants displayed relatively low willingness to consider PAS in the case of a chronically depressed patient. This study highlights the substantial influence of theoretical medical-ethical arguments and the broader public discourse, underscoring the necessity of an ethical discussion on PAS for mental illnesses.

N-Acetylcysteine and a Specialized Preventive Intervention for Individuals at High Risk for Psychosis: A Randomized Double-Blind Multicenter Trial.

Background and Hypothesis: Clinical high risk for psychosis (CHR-P) offers a window of opportunity for early intervention and recent trials have shown promising results for the use of N-acetylcysteine (NAC) in schizophrenia. Moreover, integrated preventive psychological intervention (IPPI), applies social-cognitive remediation to aid in preventing the transition to the psychosis of CHR-P patients. Study Design: In this double-blind, randomized, controlled multicenter trial, a 2 × 2 factorial design was applied to investigate the effects of NAC compared to placebo (PLC) and IPPI compared to psychological stress management (PSM). The primary endpoint was the transition to psychosis or deterioration of CHR-P symptoms after 18 months. Study Results: While insufficient recruitment led to early trial termination, a total of 48 participants were included in the study. Patients receiving NAC showed numerically higher estimates of event-free survival probability (IPPI + NAC: 72.7 ±â€…13.4%, PSM + NAC: 72.7 ±â€…13.4%) as compared to patients receiving PLC (IPPI + PLC: 56.1 ±â€…15.3%, PSM + PLC: 39.0 ±â€…17.4%). However, a log-rank chi-square test in Kaplan-Meier analysis revealed no significant difference of survival probability for NAC vs control (point hazard ratio: 0.879, 95% CI 0.281-2.756) or IPPI vs control (point hazard ratio: 0.827, 95% CI 0.295-2.314). The number of adverse events (AE) did not differ significantly between the four groups. Conclusions: The superiority of NAC or IPPI in preventing psychosis in patients with CHR-P compared to controls could not be statistically validated in this trial. However, results indicate a consistent pattern that warrants further testing of NAC as a promising and well-tolerated intervention for CHR patients in future trials with adequate statistical power.

'The mirror of the soul?' Inferring sadness in the eyes.

The eyes are widely regarded as the mirror of the soul, providing reliable nonverbal information about drives, feelings, and intentions of others. However, it is unclear how accurate emotion recognition is when only the eyes are visible and whether inferring of emotions is altered across healthy adulthood. To fill this gap, the present piece of research was directed at comparing the ability to infer basic emotions in two groups of typically developing females that differed in age. We set a focus on females seeking group homogeneity. In a face-to-face study, in a two-alternative forced choice paradigm (2AFC), participants had to indicate emotions for faces covered by masks. The outcome reveals that although the recognition pattern is similar in both groups, inferring sadness in the eyes substantially improves with age. Inference of sadness is not only more accurate and less variable in older participants, but also positively correlates with age from early through mid-adulthood. Moreover, reading sadness (and anger) is more challenging in the eyes of male posers. A possible impact of poser gender and cultural background, both in expressing and inferring sadness in the eyes, is highlighted.

Reading language of the eyes in female depression.

Aberrations in non-verbal social cognition have been reported to coincide with major depressive disorder. Yet little is known about the role of the eyes. To fill this gap, the present study explores whether and, if so, how reading language of the eyes is altered in depression. For this purpose, patients and person-by-person matched typically developing individuals were administered the Emotions in Masked Faces task and Reading the Mind in the Eyes Test, modified, both of which contained a comparable amount of visual information available. For achieving group homogeneity, we set a focus on females as major depressive disorder displays a gender-specific profile. The findings show that facial masks selectively affect inferring emotions: recognition of sadness and anger are more heavily compromised in major depressive disorder as compared with typically developing controls, whereas the recognition of fear, happiness, and neutral expressions remains unhindered. Disgust, the forgotten emotion of psychiatry, is the least recognizable emotion in both groups. On the Reading the Mind in the Eyes Test patients exhibit lower accuracy on positive expressions than their typically developing peers, but do not differ on negative items. In both depressive and typically developing individuals, the ability to recognize emotions behind a mask and performance on the Reading the Mind in the Eyes Test are linked to each other in processing speed, but not recognition accuracy. The outcome provides a blueprint for understanding the complexities of reading language of the eyes within and beyond the COVID-19 pandemic.

On assessing trait rumination using the Ruminative Response Scale.

Introduction: This study explores the stability of scores on psychometrically validated trait questionnaires over time. We illustrate potential pitfalls through a larger study that used the Ruminative Response Scale (RRS) to categorize participants prior to study inclusion into two groups based on their habitual tendency to ruminate. Surprisingly, when we re-administered the RRS at the start of an experimental session, significant score changes occurred, resulting in participants shifting between the two groups. Methods: To address this, we modified our recruitment process, aiming to reduce careless responses, including an online RRS assessment a week before the lab appointment. We analyzed the different samples prior to and after changing the recruitment procedure, as well as the total sample regarding the psychometric properties of the RRS. We also explored various indices to identify and predict score changes due to careless responding; however, only a subgroup of participants was successfully identified. Results: Our findings suggest that Mahalanobis distances are effective for identifying substantial score changes, with baseline state rumination emerging as a marginally significant predictor. Discussion: We discuss the importance of conducting manipulation checks and offer practical implications for research involving psychometrically validated trait questionnaires.

Neural correlates of stress-reactive rumination in depression - The role of childhood trauma and social anxiety.

Recent work showed an association of prefrontal dysfunctions in patients with Major Depressive Disorder (MDD) and social stress induced rumination. However, up to date it is unclear which etiological features of MDD might cause prefrontal dysfunctions. In the study at hand, we aimed to replicate recent findings, that showed prefrontal activation alterations during the Trier Social Stress Test (TSST) and subsequently increased stress-reactive rumination in MDD compared to healthy controls. Moreover, we aimed to explore the role of adverse childhood experiences and other clinical variables in this relationship. N = 55 patients currently suffering from MDD and n = 42 healthy controls (HC) underwent the TSST, while cortical activity in areas of the Cognitive Control Network (CCN) was measured via functional near-infrared spectroscopy (fNIRS). The TSST successfully induced a stress reaction (physiologically, as well as indicated by subjective stress ratings) and state rumination in all subjects with moderate to large effect sizes. In comparison to HC, MDD patients showed elevated levels of state rumination with large effect sizes, as well as a typical pattern of reduced cortical oxygenation during stress in the CCN with moderate effect sizes. Self-reported emotional abuse and social anxiety were moderately positively associated with increased stress-reactive rumination. Within the MDD sample, emotional abuse was negatively and social anxiety positively associated with cortical oxygenation within the CCN with moderate to large effect sizes. In conclusion, our results replicate previous findings on MDD-associated prefrontal hypoactivity during stress and extends the research toward specific subtypes of depression.

Dynamic brain communication underwriting face pareidolia.

Face pareidolia is a tendency to seeing faces in nonface images that reflects high tuning to a face scheme. Yet, studies of the brain networks underwriting face pareidolia are scarce. Here, we examined the time course and dynamic topography of gamma oscillatory neuromagnetic activity while administering a task with nonface images resembling a face. Images were presented either with canonical orientation or with display inversion that heavily impedes face pareidolia. At early processing stages, the peaks in gamma activity (40 to 45 Hz) to images either triggering or not face pareidolia originate mainly from the right medioventral and lateral occipital cortices, rostral and caudal cuneus gyri, and medial superior occipital gyrus. Yet, the difference occurred at later processing stages in the high-frequency range of 80 to 85 Hz over a set of the areas constituting the social brain. The findings speak rather for a relatively late neural network playing a key role in face pareidolia. Strikingly, a cutting-edge analysis of brain connectivity unfolding over time reveals mutual feedforward and feedback intra- and interhemispheric communication not only within the social brain but also within the extended large-scale network of down- and upstream regions. In particular, the superior temporal sulcus and insula strongly engage in communication with other brain regions either as signal transmitters or recipients throughout the whole processing of face-pareidolia images.

Microglia-neuron interactions in schizophrenia.

Multiple lines of evidence implicate increased neuroinflammation mediated by glial cells to play a key role in neurodevelopmental disorders such as schizophrenia. Microglia, which are the primary innate immune cells of the brain, are crucial for the refinement of the synaptic circuitry during early brain development by synaptic pruning and the regulation of synaptic plasticity during adulthood. Schizophrenia risk factors as genetics or environmental influences may further be linked to increased activation of microglia, an increase of pro-inflammatory cytokine levels and activation of the inflammasome resulting in an overall elevated neuroinflammatory state in patients. Synaptic loss, one of the central pathological hallmarks of schizophrenia, is believed to be due to excess removal of synapses by activated microglia, primarily affecting glutamatergic neurons. Therefore, it is crucial to investigate microglia-neuron interactions, which has been done by multiple studies focusing on post-mortem brain tissues, brain imaging, animal models and patient iPSC-derived 2D culture systems. In this review, we summarize the major findings in patients and in vivo and in vitro models in the context of neuron-microglia interactions in schizophrenia and secondly discuss the potential of anti-inflammatory treatments for the alleviation of positive, negative, and cognitive symptoms.

Validation of the Self-Report Version of the German Strengths and Weaknesses of ADHD Symptoms and Normal Behavior Scale (SWAN-DE-SB).

Adults with attention-deficit/hyperactivity disorder (ADHD) experience impairing levels of inattention and/or hyperactivity-impulsivity, while individuals without ADHD experience these symptoms to a lesser extent. Yet, ADHD self-report scales so far hardly captured continuous distributions across the general population. In addition, they focused on weaknesses and ignored strengths. To address these shortcomings, we present here the Strengths and Weaknesses of ADHD and Normal-Behavior Scale Self-Report (SWAN-DE-SB). The normal distribution of the data collected and the scale's internal consistency, and factorial and convergent validity were assessed using data from a general population sample. Its clinical utility was evaluated by comparing scores from a clinical sample and a sample of individuals without ADHD and by calculating optimal cut-off values for specificity and sensitivity. The SWAN-DE-SB demonstrated normal distribution of the data collected, high internal consistency, and factorial and convergent validity. It reliably discriminated individuals with and without ADHD, with high specificity and sensitivity. It should therefore be considered a psychometrically convincing measure to assess strengths and weaknesses of ADHD symptoms and normal behavior in clinical and general population samples.

[The German Center for Mental Health : Innovative translational research to promote prevention, targeted intervention and resilience]. / Das Deutsche Zentrum für Psychische Gesundheit : Innovative Translationsforschung zur Förderung von Prävention, zielgerichteter Intervention und Resilienz.

BACKGROUND: Due to the high disease burden, the early onset and often long-term trajectories mental disorders are among the most widespread diseases with growing significance. The German Center for Mental Health (DZPG) was established to enhance research conditions and expedite the translation of clinically relevant findings into practice. OBJECTIVE: The aim of the DZPG is to optimize mental healthcare in Germany, influence modifiable social causes and to develop best practice models of care for vulnerable groups. It seeks to promote mental health and resilience, combat the stigmatization associated with mental disorders, and contribute to the enhancement of treatment across all age groups. MATERIAL AND METHODS: The DZPG employs a translational research program that accelerates the translation of basic research findings into clinical studies and general practice. University hospitals and outpatient departments, other university disciplines, and extramural research institutions are working together to establish a collaboratively coordinated infrastructure for accelerated translation and innovation. RESEARCH PRIORITIES: The research areas encompass 1) the interaction of somatic and mental risk and resilience factors and disorders across the lifespan, 2) influencing relevant modifiable environmental factors and 3) based on this personalized prevention and intervention. CONCLUSION: The DZPG aims to develop innovative preventive and therapeutic tools that enable an improvement in care for individuals with mental disorders. It involves a comprehensive integration of experts with experience at all levels of decision-making and employs trilogue and participatory approaches in all research projects.

Young people at risk for developing bipolar disorder: Two-year findings from the multicenter prospective, naturalistic Early-BipoLife study.

Early identification and intervention of individuals with an increased risk for bipolar disorder (BD) may improve the course of illness and prevent long­term consequences. Early-BipoLife, a multicenter, prospective, naturalistic study, examined risk factors of BD beyond family history in participants aged 15-35 years. At baseline, positively screened help-seeking participants (screenBD at-risk) were recruited at Early Detection Centers and in- and outpatient depression and attention-deficit/hyperactivity disorder (ADHD) settings, references (Ref) drawn from a representative cohort. Participants reported sociodemographics and medical history and were repeatedly examined regarding psychopathology and the course of risk factors. N = 1,083 screenBD at-risk and n = 172 Ref were eligible for baseline assessment. Within the first two years, n = 31 screenBD at-risk (2.9 %) and none of Ref developed a manifest BD. The cumulative transition risk was 0.0028 at the end of multistep assessment, 0.0169 at 12 and 0.0317 at 24 months (p = 0.021). The transition rate with a BD family history was 6.0 %, 4.7 % in the Early Phase Inventory for bipolar disorders (EPIbipolar), 6.6 % in the Bipolar Prodrome Interview and Symptom Scale-Prospective (BPSS-FP) and 3.2 % with extended Bipolar At-Risk - BARS criteria). In comparison to help-seeking young patients from psychosis detection services, transition rates in screenBD at-risk participants were lower. The findings of Early-BipoLife underscore the importance of considering risk factors beyond family history in order to improved early detection and interventions to prevent/ameliorate related impairment in the course of BD. Large long-term cohort studies are crucial to understand the developmental pathways and long-term course of BD, especially in people at- risk.

Prediction of estimated risk for bipolar disorder using machine learning and structural MRI features.

BACKGROUND: Individuals with bipolar disorder are commonly correctly diagnosed a decade after symptom onset. Machine learning techniques may aid in early recognition and reduce the disease burden. As both individuals at risk and those with a manifest disease display structural brain markers, structural magnetic resonance imaging may provide relevant classification features. METHODS: Following a pre-registered protocol, we trained linear support vector machine (SVM) to classify individuals according to their estimated risk for bipolar disorder using regional cortical thickness of help-seeking individuals from seven study sites (N = 276). We estimated the risk using three state-of-the-art assessment instruments (BPSS-P, BARS, EPIbipolar). RESULTS: For BPSS-P, SVM achieved a fair performance of Cohen's κ of 0.235 (95% CI 0.11-0.361) and a balanced accuracy of 63.1% (95% CI 55.9-70.3) in the 10-fold cross-validation. In the leave-one-site-out cross-validation, the model performed with a Cohen's κ of 0.128 (95% CI -0.069 to 0.325) and a balanced accuracy of 56.2% (95% CI 44.6-67.8). BARS and EPIbipolar could not be predicted. In post hoc analyses, regional surface area, subcortical volumes as well as hyperparameter optimization did not improve the performance. CONCLUSIONS: Individuals at risk for bipolar disorder, as assessed by BPSS-P, display brain structural alterations that can be detected using machine learning. The achieved performance is comparable to previous studies which attempted to classify patients with manifest disease and healthy controls. Unlike previous studies of bipolar risk, our multicenter design permitted a leave-one-site-out cross-validation. Whole-brain cortical thickness seems to be superior to other structural brain features.

Prefrontal hypoactivation induced via social stress is more strongly associated with state rumination than depressive symptomatology.

Previous studies have consistently shown a pattern of prefrontal hypoactivation in depressed patients (DP); however, it remains unclear whether this neural correlate is a consequence or concomitant feature of depression and/or whether ruminative thinking might be underlying. Using a sample comprising 65 healthy controls (HC) and 77 DP, we investigated the behavioral and neural correlates in response to stress and their association with depressive symptomatology, trait and state rumination. Fitting repeated-measurement MANOVAs including 21 fNIRS-channels covering the bilateral Inferior Frontal Gyrus (IFG), Dorsolateral Prefrontal Cortex (DLPFC) and Somatosensory Association Cortex (SAC), we investigated the predictive value of diagnostic group (HC vs. DP) and state rumination. In DP, we observed significantly lower increases in cortical oxygenation under stress in channels of the right IFG and bilateral DLPFC. Participants reporting lower state rumination and no increases in state rumination under stress showed higher increases in cortical oxygenation compared to the other groups and in more channels compared to the analysis on diagnostic group. Re-running our fNIRS-analysis while correcting for performance resulted in time-dependent changes dependent on group (DP vs. HC) no longer yielding significance, however for the differentiation of state rumination groups.

Emotions behind a mask: the value of disgust.

The impact of face masks on social cognition and interaction became a popular topic due to the long-lasting COVID-19 pandemic. This theme persists in the focus of attention beyond the pandemic, since face covering not only reduces the overall amount of face information available but also introduces biases and prejudices affecting social perception at large. Many questions are still open. One of them is whether gender of beholders affects inferring of emotions covered by face masks. Reading covered faces may be particularly challenging for individuals with mental disorders, most of which are gender-specific. Previous findings are not only sparse, but inconclusive because most research had been conducted online with resulting samples heavily dominated by females. Here in a face-to-face study, females and males were presented with a randomized set of faces covered by masks. In a two-alternative forced-choice paradigm, participants had to indicate facial emotions displayed by posers. In general, the outcome dovetails with earlier findings that face masks affect emotion recognition in a dissimilar way: Inferring some emotions suffers more severely than others, with the most pronounced influence of mask wearing on disgust and close to ceiling recognition of fear and neutral expressions. Contrary to our expectations, however, males were on overall more proficient in emotion recognition. In particular, males substantially excelled in inferring disgust. The findings help to understand gender differences in recognition of disgust, the forgotten emotion of psychiatry, that is of substantial value for a wide range of mental disorders including schizophrenia. Watch Prof. Marina Pavlova discussing this her work and this article: https://vimeo.com/860126397/5966610f49?share=copy .

Older adults' coping strategies during the COVID-19 pandemic - a longitudinal mixed-methods study.

Introduction: Older age is a main risk factor for severe COVID-19. In 2020, a broad political debate was initiated as to what extent older adults need special protection and isolation to minimize their risk for SARS-CoV-2 infection. However, isolation might also have indirect negative psychological (e.g., loneliness, stress, fear, anxiety, depression) or physical (e.g., lack of exercise, missing medical visits) consequences depending on individual strategies and personality traits to cope longitudinally with this crisis. Methods: To examine the impact of individuals' coping with the pandemic on mental health, a large sample of 880 older adults of the prospective longitudinal cohort TREND study were surveyed six times about their individual coping strategies in the COVID-19 pandemic between May 2020 (05/2020: Mage = 72.1, SDage = 6.4, Range: 58-91 years) and November 2022 in an open response format. The relevant survey question was: "What was helpful for you to get through the last months despite the COVID-19 pandemic? E.g., phone calls, going for a walk, or others." Results and Discussion: In total, we obtained 4,561 records containing 20,578 text passages that were coded and assigned to 427 distinct categories on seven levels based on qualitative content analysis using MAXQDA. The results allow new insights into the impact of personal prerequisites (e.g., value beliefs, living conditions), the general evaluation of the pandemic (e.g., positive, irrelevant, stressful) as well as the applied coping strategies (e.g., cognitive, emotional- or problem-focused) to deal with the COVID-19 pandemic by using an adapted Lazarus stress model. Throughout the pandemic emotional-focused as well as problem-focused strategies were the main coping strategies, whereas general beliefs, general living conditions and the evaluation were mentioned less frequently.

Training medical students in motivational interviewing using a blended learning approach: a proof-of-concept study.

Background: Difficulties in implementing behavior change in patients with chronic diseases are common in clinical practice. Motivational interviewing (MI) helps clinicians to support patients in overcoming ambivalence while maintaining self-determination. The inclusion of MI in German medical training curricula is still rare. Furthermore, the effects of systematic teaching of MI, especially via blended learning, have hardly been investigated. Methods: Medical students participated in three curricular events related to MI, consisting of instructional videos and theoretical and practical components in a blended learning format. The aim of the study was to investigate the effect of teaching MI in students' medical education. A controlled, non-randomized study was conducted with an intervention group and a control group. Both groups completed questionnaires on their experience and knowledge related to MI, completed a knowledge test and rated their satisfaction with the course. MI was taught in the 6th semester of medical coursework as part of a psychosomatic course, in the 8th semester during a psychiatry course and in the 9th semester during a weekly psychiatry clerkship. Results: Data from the intervention group (n = 35) and control group (n = 14) were analyzed, with 65.7% of students participating in all three parts of the curriculum. Overall interest in learning MI was high, with M = 2.92 (SD = 1.00). The results indicate a greater increase in knowledge over time in the intervention group. The majority (62.86%) stated that the curriculum was relevant to their future career. Free-form text responses indicated a high level of satisfaction with practical relevance. Conclusion: This study demonstrates the usefulness of an MI curriculum for medical students. The integration of MI into medical curricula is a promising curricular addition to improve doctor-patient communication. Future research should address patient perceptions of MI competencies and the persistence of acquired competencies.

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.

Machine Learning Prediction of Estimated Risk for Bipolar Disorders Using Hippocampal Subfield and Amygdala Nuclei Volumes.

The pathophysiology of bipolar disorder (BD) remains mostly unclear. Yet, a valid biomarker is necessary to improve upon the early detection of this serious disorder. Patients with manifest BD display reduced volumes of the hippocampal subfields and amygdala nuclei. In this pre-registered analysis, we used structural MRI (n = 271, 7 sites) to compare volumes of hippocampus, amygdala and their subfields/nuclei between help-seeking subjects divided into risk groups for BD as estimated by BPSS-P, BARS and EPIbipolar. We performed between-group comparisons using linear mixed effects models for all three risk assessment tools. Additionally, we aimed to differentiate the risk groups using a linear support vector machine. We found no significant volume differences between the risk groups for all limbic structures during the main analysis. However, the SVM could still classify subjects at risk according to BPSS-P criteria with a balanced accuracy of 66.90% (95% CI 59.2-74.6) for 10-fold cross-validation and 61.9% (95% CI 52.0-71.9) for leave-one-site-out. Structural alterations of the hippocampus and amygdala may not be as pronounced in young people at risk; nonetheless, machine learning can predict the estimated risk for BD above chance. This suggests that neural changes may not merely be a consequence of BD and may have prognostic clinical value.

Blood transcriptome analysis suggests an indirect molecular association of early life adversities and adult social anxiety disorder by immune-related signal transduction.

Social anxiety disorder (SAD) is a psychiatric disorder characterized by severe fear in social situations and avoidance of these. Multiple genetic as well as environmental factors contribute to the etiopathology of SAD. One of the main risk factors for SAD is stress, especially during early periods of life (early life adversity; ELA). ELA leads to structural and regulatory alterations contributing to disease vulnerability. This includes the dysregulation of the immune response. However, the molecular link between ELA and the risk for SAD in adulthood remains largely unclear. Evidence is emerging that long-lasting changes of gene expression patterns play an important role in the biological mechanisms linking ELA and SAD. Therefore, we conducted a transcriptome study of SAD and ELA performing RNA sequencing in peripheral blood samples. Analyzing differential gene expression between individuals suffering from SAD with high or low levels of ELA and healthy individuals with high or low levels of ELA, 13 significantly differentially expressed genes (DEGs) were identified with respect to SAD while no significant differences in expression were identified with respect to ELA. The most significantly expressed gene was MAPK3 (p = 0.003) being upregulated in the SAD group compared to control individuals. In contrary, weighted gene co-expression network analysis (WGCNA) identified only modules significantly associated with ELA (p ≤ 0.05), not with SAD. Furthermore, analyzing interaction networks of the genes from the ELA-associated modules and the SAD-related MAPK3 revealed complex interactions of those genes. Gene functional enrichment analyses indicate a role of signal transduction pathways as well as inflammatory responses supporting an involvement of the immune system in the association of ELA and SAD. In conclusion, we did not identify a direct molecular link between ELA and adult SAD by transcriptional changes. However, our data indicate an indirect association of ELA and SAD mediated by the interaction of genes involved in immune-related signal transduction.

Do subtle cultural differences sculpt face pareidolia?

Face tuning to non-face images such as shadows or grilled toasts is termed face pareidolia. Face-pareidolia images represent a valuable tool for investigation of social cognition in mental disorders. Here we examined (i) whether, and, if so, how face pareidolia is affected by subtle cultural differences; and (ii) whether this impact is modulated by gender. With this purpose in mind, females and males from Northern Italy were administered a set of Face-n-Thing images, photographs of objects such as houses or waves to a varying degree resembling a face. Participants were presented with pareidolia images with canonical upright orientation and display inversion that heavily affects face pareidolia. In a two-alternative forced-choice paradigm, beholders had to indicate whether each image resembled a face. The outcome was compared with the findings obtained in the Southwest of Germany. With upright orientation, neither cultural background nor gender affected face pareidolia. As expected, display inversion generally mired face pareidolia. Yet, while display inversion led to a drastic reduction of face impression in German males as compared to females, in Italians, no gender differences were found. In a nutshell, subtle cultural differences do not sculpt face pareidolia, but instead affect face impression in a gender-specific way under unusual viewing conditions. Clarification of the origins of these effects requires tailored brain imaging work. Implications for transcultural psychiatry, in particular, for schizophrenia research, are highlighted and discussed.