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.

[Implementation of an Open Door Policy on Two Acute Care Units]. / Implementierung eines Konzepts der offenen Türen auf zwei psychiatrischen Akutstationen an zwei Kliniken.

BACKGROUND: Since the amendments to the Baden-Württemberg Psychiatric Assistance Act, psychiatric patients who are treated involuntarily can be admitted to open wards. As a result, a comprehensive research project was carried out to implement an open-door policy. This work evaluates the attitudes of patients and therapeutic teams. METHODS: Over the course of a year, 8 focus groups with 6 to 11 participants were conducted with patients and staff before and at the end of the intervention phase and analyzed qualitatively. RESULTS: The concept of open doors was received positively. The staff raised safety concerns whereas on the patient side the door status seemed to be of limited relevance regarding the experience of autonomy or stigmatization. DISCUSSION: The elaboration of conflict issues allows a further development of specific concepts towards the implementation of open doors on psychiatric acute wards.

Trait-dependent effects of theta burst stimulation after psychosocial stress: a sham-controlled study in healthy individuals.

OBJECTIVE: Previous studies suggest that theta burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), applied to the left dorsolateral prefrontal cortex (DLPFC) might be a promising approach to modulate stress-reactive rumination and the associated psychophysiological stress response. Crucially, individuals showing higher levels of trait rumination might benefit more from prefrontal stimulation. METHODS: In this sham-controlled study, 127 healthy individuals, with varying ruminative tendencies, received a single-session of intermittent TBS (iTBS), continuous TBS (cTBS) or sham TBS (sTBS) over the left DLPFC before being confronted with a Trier Social Stress Test. RESULTS: Results showed significant TBS effects on salivary cortisol as a function of trait rumination. cTBS, as compared to sTBS and iTBS, resulted in an attenuated stress-induced cortisol response in high compared to low trait ruminators. Although independent of trait rumination levels, cTBS showed positive effects on stress-related changes in mood and, both cTBS and iTBS (versus sham) presented an enhanced heart rate recovery following the stressor. We found no evidence for (trait rumination-dependent) TBS effects on stress-reactive rumination, negative affect, subjective stress or heart rate variability. CONCLUSIONS: cTBS shows beneficial effects on certain measures of stress, especially in high trait ruminators. SIGNIFICANCE: These findings highlight the importance of accounting for individual differences when examining TBS effects.

[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.

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.

Neurocognitive function as outcome and predictor for prefrontal transcranial direct current stimulation in major depressive disorder: an analysis from the DepressionDC trial.

Transcranial direct current stimulation (tDCS) of the prefrontal cortex might beneficially influence neurocognitive dysfunctions associated with major depressive disorder (MDD). However, previous studies of neurocognitive effects of tDCS have been inconclusive. In the current study, we analyzed longitudinal, neurocognitive data from 101 participants of a randomized controlled multicenter trial (DepressionDC), investigating the efficacy of bifrontal tDCS (2 mA, 30 min/d, for 6 weeks) in patients with MDD and insufficient response to selective serotonin reuptake inhibitors (SSRI). We assessed whether active tDCS compared to sham tDCS elicited beneficial effects across the domains of memory span, working memory, selective attention, sustained attention, executive process, and processing speed, assessed with a validated, digital test battery. Additionally, we explored whether baseline cognitive performance, as a proxy of fronto-parietal-network functioning, predicts the antidepressant effects of active tDCS versus sham tDCS. We found no statistically significant group differences in the change of neurocognitive performance between active and sham tDCS. Furthermore, baseline cognitive performance did not predict the clinical response to tDCS. Our findings indicate no advantage in neurocognition due to active tDCS in MDD. Additional research is required to systematically investigate the effects of tDCS protocols on neurocognitive performance in patients with MDD.

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.

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.

Prevalence of COVID-19 and Psychotropic Drug Treatment in Psychiatric In-patients in Germany in 2020: Results from a Nationwide Pilot Survey.

INTRODUCTION: In patients with a pre-existing mental disorder, an increased risk for a first manifestation of a psychiatric disorder in COVID-19 patients, a more severe course of COVID-19 and an increased mortality have been described. Conversely, observations of lower COVID-19 incidences in psychiatric in-patients suggested protective effects of psychiatric treatment and/or psychotropic drugs against COVID-19. METHODS: A retrospective multi-center study was conducted in 24 German psychiatric university hospitals. Between April and December 2020 (the first and partly second wave of COVID-19), the effects of COVID-19 were assessed on psychiatric in-patient care, the incidence and course of a SARS-CoV-2 infection, and treatment with psychotropic drugs. RESULTS: Patients (n=36,322) were admitted to the hospitals. Mandatory SARS-CoV-2 tests before/during admission were reported by 23 hospitals (95.8%), while 18 (75%) conducted regular testing during the hospital stay. Two hundred thirty-two (0.6%) patients were tested SARS-CoV-2-positive. Thirty-seven (16%) patients were receiving medical treatment for COVID-19 at the psychiatric hospital, ten (4.3%) were transferred to an intermediate/intensive care unit, and three (1.3%) died. The most common prescription for SARS-CoV-2-positive patients was for second-generation antipsychotics (n=79, 28.2%) and antidepressants (SSRIs (n=38, 13.5%), mirtazapine (n=36, 12.9%) and SNRIs (n=29, 10.4%)). DISCUSSION: Contrary to previous studies, our results showed a low number of infections and mortality in SARS-CoV-2-positive psychiatric patients. Several preventive measures seem effective to protect this vulnerable group. Our observations are compatible with the hypothesis of a protective effect of psychotropic drugs against COVID-19 as the overall mortality and need for specific medical treatment was low.

In situ fNIRS measurements during cognitive behavioral emotion regulation training in rumination-focused therapy: A randomized-controlled trial.

Repetitive negative thinking (RNT), including rumination, plays a key role in various psychopathologies. Although several psychotherapeutic treatments have been developed to reduce RNT, the neural correlates of those specific treatments and of psychotherapy in general are largely unknown. Functional near-infrared spectroscopy (fNIRS) offers the potential to investigate the neural correlates of psychotherapeutic techniques in situ. Therefore, in this study we investigated the efficacy and neural correlates of a fNIRS adapted Mindfulness-based Emotion Regulation Training (MBERT) for the treatment of depressive rumination in 42 subjects with major depressive disorder (MDD) in a cross-over designed randomized controlled trial. Using psychometric measures, subjective ratings and fNIRS, we analyzed in situ changes in depressive symptom severity, ruminative thoughts and cortical activity in the Cognitive Control Network (CCN). Our results show that MBERT is effective in treating depressive symptoms and rumination. On a neural level, we found consistently higher cortical activation during emotion regulation training compared to control trials in the bilateral inferior frontal gyrus (IFG) and dorsolateral prefrontal cortex (DLPFC). Furthermore, cortical oxygenation decreased from session to session in the bilateral DLPFC. The relevance of the results for the psychotherapeutic treatment of MDD as well as further necessary investigations are discussed.

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.

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 .

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.

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.

Transcranial direct current stimulation as an additional treatment to selective serotonin reuptake inhibitors in adults with major depressive disorder in Germany (DepressionDC): a triple-blind, randomised, sham-controlled, multicentre trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been proposed as a feasible treatment for major depressive disorder (MDD). However, meta-analytic evidence is heterogenous and data from multicentre trials are scarce. We aimed to assess the efficacy of tDCS versus sham stimulation as an additional treatment to a stable dose of selective serotonin reuptake inhibitors (SSRIs) in adults with MDD. METHODS: The DepressionDC trial was triple-blind, randomised, and sham-controlled and conducted at eight hospitals in Germany. Patients being treated at a participating hospital aged 18-65 years were eligible if they had a diagnosis of MDD, a score of at least 15 on the Hamilton Depression Rating Scale (21-item version), no response to at least one antidepressant trial in their current depressive episode, and treatment with an SSRI at a stable dose for at least 4 weeks before inclusion; the SSRI was continued at the same dose during stimulation. Patients were allocated (1:1) by fixed-blocked randomisation to receive either 30 min of 2 mA bifrontal tDCS every weekday for 4 weeks, then two tDCS sessions per week for 2 weeks, or sham stimulation at the same intervals. Randomisation was stratified by site and baseline Montgomery-Åsberg Depression Rating Scale (MADRS) score (ie, <31 or ≥31). Participants, raters, and operators were masked to treatment assignment. The primary outcome was change on the MADRS at week 6, analysed in the intention-to-treat population. Safety was assessed in all patients who received at least one treatment session. The trial was registered with ClinicalTrials.gov (NCT02530164). FINDINGS: Between Jan 19, 2016, and June 15, 2020, 3601 individuals were assessed for eligibility. 160 patients were included and randomly assigned to receive either active tDCS (n=83) or sham tDCS (n=77). Six patients withdrew consent and four patients were found to have been wrongly included, so data from 150 patients were analysed (89 [59%] were female and 61 [41%] were male). No intergroup difference was found in mean improvement on the MADRS at week 6 between the active tDCS group (n=77; -8·2, SD 7·2) and the sham tDCS group (n=73; -8·0, 9·3; difference 0·3 [95% CI -2·4 to 2·9]). Significantly more participants had one or more mild adverse events in the active tDCS group (50 [60%] of 83) than in the sham tDCS group (33 [43%] of 77; p=0·028). INTERPRETATION: Active tDCS was not superior to sham stimulation during a 6-week period. Our trial does not support the efficacy of tDCS as an additional treatment to SSRIs in adults with MDD. FUNDING: German Federal Ministry of Education and Research.

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.

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.