Testing a Motor Score Based on PANSS Ratings: A Proxy for Comprehensive Motor Assessment.

BACKGROUND AND HYPOTHESIS: Abnormal psychomotor behavior is a core schizophrenia symptom. However, assessment of motor abnormalities with expert rating scales is challenging. The Positive and Negative Syndrome Scale (PANSS) includes 3 items broadly related to hypokinetic motor behavior. Here, we tested whether a sum score of the PANSS items mannerisms and posturing (G5), motor retardation (G7), and disturbance of volition (G13) corresponds to expert ratings, potentially qualifying as a proxy-marker of motor abnormalities. STUDY DESIGN: Combining baseline datasets (n = 196) of 2 clinical trials (OCoPS-P, BrAGG-SoS), we correlated PANSS motor score (PANSSmot) and 5 motor rating scales. In addition, we tested whether the cutoff set at ≥3 on each PANSS motor item, ie, "mild" on G05, G07, and G13 (in total ≥9 on PANSSmot) would differentiate the patients into groups with high vs low scores in motor scales. We further sought for replication in an independent trial (RESIS, n = 102), tested the longitudinal stability using week 3 data of OCoPS-P (n = 75), and evaluated the validity of PANSSmot with instrumental measures of physical activity (n = 113). STUDY RESULTS: PANSSmot correlated with all motor scales (Spearman-Rho-range 0.19-0.52, all P ≤ .007). Furthermore, the cutoff set at ≥3 on each PANSS motor item was able to distinguish patients with high vs low motor scores in all motor scales except using Abnormal Involuntary Movement Scale (Mann-Whitney-U-Tests: all U ≥ 580, P ≤ .017). CONCLUSIONS: Our findings suggest that PANSSmot could be a proxy measure for hypokinetic motor abnormalities. This might help to combine large datasets from clinical trials to explore whether some interventions may hold promise to alleviate hypokinetic motor abnormalities in psychosis.

EEG-based Signatures of Schizophrenia, Depression, and Aberrant Aging: A Supervised Machine Learning Investigation.

BACKGROUND: Electroencephalography (EEG) is a noninvasive, cost-effective, and robust tool, which directly measures in vivo neuronal mass activity with high temporal resolution. Combined with state-of-the-art machine learning (ML) techniques, EEG recordings could potentially yield in silico biomarkers of severe mental disorders. HYPOTHESIS: Pathological and physiological aging processes influence the electrophysiological signatures of schizophrenia (SCZ) and major depressive disorder (MDD). STUDY DESIGN: From a single-center cohort (N = 735, 51.6% male) comprising healthy control individuals (HC, N = 245) and inpatients suffering from SCZ (N = 250) or MDD (N = 240), we acquired resting-state 19 channel-EEG recordings. Using repeated nested cross-validation, support vector machine models were trained to (1) classify patients with SCZ or MDD and HC individuals and (2) predict age in HC individuals. The age model was applied to patient groups to calculate Electrophysiological Age Gap Estimation (EphysAGE) as the difference between predicted and chronological age. The links between EphysAGE, diagnosis, and medication were then further explored. STUDY RESULTS: The classification models robustly discriminated SCZ from HC (balanced accuracy, BAC = 72.7%, P < .001), MDD from HC (BAC = 67.0%, P < .001), and SCZ from MDD individuals (BAC = 63.2%, P < .001). Notably, central alpha (8-11 Hz) power decrease was the most consistently predictive feature for SCZ and MDD. Higher EphysAGE was associated with an increased likelihood of being misclassified as SCZ in HC and MDD (ρHC = 0.23, P < .001; ρMDD = 0.17, P = .01). CONCLUSIONS: ML models can extract electrophysiological signatures of MDD and SCZ for potential clinical use. However, the impact of aging processes on diagnostic separability calls for timely application of such models, possibly in early recognition settings.

Impact of excessive abdominal obesity on brain microstructural abnormality in schizophrenia.

Significant evidence links obesity and schizophrenia (SZ), but the brain associations are still largely unclear. 48 people with SZ were divided into two subgroups: patients with lower waist circumference (SZ-LWC: n = 24) and patients with higher waist circumference (SZ-HWC: n = 24). Healthy controls (HC) were included for comparison (HC: n = 27). Using tract-based spatial statistics, we compared fractional anisotropy (FA) of the whole-brain white matter skeleton between these three groups (SZ-LWC, SZ-HWC, HC). Using Free Surfer, we compared whole-brain cortical thickness and the selected subcortical volumes between the three groups. FA of widespread white matter and the mean cortical thickness in the right temporal lobe and insular cortex were significantly lower in the SZ-HWC group than in the HC group. The FA of regional white matter was significantly lower in the SZ-LWC group than in the HC group. There were no significant differences in mean subcortical volumes between the groups. Additionally, the cognitive performances were worse in the SZ-HWC group, who had more severe triglycerides elevation. This study provides evidence for microstructural abnormalities of white matter, cortical thickness and neurocognitive deficits in SZ patients with excessive abdominal obesity.

Dose-dependent target engagement of a clinical iTBS protocol: An interleaved TMS-fMRI study in healthy subjects.

BACKGROUND: Intermittent theta burst stimulation (iTBS) of the dorsolateral prefrontal cortex (DLPFC) is widely applied as therapeutic intervention in mental health, however understanding of its mechanisms is still incomplete. Prior MRI studies have mainly used offline iTBS or short sequences in concurrent TMS-fMRI. This study investigated a full 600 stimuli iTBS protocol using interleaved TMS-fMRI in comparison with two control conditions in healthy subjects. METHODS: In a crossover design, 18 participants underwent three sessions of interleaved iTBS-fMRI: 1) left DLPFC at 40% resting motor threshold (rMT) intensity, 2) left DLPFC at 80% rMT intensity, and 3) left primary motor cortex (M1) at 80% rMT intensity. We compared immediate blood-oxygen-level-dependent (BOLD) responses during interleaved iTBS-fMRI across these conditions including correlations between individual fMRI BOLD activation and iTBS induced electric field (E-field) strength at the target sites. RESULTS: Whole-brain analysis showed increased activation in several regions following iTBS. Specifically, left DLPFC, as well as bilateral M1, anterior cingulate cortex, and insula showed increased activation during 80% rMT left DLPFC stimulation. Increased BOLD activity in the left DLPFC was not observed with 40% rMT left DLPFC stimulation nor left M1 80% rMT iTBS, whereas activation in other regions was found to overlap between conditions. Of note, BOLD activation and E-field intensities were only correlated for M1 stimulation, but not for the DLPFC conditions. CONCLUSIONS: The study showed dosage and target specific BOLD activation during interleaved TMS-fMRI with 600 stimuli iTBS in healthy subjects. Future studies may use our approach for demonstrating target engagement.

The impact of a digital guideline version on schizophrenia guideline knowledge: results from a multicenter cluster-randomized controlled trial.

BACKGROUND: Clinical practice guidelines are crucial for enhancing healthcare quality and patient outcomes. Yet, their implementation remains inconsistent across various professions and disciplines. Previous findings on the implementation of the German guideline for schizophrenia (2019) revealed low adherence rates among healthcare professionals. Barriers to guideline adherence are multifaceted, influenced by individual, contextual, and guideline-related factors. This study aims to investigate the effectiveness of a digital guideline version compared to print/PDF formats in enhancing guideline adherence. METHODS: A multicenter, cluster-randomized controlled trial was conducted in South Bavaria, Germany, involving psychologists and physicians. Participants were divided into two groups: implementation of the guideline using a digital online version via the MAGICapp platform and the other using the traditional print/PDF version. The study included a baseline assessment and a post-intervention assessment following a 6-month intervention phase. The primary outcome was guideline knowledge, which was assessed using a guideline knowledge questionnaire. RESULTS: The study included 217 participants at baseline and 120 at post-intervention. Both groups showed significant improvements in guideline knowledge; however, no notable difference was found between both study groups regarding guideline knowledge at either time points. At baseline, 43.6% in the control group (CG) and 52.5% of the interventional group (IG) met the criterion. There was no significant difference in the primary outcome between the two groups at either time point (T0: Chi2(1) = 1.65, p = 0.199, T1: Chi2(1) = 0.34, p = 0.561). At post-intervention, both groups improved, with 58.2% in the CG and 63.5% in the IG meeting this criterion. CONCLUSIONS: While the study did not include a control group without any implementation strategy, the overall improvement in guideline knowledge following an implementation strategy, independent of the format, was confirmed. The digital guideline version, while not superior in enhancing knowledge, showed potential benefits in shared decision-making skills. However, familiarity with traditional formats and various barriers to digital application may have influenced these results. The study highlights the importance of tailored implementation strategies, especially for younger healthcare providers. TRIAL REGISTRATION: https://drks.de/search/de/trial/DRKS00028895.

Distinct genetic liability profiles define clinically relevant patient strata across common diseases.

Stratified medicine holds great promise to tailor treatment to the needs of individual patients. While genetics holds great potential to aid patient stratification, it remains a major challenge to operationalize complex genetic risk factor profiles to deconstruct clinical heterogeneity. Contemporary approaches to this problem rely on polygenic risk scores (PRS), which provide only limited clinical utility and lack a clear biological foundation. To overcome these limitations, we develop the CASTom-iGEx approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue specific gene expression levels. The paradigmatic application of this approach to coronary artery disease or schizophrenia patient cohorts identified diverse strata or biotypes. These biotypes are characterized by distinct endophenotype profiles as well as clinical parameters and are fundamentally distinct from PRS based groupings. In stark contrast to the latter, the CASTom-iGEx strategy discovers biologically meaningful and clinically actionable patient subgroups, where complex genetic liabilities are not randomly distributed across individuals but rather converge onto distinct disease relevant biological processes. These results support the notion of different patient biotypes characterized by partially distinct pathomechanisms. Thus, the universally applicable approach presented here has the potential to constitute an important component of future personalized medicine paradigms.

Two Sides of the Same Coin in Female Borderline Personality Disorder: Self-Reported Guilt and Shame and Their Neurofunctional Correlates.

OBJECTIVE: Patients with borderline personality disorder (BPD) report to be especially prone to social emotions like shame and guilt. At the same time, these emotions seem to play an important role in BPD pathology. The present study aimed to deepen the knowledge about the processes behind shame and guilt in patients with BPD. METHODS: Twenty patients with BPD and twenty healthy controls (HCs) took part in an experiment that induced shame and guilt by imagining scenarios during scanning using functional brain imaging. Participants also filled out self-report questionnaires and took part in diagnostic interviews. RESULTS: BPD patients reported more proneness to guilt but not to shame than the HCs. There was no difference in the self-reported intensity rating of experimentally induced emotions between the groups. Between-group contrast of neural signals in the shame condition revealed a stronger activation of cingulate and fusiform gyrus for the BPD patients compared to the controls, and a more pronounced activation in the lingual gyrus and cuneus for the HCs. In the guilt condition, activation in the caudate nucleus, the fusiform gyrus, and the posterior cingulate cortex was stronger in BPD patients, while HC showed stronger activations in cuneus, lingual gyrus, and fronto-temporal regions. CONCLUSIONS: Differences in the neuro-functional processes between BPD patients and HC were found, even though the two groups did not differ in their self-report of subjective proneness to guilt and emotional intensity of shame and guilt during the experiment. While the HCs may be engaged more by the emotional scenarios themselves, the BPD patients may be more occupied with cognitive regulatory and self-referential processing.

Exploring the genetics of lithium response in bipolar disorders.

BACKGROUND: Lithium (Li) remains the treatment of choice for bipolar disorders (BP). Its mood-stabilizing effects help reduce the long-term burden of mania, depression and suicide risk in patients with BP. It also has been shown to have beneficial effects on disease-associated conditions, including sleep and cardiovascular disorders. However, the individual responses to Li treatment vary within and between diagnostic subtypes of BP (e.g. BP-I and BP-II) according to the clinical presentation. Moreover, long-term Li treatment has been linked to adverse side-effects that are a cause of concern and non-adherence, including the risk of developing chronic medical conditions such as thyroid and renal disease. In recent years, studies by the Consortium on Lithium Genetics (ConLiGen) have uncovered a number of genetic factors that contribute to the variability in Li treatment response in patients with BP. Here, we leveraged the ConLiGen cohort (N = 2064) to investigate the genetic basis of Li effects in BP. For this, we studied how Li response and linked genes associate with the psychiatric symptoms and polygenic load for medical comorbidities, placing particular emphasis on identifying differences between BP-I and BP-II. RESULTS: We found that clinical response to Li treatment, measured with the Alda scale, was associated with a diminished burden of mania, depression, substance and alcohol abuse, psychosis and suicidal ideation in patients with BP-I and, in patients with BP-II, of depression only. Our genetic analyses showed that a stronger clinical response to Li was modestly related to lower polygenic load for diabetes and hypertension in BP-I but not BP-II. Moreover, our results suggested that a number of genes that have been previously linked to Li response variability in BP differentially relate to the psychiatric symptomatology, particularly to the numbers of manic and depressive episodes, and to the polygenic load for comorbid conditions, including diabetes, hypertension and hypothyroidism. CONCLUSIONS: Taken together, our findings suggest that the effects of Li on symptomatology and comorbidity in BP are partially modulated by common genetic factors, with differential effects between BP-I and BP-II.

[Discharged, but where to? The Current Situation of Long Stay Patients in German Psychiatric Clinics]. / Entlassen, aber wohin? Zur aktuellen Situation der "Langlieger" in deutschen psychiatrischen Kliniken.

OBJECTIVE: The study analyses the number, characteristics and reasons for a length of stay of patients in German psychiatric clinics in excess of 6 months. METHODS: The study was implemented in the form of a nationwide online survey, which was addressed to chief physicians of psychiatric clinics. RESULTS: In the sample, 174 patients in 80 psychiatric clinics were identified who could not be discharged because no suitable follow-up services were available in the region. The majority of patients are male, often have an F2 diagnosis and exhibit aggressive behaviour during their hospital stay. CONCLUSION: To avoid inappropriate health care and prevent prolonged stays for a subgroup of mentally ill people, individual complex services should be implemented in community psychiatry.

Characterization of cognitive symptoms in post COVID-19 patients.

Cognitive symptoms (CS) belong to the most common manifestations of the Post COVID-19 (PC) condition. We sought to objectify CS in PC patients using routine diagnostic assessments: neurocognitive testing (NCT) and brain imaging (BI). Further, we investigated possible associations of CS with patient reported outcomes (PROs), and risk factors for developing CS. Clinical data and PROs of 315 PC patients were assessed at a mean of 6 months after SARS-CoV-2 infection. 231 (73.3%) patients reported any sort of CS. Among them, 78 underwent NCT and 55 received BI. In NCT, the cognitive domains most affected were the working memory, attention, and concentration. Nonetheless, pathological thresholds were exceeded only in few cases. Neurocognitive performance did not differ significantly between patients complaining of severe (n = 26) versus non-severe (n = 52) CS. BI findings were abnormal in 8 (14.5%) cases with CS but were most likely not related to PC. Patients reporting high severity of CS scored worse in the PHQ-9, FSS, WHOQOL-BREF, were more likely to report impaired sleep, and had a higher prevalence of psychiatric diagnoses. Overall, NCT could confirm mild impairment in some but not all PC patients with CS, while BI studies were abnormal in only few cases. CS severity did not affect NCT results, but severe CS were associated with symptoms of depression (PHQ-9), fatigue (FSS), reduced quality of life (WHOQOL-BREF) and higher prevalence of psychiatric illnesses. These findings support the importance of NCT, BI, and neuro-psychological assessment in the work-up of PC patients reporting CS. TRIAL REGISTRATION: Trial registration number and date of registration: DRKS00030974, 22 Dec 2022, retrospectively registered.

[Providing Cognitive Remediation Therapy to People with Schizophrenia: Results of a Survey in Psychiatric Clinics in Germany]. / Die Versorgung von an Schizophrenie erkrankten Menschen mit Kognitiver Remediationstherapie ­ Ergebnisse einer Befragung in psychiatrischen Kliniken in Deutschland.

Schizophrenia is accompanied by significant cognitive impairments, which often persist to a relevant extent after remission of clinical symptoms and has a negative impact on psychosocial functioning. These impairments are often experienced as very stressful by those affected. Under the umbrella term of Cognitive Remediation Therapy (CRT), evidence-based therapy options are available that improve both the respective cognitive target functions and the psychosocial functioning. According to expert recommendations, at least 20 sessions should be carried out, accompanied by qualified therapeutic staff. The current edition of the S3 treatment guideline schizophrenia of the German Society for Psychiatry and Psychotherapy, Psychosomatics and Neurology recommends CRT with the highest level of recommendation. It is unclear to what extent CRT has become part of routine inpatient care. Between July 2021 and May 2022, 395 psychiatric university hospitals and non-university psychiatric specialist hospitals in Germany were invited to fill in a 14-item questionnaire. A total of 103 institutions took part in the survey; 56.3% of these hospitals used at least one evidence-based CRT programme. Among the CRT programmes used, Cogpack, Rehacom and the Integriertes Psychologisches Therapieprogramm (IPT) were named most frequently. In 87.5% of the participating facilities, fewer than half of the people with schizophrenia received CRT. With regard to the clinics which used evidence-based CRT, 64.3% carried out fewer than 11 therapy sessions, 28.6% between 11 and 20 sessions and 7.2% more than 20 sessions. It is thus clear that CRT is not yet offered in all of the participating psychiatric hospitals in Germany, not yet for all people with schizophrenia, and not yet with sufficient intensity, with clinics indicating the need for more technical and personnel resources and more extensive development of competencies for CRT application.The low response rate of 26.1% and possible selection effects for participation in the study are addressed and are to be seen as limitations.

Climate change and mental health: Position paper of the European Psychiatric Association.

BACKGROUND: Climate change is one of the greatest threats to health that societies face and can adversely affect mental health. Given the current lack of a European consensus paper on the interplay between climate change and mental health, we signal a need for a pan-European position paper about this topic, written by stakeholders working in mental health care. METHODS: On behalf of the European Psychiatric Association (EPA), we give recommendations to make mental health care, research, and education more sustainable based on a narrative review of the literature. RESULTS: Examples of sustainable mental healthcare comprise preventive strategies, interdisciplinary collaborations, evidence-based patient care, addressing social determinants of mental health, maintaining health services during extreme weather events, optimising use of resources, and sustainable facility management. In mental health research, sustainable strategies include investigating the impact of climate change on mental health, promoting research on climate change interventions, strengthening the evidence base for mental health-care recommendations, evaluating the allocation of research funding, and establishing evidence-based definitions and clinical approaches for emerging issues such as 'eco-distress'. Regarding mental health education, planetary health, which refers to human health and how it is intertwined with ecosystems, may be integrated into educational courses. CONCLUSIONS: The EPA is committed to combat climate change as the latter poses a threat to the future of mental health care. The current EPA position paper on climate change and mental health may be of interest to a diverse readership of stakeholders, including clinicians, researchers, educators, patients, and policymakers.

Association of symptom severity and cerebrospinal fluid alterations in recent onset psychosis in schizophrenia-spectrum disorders - An individual patient data meta-analysis.

Neuroinflammation and blood-cerebrospinal fluid barrier (BCB) disruption could be key elements in schizophrenia-spectrum disorders(SSDs) etiology and symptom modulation. We present the largest two-stage individual patient data (IPD) meta-analysis, investigating the association of BCB disruption and cerebrospinal fluid (CSF) alterations with symptom severity in first-episode psychosis (FEP) and recent onset psychotic disorder (ROP) individuals, with a focus on sex-related differences. Data was collected from PubMed and EMBASE databases. FEP, ROP and high-risk syndromes for psychosis IPD were included if routine basic CSF-diagnostics were reported. Risk of bias of the included studies was evaluated. Random-effects meta-analyses and mixed-effects linear regression models were employed to assess the impact of BCB alterations on symptom severity. Published (6 studies) and unpublished IPD from n = 531 individuals was included in the analyses. CSF was altered in 38.8 % of individuals. No significant differences in symptom severity were found between individuals with and without CSF alterations (SMD = -0.17, 95 %CI -0.55-0.22, p = 0.341). However, males with elevated CSF/serum albumin ratios or any CSF alteration had significantly higher positive symptom scores than those without alterations (SMD = 0.34, 95 %CI 0.05-0.64, p = 0.037 and SMD = 0.29, 95 %CI 0.17-0.41p = 0.005, respectively). Mixed-effects and simple regression models showed no association (p > 0.1) between CSF parameters and symptomatic outcomes. No interaction between sex and CSF parameters was found (p > 0.1). BCB disruption appears highly prevalent in early psychosis and could be involved in positive symptoms severity in males, indicating potential difficult-to-treat states. This work highlights the need for considering BCB breakdownand sex-related differences in SSDs clinical trials and treatment strategies.

Signature of Altered Retinal Microstructures and Electrophysiology in Schizophrenia Spectrum Disorders Is Associated With Disease Severity and Polygenic Risk.

BACKGROUND: Optical coherence tomography and electroretinography studies have revealed structural and functional retinal alterations in individuals with schizophrenia spectrum disorders (SSDs). However, it remains unclear which specific retinal layers are affected; how the retina, brain, and clinical symptomatology are connected; and how alterations of the visual system are related to genetic disease risk. METHODS: Optical coherence tomography, electroretinography, and brain magnetic resonance imaging were applied to comprehensively investigate the visual system in a cohort of 103 patients with SSDs and 130 healthy control individuals. The sparse partial least squares algorithm was used to identify multivariate associations between clinical disease phenotype and biological alterations of the visual system. The association of the revealed patterns with individual polygenic disease risk for schizophrenia was explored in a post hoc analysis. In addition, covariate-adjusted case-control comparisons were performed for each individual optical coherence tomography and electroretinography parameter. RESULTS: The sparse partial least squares analysis yielded a phenotype-eye-brain signature of SSDs in which greater disease severity, longer duration of illness, and impaired cognition were associated with electrophysiological alterations and microstructural thinning of most retinal layers. Higher individual loading onto this disease-relevant signature of the visual system was significantly associated with elevated polygenic risk for schizophrenia. In case-control comparisons, patients with SSDs had lower macular thickness, thinner retinal nerve fiber and inner plexiform layers, less negative a-wave amplitude, and lower b-wave amplitude. CONCLUSIONS: This study demonstrates multimodal microstructural and electrophysiological retinal alterations in individuals with SSDs that are associated with disease severity and individual polygenic burden.

Distinct multimodal biological and functional profiles of symptom-based subgroups in recent-onset psychosis.

Symptom heterogeneity characterizes psychotic disorders and hinders the delineation of underlying biomarkers. Here, we identify symptom-based subtypes of recent-onset psychosis (ROP) patients from the multi-center PRONIA (Personalized Prognostic Tools for Early Psychosis Management) database and explore their multimodal biological and functional signatures. We clustered N = 328 ROP patients based on their maximum factor scores in an exploratory factor analysis on the Positive and Negative Syndrome Scale items. We assessed inter-subgroup differences and compared to N = 464 healthy control (HC) individuals regarding gray matter volume (GMV), neurocognition, polygenic risk scores, and longitudinal functioning trajectories. Finally, we evaluated factor stability at 9- and 18-month follow-ups. A 4-factor solution optimally explained symptom heterogeneity, showing moderate longitudinal stability. The ROP-MOTCOG (Motor/Cognition) subgroup was characterized by GMV reductions within salience, control and default mode networks, predominantly throughout cingulate regions, relative to HC individuals, had the most impaired neurocognition and the highest genetic liability for schizophrenia. ROP-SOCWD (Social Withdrawal) patients showed GMV reductions within medial fronto-temporal regions of the control, default mode, and salience networks, and had the lowest social functioning across time points. ROP-POS (Positive) evidenced GMV decreases in salience, limbic and frontal regions of the control and default mode networks. The ROP-AFF (Affective) subgroup showed GMV reductions in the salience, limbic, and posterior default-mode and control networks, thalamus and cerebellum. GMV reductions in fronto-temporal regions of the salience and control networks were shared across subgroups. Our results highlight the existence of behavioral subgroups with distinct neurobiological and functional profiles in early psychosis, emphasizing the need for refined symptom-based diagnosis and prognosis frameworks.

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.

Multimodal workflows optimally predict response to repetitive transcranial magnetic stimulation in patients with schizophrenia: a multisite machine learning analysis.

The response variability to repetitive transcranial magnetic stimulation (rTMS) challenges the effective use of this treatment option in patients with schizophrenia. This variability may be deciphered by leveraging predictive information in structural MRI, clinical, sociodemographic, and genetic data using artificial intelligence. We developed and cross-validated rTMS response prediction models in patients with schizophrenia drawn from the multisite RESIS trial. The models incorporated pre-treatment sMRI, clinical, sociodemographic, and polygenic risk score (PRS) data. Patients were randomly assigned to receive active (N = 45) or sham (N = 47) rTMS treatment. The prediction target was individual response, defined as ≥20% reduction in pre-treatment negative symptom sum scores of the Positive and Negative Syndrome Scale. Our multimodal sequential prediction workflow achieved a balanced accuracy (BAC) of 94% (non-responders: 92%, responders: 95%) in the active-treated group and 50% in the sham-treated group. The clinical, clinical + PRS, and sMRI-based classifiers yielded BACs of 65%, 76%, and 80%, respectively. Apparent sadness, inability to feel, educational attainment PRS, and unemployment were most predictive of non-response in the clinical + PRS model, while grey matter density reductions in the default mode, limbic networks, and the cerebellum were most predictive in the sMRI model. Our sequential modelling approach provided superior predictive performance while minimising the diagnostic burden in the clinical setting. Predictive patterns suggest that rTMS responders may have higher levels of brain grey matter in the default mode and salience networks which increases their likelihood of profiting from plasticity-inducing brain stimulation methods, such as rTMS. The future clinical implementation of our models requires findings to be replicated at the international scale using stratified clinical trial designs.

Clinician treatment choices for post-traumatic stress disorder: ambassadors survey of psychiatrists in 39 European countries.

BACKGROUND: Considering the recently growing number of potentially traumatic events in Europe, the European Psychiatric Association undertook a study to investigate clinicians' treatment choices for post-traumatic stress disorder (PTSD). METHODS: The case-based analysis included 611 participants, who correctly classified the vignette as a case of PTSD, from Central/ Eastern Europe (CEE) (n = 279), Southern Europe (SE) (n = 92), Northern Europe (NE) (n = 92), and Western Europe (WE) (N = 148). RESULTS: About 82% woulduse antidepressants (sertraline being the most preferred one). Benzodiazepines and antipsychotics were significantly more frequently recommended by participants from CEE (33 and 4%, respectively), compared to participants from NE (11 and 0%) and SE (9% and 3%). About 52% of clinicians recommended trauma-focused cognitive behavior therapy and 35% psychoeducation, irrespective of their origin. In the latent class analysis, we identified four distinct "profiles" of clinicians. In Class 1 (N = 367), psychiatrists would less often recommend any antidepressants. In Class 2 (N = 51), clinicians would recommend trazodone and prolonged exposure therapy. In Class 3 (N = 65), they propose mirtazapine and eye movement desensitization reprocessing therapy. In Class 4 (N = 128), clinicians propose different types of medications and cognitive processing therapy. About 50.1% of participants in each region stated they do not adhere to recognized treatment guidelines. CONCLUSIONS: Clinicians' decisions for PTSD are broadly similar among European psychiatrists, but regional differences suggest the need for more dialogue and education to harmonize practice across Europe and promote the use of guidelines.