Rapid weight gain commonly occurs following the onset of first-episode psychosis (FEP), leading to cardiometabolic disease. Most weight gain in FEP occurs in the first 3 months of treatment, offering a critical window for prevention. Despite this, most studies aiming to prevent antipsychotic-induced weight gain include people with chronic illness or people who have had lengthy exposure to antipsychotic medication. We aimed to synthesize and analyze the literature on interventions aimed at preventing antipsychotic-induced weight gain.

We conducted a systematic review in PsycInfo, MEDLINE, CINAHL, and EMBASE of studies that examined the effectiveness of interventions in preventing antipsychotic-induced weight gain in FEP. We examined their effect on weight gain and a range of cardiometabolic markers.

We screened 2,092 articles, 13 of which were eligible. Behavioral interventions, all three of which consisted of a multidisciplinary team approach, resulted in a mean of 3.05 kg less weight gain than treatment-as-usual (95% CI 1.36 kg to 4.73 kg). Pharmacological interventions displayed marked clinical and statistical heterogeneity, with each of the seven trials in adults using a different pharmacological intervention. Few studies collected comprehensive data on metabolic health. Only two pharmacological studies, and five studies in total, have been published since 2010.

Despite the importance of preventing weight gain in FEP, there have been few recent studies investigating this topic. Our results indicate that multidisciplinary team interventions are effective in preventing weight gain in FEP and should be offered to all patients.

While the relationships between somatic movement, mental well-being, and brain health have been well established, the causal nature and underlying mechanisms of such associations remain incompletely understood.

By applying multi-stage Mendelian randomization to multi-source summary data derived from genome-wide association studies, we examined the causal effects of 4 somatic movement measures on 2 mental well-being indices and 13 types of brain structures, followed by testing the mediating roles of brain structures in accounting for the causal associations between somatic movement and mental well-being.

Two-sample Mendelian randomization revealed that more physical activity was causally associated with greater mental well-being (life satisfaction and positive affect), while more sedentary behavior (longer leisure screen time and more sedentary behavior at work) with lower mental well-being. With respect to brain structures, sedentary behavior was causally linked to decreased volume, surface area, and local gyrification index in distributed cortical regions. Remarkably, decreased surface area of the piriform cortex was found to mediate the causal associations between sedentary behavior and lower mental well-being.

Our findings not only complement and extend earlier reports on the associations of somatic movement with mental well-being and brain health by further resolving the causality but also help elucidate the neural mechanisms by which sedentary behavior adversely affects mental well-being.

A novel transdiagnostic blended Ecological Momentary Intervention (EMI) for improving self-esteem in youth who experienced childhood adversity has shown beneficial effects. However, evidence on the cost-effectiveness of SELFIE and EMIs overall is lacking.

In this RCT-based economic evaluation, participants aged 12–26 years with low self-esteem (<26 on the Rosenberg Self-Esteem Scale [RSES]) and experienced childhood adversity were recruited from specialized mental health services and the general population and randomly allocated to CAU (control condition) or CAU + SELFIE (experimental condition). The Trimbos/iMTA Questionnaire for Costs Associated with Psychiatric Illness (TiC-P), the RSES, and EQ-5D-5L were assessed at baseline, post-intervention, and 6-, 18-, and 24-month follow-up. Incremental cost-effectiveness (ICER) and cost-utility (ICUR) ratios, and acceptability curves, were generated. Sensitivity and subgroup analyses assessed robustness.

From a societal perspective, the ICER presented €1,219 per improved point of self-esteem, and the ICUR presented €53,986 per QALY gained. The probability of cost-effectiveness was 26% at a willingness-to-pay (WTP) threshold of €20,000/QALY and 49% at €50,000/QALY. At €50,000/QALY, the probability of cost-effectiveness was 77% from a healthcare perspective (ICUR €15,671/QALY gained) and 87% for participants recruited from specialized mental health services (ICUR €–14,567/QALY gained).

At the societal level, the SELFIE intervention exceeded the WTP threshold. Tests for robustness showed higher probabilities of cost-effectiveness from a healthcare perspective, likely reflecting the absence of educational productivity loss costs in the societal perspective, and in youth recruited from specialized mental health services. The innovative field of blended EMIs yields encouraging first results, urging more cost-effectiveness research.

Functional neurological disorder (FND) is a common and disabling neuropsychiatric condition in which women comprise approximately 75% of cases. This paper examines whether the gender imbalance seen in FND is unique among neurological and psychiatric conditions and explores the biological, psychological, and social contributors to this disparity.

A narrative review was conducted using MEDLINE, PsycINFO, and Web of Science. Gender ratios were compared across depression, anxiety, post-traumatic stress disorder, schizophrenia, eating disorders, Parkinson’s disease, and multiple sclerosis. Evidence regarding sex hormones, early life trauma, gender-based social determinants, and diagnostic biases were synthesized thematically.

Amongst the psychiatric and neurological conditions reviewed, FND shows a pronounced female predominance (approximately 3:1), placing it amongst the most gender imbalanced disorders in our sample, with only eating disorders showing a larger female predominance. Biological factors (particularly the influence of estrogen and progesterone on stress reactivity, neuronal excitability, and agency), may heighten female vulnerability. Social determinants (increased exposure to trauma, socioeconomic inequality, and gender norms) further contribute to this risk. FND shares clinical and demographic similarities with other internalizing disorders and conditions linked to dissociation and trauma. The literature suggests FND emerges from a bidirectional interaction between gonadal hormones and psychosocial stressors.

The marked gender imbalance in FND arises from the interplay of biological vulnerability and gendered social adversity. Understanding these intersecting influences is essential for reducing stigma and guiding future research, diagnosis, and treatment. The findings support the need for a gender-sensitive, biopsychosocial approach to FND care, and investigation.

C-reactive protein (CRP) has been studied in relation to bipolar disorder (BD) and suicidality independently. Although suicide risk is elevated in youth with BD, little is known about the association of CRP with suicidality in this population.

211 youth participated, including 23 BD with lifetime suicide attempts (BDSA), 45 BD with lifetime non-suicidal self-injury (NSSI; BDNSSI), 39 BD without lifetime suicide attempt or NSSI (BDNo-SA/NSSI), and 104 healthy controls (HC). Suicide attempts and NSSI were assessed systematically. Fasting blood samples yielded CRP levels. Primary analyses controlled for age, sex, and body mass index percentile.

CRP levels differed across groups (F3,204 = 3.40, p = 0.02, ηp2 = 0.05). In post hoc analyses, CRP levels were significantly higher among BDSA (3.44 ± 6.42 mg/L) vs HC (0.81 ± 0.90 mg/L; p < 0.01) and BDNo-SA/NSSI (1.42 ± 3.31 mg/L; p = 0.01) groups; however, no difference was seen with the BDNSSI group (1.83 ± 2.22 mg/L; p = 0.12). Between-group differences in CRP levels persisted in independent sensitivity analyses controlling for current mood symptoms, lifetime mania score, lifetime smoking, and medications, but not with lifetime depression score.

Suicide attempts among youth with BD are associated with elevated CRP. Given accessibility of CRP testing, the present findings have potential clinical implications. Larger, longitudinal studies with repeated measures are needed to examine time-varying associations between CRP and suicide risk among youth with BD.

Formal thought disorder (FTD), characterized by disruptions in the flow and form of thought, is a core feature of psychosis. But its measurement is fragmented across numerous rating scales, leading to its continued neglect in both research and clinical practice. To determine if different FTD scales measure the same underlying construct, we need to assess the degree to which the content of commonly used FTD scales overlaps with each other.

We conducted a systematic review to identify all standardized, clinician-rated scales used to measure FTD in psychotic disorders. From this set, we extracted individual items and derived a consensus list of 56 discrete FTD phenomena. Two independent clinical experts conducted item-to-item mapping for every scale item onto these FTD phenomena. Content overlap between scales was quantified using Jaccard Similarity Index (JSI). We determined the overall coverage achieved via several combinations of FTD scales.

The 15 scales, comprising 207 items, showed weak content overlap. The mean JSI across all scale pairs was low, and no single phenomenon featured across all scales. While some core FTD phenomena (e.g. ‘incoherence’, ‘poor speech content’, ‘drifting-off’) were represented in many scales, 20% of all identified features were idiosyncratic, appearing in only one scale.

Existing FTD rating scales capture a wide but heterogeneous array of symptoms with poor content overlap. This lack of harmonization challenges the comparability of mechanistic and interventional studies. We highlight the need for a consensus-based, standardized measurement of FTD and provide a comprehensive checklist to advance the research and clinical practice.

Postinfectious autoimmune processes are hypothesized to be causally implicated in tic disorders, including Tourette syndrome and chronic tic disorder. However, this hypothesis remains controversial. In this nationwide cohort study, we aimed to clarify the mechanisms underlying the association between proneness to infections and tic disorders.

Using Swedish national registers, we identified 3,886,533 individuals (probands) born between 1970 and 2008 with available data on both biological parents. Probands were linked to six clusters of relatives: parents, full siblings, maternal half-siblings, paternal half-siblings, aunts/uncles, and cousins. Cox proportional hazards regression models were used to estimate the risk of tic disorders in probands exposed to infections and their relatives, compared with unexposed probands and their relatives. We also examined dose–response associations using logistic regression models.

Probands exposed to infections had an increased risk of tic disorders (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.40–1.52), as did their relatives. The observed risks increased with the degree of genetic relatedness, from HR (95% CI) of 1.15 (1.12–1.19) in cousins to 1.31 (1.25–1.37) in first-degree relatives. There was a dose–response association between the number of infections in the probands and the odds for tic disorders in the probands and their relatives. Results remained consistent after adjustment for infections in relatives, tic disorders in probands, and autoimmune diseases in probands and relatives.

Our results suggest an important role of shared genetic factors in the association between infections and tic disorders, potentially pointing to pleiotropic mechanisms.

Inconsistent findings persist across resting-state functional imaging studies of regional brain alterations in postpartum depression (PPD), while connections to transcriptional profiles and neurotransmitter systems remain largely uncharacterized.

We performed a whole-brain voxel-wise meta-analysis of resting-state functional imaging studies comparing PPD patients and healthy controls using SDM-PSI software. JuSpace toolbox analyzed atlas-based nuclear imaging-derived neurotransmitter maps, and transcriptional data were sourced from the Allen Human Brain Atlas.

Our systematic review identified 12 functional imaging studies (475 PPD patients, 504 controls). Patients with PPD displayed increased resting-state functional activity in the left inferior occipital gyrus and left precuneus as well as decreased resting-state functional activity in the right amygdala and left precentral gyrus. These functional alterations spatially overlapped with serotonergic, dopaminergic, and VAChT systems. Transcriptional analysis revealed PPD-related gene enrichments in ion channel function (transmembrane transport, gated/passive channels) and channel complexes.

The meta-analysis revealed functional alterations within the DMN, limbic, and primary sensorimotor systems in PPD patients. These changes were linked to neurotransmitter alterations and genetic modulations underlying brain dysfunction. Collectively, these findings advance mechanistic understanding of PPD pathophysiology.

Subcortical nuclei – including the thalamus, basal ganglia, and hippocampus-amygdala complex – are key regions in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). While cortical–subcortical connectivity is well studied, fine intra- and inter-subcortical patterns are less known. This study aimed to identify shared and distinct functional connectivity alterations across SZ, BD, and MDD using a high-resolution subcortical atlas.

Resting-state functional magnetic resonance imaging data from 800 participants (200 per group: SZ, BD, MDD, and healthy controls) in a single-site cohort were analyzed. Subcortical structures were parcellated into 27 regions per hemisphere – thalamus (8 regions), hippocampus (5 regions), amygdala (2 regions), and striatum (12 regions) – based on the a priori atlas. Pairwise functional connectivity among the 54 regions was computed for each participant, and group differences were assessed using general linear models.

Patients with SZ exhibited significantly reduced intra-thalamic connectivity and increased intra-striatal connectivity, as well as enhanced connectivity between the thalamus, striatum, and limbic regions. Patients with BD showed reduced intra-thalamic and intra-striatal connectivity, along with decreased thalamus–amygdala and thalamus–striatum connectivity. In MDD, the predominant finding was reduced intra-limbic connectivity, accompanied by mild reductions in intra-thalamic and striatum–limbic connectivity.

The results suggest that intra-thalamic hypoconnectivity appears common to SZ, BD, and MDD, with graded degrees of severity. In contrast, distinct alterations in intra-striatal and striatum–limbic connectivity may differentiate mood disorders from SZ. These shared and disorder-specific subcortical connectivity patterns enhance the understanding of psychiatric neurobiology and may guide the development of targeted, disorder-tailored interventions.

Occupational stress triggers psychological/physical health issues, elevating the risk of burnout and depression. This study explored the interrelationships among these constructs via network analysis (undirected/directed graphs).

A total of 1363 participants from Beijing hospitals and a university completed House and Rizzo’s Work Stress Scale, Zung’s Self-Report Depression Scale, and Maslach Burnout Inventory-General Survey. Graphical Gaussian Model and directed acyclic graphs (DAG) identified core/bridge/upstream nodes and causal pathways.

Emotional exhaustion (EE) was the core node (expected influence = 2.11). The strongest edge was D11–D12 (weight = 0.46). EE, occupational stress 11, cynicism (CY), and personal accomplishment (PA) served as key bridging nodes. The network showed high stability (0.75). DAG identified upstream occupational stress 1/7/8, confirming direct occupational stress to depression pathways (emotional dysregulation model) and CY/PA mediated pathways (burnout structural theory).

Targeted interventions on core/bridge/upstream nodes may prevent depression onset and progression in occupational settings.

The positive valence systems (PVS) domain, a key focus of the Research Domains Criteria framework, divides reward-related processes into three constructs: reward responsiveness, reward learning, and reward valuation. Difficulties with several of these reward constructs have been reported in people with mood-psychosis spectrum disorders. This study aims to examine how performance on tasks corresponding to these three constructs covaries, and how performance relates to mood and psychotic symptoms in adults with mood-psychosis spectrum disorders, those at familial risk, and controls.

Data from two studies (N = 278 and N = 332) were analyzed, which both included people with a psychotic disorder or bipolar disorder (patients), their first-degree relatives (FDRs), and controls. PVS constructs were measured using the Multi-Armed Bandit Task, Effort-Expenditure for Rewards Task, and Monetary Incentive Delay Task. Depression, mania, and psychosis symptoms were measured with self-report and interview instruments. Confirmatory factor analysis was used to examine covariation, and path analysis to test associations with symptoms.

The three reward constructs showed weak (nonsignificant) covariance in all groups. There were a few impairments in reward-related performance in patients or FDRs, none that survived multiple-comparison correction. There were no associations between symptoms and performance on the PVS constructs after multiple comparisons correction.

The findings showed no evidence that performance on any of the three PVS constructs could constitute an endophenotype of mood-psychosis spectrum disorders. We recommend future research examining the contribution of specific cognitive skills to reward-related behavior, and to sources of heterogeneity in reward functioning within the patient group.

Cognitive reserve (CR) is a protective factor in first-episode psychosis (FEP), influencing cognitive, clinical, and functional outcomes. CR is shaped by a combination of genetic, clinical, and environmental factors, yet the extent of their respective contributions remains unclear. This study investigates the influence of polygenic risk scores (PRS), clinical and environmental variables on CR in FEP.

A cohort of 174 individuals with non-affective FEP, aged 25.5 (SD=5.3), was analyzed. CR was assessed using a socio-behavioral proxy. PRS for educational attainment (PRSEA), intelligence (PRSIQ), cognitive performance (PRSCP), occupational attainment (PRSOA), physical activity (PRSPA), and schizophrenia (PRSSZ) were calculated. Age at onset, socioeconomic status, birth weight, and family history of psychosis were considered. Multiple regression models were employed to evaluate the impact of the different predictors on CR.

PRSEA (p=0.002), age at onset (p=5.32x10-5), and family history of psychosis (p=0.001) emerged as the strongest contributors to CR. Higher PRSEA was associated with higher levels of CR, while earlier age at onset and positive family history were associated with lower CR. The model incorporating environmental, clinical, and genetic variables explained 17.7% of the variance in CR, and the one without PRS explained 13.5%. The inclusion of PRSEA in the model improved the explanatory power (Δadj.R2=0.042) and predictive accuracy (ΔRMSE=−0.288).

These findings highlight the role of precision psychiatry in better understanding CR. Early identification of individuals with earlier onset, family history of psychosis, and lower genetic predisposition to educational attainment may help characterize those with lower CR.

The term ‘schizo-obsessive comorbidity (SOC)’ is used to describe the presence of obsessive-compulsive symptoms or obsessive-compulsive disorder (OCD) in patients with schizophrenia (SOC). Recent studies have found overlapped executive dysfunctions in SCZ and OCD implicating shared pathophysiology. However, specific deficits in the components of executive function (EF) in patients with SOC remains unclear.

We recruited 37 patients with SOC, 68 patients with SCZ, 70 patients with OCD, and 59 healthy controls (HCs). All participants completed a battery of measures for EF components, namely initiation, sustained attention, online updating, switching, disinhibition, and planning. Apart from traditional group-mean analysis, we applied machine learning approaches to identify the unique patterns of EF among different clinical groups.

The results showed that the three clinical groups could be distinguished from HCs. The feature importance analysis showed that, to classify clinical groups from HC, online updating was the core feature of SCZ patients, whereas disinhibition and online updating jointly determine classification between OCD patients and HC. In differentiating SOC from HC, online updating, planning, and disinhibition collectively served as key features. Machine learning algorithms classified SOC and OCD with acceptable performance but classified SOC and SCZ with lower performance.

Deficits of EF are shared features among patients with SOC, SCZ, and OCD. However, the specific components of executive dysfunction in these clinical groups appeared distinct.

This exploratory study examined baseline characteristics modifying treatment effects on paranoia in individuals diagnosed with schizophrenia spectrum disorders following a 10-session virtual reality-based cognitive behavioral therapy for psychosis (VR-CBTp) or standard CBTp.

All participants in the FaceYourFears trial were included (n=254; CBTp n=128; VR-CBTp n=126). General linear and logistic regression models examined baseline variables associated with end-of-treatment paranoia. In covariate analyses, regression coefficients quantified associations across treatments. In moderation analyses, interaction terms (randomization x moderator) were tested, with corresponding regression coefficients estimated and assessed at the 25th (low), 50th (medium), and 75th (high) percentiles of continuous variables.

Across treatments, higher baseline avolition, safety behavior, delusion severity, and cognitive biases were associated with end-of-treatment paranoia. Moderation analyses revealed interactions for avolition, delusion severity, and negative other-beliefs. Although avolition and delusion severity were associated with poorer outcomes overall, individuals with high avolition and those with moderate-to-high delusion severity improved more in VR-CBTp than CBTp, whereas participants with lower delusion severity showed better outcomes in CBTp. No demographic (age, gender, education, and occupation) or other clinical characteristics (diagnosis, paranoia, social anxiety, depression, anhedonia, total negative symptoms, functioning, core beliefs, or interpersonal trauma) were significantly associated with outcome.

This exploratory study generates hypotheses for future research, including VR-CBTp’s potential to engage individuals with high avolition. Given the modest effects and largely nonsignificant findings, both CBTp and VR-CBTp appear suitable for a wide range of individuals with paranoia, highlighting the importance of considering patient preferences.

Cognitive impairment in first-episode schizophrenia (FES) is a major contributor to functional decline, but antipsychotics provide limited cognitive improvement, and few repetitive transcranial magnetic stimulation (rTMS) studies have targeted the orbitofrontal cortex (OFC). This study investigated whether right OFC rTMS enhances specific cognitive functions in FES and its relationship with symptom reduction.

Ninety drug-naive FES patients were enrolled, with 48 receiving active right OFC rTMS and 42 sham stimulation for 20 sessions over 8 weeks, while all patients took olanzapine (10–20 mg/day). Cognitive function was assessed using the Chinese version of the MATRICS Consensus Cognitive Battery (MCCB) at baseline and week 4, and psychotic symptoms were rated with the Positive and Negative Syndrome Scale (PANSS).

Repeated-measures analysis of variance (RMANOVA) demonstrated a significant Time×Group interaction for visuospatial memory (assessed via the Brief Visuospatial Memory Test-Revised, BVMT; F = 5.079, df = 1, 83, p = 0.027, η2 = 0.058). Post hoc tests revealed significant BVMT improvement in the active group (p < 0.001) but not in the sham group (p = 0.312). In the active group, improvements in BVMT and Neuropsychological Assessment Battery (NAB) scores were significantly correlated with lower PANSS total scores after Bonferroni correction.

These findings indicate that right OFC rTMS improves specific cognitive functions in FES, with cognitive benefits associated with symptom alleviation, supporting the right OFC as a promising target for cognitive intervention in FES.