Abstract Background Exposure to stress is a well-established risk factor for psychotic experiences, yet the cognitive mechanisms underlying this association remain insufficiently understood. This study examined whether longitudinal changes in cognitive biases mediate the relationship between stress exposure and changes in psychotic-like experiences (PLEs) in the general population sample of adults aged 18–40 years. Methods Adults without a history of psychiatric treatment were assessed at baseline and at 12-month follow-up. Change-score mediation models with bootstrap confidence intervals were estimated, adjusting for age, gender, and education. Results Of 5,126 adults who completed the baseline assessment, 2,290 (44.7%) participated in the follow-up. Greater stress exposure predicted increases in PLEs, negative, and depressive symptoms. After correction for multiple testing, significant indirect effects consistent with mediation by cognitive biases were observed for PLEs, but not for negative or depressive symptoms. These effects were significant for changes in belief inflexibility, safety behaviors, external attribution, and subjective cognitive and social cognitive problems, but not for attention to threat or jumping to conclusions. Reverse mediation models indicated consistently smaller indirect effects. In parallel multiple-mediator models, no individual bias showed a unique indirect effect on PLEs, yet the total indirect effect remained significant, suggesting mediation through interrelated biases. Social cognitive problems emerged as the only bias with a specific indirect effect on negative and depressive symptoms. Conclusions Longitudinal changes in cognitive biases might represent an indirect pathway to the association between stress exposure and increases in PLEs. These findings highlight cognitive biases as potential targets for preventive interventions.
Abstract Background Formal thought disorder (FTD) has been conceptualized as a categorical syndrome of psychosis, but this remains untested. Clarifying whether FTD is categorical or continuous and its supra-thres hold prevalence in non-clinical populations has direct implications for bears directly on mechanistic studies of FTD, psychosis prediction, and early intervention. Methods In a multi-site cross-sectional study of 520 individuals (352 clinical, 168 non-clinical), we used the Thought and Language Index to assess FTD across three subconstructs: Loosening, Peculiarities , and Impoverishment. Using complementary taxometric procedures (MAMBAC, MAXEIG, and L-Mode) with simulation of comparison data and multiple thresholding approaches (minimally important change criteria, ROC analysis, intuitive binarization), we evaluated the latent structure of FTD, optimal cutoff points to estimate FTD prevalence, and the frequency of co-occurrence of subconstructs. Results Taxometric analyses revealed a predominantly dimensional latent structure for FTD across various base rates. Among healthy individuals, Peculiarities were uncommon (1.2%), but 11.3% exhibited Loosening and 8.9% had Impoverishment even with conservative thresholds. Multi-construct co-occurrence exceeded chance across the sample but was restricted to patients at conservative clinical thresholds. Conclusions FTD exists in a continuous dimensional structure extending into healthy populations. Each dimension is measurable in healthy individuals, but multi-dimensional convergence at clinical thresholds (i.e. disorder with functional impairment) appears specific to patients. This suggests that common vulnerability factors increase the likelihood of elevations across multiple but substantially independent dimensions of FTD. As a hypothesis requiring prospective validation, clinical risk of psychosis may depend on the coalescence rather than single-dimensional severity of FTD subconstructs.
Abstract Background Bipolar disorders (BD) are associated with a wide range of brain white matter abnormalities, but results vary across studies. This heterogeneity likely relates to effects of additional clinical/diagnostic variables, including medications and obesity, on white matter in BD. In this mega-analysis, we studied the links between relevant clinical variables and four diffusivity measures. Methods We obtained diffusion tensor imaging-derived fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, RD) values from 910 individuals with BD and 1256 healthy controls across 16 research sites in the ENIGMA-BD Working Group. We used principal component analysis to detect patterns of covariance across white matter tracts and studied associations between multivariate patterns of white matter alterations and demographic and clinical variables, including body mass index (BMI), medications, and diagnostic information, using mixed regression models. Results Higher BMI was associated with lower PC1 FA and higher PC1 RD; BD was associated with higher PC1 MD, while treatment with antiepileptic medications was associated with lower PC1 FA, higher PC1 MD, and PC1 RD. Conclusions We found FA and MD are weakly associated, providing complementary information, and there are unique associations between specific diffusivity measures and clinical predictors. Treatment with antiepileptics may inflate the statistical effects of BD on white matter. By using all diffusivity measures and accounting for additional clinical factors, we can gain new insights into brain correlates of severe mental illness.
Abstract Background Biological factors affecting motor, sensory, and integrative processing may predispose to functional neurological disorder (FND) and functional somatic symptoms. While early-life influences have traditionally been conceptualized within psychological frameworks, the contribution of early-life biological vulnerabilities to symptom expression remains unclear. Methods Using TriNetX, a large electronic health records database, we assessed proportions of inherited, congenital, perinatal, and neurodevelopmental diagnoses, capturing a range of early-life conditions. We compared 188,868 individuals with FND and 406,202 with functional somatic symptoms to demographically matched migraine and depression cohorts. Subgroup analyses contrasted motor FND with functional seizures and system-predominant functional somatic symptom clusters (e.g. bowel and bladder) with the general cluster. Results Compared with migraine and depression, individuals with FND and functional somatic symptoms showed higher proportions of multiple inherited and early-life vulnerability factors. Congenital and inherited conditions, including Ehlers – Danlos syndrome (OR = 2.1 – 3.6 across comparisons), congenital musculoskeletal malformations (1.7 – 2.0), and chromosomal abnormalities (2.5 – 3.2), were more prevalent. Perinatal factors such as low birth weight (1.8 – 2.4) were enriched, alongside neurodevelopmental disorders, including intellectual disability (1.9 – 5.4) and autism spectrum disorder (1.2 – 3.5). Subgroup analyses revealed phenotype-specific patterns: joint hypermobility and musculoskeletal malformations were more common in functional motor disorder and musculoskeletal functional somatic symptoms, whereas neurodevelopmental disorders were enriched in functional seizures and the general functional somatic symptom cluster. Conclusions Inherited and early-life biological vulnerabilities were more common in FND and functional somatic symptom cohorts. Their prevalence differed among phenotypes. Our findings suggest that developmental variation in brain–body systems may influence the risk and clinical expression of functional symptoms.
