How psychotic symptoms, depressive symptoms, cognitive deficits, and functional impairment may interact with one another in schizophrenia or bipolar disorder is unclear.

This study explored these interactions in a discovery sample of 339 Chinese, of whom 146 had first-episode schizophrenia and 193 had bipolar disorder. Psychotic symptoms were assessed using the Positive and Negative Symptom Scale; depressive symptoms, using the Hamilton Depression Rating Scale; cognitive deficits, using tests of processing speed, executive function, and logical memory; and functional impairment, using clinical assessments. Network models connecting the four types of variables were developed and compared between men and women and between disorders. Potential causal relationships among the variables were explored through directed acyclic graphing. The results in the discovery sample were compared to those obtained for a validation sample of 235 Chinese, of whom 138 had chronic schizophrenia and 97 had bipolar disorder.

In the discovery and validation cohorts, schizophrenia and bipolar disorder showed similar networks of associations, in which the central hubs included ‘disorganized’ symptoms, depressive symptoms, and deficits in processing speed during the digital symbol substitution test. Directed acyclic graphing suggested that disorganized symptoms were upstream drivers of cognitive impairment and functional decline, while core depressive symptoms (e.g. low mood) drove somatic and anxiety symptoms.

Our study advocates for transdiagnostic, network-informed strategies prioritizing the mitigation of disorganization and depressive symptoms to disrupt symptom cascades and improve functional outcomes in schizophrenia and bipolar disorder.

The nosology of mania has long been a conundrum. Prior studies have alternately concluded that it is an internalizing disorder, a thought disorder, or a unique condition. Unfortunately, nearly all existing studies assessed symptoms cross-sectionally. This is problematic for syndromes that follow a more episodic course, such as mania. Here, we test whether including a history of episodes, not simply current symptoms, can help resolve the placement of mania in the meta-structure of psychopathology.

First-admission patients with psychosis from the Suffolk County Mental Health Project (N = 337) were followed across 20 years. Internalizing, thought disorder, and mania symptoms were assessed at year 20, whereas corresponding episodes (i.e. depressive, psychotic, and manic) were assessed across three intervals spanning the previous 20 years. We tested five models to determine whether mania (current and past) loaded onto the internalizing factor, the thought disorder factor, or an independent factor. A final model was validated against established markers of bipolar disorder.

For depression and psychosis, current and past markers were congruent in loading onto internalizing and thought disorder factors, respectively. However, current and past markers of mania diverged: current mania was most strongly related to the thought disorder dimension, whereas past mania formed an independent factor. Classic correlates of mania – including family history, genetic risk, and neuropsychological function – were associated only with the history of mania dimension.

Including illness course in structural models of psychopathology suggests that mania is distinguished from internalizing and thought disorder factors, whereas assessments of current symptoms place it with psychosis. These findings require independent validation, but if replicated, they would support a separate spectrum of mania defined by the occurrence of episodes across the lifetime.

Subtle behavioral and cognitive symptoms precede schizophrenia (SCZ) and appear in individuals with elevated risk based on polygenic risk scores (SCZ-PRS) and family history of psychosis (SCZ-FH). However, most SCZ-PRS studies focus on European ancestry youth, limiting generalizability. Furthermore, it remains unclear whether SCZ-FH reflects common-variant polygenic risk or broader SCZ liability.

Using baseline data from the Adolescent Brain Cognitive Development (ABCD) study, we investigated associations of SCZ-FH and SCZ-PRS with cognitive, behavioral, and emotional measures from NIH-Toolbox, Child Behavior Checklist (CBCL), and Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) for 9,636 children (mean age = 9.92 yrs, 47.4% female), specifically, 5,636 European, 2,093 African, and 1,477 Admixed American ancestry individuals.

SCZ-FH was associated with SCZ-PRS (b = 0.05, FDR-p = 0.02) and subthreshold psychotic symptoms (b = 0.46, FDR-p = 0.01) in European youth, higher CBCL scores (b range = 0.36–0.6, FDR-p < 0.001), and higher odds of multiple internalizing and externalizing disorders (OR = 1.10–1.22, FDR-p < 0.001) across ancestries. SCZ-PRS was associated with lower cognition across ancestries (b = −0.43, FDR-p = 0.02), higher CBCL total problems, anxious/depressed, rule-breaking and aggressive behaviors in European youth (b range = 0.16–0.33, FDR-p < 0.04), and depressive disorders in Admixed American youth (OR = 1.37, FDR-p = 0.02). Results remained consistent when SCZ-PRS and SCZ-FH were jointly modeled. Some SCZ-FH associations weakened when income-to-needs was accounted for, suggesting that SCZ-FH may capture both genetic and environmental influences.

SCZ-FH showed associations with broad psychopathology, while SCZ-PRS was associated with cognition and specific symptoms in European youth. Findings highlight their complementary role in SCZ risk assessment and the need to improve PRS utility across ancestries.

Childhood maltreatment (CM) increases the risk for psychopathology and CM type, severity and timing are considered important modulating factors in this relationship. However, reported associations are heterogeneous and hardly considered vulnerable groups broadly exposed to CM.

We investigated the association between CM types and timing and psychopathology in formerly out-of-home placed young adults (N = 185; 32% women, age mean = 26.38 years, SD = 3.49). CM was assessed using the Maltreatment and Abuse Chronology of Exposure Scale. Conditional random forest regression was used to estimate the importance of CM types (abuse, neglect, peer victimization, and sexual abuse), timing (ages 3–18), and global measures (severity, multiplicity, and duration) on adult general, internalizing, and externalizing problems (Achenbach System of Empirically Based Assessment). We validated the results using diagnoses of mental disorders clustered with the Hierarchical Taxonomy of Psychopathology model.

Global CM measures were stronger predictors of internalizing problems than CM type and timing. Abuse in early childhood was a stronger predictor of externalizing problems compared to global CM measures.

Considering CM type and timing might be valuable to guide maltreatment-informed interventions in therapeutic settings.

It has been argued that disruptions to epistemic trust are implicated in psychopathology; however, this requires empirical testing, and an existing scale evaluating epistemic trust, the Epistemic Trust, Mistrust and Credulity Questionnaire (ETMCQ), requires improvement.

This study tested a revised version of the Epistemic Trust, Mistrust and Credulity Questionnaire (the ETMCQ-R), examining the strength of associations between the updated scale and mental health symptoms, epistemic vice, psychological resilience, perceived social support, attachment style, history of childhood adversity and an experimental measure of trust, and epistemic stance as a mediator between adversity and psychopathology.

Using an online survey design, 525 participants completed the ETMCQ-R alongside other measures. Exploratory and confirmatory factor analyses were conducted to assess the structure of the ETMCQ-R and correlational and mediational analyses were used to further assess validity of the measure.

The ETMCQ-R possesses greater model fit and a stronger three-factor structure (Trust, Mistrust and Credulity) compared with the ETMCQ. Significant negative correlations were identified between Trust (r = −0.12) and higher scores on global psychopathology severity, while Mistrust (r = 0.41) and Credulity (r = 0.36) showed positive correlations. Trust negatively correlated with borderline features (r = −0.10), whereas Mistrust and Credulity positively correlated (r = 0.54 and r = 0.48, respectively). Mistrust and credulity partially mediated the relationship between childhood adversity and psychopathology, with stronger mediation effects for borderline features than general psychopathology.

The study demonstrated strong psychometric properties of the ETMCQ-R, and further analyses indicate the three factors are differentially related to wider domains of socio-emotional functioning.

Cannabis use in young adulthood is common, yet few studies have explored how it predicts changes in psychopathology and functional well-being in community samples. We assessed these links using both self-reported frequency of cannabis use and hair THC concentrations.

Data came from a community sample of young adults (N = 863) who reported cannabis use (weekly-to-daily use: n = 150) and provided hair samples at age 20 (cannabis detected: n = 110). Liquid chromatography–tandem mass spectrometry quantified delta-9-tetrahydrocannabinol (THC) and cannabinol (CBN) concentrations in hair. At ages 20 and 24, participants reported psychopathology (psychotic-like experiences, problematic substance use, internalizing symptoms, and aggression) and functional wellbeing (general well-being, delinquency, and not being in employment, education, or training). Multiple linear and logit regression models tested associations between six different continuous and dichotomous operationalizations of self-reported and objective cannabis exposure at age 20 and psychological and functional well-being at age 24, adjusting for sex, sociodemographic characteristics, and the outcomes measured at age 20.

Both self-reported frequency of cannabis use and hair THC concentrations predicted increases in psychotic-like experiences and internalizing symptoms, increased aggression, decreased general well-being, higher odds of not being in employment, training, or education, and more problematic substance use from age 20 to 24, with small effect sizes. Composite exposure scores derived from self-reports and hair data were not more informative than either source alone.

Frequent cannabis use predicted adverse changes in psychopathological outcomes from ages 20 to 24, regardless of how it was assessed.

Longitudinal studies have revealed that raised levels of inflammatory markers and trauma in childhood are associated with psychopathology in adulthood.

To examine whether inflammation in childhood mediates the effects of genetic risk and trauma on psychopathology in early adulthood.

Measures of trauma exposure, inflammation and psychopathology were collected from the Avon Longitudinal Study of Parents and Children. Exposure to trauma was measured from 5 to 11 years of age; C-reactive protein and interleukin-6 levels were measured at 9 years; and depression, anxiety disorders, negative symptoms and psychotic experiences were assessed at 24 years. Polygenic risk scores (PRSs) were created for schizophrenia, depression, anxiety and psychotic experiences. Mediation analyses were conducted using imputed data (N: 7859 to 8700) to investigate whether inflammation mediated the associations of genetic risk and childhood trauma with psychopathology.

Most psychiatric PRSs were associated with multiple psychopathological outcomes in adulthood, with the exception of the PRS for psychotic experiences. Childhood trauma was associated with all psychopathology. However, there was no strong evidence that inflammatory markers in childhood mediated associations among PRSs, trauma and psychopathology. Sensitivity analyses using outcomes from age 18 and PRSs based on single-nucleotide polymorphisms that met more stringent standards of evidence of association gave results consistent with those of our primary analyses.

We found little evidence that interleukin-6 or C-reactive protein mediated the pathway between genetic liability for psychiatric phenotypes or trauma and subsequent psychopathology. Longitudinal investigation of other inflammatory and non-inflammatory pathways is required to identify modifiable targets and inform novel treatment strategies for individuals at genetic or trauma-related risk of psychiatric illness.

Measurement-based care (MBC) is widely recommended in psychiatry but remains underutilized in routine clinical settings. The Transdiagnostic Global Impression – Psychopathology (TGI-P) scale was developed to provide a brief yet comprehensive assessment of 10 core transdiagnostic symptom domains. To support more inclusive care and promote patient and caregiver engagement in treatment planning, two new versions of the TGI-P, that is, a patient-rated and a separate informant-rated, were developed, complementing the previously published clinician-rated version.

The patient and informant versions mirror the original clinician-rated TGI-P, assessing the identical 10 domains using a seven-point Likert severity scale, with results displayed via a personalized symptom map. A user satisfaction/feasibility study was conducted with 50 participants (25 patients and 25 caregivers) from the UK and US. After completing the scale, participants provided feedback on its clarity, usability, emotional impact, and comparative utility.

Most participants completed the scale in less than 5 min. Instructions were considered clear, and the format was rated easy to follow. Response options were deemed appropriate by 86% of participants, and the visual output was widely appreciated. While one-third reported mild emotional triggering, overall burden was described as manageable. Approximately, three-quarters of participants rated the TGI-P as equal to or better than other tools they had used.

TGI-P patient and informant versions were developed and, informed by the feasibility study, refined to offer brief, user-friendly tools that support multi-informant assessment as input to MBC. Both versions of the TGI-P, with their graphical output, may support shared understanding and collaborative decision making among clinicians, patients, and caregivers. A validation study of the TGI-P is underway.

Executive functioning (EF) impairments are widely known to represent transdiagnostic risk factors of psychopathology. However, a recent alternative account has been proposed, according to which EF impairments emerge as consequences of psychopathology.

Using a longitudinal cross-lagged panel network analysis approach, we tested these competing theoretical accounts at different stages during adolescence. We used data from the Brazilian High-Risk Cohort Study for the Development of Childhood Psychiatric Disorders, in which 61% of individuals at wave 1 were selected due to their high risk for psychopathology. Participants were assessed across three assessment waves during early (wave 1: n = 1,992, mean age = 10.20 years) and middle adolescence (wave 2: n = 1,633, mean age = 13.48 years; wave 3: n = 1,439, mean age = 18.20 years). We examined associations between working memory, inhibitory control, and broad-band measures of psychopathology.

During early adolescence, lower inhibitory control was a risk factor for externalizing problems that, in turn, predicted lower working memory capacity. During middle adolescence, bidirectional associations became more prominent: inhibitory control and working memory functioned as both risk factors and consequences. Externalizing problems both predicted and were predicted by poor inhibitory control. Internalizing and externalizing symptoms showed bidirectional associations over time. Externalizing problems predicted more internalizing symptoms, whereas internalizing symptoms predicted fewer externalizing problems during middle adolescence.

Our results corroborate dynamic theories that describe executive dysfunctions as precursors and consequences of psychopathology in middle adolescence.