To describe the demographic, clinical, and treatment characteristics of individuals admitted with hexahydrocannabinol (HHC)-associated psychosis and compare with cannabis-associated psychosis.

A retrospective chart review was undertaken of all admissions to the Adult Acute Mental Health Unit at University Hospital Galway, Ireland, between 1 May 2023 and 31 July 2025, with psychosis and documented HHC or cannabis use in the seven days preceding admission. Demographic, clinical, and treatment variables were compared across three groups: HHC-only, cannabis-only, and combined HHC + cannabis associated psychosis. Group differences were examined using ANOVA for continuous variables and Fisher’s exact tests for categorical variables, with repeated-measures ANOVA used to examine antipsychotic dosing. Analyses were exploratory in nature.

Thirty-three individuals (79% male) met inclusion criteria. All HHC-related cases occurred in a first episode of psychosis. Affective symptoms were more frequent in the HHC-only group (89%) than in the cannabis-only (54%) and combined HHC + cannabis groups (27%) (p = 0.024). Formal thought disorder appeared more common in HHC-exposed groups (80%) compared with cannabis-only presentations (38%), reaching statistical significance in an exploratory comparison between cannabis-only and combined HHC-exposed groups (p = 0.027). Urine toxicology screening for THC metabolites, length of stay and maximum antipsychotic dose were similar across groups.

In this cohort, HHC-associated psychosis was associated with higher rates of affective symptoms and formal thought disorder than cannabis-related presentations, despite otherwise similar clinical features. Findings are hypothesis-generating, given the exploratory analyses, small sample and uncorrected multiple testing. They suggest a potential role for novel cannabinoid screening to support earlier identification and management.

The psychosis continuum conceptualises psychotic phenomena as existing on a spectrum from subclinical experiences to psychotic disorders. Despite epidemiological and clinical evidence in support of this model, few studies have examined polygenic liability across the severity continuum: from subclinical experiences to first-episode psychosis (FEP).

To map polygenic liability for schizophrenia (SCZ), bipolar disorder and major depressive disorder (MDD) across the psychosis continuum. We hypothesised that schizophrenia polygenic scores (SCZ-PGS) would track phenotypic severity most closely across this continuum.

We harmonised data from 5 south-east London cohorts (N = 1315; 860 European, 455 African ancestries) across 4 ordered groups indicative of different levels of phenotypic severity: controls (n = 647), individuals with self-reported psychotic experiences (n = 89), individuals at clinical high risk (CHR) that did not convert to psychosis (n = 124) and individuals with FEP (n = 455). We computed ancestry-specific PGS for SCZ, bipolar disorder and MDD and compared these across groups using ordinal logistic regression.

In European ancestry participants, elevated SCZ-PGS (odds ratio 1.72, p = 4.57 × 10−15), bipolar disorder-PGS (odds ratio 1.56, p = 1.03 × 10−10) and MDD-PGS (odds ratio 1.44, p = 4.86 × 10−8) were individually associated with increasing phenotypic severity. SCZ-PGS explained the largest variance (R2 = 0.084) across the psychosis continuum and showed pairwise differences between CHR and controls (β = 0.32, p = 0.027), and between FEP and CHR (β = 0.38, p = 0.017). Multivariable models, combining three PGS, outperformed univariable models (R2 = 0.105). Similar trends in SCZ-PGS across the psychosis continuum phenotype were seen in African ancestry participants, but only controls and FEP groups differed significantly (β = 0.27, p = 0.037).

Our findings provide biological evidence supporting the psychosis continuum framework. In European ancestry, SCZ-PGS differences suggest that CHR who do not transition to psychosis have intermediate genetic vulnerability. Multivariable models, utilising all three PGS, explained additional variance compared with univariable ones, supporting transdiagnostic genetic liability. Improving PGS predictive power in African ancestry remains a priority.

Cerebral perfusion abnormalities may contribute to the pathophysiology of psychosis spectrum disorders (PSD), including schizophrenia (SZ), schizoaffective disorder (SAD), and bipolar disorder with psychotic features (BP), yet large-scale investigations remain limited.

Pseudo-continuous arterial spin labeling scans were acquired from 2412 SZ, 2278 SAD, 158 BP, 401 neurotypical controls (NC) and processed using ExploreASL and FreeSurfer to quantify resting-state cerebral blood flow (CBF) across total gray matter and 60 brain regions. General linear regression compared CBF between NC and diagnostic groups or biologically informed biotypes derived from neurophysiological clustering. Within patient groups, Spearman correlations assessed associations between cognitive/clinical measures and CBF. Analyses were corrected for multiple comparisons.

Compared to NC, patient groups showed significantly lower total gray matter CBF (PSD: Cohen’s d=-0.124, p-adjusted=0.037; BP: d=-0.259, p-adjusted=0.004; the most severe biotype, Biotype 1: d=-0.222, p-adjusted=0.006). BP and Biotype 1 exhibited significant hypoperfusion in 25 regions spanning bilateral temporal, occipital, inferior frontal cortices, and subcortical structures (BP d= -0.21 to -0.33; Biotype 1 d=-0.19 to -0.26). No significant CBF-cognition associations were observed. Within PSD, higher total gray matter CBF correlated with greater psychotic symptom severity, while right superior temporal sulcus hyperperfusion was associated with greater psychotic, manic, and depressive symptoms.

Distinct perfusion patterns exist in PSD, with widespread hypoperfusion in BP and Biotype 1 and hyperperfusion associated with greater symptom severity, supporting perfusion as a potential biomarker to stratify PSD subtypes.

Childhood trauma increases the risk for psychosis. However, mechanisms underlying this relationship remain unclear. In the present study, we aimed to investigate whether negative cognitive self-schemas or basic self-disturbance mediate the association between childhood trauma subtypes (abuse and neglect) and psychotic experiences in patients with psychotic disorders, unaffected siblings, and healthy controls.

This study was performed in a subsample of 110 patients, 120 siblings, and 48 healthy controls within the Genetic Risk and Outcome of Psychosis (GROUP) study. Parallel mediation models were used while correcting for age and sex. Abuse and neglect were measured with the childhood trauma questionnaire (CTQ), psychotic experiences with the Community Assessment of Psychic Experiences (CAPE), self-disturbance phenomena with the Self-Experience Lifetime Frequency Scale (SELF), and negative self-schemas with the Brief Core Schemas Scale (BCSS).

In patients, negative self-schemas fully mediated the association between abuse and psychotic experiences, whereas self-disturbance partly mediated the effect of neglect on psychotic experiences. In siblings, both negative self-schemas and self-disturbance fully mediated the association between abuse/neglect and psychotic experiences. In controls, only negative self-schemas mediated the association between abuse and neglect and psychotic experiences.

Our findings suggest that negative self-schemas and self-disturbance phenomena are relevant factors in explaining the association between childhood trauma and psychotic experiences across illness liability groups. Further research is needed to explore the causal pathways between trauma, negative self-schemas, self-disturbance phenomena, and psychotic experiences.

Charting developmental abnormalities in future psychotic disorder could help identify pathogenic processes. Head circumference (HC) is a proxy for brain size. Studies of HC and its developmental trajectories in future psychotic disorder cases and across the psychosis spectrum are inconclusive. It is important to determine whether deviations in HC are specific or reflect a general growth disorder.

We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC) to chart HC trajectories from birth to 15 years in individuals with operationally-defined psychotic disorder (N = 62), psychotic experiences (PE; N = 339) and controls (N = 3,527). We extracted total intracranial volume (TIV) from MRI data on a subset (N = 347) scanned at age 20.

HC at birth, 7 and 15 years was correlated with TIV at age 20 (r’s = 0.45–0.77). The psychotic disorder group had consistently smaller HC from birth through to adolescence (B = −0.26, p = 0.02). Females with PE had smaller HC across childhood and adolescence (B = −0.27, p = 0.016), while males with PE had consistently larger HC (B = 0.35, p = 0.023). The effects did not change when controlling for maternal and pregnancy-related characteristics but attenuated after controlling for height, except in males with PE.

Deviations in head and hence brain size across the psychosis spectrum likely reflect a more general growth abnormality. Future studies should examine factors regulating growth during early life in relation to psychosis, including sex, to understand underlying mechanisms.

The influential predictive processing theory of psychosis posits that symptoms arise from an imbalanced weighting of predictions (priors) and sensory evidence, yet studies present conflicting results. This is particularly problematic as findings from single tasks with modest sample sizes are frequently used to advance a theory for a generalized altered reliance on priors in psychosis.

This study presents a random-effects, multi-level meta-analysis (PROSPERO CRD42024574379) evaluating evidence for aberrant reliance on priors in psychosis across perceptual tasks. The search identified articles in Embase, MEDLINE, APA PsycINFO, and APA PsycArticles published between 1st January 2005—31st October 2024, with risk of bias assessed using the Newcastle-Ottawa Scale. Included articles (34 results from 27 studies) compared adults with schizophrenia-spectrum psychosis (SZ; n = 904) to healthy controls (n = 1,039) on behavioral measures representing reliance on priors.

Results provided no evidence for atypical reliance on priors in psychosis (g = .03, 95% CI [−0.27, 0.34]; p = .818) or associations with delusions (6 results; SZ = 183; r = −.16, 95% CI [−0.51, 0.19]; p = .293) or hallucinations (10 results; SZ = 370; r = .04, 95% CI [−0.28, 0.36]; p = .780). In contrast with the theory that psychosis differentially affects priors at different levels of the cognitive hierarchy, a sub-group analysis indicated that a two-level hierarchical model of priors did not reconcile conflicting results (F (1,32) = 0.1, p = .758).

These findings do not suggest that psychosis is associated with a generalized predictive processing deficit spanning multiple aspects of perception.

Psychosis, social anxiety, and autism are clinical constructs that share important phenotypic features, particularly social dysfunction. A critical determinant of social functioning is an individual’s ability to recognize when social cues, such as eye gaze, are meant for them. Emerging computational modeling data in psychosis suggest that altered gaze perception stems from deficits in evidence accumulation – the process of gathering and integrating information – when processing social cues. We investigated whether aberrant evidence accumulation during gaze perception is associated with social functioning or, as a secondary aim, with psychopathology in a transdiagnostic sample with varying levels of psychotic, socially anxious, or autistic characteristics.

We examined gaze perception in 111 individuals (aged 14–30) with varying levels of social dysfunction, psychosis proneness, social anxiety, and autistic traits. Drift diffusion models (DDM) characterized key processes driving perceptual judgements in a self-referential gaze perception task, including the efficiency of evidence accumulation. We tested whether evidence accumulation was associated with social functioning, social cognition, and these different psychopathology dimensions.

Impaired evidence accumulation during gaze perception showed strong associations with impaired social cognition and modest associations with diminished social functioning and elevated psychosis and social anxiety symptoms. Evidence accumulation was not associated with autism traits.

Evidence accumulation for social cues relates to social cognition – a key determinant of social functioning. It may also be relevant to real-world social functioning and multiple psychopathology dimensions, including psychosis and social anxiety. Therefore, evidence accumulation should be investigated as a mechanism supporting social difficulties and related psychopathology.

Cannabis use is common in people with psychosis and is associated with poor outcomes.

To assess insight into cannabis use disorder, perceptions about how cannabis use influences mental health and the desire to change cannabis use among people with psychotic disorders.

Adults with a psychotic disorder and comorbid cannabis use disorder were asked about the impact of cannabis use on their illness and their desire to change cannabis use. Cannabis use disorder was determined using DSM-5 criteria. Participants completed the Substance Use Awareness and Insight Scale.

Sixty-two participants (mean age: 42 years; 95% male; 65% Black ethnicity; 85% severe DSM-5 cannabis use disorder) completed the study. The mean total Substance Use Awareness and Insight Scale score was 4.8 (s.d.: 2.1), with subdomain scores of 3.7 (s.d.: 2.8) for general illness awareness, 6.2 (s.d.: 2.8) for symptom attribution, 3.5 (s.d.: 2.9) for awareness of need for treatment and 5.6 (s.d.: 3.8) for awareness of negative consequences. Fifty-eight per cent said that cannabis use made their mental health ‘better’, whereas only 15% said it made it ‘worse’; 27% reported that cannabis made their psychotic symptoms ‘better’, and 21% said it made them ‘worse’. Nevertheless, more than half the sample (53%) said they wanted to reduce or stop using cannabis.

Many people with psychotic disorders have impaired insight into cannabis use disorder or believe that cannabis improves their mental health; these factors may contribute to persistent use in this population. Interventions that improve insight may help to address ambivalence and support those already wishing to reduce use.

Adults with mental disorders more frequently report getting into serious trouble with the police and the law than do adults with no mental health diagnosis. The mechanisms underlying this statistical association remain unclear.

The study used data from a US population survey to examine whether the previously recognized association between psychiatric diagnosis and getting into serious police or legal trouble is mediated by impaired psychosocial function or psychiatric symptoms. The predictor variable was psychiatric diagnosis. The mediator variables were two forms of psychosocial function, social and role-emotional, and the presence of recent symptoms. The outcome variable was police or legal trouble.

When known risk factors are included as covariates, the association between mental disorder and serious police or legal trouble over the past year is maintained and is significantly mediated (p < 0.05) both by social and role-emotional function (social, excess relative risk [ERR] 1.42 [95% CI: 0.96, 1.88]; role-emotional, ERR 1.45 [95% CI: 0.98, 1.91]) and by recent symptoms(ERR 1.63 [95% CI: 1.13, 2.13]). The contribution of mediation varies by diagnosis.

Previous research suggested that it is unusual for psychiatric symptoms to lead directly to violence. These results suggest that symptoms and signs of mental disorder nevertheless contribute indirectly to violence and other adverse outcomes. The identification of these mediators may, in turn, suggest new approaches to reducing the risk of those outcomes. Future research should further examine and describe the mechanisms that underlie these and other forms of mediation.

Post-traumatic sequelae are theorized to contribute to and maintain psychotic symptoms. The relative contribution of core posttraumatic stress disorder (PTSD) symptoms and those of complex PTSD are understudied. Network analysis was used to examine interactions between psychosis, core PTSD, and complex post-traumatic symptoms. Based on previous evidence, it was predicted that trauma-related beliefs would have the greatest predictability. It was also hypothesized that the association between voices and trauma-related beliefs would be greater than the association between voices and re-experiencing.

Baseline data from the Study of Trauma and Recovery (STAR), a randomized controlled therapy trial of people with schizophrenia-spectrum disorder who experience distressing delusions and/or hallucinations and comorbid PTSD (N = 305). A network was estimated using a Bayesian Gaussian graphical model, comprised of psychosis symptoms (delusions and voices), posttraumatic stress symptoms (re-experiencing, avoidance, and sense of threat), complex posttraumatic stress symptoms (affective dysregulation, negative self-concept, disturbed relationships), and trauma-related beliefs (negative cognitions about the self and world, self-blame). A direct acyclic graph was plotted to estimate the potential directionality of associations between symptoms.

The hypotheses were not supported. All symptoms had similar predictability scores. There was no evidence for conditionally dependent relations between re-experiencing and voices nor between trauma-related beliefs and voices. However, self-blame was associated with delusions, and affective dysregulation was found to predict voices.

Affective dysregulation and self-blame may maintain voices and delusions, respectively. Heterogeneity in trauma-related psychosis could explain inconsistent findings; future research should identify symptom presentation subgroups to improve network reliability.

Brain-structural and language abnormalities in people with psychotic symptoms (PSx) have long been reported. A key question is whether language alterations are a potential behavioral readout of brain cortical gray matter changes. Adding to previous evidence for this in the cases of cortical thinning and gyrification, we here used structural MRI (sMRI) to relate a complexity-theoretical metric, the Largest Lyapunov Exponent (lambda [λ]), to computational linguistic complexity metrics extracted from spontaneous speech. This study aimed to identify psychosis-related regional changes in structural complexity using λ and an explainable AI (XAI) approach. We hypothesized that altered structural complexity will relate to computational language features that have previously been shown to track brain dysconnectivity in schizophrenia in fMRI.

MRI data were acquired from 92 patients with PSx and 38 healthy controls (HCs) from the TOPSY study. Nonlinear analysis of gray matter distribution was performed by extracting the λ for gray matter voxels. XAI was employed to identify the voxels contributing significantly to classifying PSx against HCs. Finally, the brain voxels’ contribution was tested for associations with word perplexity and syntactic and semantic complexity metrics, from spontaneous speech as obtained from picture descriptions, and with clinical symptom severity (SOFAS and PANSS scores).

The classification framework resulted in a balanced accuracy of 75.9%. The voxels contributing most to the classification decision were located in the temporal lobe, cingulum, angular, lingual, calcarine, occipital, fusiform, and parietal cortices, and parts of the cerebellum and vermis. Structural complexity in these regions was significantly associated with clinical variables (SOFAS and PANSS), word perplexity, and lexical diversity.

We present a new analytical framework using spatial series extracted from sMRI, demonstrating that alterations in structural complexity are an identifiable feature of psychosis, which co-vary with probabilistic and structural changes in speech as a behavioral readout.

Although mental health and healthy lifestyle interventions are associated with functional outcomes in adolescence, the extent to which particular lifestyle factors explain relationships between mental health and outcome are unclear. Here we examined mediating effects of lifestyle factors on relationships between mental health and two functional outcomes measured 2–3 years later, as well as moderating effects of environmental risk factors on mediation strength in early adolescence.

We analyzed data from three waves of the Adolescent Brain Cognitive Development Study (ages 10–11, 11–12, and 12–13 years). Mediating effects of sleep quality, screen time, physical activity, and Mediterranean diet on the relationships between depression, anxiety, psychotic-like experience (PLE) distress, and total problems with two subsequent functional outcomes (academic functioning and social problems) were examined. Secondary analyses included environmental factors as moderators.

Sleep quality mediated 18.5%, 36.3%, and 8.3% of the relationships between depression, anxiety, and PLE distress with academic functioning, respectively (total problems mediation was nonsignificant). Screen time was the second strongest mediator. For social problems, only sleep quality showed >3% mediation (19.6–23.3%). Mediating effects of sleep and screen time on academic functioning decreased as financial adversity increased. Conversely, mediating effects of sleep quality on social problems increased with worsening family conflict, financial adversity, and school environment.

These results suggest that healthy lifestyle factors (particularly sleep quality) may partially explain associations between mental health and functioning in adolescents and suggest that these effects are modulated by environmental factors. These results may have implications for future intervention studies.

Antipsychotic medications are recommended for schizophrenia spectrum disorders, yet their long-term effects on functional recovery remain unclear, with conflicting evidence often derived from between-subject comparisons vulnerable to confounding by indication.

We conducted a nationwide register-based cohort study of 65,630 individuals with incident schizophrenia spectrum disorders in Denmark (1998–2023). We modeled antipsychotic exposure against ‘productive engagement’ (employment or education). We used two analytical approaches: (1) within-subject stratified Cox models with time-varying covariates to eliminate time-invariant confounding; and (2) Fine–Gray competing risks models with baseline exposure, accounting for mortality and emigration.

Over 26.9 million person-weeks, the overall productive engagement rate was 48.2%. Integration of hospital pharmacy data revealed 6.1% exposure misclassification in studies relying solely on community records. The primary within-subject analysis revealed significant temporal heterogeneity: medication use was associated with reduced engagement rates in the acute (0–2 years; HR = 0.908) and consolidation phases (2–5 years; HR = 0.946), but reversed to a small positive association in the maintenance phase (5+ years; HR = 1.019). The between-subject Fine–Gray model, which estimates cumulative engagement probabilities, yielded an SHR of 1.002 (95% CI = 0.988–1.015), a population-level average that obscured these phase-specific dynamics.

Antipsychotic pharmacotherapy exerts a time-dependent, biphasic impact on vocational recovery. We identified a window of vulnerability during the post-acute ‘consolidation’ phase (years 2–5) where treatment is associated with a transient reduction in productive engagement, before becoming protective after 5 years. These findings challenge the assumption that symptomatic stability automatically facilitates functional reintegration.