Developmental trauma increases psychosis risk in adulthood and is associated with poor prognosis and treatment response. It has been proposed that developmental trauma may give rise to a distinct psychosis phenotype. Our aim was to explore this by systematically reviewing neuroimaging studies of brain structure and function in adults with psychosis diagnoses, according to whether or not they had survived developmental trauma. We registered our search protocol in PROSPERO (CRD42018105021).

We systematically searched literature databases for relevant studies published before May 2024. We identified 31 imaging studies (n = 1,761 psychosis patients, n = 1,775 healthy controls or healthy siblings).

Developmental trauma was associated with global and regional differences in gray matter; corticolimbic structural dysconnectivity; a potentiated threat detection system; dysfunction in regions associated with mentalization; and elevated striatal dopamine synthesis capacity.

These findings warrant further research to elucidate vulnerability and resilience mechanisms for psychosis in developmental trauma survivors.

Dissociative experiences are common transdiagnostically, and particularly prevalent in psychosis. Such experiences have long been under-recognised in routine clinical practice, despite evidence that dissociation is related to clinical complexity and increased risk of self-harm and suicidality. Adopting a symptom-specific, targeted approach to conceptualisation and intervention for dissociation may help improve outcomes.

The evidence base for psychological treatments targeting dissociation is building, but training and guidance for clinicians remains sparse. This review outlines a preliminary approach to the treatment of a subtype of dissociative experience (felt sense of anomaly dissociation), based on emerging research evidence and clinical practice. The guidance is tailored to the context of psychosis, and may also have broader clinical relevance.

We present symptom-specific guidance for clinicians, including factors to consider in the assessment, formulation, and intervention for felt sense of anomaly dissociation in the context of psychosis, and reflections on process issues. We present a cognitive behavioural model, where affect-related changes are interpreted as an internal threat, driving a maintenance cycle of catastrophic appraisals and safety behaviours. Using this formulation, evidence-based therapy techniques familiar to most readers can then be applied.

It is important for clinicians to consider dissociation. As well as generating new avenues for translational intervention research, we anticipate that the novel insights and specific advice outlined here will be of use to professionals working with dissociation in psychosis (and beyond). Encouragingly, we demonstrate that widely used, evidence-based skills and techniques can be employed to address distress arising from dissociation.

The rate at which psychosis drugs can be reduced in dose remains unclear. Anecdotal reports exist of people experiencing worsening of mental state before their next dose of long-acting injectable antipsychotic. No research has previously explored this phenomenon, but understanding this may advise on the rate of receptor occupancy change that provokes the emergence of psychotic symptoms.

Exploring the relationship between psychotic symptoms and variations in plasma concentration (and calculated receptor occupancy) of long-acting injectable antipsychotics.

This longitudinal study monitored mental state variation within dosing cycles of people taking depot flupentixol and zuclopenthixol. The Positive and Negative Syndrome Scale (PANSS) monitored global mental state changes, and was stratified into domains according to a five-factor model. Plasma assays at maximal and minimal concentrations allowed prediction of striatal D2 occupancy from published data. We examined correlations between receptor occupancy and the emergence of psychotic symptoms.

Preliminary results from ten participants with psychotic disorders suggest that global mental state deterioration may correlate with increased rate of D2 occupancy reduction. Increased rate of D2 occupancy reduction led to deterioration in ‘positive’ (r = 0.637 [CI: 0.013, 0.904], P = 0.047) and ‘resistance’ (r = 0.726 [CI: 0.177, 0.930], P = 0.018) PANSS clinical domains at minimal concentrations. PANSS score differences were not related to absolute reduction in D2 occupancy.

Our novel observational study design has been demonstrated to be feasible and practicable. Faster reductions in D2 occupancy may increase the risk of increased positive psychotic symptoms and irritability. Slower reductions may minimise this effect. Further recruitment is required before this can be confirmed.

Some psychotic experiences in the general population show associations with higher schizophrenia and other mental health-related polygenic risk scores (PRSs), but studies have not usually included interviewer-rated positive, negative and disorganised dimensions, which show distinct associations in clinical samples.

To investigate associations of these psychotic experience dimensions primarily with schizophrenia PRS and, secondarily, with other relevant PRSs.

Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort participants were assessed for positive, negative and disorganised psychotic experience dimensions from interviews, and for self-rated negative symptoms, at 24 years of age. Regression models were used to investigate associations between psychotic experience dimensions and schizophrenia and other PRSs (2500+ participants for each analysis).

Against expectation, none of the positive, negative or disorganised dimensions was associated with schizophrenia PRS. In secondary analysis, self-rated negative symptoms were associated with higher depression (β = 0.10 [95% CI 0.06–0.15]), anxiety (β = 0.09 [95% CI 0.04–0.13]), neuroticism (β = 0.11 [95% CI 0.06–0.15]) and autism (β = 0.09 [95% CI 0.05–0.13]) PRSs (all P < 0.001); and first-rank delusions were nominally associated with higher schizophrenia PRS (odds ratio 7.35 [95% CI 2.10–25.77], P = 0.002), although these experiences/symptoms were rare.

Positive, negative and disorganised psychotic experiences are probably not strongly associated with polygenic liability to schizophrenia in this general population cohort of young adults. Self-rated negative symptoms may indicate social withdrawal/low motivation due to higher polygenic liability to affective disorders or autism, and first-rank delusions may indicate higher polygenic liability to schizophrenia, but these findings require independent confirmation.

Psychological therapy (PT) along with antipsychotic medication is the recommended first line of treatment for first-episode psychosis (FEP). We investigated whether ethnicity, clinical, pathways to care (PtC) characteristics, and access to early intervention service (EIS) influenced the offer, uptake, and type of PT in an FEP sample.

We used data from the Clinical Record Interactive Search-First Episode Psychosis study. Inferential statistics determined associations between ethnicity, clinical, PtC, and PT offer/uptake. Multivariable logistic regression estimated the odds of being offered a PT and type of PT by ethnicity, clinical and PtC characteristics adjusting for confounders.

Of the 558 patients included, 195 (34.6%) were offered a PT, and 193 accepted. Cognitive behavioral therapy (CBT) (n = 165 of 195; 84.1%) was commonly offered than group therapy (n = 30 of 195; 13.3%). Patients who presented via an EIS (adj. OR = 2.24; 95%CI 1.39–3.59) were more likely to be offered a PT compared with those in non-EIS. Among the patients eligible for an EIS, Black African (adj. OR = 0.49; 95%CI = 0.25–0.94), Black Caribbean (adj. OR = 0.45; 95%CI = 0.21–0.97) patients were less likely to be offered CBT compared with their White British counterparts. Patients with a moderate onset of psychosis (adj. OR = 0.34; 95%CI = 0.15–0.73) had a reduced likelihood of receiving CBT compared with an acute onset.

Accessing EIS during FEP increased the likelihood of being offered a PT. However, treatment inequalities remain by ethnicity and clinical characteristics.

There is a substantial body of literature on environmental risk associated with schizophrenia. Most research has largely been conducted in Europe and North America, with little representation of the rest of the world; hence generalisability of findings is questionable. For this reason, we performed a mapping review of studies on environmental risk for schizophrenia spectrum disorders, recording the country where they were conducted, and we linked our findings with publicly available data to identify correlates with the uneven global distribution. Our aim was to evaluate how universal is the ‘common knowledge’ of environmental risk for psychosis collating the availability of evidence across different countries and to generate suggestions for future research identifying gaps in evidence.

We performed a systematic search and mapping of studies in the PubMed and PsycINFO electronic databases reporting on exposure to environmental risk for schizophrenia including obstetric complications, paternal age, migration, urbanicity, childhood trauma, and cannabis use and subsequent onset of schizophrenia spectrum disorders. This search focused on articles published from the date of the first available publication until 31 May 2023. We recorded the country where they were conducted. We downloaded publicly available data on population size, measures of wealth, medical provisions, research investment, and of quality research outputs per country and performed regression analyses of each predictor with the number of studies and recruited cases in each country.

We identified 308 publications that included a sample size of 445,000 patients with schizophrenia spectrum disorders. The majority were conducted in northern Europe and North America, with large parts of the world totally unrepresented. In the associations between the number of environmental risk studies for schizophrenia with potential predictors, we found that neither population nor wealth or research investment were strong predictors of research outputs in the field. Interestingly, the stronger correlations were found for number of researchers per population and for indicators of top-end scientific achievements, such as number of Nobel laureates per country.

Our results demonstrate a gap of knowledge due to the underrepresentation of studies on environmental risk of schizophrenia spectrum disorders in large parts of the world. This has implications not only in the generalisability of any findings from research conducted in the Northern hemisphere but also in our ability to progress in efforts to make causal inferences about biological pathways to schizophrenia. These findings reinforce the need to focus research on populations that are underrepresented in research and underserved in health care.

During puberty, sex-specific processes shape distinct mental health outcomes. However, research on puberty and psychosis has been limited, and the findings are conflicting.

To explore how puberty status and timing and oestradiol levels influence psychotic experiences and whether they interact with genetic and exposomic vulnerabilities to schizophrenia in female adolescents.

We analysed data from female participants in the Adolescent Brain Cognitive Development Study at baseline (n = 5673) and two annual follow-up assessments. Psychotic experiences were assessed using the Prodromal Psychosis Scale and puberty status with the Pubertal Development Scale. Age at menarche and salivary oestradiol concentration were recorded. Exposomic vulnerability to schizophrenia (ES-SCZ) and polygenic risk score for schizophrenia (PRS-SCZ) were calculated. Longitudinal mixed logistic regression models were used to test associations of psychotic experiences with hormone levels and puberty status. Age of menarche was analysed using second follow-up data.

Earlier menarche (odds ratio 0.68, 95% CI: 0.59 to 0.78) and higher oestradiol concentration (odds ratio = 1.08, 95% CI: 1.01 to 1.16) were associated with greater likelihood of psychotic experiences, as were mid-pubertal (odds ratio 1.41, 95% CI: 1.18 to 1.69) and late to post-pubertal (odds ratio 2.23, 95% CI: 1.74 to 2.86) compared with pre-pubertal stage. ES-SCZ and PRS-SCZ were associated with greater likelihood of psychotic experiences. No significant interactions of puberty factors with ES-SCZ or PRS-SCZ were detected.

Physical and hormonal puberty factors have critical roles in development of psychosis. The absence of interaction effects could be attributed to the age range of the cohort. Further research during follow-ups is essential.

The environment shapes the risk of psychosis. In particular, urbanicity, deprivation or inequality, migrant density and cannabis availability may not only influence psychosis incidence, but also the characteristics of individuals who arrive at clinical services. This study examined how socioeconomic factors influence the incidence and characteristics of cases of First-Episode Psychosis (FEP).

We analysed prospective data collected from the FEP early detection programme of Emilia-Romagna, a high-income Italian region. Participants were 1240 individuals aged 18–35 years, who presented at the public healthcare services for a FEP. Exposures were derived from area-level data of 331 municipalities. We used population density, socioeconomic deprivation, educational deprivation, economic inequality, migrant density (proportion of migrants), frequent cannabis use (proportion of people aged 15–19 years old who reported frequent cannabis use). Outcome measures were FEP incidence (cases/100 000 inhabitants at risk per year) and characteristics (age of onset, migrant status, unemployment, substance use, treatment lag [DUP], family and resource problems). We reviewed pertinent literature, and formulated a Directed Acyclic Graph to present causal assumptions and provide adjustment sets for Bayesian spatial and multilevel models of social causation. To compare the effects of different exposures, we computed Average Marginal Effects and report the outcome changes that correspond to one standard deviation change of the exposure, incidence rate ratios (IRR) or odds ratios (OR).

The exposures and incidence of FEP displayed heterogeneous spatial distribution, with no spatially organized pattern. Accordingly, incidence and characteristics were best modelled as non-spatial, three-level hierarchical models. The incidence of FEP was influenced by population density (IRR, 1.14; 95% CrI, 1.03; 1.29), educational deprivation (IRR, 1.15; 95% CrI, 1.02; 1.31) and frequent cannabis use (IRR, 1.31; 95% CrI, 0.98; 1.82), more than socioeconomic deprivation. Higher migrant density in an area shortened the DUP on average by 3.4 months (95% CrI, −1.122; 0.76), while an increase of cannabis use of one standard deviation increased the DUP of 12.9 months (95% CrI, −2.86; 6229). Socioeconomic deprivation increased the likelihood of FEP cases being substance users (OR, 1.12; 95% CrI, 1.01; 1.26), while population density decreased it (OR, 0.91; 95% CrI, 0.83; 1.00).

Area-level socioeconomic features affect both the incidence and the characteristics of FEP, including the probability of individual being migrants, substance users or having a different DUP. Educational deprivation may function as a proxy for culture- or cognitive-related factors. Area-level socioeconomic data may inform public healthcare strategies for early identification and availability of tertiary clinical services.

Defence behaviours – actions carried out to reduce perceived threat – are an important maintenance factor for persecutory delusions. Avoidance of feared situations and subtle in-situation behaviours reduce opportunities for new learning and are erroneously credited for the non-occurrence of harm; hence inaccurate fears are maintained. In contrast, exposure to feared situations whilst dropping defence behaviours – a key technique of cognitive therapy for paranoia – allows the discovery of new information concerning safety, thereby reducing persecutory delusions.

We aimed to develop for use in research and clinical practice a self-report assessment of paranoia-related defence behaviours.

A 64-item pool was developed from interviews with 106 patients with persecutory delusions, and completed by 53 patients with persecutory delusions, 592 people with elevated paranoia, and 2108 people with low paranoia. Exploratory and confirmatory factor analyses were used to derive the measure. Reliability and validity were assessed.

Two scales were developed: a 12-item avoidance scale and a 20-item in-situation defences scale. The avoidance scale had three factors (indoor spaces, outdoor spaces, and interactions) with an excellent model fit (CFI=0.98, TLI=0.97, RMSEA=0.04, SRMR=0.027). The in-situation defences scale had a 5-factor model (maintaining safety at home, mitigating risk, staying vigilant, preparing for escape, and keeping a low profile) with a good fit (CFI=0.95, TLI=0.94, RMSEA=0.046, SRMR=0.039). Both scales demonstrated good internal reliability, test–retest reliability, and construct validity.

The Oxford Paranoia Defence Behaviours Questionnaire is a psychometrically robust scale that can assess a key factor in the maintenance of persecutory delusions.

Second-generation antipsychotics (SGAs) are moderately effective treatments for psychotic disorders but are associated with significant weight gain and metabolic complications. These contribute to a nearly 20-year reduction in life expectancy for individuals with enduring psychotic illness. Weight gain can also negatively impact adherence, increase relapse risk, and worsen psychosocial outcomes.

To highlight the mechanisms underlying antipsychotic-induced weight gain (AIWG), examine pharmacological strategies for its prevention and treatment, and argue for the early use of metformin.

This perspective article synthesises current evidence on the pathophysiology of AIWG and evaluates the role of metformin in mitigating these effects.

Weight gain can occur rapidly after initiating antipsychotic treatment, particularly in young people and those prescribed antipsychotics for non-psychotic indications. Presentation and response to interventions vary. Of all pharmacological strategies, metformin has the most robust evidence for both prevention and treatment of AIWG. It is a well-tolerated, low-cost antihyperglycaemic agent with an established safety profile. Metformin should be considered early in the course of antipsychotic treatment for all individuals, regardless of diagnosis, to prevent clinically significant weight gain and reduce long-term health risks. Early intervention may improve adherence, reduce relapse, and enhance overall quality of life.

Chronic pain (CP) and mental disorders often coexist, yet their relationship lacks comprehensive synthesis. This first hierarchical umbrella review examined systematic reviews and meta-analyses, also observational studies and randomized controlled trials (where reviews are currently lacking) to report CP prevalence, risk factors, and treatment across mental disorders.

We searched MEDLINE, PsycINFO, Embase, Web of Science, and CINAHL, identifying 20 studies on anxiety, depression, bipolar disorder, schizophrenia, ADHD, autism, or dementia, and CP. Quality was assessed using AMSTAR and Newcastle-Ottawa Scale.

Prevalence varied widely—23.7% (95% CI 13.1–36.3) in bipolar disorder to 96% in PTSD—consistently exceeding general population rates (20–25%). Risks were elevated, with bidirectional links in depression (OR = 1.26–1.88). Risk factors included female gender, symptom severity, and socioeconomic disadvantage, though data were limited beyond PTSD and depression. Treatment evidence was sparse: cognitive behavioral therapy showed small effects on pain (SMD = 0.27, 95% CI -0.08–0.61), acupuncture with medication improved pain (MD = -1.06, 95% CI -1.65–-0.47), and transcranial direct current stimulation reduced pain in dementia (d = 0.69–1.12). Methodological issues were evident, including heterogeneous designs and inconsistent pain definitions.

This review confirms CP as a significant comorbidity in mental disorders. Clinicians should prioritize routine pain screening and multimodal treatments. Researchers need longitudinal studies with standardized assessments to clarify causality and improve interventions. Taken together, this work highlights an urgent need for integrated psychiatric care approaches, emphasizing that addressing CP could enhance mental health outcomes and overall patient well-being.

Establishing appropriate action–outcome associations can allow animals and humans to control behavior and the environment in a goal-directed manner. Deficits in instrumental learning in psychosis have been widely reported in past studies, but the results remain elusive.

To explore the consistent neural representations of instrumental learning in functional magnetic resonance imaging (fMRI) in individuals with psychosis, a total of 18 studies (458 individuals with psychosis and 454 controls) were included in our coordinate-based meta-analysis.

Patients with psychosis presented increased activation in the left middle occipital gyrus, insula, and lingual and postcentral gyri; decreased activation in cortico-striato-thalamo-cortical (CSTC) networks, including the dorsal striatum, insula, thalamus, middle cingulate cortex, posterior cingulate cortex, dorsolateral, orbital, and medial prefrontal cortices (DLPFC, OFC, and mPFC), cerebellum, and associated sensory areas, during instrumental learning. Moreover, mPFC hypoactivation was negatively associated with the percentage of first-generation antipsychotic users, and insula hyperactivation was negatively associated with the percentage of medicated individuals.

Our study revealed that the CSTC circuit could facilitate action-based reward learning in psychosis and may help explain the neuropathological mechanisms underlying these deficits in this disorder.

The use of community treatment orders (CTOs) has increased in many jurisdictions despite very limited evidence for their efficacy. In this context, it is important to investigate any differences in outcome by subgroup.

To investigate the variables associated with CTO placement and the impact of CTOs on admissions and bed-days over the following 12 months, including differences by diagnosis.

Cases and controls from a complete jurisdiction, the state of Queensland, Australia, were analysed. Administrative health data were matched by age, sex and time of hospital discharge (index date) with two controls per case subject to a CTO. Multivariate analyses were used to examine factors associated with CTOs, as well as the impact on admissions and bed-days over the 12 months after CTO placement. Registration: Australian and New Zealand Clinical Trials Registry (ACTRN12624000152527).

We identified 10 872 cases and 21 710 controls from January 2018 to December 2022 (total n = 32 582). CTO use was more likely in First Nations people (adjusted odds ratio = 1.14; 95% CI: 1.06–1.23), people from culturally diverse backgrounds (adjusted odds ratio = 1.45; 95% CI: 1.33–1.59) and those with a preferred language other than English (adjusted odds ratio = 1.21; 95% CI: 1.02–1.44). When all diagnostic groups were considered, there were no differences in subsequent admissions or bed-days between cases and controls. However, both re-admissions and bed-days were significantly reduced for CTO cases compared with controls in analyses restricted to non-affective psychoses (e.g. adjusted odds ratio = 0.77, 95% CI: 0.71–0.84 for re-admission).

Queenslanders from culturally or linguistically diverse backgrounds and First Nations peoples are more likely to be placed on CTOs. Targeting CTO use to people with non-affective psychosis would both address rising CTO rates and mean that people placed on these orders derive possible benefit. This has implications for both clinical practice and policy.

Cognitive deficits and immune system dysregulation are core features of psychotic disorders. Among inflammatory markers, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) have been linked to both psychosis pathophysiology and related cognitive impairments.

We investigated associations among IL-6, TNF-α, and neurocognitive performance in 107 participants: individuals at clinical high risk for psychosis (CHR-P, n = 35), first-episode psychosis (FEP, n = 39), and healthy controls (HC, n = 33). Assessments included memory, processing speed, executive function, and social cognition. Cytokines were measured from fasting serum samples. Analyses included ANOVA, correlations, and multivariate regressions controlling for age, sex, IQ, group, and symptom severity.

TNF-α levels were significantly elevated in FEP compared to CHR-P (p = 0.0251); IL-6 differences were non-significant. FEP showed poorer performance in multiple cognitive domains, especially social cognition. CHR-P individuals exhibited intermediate profiles between FEP and HC in cognition. In adjusted regression models, IL-6 was significantly associated with undermentalization on the MASC task (β = 0.28, p = 0.0337) and showed a trend-level association with slower processing speed (β = 0.98, p = 0.075). TNF-α levels predicted poorer facial emotion recognition (β = −1.37, p = 0.0022). IQ and group were significant covariates in most models.

Our findings suggest that peripheral inflammation, particularly IL-6 and TNF-α, may selectively impact social cognitive functioning in early psychosis. Though modest, these associations highlight potential inflammatory contributions to functional impairment and support further investigation of immunological targets in early intervention.