Clinical characteristics of psychosis in HIV infection have been described, but there have been limited comparative studies in HIV-endemic low-resource regions.

To compare clinical characteristics of psychosis in HIV-positive and HIV-negative patients at the main psychiatric referral units in Uganda.

Patients with psychosis were consecutively recruited and completed a standardised demographic questionnaire and psychiatric and laboratory assessments including an HIV test. The Mini International Neuropsychiatric Interview was used to diagnose psychiatric illness. Psychosis symptoms were compared between HIV-positive and HIV-negative individuals using bivariate methods. A logistic regression model was used to assess the effects of age, gender and HIV status on different types of psychosis.

There were 478 patients enrolled, of which 156 were HIV positive and 322 were HIV negative. The mean age was 33.2 years (95% CI 31.8–34.5) for the HIV-positive group and 29.6 years (95% CI 28.7–30.5) for the HIV-negative group (P < 0.001). Female patients had a higher proportion of seropositivity 40.6% (95% CI 34.8–46.4) compared with males 21.8% (95% CI 16.1–27.5) (P < 0.001). Psychotic disorder not otherwise specified occurred more in the HIV-positive individuals (88% (95% CI 82.9–93.1) v. 12% (95% CI 8.4–15.5), P < 0.001). Motor activity, irritability, emotional withdrawal, feelings of guilt, mannerisms and posturing, grandiosity, suspiciousness, unusual thoughts, blunted affect, excitement and disorientation were associated with HIV seropositivity.

The presentation of psychosis in patients with HIV is unique to this HIV endemic setting. Characterisation of the symptomatology of patients presenting with psychosis is important for proper diagnosis and care.

Cannabis use severely affects the outcome of people with psychotic disorders, yet there is a lack of treatments. To address this, in 2019 the National Health Service (NHS) Cannabis Clinic for Psychosis (CCP) was developed to support adults suffering from psychosis to reduce and/or stop their cannabis use.

Examine outcome data from the first 46 individuals to complete the CCP's intervention.

The sample (N = 46) consisted of adults (aged ≥ 18) with psychosis under the care of the South London and Maudsley NHS Foundation Trust, referred to the CCP between January 2020 and February 2023, who completed their intervention by September 2023. Clinical and functional measures were collected before (T0) and after (T1) the CCP intervention (one-to-one sessions and peer group attendance). Primary outcomes were changes in the Cannabis Use Disorders Identification Test-Revised (CUDIT-R) score and pattern of cannabis use. Secondary outcomes included T0–T1 changes in measures of delusions, paranoia, depression, anxiety and functioning.

A reduction in the mean CUDIT-R score was observed between T0 (mean difference = 17.10, 95% CI = 15.54–18.67) and T1, with 73.91% of participants achieving abstinence and 26.09% reducing the frequency and potency of their use. Significant improvements in all clinical and functional outcomes were observed, with 90.70% being in work or education at T1 compared with 8.70% at T0. The variance in CUDIT-R scores explained between 34 and 64% of the variance in our secondary measures.

The CCP intervention is a feasible strategy to support cannabis use cessation/reduction and improve clinical and functional outcomes of people with psychotic disorders.

Suicide accounts for a proportion of the early mortality in people affected by psychotic disorders. The early phase of illness can represent a particularly high-risk time for suicide. Therefore, in a cohort of young people presenting with first-episode psychosis, this study aimed to determine: (i) the prevalence of suicidal ideation, intent with plan and self-harm and any associated demographic or clinical factors and (ii) the prevalence of depressive symptoms and any associated demographic or clinical factors.

Young people with a first episode of psychosis attending the Early Psychosis Prevention and Intervention Centre in Melbourne were included. Suicidal behaviours were recorded using a structured risk assessment – ‘Clinical Risk Assessment and Management in the Community’, and depressive symptoms were measured using the PHQ-9.

A total of 355 young people were included in the study. 57.2% were male, 95.4% were single and over one quarter were migrants. At the time of presentation, 34.6% had suicidal ideation, 6.2% had suicidal intent with a plan, and 21.4% had engaged in self-harm before their presentation. Combined, 39.7% (n = 141) presented with suicidal ideation, intent with plan or self-harm. A total of 71.5% (n = 118) had moderately severe or severe depressive symptoms, which was strongly associated with suicidal ideation or behaviours at the time of presentation (OR = 4.21, 95% C.I. 2.10–8.44).

Depressive symptoms, self-harm and suicidal behaviours are commonly present in the early phases of a psychotic disorder, which has important clinical implications for assessment and management.

The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis.

Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use.

In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10−10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use.

Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide.

Cognitive impairment constitutes a prevailing issue in the schizophrenia spectrum, severely impacting patients' functional outcomes. A global cognitive score, sensitive to the stages of the spectrum, would benefit the exploration of potential factors involved in the cognitive decline.

First, we performed principal component analysis on cognitive scores from 768 individuals across the schizophrenia spectrum, including first-degree relatives of patients, individuals at ultra-high risk, who had a first-episode psychosis, and chronic schizophrenia patients, alongside 124 healthy controls. The analysis provided 10 g-factors as global cognitive scores, validated through correlations with intelligence quotient and assessed for their sensitivity to the stages on the spectrum using analyses of variance. Second, using the g-factors, we explored potential mechanisms underlying cognitive impairment in the schizophrenia spectrum using correlations with sociodemographic, clinical, and developmental data, and linear regressions with genotypic data, pooled through meta-analyses.

The g-factors were highly correlated with intelligence quotient and with each other, confirming their validity. They presented significant differences between subgroups along the schizophrenia spectrum. They were positively correlated with educational attainment and the polygenic risk score (PRS) for cognitive performance, and negatively correlated with general psychopathology of schizophrenia, neurodevelopmental load, and the PRS for schizophrenia.

The g-factors appeared as valid estimators of global cognition, enabling discerning cognitive states within the schizophrenia spectrum. Educational attainment and genetics related to cognitive performance may have a positive influence on cognitive functioning, while general psychopathology of schizophrenia, neurodevelopmental load, and genetic liability to schizophrenia may have an adverse impact.

Transition to psychosis rates within ultra-high risk (UHR) services have been declining. It may be possible to ‘enrich’ UHR cohorts based on the environmental characteristics seen more commonly in first-episode psychosis cohorts. This study aimed to determine whether transition rates varied according to the accumulated exposure to environmental risk factors at the individual (migrant status, asylum seeker/refugee status, indigenous population, cannabis/methamphetamine use), family (family history or parental separation), and neighborhood (population density, social deprivation, and fragmentation) level.

The study included UHR people aged 15–24 who attended the PACE clinic from 2012 to 2016. Cox proportional hazards models (frequentist and Bayesian) were used to assess the association between individual and accumulated factors and transition to psychosis. UHR status and transition was determined using the CAARMS. Benjamini–Hochberg was used to correct for multiple comparisons in frequentist analyses.

Of the 461 young people included, 55.5% were female and median follow-up was 307 days (IQR: 188–557) and 17.6% (n = 81) transitioned to a psychotic disorder. The proportion who transitioned increased incrementally according to the number of individual-level risk factors present (HR = 1.51, 95% CIs 1.19–1.93, p < 0.001, pcorr = 0.01). The number of family- and neighborhood-level exposures did not increase transition risk (p > 0.05). Cannabis use was the only specific risk factor significantly associated with transition (HR = 1.89, 95% CIs 1.22–2.93, pcorr = 0.03, BF = 6.74).

There is a dose–response relationship between exposure to individual-level psychosis-related environmental risk factors and transition risk in UHR patients. If replicated, this could be incorporated into a novel approach to identifying the highest-risk individuals within clinical services.

Early intervention in psychosis (EIP) services improve outcomes for young people, but approximately 30% disengage.

To test whether a new motivational engagement intervention would prolong engagement and whether it was cost-effective.

We conducted a multicentre, single-blind, parallel-group, cluster randomised controlled trial involving 20 EIP teams at five UK National Health Service (NHS) sites. Teams were randomised using permuted blocks stratified by NHS trust. Participants were all young people (aged 14–35 years) presenting with a first episode of psychosis between May 2019 and July 2020 (N = 1027). We compared the novel Early Youth Engagement (EYE-2) intervention plus standardised EIP (sEIP) with sEIP alone. The primary outcome was time to disengagement over 12–26 months. Economic outcomes were mental health costs, societal costs and socio-occupational outcomes over 12 months. Assessors were masked to treatment allocation for primary disengagement and cost-effectiveness outcomes. Analysis followed intention-to-treat principles. The trial was registered at ISRCTN51629746.

Disengagement was low at 15.9% overall in standardised stand-alone services. The adjusted hazard ratio for EYE-2 + sEIP (n = 652) versus sEIP alone (n = 375) was 1.07 (95% CI 0.76–1.49; P = 0.713). The health economic evaluation indicated lower mental healthcare costs linked to reductions in unplanned mental healthcare with no compromise of clinical outcomes, as well as some evidence for lower societal costs and more days in education, training, employment and stable accommodation in the EYE-2 group.

We found no evidence that EYE-2 increased time to disengagement, but there was some evidence for its cost-effectiveness. This is the largest study to date reporting positive engagement, health and cost outcomes in a total EIP population sample. Limitations included high loss to follow-up for secondary outcomes and low completion of societal and socio-occupational data. COVID-19 affected fidelity and implementation. Future engagement research should target engagement to those in greatest need, including in-patients and those with socio-occupational goals.

Psychedelic drugs are a focus of interest in the treatment of depression and other disorders but there are longstanding concerns about possible adverse psychiatric consequences. Because the relevant literature is largely informal, the seriousness of these risks is difficult to evaluate.

Searches were made for case reports of schizophrenia-spectrum, affective or other psychiatric disorders after use of psychedelic drugs. Case reports of flashbacks were also searched for. Individuals with recent use of other drugs (apart from cannabis and alcohol) and/or a previous history of major psychiatric disorder were excluded. Symptoms were tabulated using the Syndrome Check List of the Present State Examination (PSE-9).

We found 17 case reports of schizophrenia spectrum disorder, 17 of affective disorder (depression, mania, or both), 3 cases of anxiety, 1 of depersonalization, and 1 of unclassifiable illness. The states could develop after a single use of the drug (5/17 schizophrenia; 6/17 affective disorder), and duration was highly variable. Recovery was the rule in cases of affective disorder but not in schizophrenia spectrum disorder. Twelve of 29 cases of flashbacks showed psychiatric symptomatology definitely outlasting the attacks, mainly anxiety (5 cases) and depression (8 cases). Flashback symptoms resolved within twelve months in approximately half of the cases but in a few persisted for years.

Reliable descriptions of schizophrenia spectrum disorder and major affective disorder after psychedelic drug use disorder exist but are relatively uncommon. Flashbacks are sometimes but not always associated with psychiatric symptomatology, mainly anxiety or depression.

The relationship between psychosis and violence is often construed focusing on a narrow panel of factors; however, recent evidence suggests violence might be linked to a complex interplay of biopsychosocial factors among forensic psychiatric patients with psychosis (FPPP). This review describes violence incidents in FPPP, the factors associated with violence, and relevant implications.

This review was conducted following the preferred reporting items for systematic reviews and meta-analyses guideline. Databases, including CINAHL, EMBASE, Medline/PubMed, PsycINFO, and Web of Science, were searched for eligible studies that examined violence among adult FPPP. Screening of reports and data extraction were completed by at least two independent reviewers.

Across the 29 included studies, violence was consistently related to prior contact with psychiatric services, active psychotic symptoms, impulsivity, adverse experiences, and low social support. However, FPPP who reported violence varied in most other biopsychosocial domains, suggesting the underlying combinatorial effects of multiple risk factors for violence rather than individual factors. Variability in violence was addressed by stratifying FPPP into subgroups using composite/aggregate of identifiable factors (including gender, onset/course of illness, system-related, and other biopsychosocial factors) to identify FPPP with similar risk profiles.

There are multiple explanatory pathways to violence in FPPP. Recent studies identify subgroups with underlying similarities or risk profiles for violence. There is a need for future prospective studies to replicate the clinical utility of stratifying FPPP into subgroups and integrate emerging evidence using recent advancements in technology and data mining to improve risk assessment, prediction, and management.

We aimed to identify the common types of outcome trajectories for patients with psychosis who take up specialist psychological therapy for persecutory delusions. Knowing the different potential responses to therapy can inform expectations. Further, determining predictors of different outcomes may help in understanding who may benefit.

We analyzed delusion conviction data from 767 therapy sessions with 64 patients with persistent persecutory delusions (held with at least 60% conviction) who received a six-month psychological intervention (Feeling Safe) during a clinical trial. Latent class trajectory analysis was conducted to identify groups with distinct outcome profiles. The trajectories were validated against independent assessments, including a longer-term follow-up six months after the end of therapy. We also tested potential predictors of the trajectories.

There were four outcome trajectories: (1) Very high delusion conviction/Little improvement (n = 14, 25%), (2) Very high delusion conviction/Large improvement (n = 9, 16%), (3) High delusion conviction/Moderate improvement (n = 17, 31%) and (4) High delusion conviction/Large improvement (n = 15, 27%). The groups did not differ in initial overall delusion severity. The trajectories were consistent with the independent assessments and sustained over time. Three factors predicted trajectories: persecutory delusion conviction, therapy expectations, and positive beliefs about other people.

There are variable responses to psychological therapy for persecutory delusions. Patients with very high delusion conviction can have excellent responses to therapy, though this may take a little longer to observe and such high conviction reduces the likelihood of positive responses. A trajectory approach requires testing in larger datasets but may prove highly informative.

Quality of life is decreased in bipolar disorders (BD) and contributes to poor prognosis. However, little is known about the causal pathways that may affect it. This study aimed to explore health-related QoL (HRQoL) in BD and investigate its relationship with cognition and psychosocial functioning.

This multicenter cross-sectional study used a neuropsychological battery to assess five cognition domains. Functioning was evaluated using global and domain-based tools, and health-related HRQoL was assessed using the EQ-5D-3L. Structural equation modeling was used to test whether the association between cognition and HRQoL would be mediated by functioning in BD while controlling for covariates such as residual depression, anxiety, antipsychotic medication, and psychotic features.

We included 1 190 adults with euthymic BD. The model provided a good fit for the data. In this model, the direct effect of cognition on HRQoL was not significant (β = − 0.03, z = −0.78, p = 0.433). The total effect of cognition on HRQoL was weak, albeit significant (β = 0.05, z = 3.6, p < 0.001), thus suggesting that cognition affected HRQoL only indirectly through functioning. Anxiety was associated with decreased functioning (β = −0.27, z = −7.4, p < 0.001) and QoL (β = −0.39, z = −11.8, p < 0.001).

These findings suggest that improving cognition may not directly lead to a higher HRQoL. Cognitive remediation is expected to improve HRQoL only through functioning enhancement. They also reveal the potential importance of functional remediation and reduction of comorbid anxiety symptoms in improving HRQoL in BD.