Effective implementation of novel digital technologies to improve health outcomes requires an in-depth understanding of end-users’ perspectives and experiences.

We sought the perspectives of people with schizophrenia and schizophrenia-related disorders (SSD) on the acceptability of a novel short text message-delivered intervention targeting metabolic health, called Schizophrenia and diabetes Mobile-Assisted Remote Trainer (SMART).

Twenty-nine participants with SSD and either at risk of type 2 diabetes (T2D) or with T2D, were recruited from 3 mental health sites in Brisbane, Australia. They were provided, for 12 weeks, with SMART text messages that embedded psychoeducation and behaviour change techniques to facilitate lifestyle behaviours crucial for metabolic health. Interviews explored participants’ experiences of SMART, barriers to its use and suggestions for improvement. The qualitative data were collected by three mental health researchers and analysed using thematic analysis.

Three themes were generated: acceptability and user experience, feasibility and implementation considerations, and mechanisms supporting change. SMART was found to be highly accessible and engaging, and participants reported positive lifestyle changes, including healthier eating, increased physical activity, weight loss and smoking cessation. The messages reinforced learning and supported participants’ readiness for change.

SMART is a world-first digital intervention aimed at improving metabolic health and diabetes self-management in individuals with SSD. High levels of acceptability of SMART highlight its strong potential as a digital innovation that can support its users in protecting their metabolic health while limiting the detrimental side effects of antipsychotic medications.

People diagnosed with schizophrenia can have functional impairments in multiple domains. Cognitive impairment is central to schizophrenia and has substantial prognostic value compared with other symptoms of schizophrenia. However, no study has previously investigated directed relationships in a complex system of cognitive, sociodemographic, clinical and quality of life (QOL) variables in people diagnosed with schizophrenia.

To identify the complex relationships of components of cognition with other cognitive components, as well as with clinical and QOL variables.

This study included data from 1450 participants in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. The present study reconstructed a Bayesian network from this data using cognition, clinical, sociodemographic and QOL variables.

Processing speed was centrally associated with all other cognitive domains. Cognitive domains were conditionally independent of positive symptoms but moderately associated with negative symptoms (β = −0.25; P < 0.001). The positive symptoms subscale was independent of QOL, conditioning on third variables. Negative symptoms were moderately associated with QOL (β = −0.33; P < 0.001), and processing speed had a weak association with QOL (β = −0.12; P < 0.001). Processing speed was a central variable in the network.

Intervening with respect to processing speed may be the most beneficial way of improving other cognitive functions. More research is needed on directed networks that include social cognition and global levels of functioning.

Auditory verbal hallucinations (AVH) in schizophrenia spectrum disorders (SSDs) may arise from misattributed inner speech. However, it is unclear if inner speech frequency and phenomenology differ in schizophrenia-spectrum voice-hearers compared with healthy individuals, and how different inner speech varieties relate to AVH and affect. Using experience sampling methodology (ESM), this study examined the moment-to-moment dynamics between inner speech varieties, AVH, and affect.

Participants completed 6 days of ESM on an electronic device, responding to 10 daily prompts on inner speech varieties (i.e. dialogic, evaluative, other people, condensed, and positive), AVH, and affect. Responses from 32 individuals with SSDs with current AVH (‘SSD’) and 34 healthy controls (‘HC’) were analyzed using linear mixed modeling.

SSD reported significantly more inner speech moments and higher momentary intensity of evaluative, other people, condensed, and positive inner speech compared with HC, but not for dialogic inner speech. Within SSD, higher momentary intensities of dialogic, evaluative, other people, and condensed inner speech were associated with higher AVH levels. Momentary negative affect (NA) moderated the association between evaluative inner speech and AVH, with a stronger association at higher NA levels.

SSDs with current AVH experience more frequent inner speech and exhibit a distinct phenomenological profile compared with healthy individuals. Several inner speech varieties are associated with AVH severity momentarily, supporting the hypothesis that inner speech contributes to AVH at the phenomenological level. This study highlights the emotional state as an important moderator of the inner speech–AVH relationship and as a potential therapeutic target.

The results of a previous randomized trial showed that mentalization-based treatment for psychotic disorder (MBTp) was associated with greater improvement than treatment as usual (TAU) in social functioning up to 6 months after treatment. The purpose of the present study is to examine the effect after 5 years.

The researchers tried to find all patients who had participated in the trial (n = 84) and to assess, blind to previous treatment status, their social functioning and mentalizing capacity. Social functioning was measured using the Social Functioning Scale, mentalizing using the Social Cognition and Object Relations Scale and the Hinting Task.

Twenty-three MBTp patients and 23 TAU patients collaborated. There was no evidence of selective drop-out. A complete case, repeated measure analysis of variance on the basis of intention-to-treat showed that, 5 years post-treatment, MBTp patients still scored better on social functioning compared to baseline [ηp2 = .25, p = .01], whereas TAU patients did not [ηp2 = .01, p = .67], with a significant difference between the conditions [ηp2 = .10, p = .03]. A sensitivity analysis with linear mixed models, however, showed weaker evidence for an additive effect of MBTp over TAU on social functioning 5 years post-treatment, F = 3.731, p = .06. MBT patients also showed a greater improvement in one aspect of mentalizing, understanding of social causality [ηp2 = 0.17, p = .04], but not other aspects of mentalizing.

The results suggest a durable effect of MBTp.

Adverse childhood experiences (ACEs), including abuse, neglect and household challenges, have been linked to various mental health outcomes, including psychosis and bipolar symptoms. Research indicates a 57–80% increased risk of psychosis among individuals exposed to ACEs.

This study examines the relationship between ACEs and psychotic/bipolar symptoms in Kenyan adolescents, assessing resilience as a potential moderator or mediator.

This cross-sectional study was conducted in Nairobi and Kiambu counties, Kenya. A total of 1972 youth, aged 14–25 years, were recruited and completed questionnaires focusing on ACEs (Trauma and Distress Scale), psychosis/bipolar symptoms (Washington Early Recognition Center Affectivity and Psychosis screen) and resilience (Adult Resilience Measure +16). Descriptive statistics, Pearson correlation and multiple linear regression were used to assess the relationships between ACEs and psychosis/bipolar symptoms. SPSS Process macro was employed to examine the moderating/mediating role of resilience.

Emotional abuse and physical abuse were significantly associated with higher psychosis and bipolar symptoms (P < 0.001). Emotional neglect negatively impacted bipolar symptoms (P = 0.042). Resilience moderated the relationship between sexual abuse and psychosis, but not bipolar symptoms. Mediation analysis showed that resilience partially mediated the relationships between sexual abuse and both psychosis and bipolar symptoms.

ACEs, particularly emotional and physical abuse, are significant predictors of psychosis and bipolar symptoms in Kenyan youth. Resilience may play a key role in moderating and mediating these relationships, particularly in cases of sexual abuse. Developing resilience-focused interventions could help mitigate the long-term effects of ACEs on mental health.

Evidence regarding the effects of antipsychotic medication on cognitive functioning after a first-episode psychosis (FEP) remains inconclusive. This study examined whether dopamine D2 receptor occupancy, affinity, and antipsychotic dose are related to cognitive functioning in people in remission from FEP.

278 remitted FEP participants from the HAMLETT-trial were included. Cognitive functioning was assessed with the Brief Assessment of Cognition in Schizophrenia, 3–6 months after remission. D2 receptor occupancy was estimated based on antipsychotic type and dose. Antipsychotics were categorized into partial agonists, or antagonists with high or low D2 receptor affinity. Linear regression analyses were performed with inverse probability of treatment weighting to control for differences in characteristics between groups.

D2 receptor occupancy was negatively related to global cognition (β = −0.18), verbal fluency (β = −0.22), and attention and processing speed (β = −0.17, all p < 0.003). The interaction between daily dose and D2 receptor affinity category was significant for global cognition (p = 0.0046) and working memory (p = 0.0019), but not for verbal fluency after correction for multiple testing (p = 0.029). Interactions showed that higher daily dose was related to lower cognitive functioning, with significantly stronger negative effects in high-affinity antagonists compared to other antipsychotics.

The current findings underscore the importance of antipsychotic D2 receptor occupancy and affinity for cognitive functioning and suggest better cognitive functioning in users of partial agonists and low D2 receptor affinity antipsychotics. This can be important when selecting antipsychotics for individuals with FEP.

Tobacco smoking is highly prevalent in patients with psychosis, who also often experience negative affect (NA) and stress. The relationship between these factors remains unclear in this population. We aimed to investigate everyday life associations in 158 patients with psychosis, 136 unaffected siblings, and 117 controls from the Genetic Risk and Outcome of Psychosis (GROUP) study with Experience Sampling Method measurements.

Generalized linear mixed models were used to evaluate across time and within-subject associations. Across time analyses investigated the relationship between smoking status and overall NA and stress. Within-subject analyses assessed whether smoking between two measurements (t−1 and t0) was associated with changes in NA and stress at the measurement after smoking a cigarette (t0) and at the subsequent measurement (t+1).

Across assessments, smoking status was initially associated with NA in patients (B=0.26, p=0.036), but this association disappeared after controlling for psychotic symptoms and cannabis use. Within-subject analyses in smokers showed a decrease in NA in patients after smoking (t0: −0.23, p=0.016), which remained significant after correcting for confounders (t0: −0.20, p=0.015). Siblings showed a decrease in NA (t0: −0.22, p=0.009), also after controlling for confounders (t0: −0.14, p=0.018). No time-lagged effect was found at t+1 after correction for subsequent smoking.

Overall smoking behavior was not associated with NA in patients with psychosis. In the short term, smoking in the daily life context is associated with a reduction in NA in people vulnerable to psychosis, possibly due to alleviation of withdrawal symptoms, which may complicate smoking cessation.

Decades of research have identified a strong association between heavy cannabis use and schizophrenia (SCZ), with evidence of correlated genetic factors. However, many studies on the genetic relationship between cannabis use and psychosis have lacked data on both phenotypes within the same individuals, creating challenges due to unmeasured confounding. We aimed to address this by using multimodal data from the All of Us Research Program, which contains genetic data as well as information on SCZ diagnosis and cannabis use.

We tested the association between cannabis use disorder (CUD) and SCZ polygenic scores (PGSs) with SCZ and heavy cannabis use. We tested models where both CUD and SCZ PGSs were included as joint predictors of heavy cannabis use and SCZ case status. We defined three sets of cases based on comorbidities: relaxed (assessing for only the primary condition), strict (excluding comorbidity), and dual-comorbidity.

CUD and SCZ polygenic liability were independently associated with heavy cannabis use; the SCZ PGS effect was very modest. In contrast, both SCZ and CUD PGSs were independently associated with SCZ, with independent significant effects of CUD PGS. Polygenic liability to CUD was associated with SCZ in individuals without a documented history of cannabis use, suggesting widespread pleiotropy.

These findings underscore the need for comprehensive models that integrate genetic risk factors for heavy cannabis use to advance our understanding of SCZ etiology.

AVATAR therapy, a digitally supported intervention, utilises avatars to promote recovery in people who experience distressing auditory hallucinations. This approach was recently evaluated in a multicentre randomised controlled trial comparing brief (AV-BRF) and extended (AV-EXT) forms of therapy with treatment as usual (TAU). There was evidence for the effectiveness of therapy, particularly for AV-EXT. However, value for money needs to be assessed.

To compare separately the cost utility of the brief and extended forms of AVATAR therapy with TAU.

In a three-arm randomised controlled trial the use of health services was measured, and costs (2021/2022; pounds sterling) calculated from a health and social care perspective over a 28-week follow-up period. Quality-adjusted life years (QALYs; derived from the 5-level version of the EuroQol 5-Dimension questionnaire) were combined with costs.

AV-BRF resulted in extra costs of £319 (95% CI, −£1558 to £2496), and AV-EXT in lower costs of £1965 (95% CI, −£1912 to £1519), compared with TAU. Over the follow-up, AV-BRF resulted in 0.0159 (95% CI, −0.0103 to 0.0422) and AV-EXT in 0.0173 (95% CI, −0.0049 to 0.0395) more QALYs than TAU. The cost per QALY for AV-BRF compared with TAU was £20 016, while AV-EXT dominated TAU (lower costs and more QALYs).

Neither version of AVATAR had a substantial impact on QALYs. However, AV-EXT did result in reduced care costs − albeit not statistically significant − and was potentially cost-effective compared with TAU. AV-BRF had an incremental cost-effectiveness ratio that indicated lower potential cost-effectiveness. These findings are uncertain, but could still inform decision-making regarding interventions in this field.

Clinical progression during psychosis has been closely associated with grey matter abnormalities resulting from atypical brain development. However, the complex interplay between psychopathology and heterogeneous maturational trajectories challenges the identification of neuroanatomical features that anticipate symptomatic decline.

To investigate cortical volume longitudinal deviations in first-episode psychosis (FEP) using normative modelling, exploring their relationship with long-term cognitive and symptomatic outcomes, as well as their cytoarchitectural and neurobiological underpinnings.

We collected magnetic resonance imaging (MRI), cognitive and symptomatic data from 195 healthy controls and 357 drug-naïve or minimally medicated FEP individuals that were followed up 1, 3, 5 and 10 years following the first episode (1209 MRI scans and assessments in total). Using normative modelling, we derived subject-specific centile scores for cortical volume to investigate atypical deviations in FEP and their relationship to long-term cognitive and symptomatic deterioration. The resulting centile association maps were further characterised by examining their cytoarchitectural and neurobiological attributes using normative atlases.

FEP centiles demonstrated a widespread reduction at treatment initiation, with longitudinal analysis showing an increase during treatment time, indicating convergence towards normal maturation trajectories. Interestingly, this effect was reduced in highly medicated individuals. Additionally, we found that cognitive impairments experienced during early FEP stages worsened under long-term medication. Positive symptomatology was negatively associated with regional centiles, and individuals with higher centiles benefited most from treatment. Cytoarchitectural and neurobiological analyses revealed that regional centiles related to FEP, as well as to symptomatology, were associated with specific molecular features, such as regional serotonin and dopamine receptor densities.

Collectively, these findings underscore the potential use of centile-based normative modelling for a better understanding of how atypical cortical development contributes to the long-term clinical progression of neurodevelopmental conditions.

According to existing evidence, during menopause transition, women with psychosis may present with exacerbated psychiatric symptoms, due to age-related hormonal changes.

We aimed to (a) replicate this evidence, using age as a proxy for peri/menopausal status; (b) investigate how clinical presentation is affected by concomitant factors, including hyperprolactinaemia, dose and metabolism of prescribed antipsychotics using cross-sectional and longitudinal analyses.

Secondary analysis on 174 women aged 18–65, from the IMPaCT (Improving physical health and reducing substance use in psychosis) randomised controlled trial. We compared women aged below (N = 65) and above 40 (N = 109) for (a) mental health status with the Positive and Negative Syndrome Scale (PANSS) and Montgomery Asberg Depression Rating Scale; (b) current medications and (c) prolactin levels, at baseline and at follow-up (12/15 months later).

Women aged above 40 showed higher baseline PANSS total score (mean ± s.d. = 53.4 ± 14.1 v. 48.0 ± 13.0, p = 0.01) and general symptoms scores (28.0 ± 7.4 v. 25.7 ± 7.8, p = 0.03) than their younger counterparts. Progressive sub-analysis revealed that this age-related difference was observed only in women with non-affective psychosis (n = 93) (PANSS total score: 57.1 ± 13.6 v. 47.0 ± 14.4, p < 0.005) and in those prescribed antipsychotic monotherapy with olanzapine or clozapine (n = 25) (PANSS total score: 63 ± 16.4 v. 42.8 ± 10.9, p < 0.05).

Among all women with hyperprolactinaemia, those aged above 40 also had higher PANSS positive scores than their younger counterparts. No longitudinal differences were found between age groups.

Women aged above 40 showed worse psychotic symptoms than younger women. This difference seems diagnosis-specific and may be influenced by antipsychotics metabolism. Further longitudinal data are needed considering the menopause transition.

Insight into psychosis is a multidimensional construct involving awareness of illness, attribution of symptoms, and perceived need for treatment. Despite extensive research, substantial variability in how insight is conceptualized and measured continues to hinder clinical assessment and cross-study comparisons.

Following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines and a registered International Prospective Register of Systematic Reviews protocol (CRD42024558386), we conducted a systematic search across five databases (n = 2,184). Twenty-nine studies met the inclusion criteria, comprising 15 primary scale development papers and 10 independent validation studies. We included instruments explicitly designed to assess insight in schizophrenia-spectrum, and evaluated them using the COnsensus-based Standards for the selection of health Measurement INstruments Risk of Bias checklist. Psychometric domains assessed included content validity, structural validity, construct validity, criterion validity, internal consistency, reliability, responsiveness, and interpretability.

Fifteen distinct insight scales were identified, comprising nine clinician-rated instruments, five self-report tools, and one hybrid format. Most demonstrated adequate content and structural validity, with 11 achieving ‘very good’ reliability ratings. Four scales showed the strongest overall psychometric support. However, responsiveness to clinical change was rarely tested, and cross-cultural validation remained limited. Earlier instruments primarily emphasized clinician-rated illness awareness, whereas more recent tools incorporated cognitive, neurocognitive, and subjective dimensions. Discrepancies between self-report and clinician ratings were common and often clinically meaningful. These findings underscore the need for multidimensional, psychometrically robust, and context-sensitive tools to advance both clinical assessment and research on insight in psychotic disorders.

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.

Adolescence is a critical period for brain maturation, influenced by stress and hormonal changes. Chronic stress can lead to increased allostatic load (AL), a cumulative measure of multisystem dysregulation, and insulin resistance (IR), both of which are linked to mental health disorders. We hypothesized that heightened AL and IR during adolescence (age 17) would predict the emergence of mood and psychotic symptoms in young adults.

This study used data from the Avon Longitudinal Study of Parents and Children, a population cohort from Bristol, United Kingdom.

Our results showed that elevated AL at age 17 was significantly associated with the development of mood disorder symptoms (MDS) and psychotic disorder symptoms (PDS) and the co-occurrence of mood and psychotic disorder symptoms (MPDS) at age 24 (p < 0.001). Mean AL increased progressively across these symptom groups, indicating a dose–response relationship between physiological dysregulation and mental health burden (MDS = 3.67, PDS = 3.89, and MPDS = 4.03). We also observed that IR was significantly elevated in the MDS, PDS, and MPDS groups compared to healthy controls (HCs). IR was most prevalent in the PDS group, suggesting a possible association between metabolic dysfunction and psychosis risk.

This study demonstrated that multisystem dysregulation in late adolescence precedes the onset of mood and psychotic symptoms in early adulthood. These results support the use of AL and metabolic markers as early indicators of psychiatric vulnerability and highlight the potential for early intervention targeting systemic dysregulation to prevent the onset of mental health disorders.