While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis.

We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case–control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.

We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case–control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case–control status.

Controls (86.1%) and FEPp (75.63%) were most likely to report ‘because of friends’ as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: ‘to feel better’ as their RFUC (χ2 = 50.97; p < 0.001). RFUC ‘to feel better’ was associated with being a FEPp (OR 1.74; 95% CI 1.03–2.95) while RFUC ‘with friends’ was associated with being a control (OR 0.56; 95% CI 0.37–0.83). The path model indicated an association between RFUC ‘to feel better’ with heavy cannabis use and with FEPp-control status.

Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use ‘to feel better’. People who reported their reason for first using cannabis to ‘feel better’ were more likely to progress to heavy use and develop a psychotic disorder than those reporting ‘because of friends’.

Cognitive and motor dysfunction are hallmark features of the psychosis continuum, and have been detected during late childhood and adolescence in youth who report psychotic experiences (PE). However, previous investigations have not explored infancy and early childhood development. It remains unclear whether such deficits emerge much earlier in life, and whether they are associated with psychotic, specifically hallucinatory, experiences (HE).

This study included data from Gen2 participants of The Raine Study (n = 1101), a population-based longitudinal cohort study in Western Australia. Five areas of childhood development comprising: communication; fine motor; gross motor; adaptive (problem-solving); and personal-social skills, were assessed serially at ages 1, 2 and 3 years. Information on HE, depression and anxiety at ages 10, 14 and 17 years was obtained. HE were further subdivided into those with transient or recurrent experiences. Mixed effects logistic regression models and cumulative risk analyses based on multiple domain delays were performed.

Early poorer development in multiple areas was noted from ages 1, 2 and 3 years among youth who reported HE. Early developmental delays significantly increased the risk for later HE. This association was particularly marked in the recurrent HE group, with over 40% having early developmental delays in multiple domains. There was no significant association between early childhood development and later anxiety/depression apart from lower gross motor scores at age 3.

The findings suggest that early pan-developmental deficits are associated with later HE, with the effect strongest for young people who report recurrent HE throughout childhood and adolescence.

The juvenile justice system in the USA adjudicates over seven hundred thousand youth in the USA annually with significant behavioral offenses. This study aimed to test the effect of juvenile justice involvement on adult criminal outcomes.

Analyses were based on a prospective, population-based study of 1420 children followed up to eight times during childhood (ages 9–16; 6674 observations) about juvenile justice involvement in the late 1990 and early 2000s. Participants were followed up years later to assess adult criminality, using self-report and official records. A propensity score (i.e. inverse probability) weighting approach was used that approximated an experimental design by balancing potentially confounding characteristics between children with v. without juvenile justice involvement.

Between-groups differences on variables that elicit a juvenile justice referral (e.g. violence, property offenses, status offenses, and substance misuse) were attenuated after applying propensity-based inverse probability weights. Participants with a history of juvenile justice involvement were more likely to have later official and violent felony charges, and to self-report police contact and spending time in jail (ORs from 2.5 to 3.3). Residential juvenile justice involvement was associated with the highest risk of both, later official criminal records and self-reported criminality (ORs from 5.1 to 14.5). Sensitivity analyses suggest that our findings are likely robust to potential unobserved confounders.

Juvenile justice involvement was associated with increased risk of adult criminality, with residential services associated with highest risk. Juvenile justice involvement may catalyze rather than deter from adult offending.

Preliminary evidence shows that discordance in stress experience, expression, and physiology (EEP) in adolescents is linked to depression, suicidal ideation (SI), non-suicidal self-injury (NSSI), and brain functioning. This study employs person-centered analysis to probe the relationship between stress responses, psychopathology, and neural patterns in female adolescents who are oversampled for engagement in NSSI.

Adolescent females (N = 109, ages 12–17) underwent a social stress test from which self-report measures of stress experience, observer ratings of stress expression, and physiological metrics of stress (via salivary cortisol) were obtained. Multi-trajectory modeling was employed to identify concordant and discordant stress EEP groups. Depressive symptoms, SI and attempt, NSSI engagement, frontal and limbic activation to emotional stimuli, and resting state fronto-limbic connectivity were examined in the EEP groups derived from the multi-trajectory models.

Four groups were identified, three of which demonstrated relatively concordant EEP and one which demonstrated discordant EEP (High Experience-High Expression-Low Physiology). Further, replicating past research, the High Experience-High Expression-Low Physiology discordant group exhibited higher depressive symptoms, SI, suicide attempt, and NSSI episodes (only for sensitivity analyses based on past year) relative to other EEP groups. No significant group differences in brain functioning emerged.

Results indicate that within-person, multi-level patterns in stress responding capture risk for dysfunction including depression and self-injurious thoughts and behaviors. Further interrogating of system-level stress functioning may better inform assessment and intervention efforts.

Research on biased processing of aversive stimuli in posttraumatic stress disorder (PTSD) has produced inconsistent results between response time (RT) and eye-tracking studies. Recent RT-based results of dot-probe studies showed no attentional bias (AB) for threat while eye-tracking research suggested heightened sustained attention for this information. Here, we used both RT-based and eye-tracking measures to explore the dynamics of AB to negative stimuli in PTSD.

Twenty-three individuals diagnosed with PTSD, 23 trauma-exposed healthy controls, and 23 healthy controls performed an emotional dot-probe task with pairs of negative and neutral scenes presented for either 1 or 2 s. Analyses included eye movements during the presentation of the scenes and RT associated with target localization.

There was no evidence for an AB toward negative stimuli in PTSD from RT measures. However, the main eye-tracking results revealed that all three groups showed longer dwell times on negative pictures than neutral pictures at 1 s and that this AB was stronger for individuals with PTSD. Moreover, although AB disappeared for the two groups of healthy controls with prolonged exposure, it persisted for individuals with PTSD.

PTSD is associated with an AB toward negative stimuli, characterized by heightened sustained attention toward negative scenes once detected. This study sheds light on the dynamics of AB to negative stimuli in PTSD and encourages us to consider optimized therapeutic interventions targeting abnormal AB patterns.

Poor sleep is a modifiable risk factor for multiple disorders. Frontline treatments (e.g. cognitive-behavioral therapy for insomnia) have limitations, prompting a search for alternative approaches. Here, we compare manualized Mindfulness-Based Therapy for Insomnia (MBTI) with a Sleep Hygiene, Education, and Exercise Program (SHEEP) in improving subjective and objective sleep outcomes in older adults.

We conducted a single-site, parallel-arm trial, with blinded assessments collected at baseline, post-intervention and 6-months follow-up. We randomized 127 participants aged 50–80, with a Pittsburgh Sleep Quality Index (PSQI) score ⩾5, to either MBTI (n = 65) or SHEEP (n = 62), both 2 hr weekly group sessions lasting 8 weeks. Primary outcomes included PSQI and Insomnia Severity Index, and actigraphy- and polysomnography-measured sleep onset latency (SOL) and wake after sleep onset (WASO).

Intention-to-treat analysis showed reductions in insomnia severity in both groups [MBTI: Cohen's effect size d = −1.27, 95% confidence interval (CI) −1.61 to −0.89; SHEEP: d = −0.69, 95% CI −0.96 to −0.43], with significantly greater improvement in MBTI. Sleep quality improved equivalently in both groups (MBTI: d = −1.19; SHEEP: d = −1.02). No significant interaction effects were observed in objective sleep measures. However, only MBTI had reduced WASOactigraphy (MBTI: d = −0.30; SHEEP: d = 0.02), SOLactigraphy (MBTI: d = −0.25; SHEEP: d = −0.09), and WASOPSG (MBTI: d = −0.26; SHEEP (d = −0.18). There was no change in SOLPSG. No participants withdrew because of adverse effects.

MBTI is effective at improving subjective and objective sleep quality in older adults, and could be a valid alternative for persons who have failed or do not have access to standard frontline therapies.

Several social determinants of health (SDoH) have been associated with the onset of major depressive disorder (MDD). However, prior studies largely focused on individual SDoH and thus less is known about the relative importance (RI) of SDoH variables, especially in older adults. Given that risk factors for MDD may differ across the lifespan, we aimed to identify the SDoH that was most strongly related to newly diagnosed MDD in a cohort of older adults.

We used self-reported health-related survey data from 41 174 older adults (50–89 years, median age = 67 years) who participated in the Mayo Clinic Biobank, and linked ICD codes for MDD in the participants' electronic health records. Participants with a history of clinically documented or self-reported MDD prior to survey completion were excluded from analysis (N = 10 938, 27%). We used Cox proportional hazards models with a gradient boosting machine approach to quantify the RI of 30 pre-selected SDoH variables on the risk of future MDD diagnosis.

Following biobank enrollment, 2073 older participants were diagnosed with MDD during the follow-up period (median duration = 6.7 years). The most influential SDoH was perceived level of social activity (RI = 0.17). Lower level of social activity was associated with a higher risk of MDD [hazard ratio = 2.27 (95% CI 2.00–2.50) for highest v. lowest level].

Across a range of SDoH variables, perceived level of social activity is most strongly related to MDD in older adults. Monitoring changes in the level of social activity may help identify older adults at an increased risk of MDD.

Previous research has highlighted the importance of understanding which psychosocial factors distinguish between those with suicide thoughts compared to those who attempt suicide. This study aims to investigate these distinguishing factors further within an ideation-to-action framework and to explore sex differences in suicide risk.

Participants (n = 7546, aged 16+) were from the cross-sectional Adult Psychiatric Morbidity Survey (APMS; 2014) of England. Face-to-face and self-completion questionnaires assessed lifetime suicidal ideation, lifetime suicide attempts, demographic characteristics, life experiences, social support, health and mental illness. Multinomial logistic regression examined factors differentiating between those with suicidal ideation only and suicide attempt histories (with or without suicidal ideation) in men and women.

Overall men were less likely to report suicidal thoughts and attempts, compared to females. More factors differentiated between suicidal thoughts and attempts in women compared to in men; these included hospital admission for mental illness, below degree level qualifications, being single and childhood adversity. In men, factors which significantly differentiated between suicidal thoughts and attempts included self-report of professional diagnosis of mental illness and childhood adversity. Higher levels of social support were associated with being in the suicidal thoughts group v. in the attempts group in men.

This study identified some key differences between men and women in factors associated with suicide attempts compared to suicidal thoughts. The findings support the use of the ideation-to-action framework to investigate sex differences in suicidal behaviour. Future research should examine the extent to which these factors are associated with suicide risk over time.

Tobacco use is common in subjects with schizophrenia (SZ) and has sometimes been associated with better functioning in short-term studies. Only few studies embrace an extensive examination of tobacco influence on clinical, cognitive and therapeutic characteristics in stabilized SZ outpatients. The objective of the present study was to assess the association between cognitive performances and smoking status in SZ subjects.

In total, 1233 SZ participants (73.9% men, mean age 31.5) were included and tested with a comprehensive battery. Tobacco status was self-declared (never-, ex-, or current smokers). Multivariable analyses including principal component analyses (PCA) were used.

In total, 53.7% were smokers with 33.7% of them nicotine-dependent. Multiple factor analysis revealed that current tobacco smoking was associated with impaired general intellectual ability and abstract reasoning (aOR 0.60, 95% IC 0.41–0.88, p = 0.01) and with a lifetime alcohol use disorder (p = 0.026) and a lifetime cannabis use disorder (p < 0.001). Ex- and never-smokers differed for age, mean outcome, cannabis history and medication [ex-smokers being older (p = 0.047), likely to have higher income (p = 0.026), a lifetime cannabis use disorder (p < 0.001) and higher CPZeq doses (p = 0.005)]. Premorbid IQ in the three groups significantly differed with, from higher to lower: ex-smokers, never-smoker, current smokers (all p < 0.001).

This study is the largest to date providing strong evidence that chronic smoking is associated with cognitive impairment in SZ, arguing against the self-medication hypothesis as a contributor to the high prevalence of smoking in SZ. Ex-smokers may also represent a specific subgroup. Longitudinal studies are warranted to determine the developmental impact of tobacco on neurocognition.

Emerging functional imaging studies suggest that schizophrenia is associated with aberrant spatiotemporal interaction which may result in aberrant global and local dynamic properties.

We investigated the dynamic functional connectivity (FC) by using instantaneous phase method based on Hilbert transform to detect abnormal spatiotemporal interaction in schizophrenia. Based on resting-state functional magnetic resonance imaging, two independent datasets were included, with 114 subjects from COBRE [51 schizophrenia patients (SZ) and 63 healthy controls (HCs)] and 96 from OpenfMRI (36 SZ and 60 HCs). Phase differences and instantaneous coupling matrices were firstly calculated at all time points by extracting instantaneous parameters. Global [global synchrony and intertemporal closeness (ITC)] and local dynamic features [strength of FC (sFC) and variability of FC (vFC)] were compared between two groups. Support vector machine (SVM) was used to estimate the ability to discriminate two groups by using all aberrant features.

We found SZ had lower global synchrony and ITC than HCs on both datasets. Furthermore, SZ had a significant decrease in sFC but an increase in vFC, which were mainly located at prefrontal cortex, anterior cingulate cortex, temporal cortex and visual cortex or temporal cortex and hippocampus, forming significant dynamic subnetworks. SVM analysis revealed a high degree of balanced accuracy (85.75%) on the basis of all aberrant dynamic features.

SZ has worse overall spatiotemporal stability and extensive FC subnetwork lesions compared to HCs, which to some extent elucidates the pathophysiological mechanism of schizophrenia, providing insight into time-variation properties of patients with other mental illnesses.

People with psychosis experience cardiometabolic comorbidities, including metabolic syndrome, coronary heart disease and diabetes. These physical comorbidities have been linked to diet, inactivity and the effects of the illness itself, including disorganisation, impairments in global function and amotivation associated with negative symptoms of schizophrenia or co-morbid depression.

We aimed to describe the dietary intake, physical activity (PA) and sedentary behaviour patterns of a sample of patients with established psychosis participating in the Improving Physical Health and Reducing Substance Use in Severe Mental Illness (IMPaCT) randomised controlled trial, and to explore the relationship between these lifestyle factors and mental health symptomatology.

A majority of participants had poor dietary quality, low in fruit and vegetables and high in discretionary foods. Only 29.3% completed ⩾150 min of moderate and/or vigorous activity per week and 72.2% spent ⩾6 h per day sitting. Cross-sectional associations between negative symptoms, global function, and PA and sedentary behaviour were observed. Additionally, those with more negative symptoms receiving IMPaCT therapy had fewer positive changes in PA from baseline to 12-month follow-up than those with fewer negative symptoms at baseline.

These results highlight the need for the development of multidisciplinary lifestyle and exercise interventions to target eating habits, PA and sedentary behaviour, and the need for further research on how to adapt lifestyle interventions to baseline mental status. Negative symptoms in particular may reduce patient's responses to lifestyle interventions.

Multiple risk behaviours (MRBs), typically beginning in adolescence, are associated with increased risk of adverse health and social outcomes. The association between autism and MRBs is little understood.

Data were from the Avon Longitudinal Study of Parents and Children, an UK-based longitudinal, birth cohort study. Exposures were diagnosed autism and four autistic traits: social communication difficulties, pragmatic language, repetitive behaviours and reduced sociability. Outcomes were participation in up to 14 risk behaviours, including alcohol consumption, smoking, risky sexual behaviours and physical inactivity. Outcome data were collected at ages approximately 12, 14, 16 and 18.

Up to 4300 participants were included in latent basis growth curve analyses with adjustment for confounders. Social communication difficulties were associated with an above average level of MRBs engagement at ~12 years (mean difference β 0.26; 95% CI 0.13–0.40), and above average rate of engagement from ages ~12–18 (β 0.08; 95% CI 0.02–0.13). Repetitive behaviours were associated with above average levels of engagement in MRBs at ~12 years (β 0.24; 95% CI 0.09–0.38). Contrastingly, reduced sociability was associated with a reduced rate of engagement in MRBs from ages ~12–18 (β −0.06; 95% CI −0.11 to −0.02). In sex-specific analyses, persisting differences in MRB engagement patterns from ages ~12–18 were observed in males with social communication difficulties and females with reduced sociability temperament.

Having elevated levels of some autistic traits appear to have differentiated effects on MRB engagement patterns. These findings could reflect difficulties fitting in and/or coping mechanisms relating to difficulties with fitting in.

Losing a parent or spouse in adulthood may result in prolonged grief disorder (PGD) symptoms. PGD levels in parents may affect PGD levels in their adult offspring and the other way around. However, research on transmission of PGD in parent–child dyads is lacking. Consequently, we aimed to examine temporal associations between PGD levels in parent and adult children.

In doing so, we analyzed longitudinal self-report data on PGD levels (using the PG-13) assessed at 2, 11, 18, and 26 months after loss in 257 adult parent–child dyads from Denmark. Cross-lagged panel modeling was used for data-analyses.

Changes in PGD levels in parents significantly predicted PGD levels in adult children, but not vice versa. Small through moderate cross-lagged effects (β = 0.05 through 0.07) were found for PGD levels in parents predicting PGD levels in adult children at a subsequent time-point. These cross-lagged effects were found while taking into account the association between PGD levels in parents and adult children at the same time-point as well as the associations between the same construct over time and relevant covariates.

Pending replication of these findings in clinical samples and younger families, our findings offer tentative support for expanding our focus in research and treatment of PGD from the individual to the family level.

To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ).

We systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ.

TWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ.

Our findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.

Neuroprogressive models of the trajectory of cognitive dysfunction in patients with bipolar disorder (BD) have been proposed. However, few studies have explored the relationships among clinical characteristics of BD, cognitive dysfunction, and aging.

We conducted a cross-sectional analysis in euthymic participants with the MATRICS Cognitive Consensus Battery, the Trail Making Test B, the Stroop Test, and the Wechsler Test of Adult Reading. Age- and gender-equated control participants without a mental disorder [‘Healthy Controls’ – HC)] were assessed similarly. We compared cognitive performance both globally and in seven domains in four groups: younger BD (age ⩽49 years; n = 70), older BD (age ⩾50 years; n = 48), younger HC (n = 153), and older HC (n = 44). We also compared the BD and HC groups using age as a continuous measure. We controlled for relevant covariates and applied a Bonferroni correction.

Our results support both an early impairment (‘early hit’) model and an accelerated aging model: impairment in attention/vigilance, processing speed, and executive function/working memory were congruent with the accelerated aging hypothesis whereas impairment in verbal memory was congruent with an early impairment model. BD and HC participants exhibited similar age-related decline in reasoning/problem solving and visuospatial memory. There were no age- or diagnosis-related differences in social cognition.

Our findings support that different cognitive domains are affected differently by BD and aging. Longitudinal studies are needed to explore trajectories of cognitive performance in BD across the lifespan.

Cognitive training (CT) and aerobic exercise both show promising moderate impact on cognition and everyday functioning in schizophrenia. Aerobic exercise is hypothesized to increase brain-derived neurotrophic factor (BDNF) and thereby synaptic plasticity, leading to increased learning capacity. Systematic CT should take advantage of increased learning capacity and be more effective when combined with aerobic exercise.

We examined the impact of a 6-month program of cognitive training & exercise (CT&E) compared to cognitive training alone (CT) in 47 first-episode schizophrenia outpatients. All participants were provided the same Posit Science computerized CT, 4 h/week, using BrainHQ and SocialVille programs. The CT&E group also participated in total body circuit training exercises to enhance aerobic conditioning. Clinic and home-based exercise were combined for a target of 150 min per week.

The MATRICS Consensus Cognitive Battery Overall Composite improved significantly more with CT&E than with CT alone (p = 0.04), particularly in the first 3 months (6.5 v. 2.2 T-score points, p < 0.02). Work/school functioning improved substantially more with CT&E than with CT alone by 6 months (p < 0.001). BDNF gain tended to predict the amount of cognitive gain but did not reach significance. The cognitive gain by 3 months predicted the amount of work/school functioning improvement at 6 months. The amount of exercise completed was strongly associated with the degree of cognitive and work/school functioning improvement.

Aerobic exercise significantly enhances the impact of CT on cognition and functional outcome in first-episode schizophrenia, apparently driven by the amount of exercise completed.

This study assessed the extent to which women's preconception binge drinking, tobacco use and cannabis use, reported prospectively in adolescence and young adulthood, predicted use of these substances during pregnancy and at 1 year postpartum.

Data were pooled from two intergenerational cohort studies: the Australian Temperament Project Generation 3 Study (395 mothers, 691 pregnancies) and the Victorian Intergenerational Health Cohort Study (398 mothers, 609 pregnancies). Alcohol, tobacco and cannabis use were assessed in adolescence (13–18 years), young adulthood (19–29 years) and at ages 29–35 years for those transitioning to parenthood. Exposures were weekly or more frequent preconception binge drinking (5 + drinks in one session), tobacco use and cannabis use. Outcomes were any alcohol, tobacco and cannabis use prior to awareness of the pregnancy, after awareness of pregnancy (up to and including the third trimester pregnancy) and at 1 year postpartum.

Frequent preconception binge drinking, tobacco use and cannabis use across both adolescence and young adulthood were strong predictors of continued use post-conception, before and after awareness of the pregnancy and at 1 year postpartum. Substance use limited to young adulthood also predicted continued use post-conception.

Persistent alcohol, tobacco use and cannabis use that starts in adolescence has a strong continuity into parenthood. Reducing substance use in the perinatal period requires action well before pregnancy, commencing in adolescence and continuing into the years before conception and throughout the perinatal period.

Body weight variability (BWV) negatively affects the incidence and outcomes of various diseases, but the nature of the association between BWV and depression remains unclear. In this study, we aimed to test the hypothesis that BWV is associated with the risk of new-onset depression.

Data from a nationwide population-based cohort in the Korean National Health Insurance Service database were analyzed for 6 598 570 adults with no history of depression and reports of at least three health examinations. BWV was estimated using variability independent of the mean indices and divided into quartiles (Q1 lowest, Q4 highest BWV). Cox proportional hazard models were applied to assess the risk of depression according to the quartile of BWV.

The incident rate for depression from Q1 to Q4 of BWV was 20.7, 20.3, 20.8, and 22.2 per 1000 person-years, respectively. BWV, especially high BWV, was associated with an increased risk of depression after adjusting for age, sex, smoking, alcohol consumption, physical activity, income, diabetes mellitus, hypertension, and dyslipidemia. The hazard ratio (HR) of new-onset depression was highest in Q4 relative to Q1 in the total population (HR 1.12, p < 0.0001) and was higher in women than in men (HR 1.72 v. 1.16, p < 0.0001). In stratified analyses, regardless of obesity or weight change status at baseline, the risk of depression was increased when bodyweight fluctuated highly during follow-up.

High BWV was associated with an increased risk of depression. Further studies need to evaluate the role of high BWV with respect to the onset of depression.

Antipsychotic polypharmacy (APP) occurs commonly but it is unclear whether it is associated with an increased risk of adverse drug reactions (ADRs). Electronic health records (EHRs) offer an opportunity to examine APP using real-world data. In this study, we use EHR data to identify periods when patients were prescribed 2 + antipsychotics and compare these with periods of antipsychotic monotherapy. To determine the relationship between APP and subsequent instances of ADRs: QT interval prolongation, hyperprolactinaemia, and increased body weight [body mass index (BMI) ⩾ 25].

We extracted anonymised EHR data. Patients aged 16 + receiving antipsychotic medication at Camden & Islington NHS Foundation Trust between 1 January 2008 and 31 December 2018 were included. Multilevel mixed-effects logistic regression models were used to elucidate the relationship between APP and the subsequent presence of QT interval prolongation, hyperprolactinaemia, and/or increased BMI following a period of APP within 7, 30, or 180 days respectively.

We identified 35 409 observations of antipsychotic prescribing among 13 391 patients. Compared with antipsychotic monotherapy, APP was associated with a subsequent increased risk of hyperprolactinaemia (adjusted odds ratio 2.46; 95% CI 1.87–3.24) and of registering a BMI > 25 (adjusted odds ratio 1.75; 95% CI 1.33–2.31) in the period following the APP prescribing.

Our observations suggest that APP should be carefully managed with attention to hyperprolactinaemia and obesity.

Mismatch negativity (MMN) amplitude is reduced in psychotic disorders and associated with symptoms and functioning. Due to these robust associations, it is often considered a biomarker for psychotic illness. The relationship between MMN and clinical outcomes has been examined well in early onset psychotic illness; however, its stability and predictive utility in chronic samples are not clear.

We examined the five-year stability of MMN amplitude over two timepoints in individuals with established psychotic disorders (cases; N = 132) and never-psychotic participants (NP; N = 170), as well as longitudinal associations with clinical symptoms and functioning.

MMN amplitude exhibited good temporal stability (cases, r = 0.53; never-psychotic, r = 0.52). In cases, structural equation models revealed MMN amplitude to be a significant predictor of worsening auditory hallucinations (β = 0.19), everyday functioning (β = −0.13), and illness severity (β = −0.12) at follow-up. Meanwhile, initial IQ (β = −0.24), negative symptoms (β = 0.23), and illness severity (β = −0.16) were significant predictors of worsening MMN amplitude five years later.

These results imply that MMN measures a neural deficit that is reasonably stable up to five years. Results support disordered cognition and negative symptoms as preceding reduced MMN, which then may operate as a mechanism driving reductions in everyday functioning and the worsening of auditory hallucinations in chronic psychotic disorders. This pattern may inform models of illness course, clarifying the relationships amongst biological mechanisms of predictive processing and clinical deficits in chronic psychosis and allowing us to better understand the mechanisms driving such impairments over time.