Duration of untreated psychosis (DUP) is an important measure of access to care as it predicts prognosis and treatment outcomes. Little is known about potential socioeconomic inequalities in DUP. The aim of this study was to investigate inequalities in DUP associated with socioeconomic deprivation in a national cohort in England.

We analysed a cohort of 887 patients with a first-episode in psychosis using the administrative Mental Health Services Dataset in England for 2012/13-2014/15. We used a Generalised Linear Model to account for non-linearity in DUP and looked at inequalities across the whole distribution of DUP using quantile regression.

The median DUP was 22 days (mean = 74 days) with considerable variations between and within the 31 hospital providers. We found evidence of significant inequalities regarding the level of socioeconomic deprivation. Patients living in the second, third and fourth deprived neighbourhood quintiles faced a 36, 24 and 31 day longer DUP than patients from the least deprived neighbourhoods. Inequalities were more prevalent in higher quantiles of the DUP distribution. Unemployment prolonged DUP by 40 days. Having been in contact with mental health care services prior to the psychosis start significantly reduced the DUP by up to 53 days.

Socioeconomic deprivation is an important factor in explaining inequalities in DUP. Policies to improve equitable access to care should particularly focus on preventing very long delays in treatment and target unemployed patients as well as people that have not been in contact with any mental health professional in the past.

In this study, we examined the relationship between polygenic liability for depression and number of stressful life events (SLEs) as risk factors for early-onset depression treated in inpatient, outpatient or emergency room settings at psychiatric hospitals in Denmark.

Data were drawn from the iPSYCH2012 case-cohort sample, a population-based sample of individuals born in Denmark between 1981 and 2005. The sample included 18 532 individuals who were diagnosed with depression by a psychiatrist by age 31 years, and a comparison group of 20 184 individuals. Information on SLEs was obtained from nationwide registers and operationalized as a time-varying count variable. Hazard ratios and cumulative incidence rates were estimated using Cox regressions.

Risk for depression increased by 35% with each standard deviation increase in polygenic liability (p < 0.0001), and 36% (p < 0.0001) with each additional SLE. There was a small interaction between polygenic liability and SLEs (β = −0.04, p = 0.0009). The probability of being diagnosed with depression in a hospital-based setting between ages 15 and 31 years ranged from 1.5% among males in the lowest quartile of polygenic liability with 0 events by age 15, to 18.8% among females in the highest quartile of polygenic liability with 4+ events by age 15.

These findings suggest that although there is minimal interaction between polygenic liability and SLEs as risk factors for hospital-treated depression, combining information on these two important risk factors could potentially be useful for identifying high-risk individuals.

In a perinatal cohort of women in urban and rural Turkey, we investigated associations between antenatal depressive symptoms and subsequent changes in perceived quality of key family relationships.

Of 730 women recruited in their third trimester (94.6% participation), 578 (79.2%) were reassessed at a mean of 4.1 (s.d. = 3.3) months after childbirth, 488 (66.8%) were reassessed at 13.7 (s.d. = 2.9) months, and 448 (61.4%) at 20.8 (s.d. = 2.7) months. At all four examinations, self-reported quality of relationship with the husband, mother and mother-in-law was ascertained using the Close Persons Questionnaire with respect to emotional support, practical support and negative aspects of the relationship. Antenatal depressive symptoms were defined using the Edinburgh Postnatal Depression Scale. A range of covariates in mixed models was considered including age, education, number of children, family structure, physical health, past emotional problems and stressful life events.

Key findings were as follows: (i) reported emotional and practical support from all three relationships declined over time in the cohort overall; (ii) reported emotional support from the husband, and emotional and practical support from the mother-in-law, declined more strongly in women with antenatal depressive symptoms; (iii) associations between depressive symptoms and worsening spouse relationship were more pronounced in traditional compared with nuclear families.

Antenatal depressive symptoms predicted marked decline in the quality of key relationships over the postnatal period. This may account for some of the contemporaneous associations between depression and worse social support, and may compound the risk of perinatal depression in subsequent pregnancies.

Maternal smoking has known adverse effects on fetal development. However, research on the association between maternal smoking during pregnancy and offspring intellectual disability (ID) is limited, and whether any associations are due to a causal effect or residual confounding is unknown.

Cohort study of all Danish births between 1995 and 2012 (1 066 989 persons from 658 335 families after exclusions), with prospectively recorded data for cohort members, parents and siblings. We assessed the association between maternal smoking during pregnancy (18.6% exposed, collected during prenatal visits) and offspring ID (8051 cases, measured using ICD-10 diagnosis codes F70–F79) using logistic generalised estimating equation regression models. Models were adjusted for confounders including measures of socio-economic status and parental psychiatric diagnoses and were adjusted for family averaged exposure between full siblings. Adjustment for a family averaged exposure allows calculation of the within-family effect of smoking on child outcomes which is robust against confounders that are shared between siblings.

We found increased odds of ID among those exposed to maternal smoking in pregnancy after confounder adjustment (OR 1.35, 95% CI 1.28–1.42) which attenuated to a null effect following adjustment for family averaged exposure (OR 0.91, 95% CI 0.78–1.06).

Our findings are inconsistent with a causal effect of maternal smoking during pregnancy on offspring ID risk. By estimating a within-family effect, our results suggest that prior associations were the result of unmeasured genetic or environmental characteristics of families in which the mother smokes during pregnancy.

The psychological risk factors of premenstrual dysphoric disorder (PMDD) are not fully understood, but initial evidence points to a potential role of unfavorable cognitive emotion regulation (ER-) strategies. Given the symptom cyclicity of PMDD, ambulatory assessment is ideally suited to capture psychological and physiological processes across the menstrual cycle. Our study examines habitual ER-strategies in women with PMDD and their predictive value for the course of mood and basal cortisol across the cycle in affected women.

Women with and without PMDD (n = 61 each) were compared regarding habitual mindfulness, reappraisal, and repetitive negative thinking (RNT). Momentary affect and cortisol output were assessed over two consecutive days per cycle phase (menstrual, follicular, ovulatory, late luteal).

Women with PMDD reported lower mindfulness, less use of reappraisal and stronger RNT than controls (ps < 0.035). In women with PMDD, higher mindfulness and reappraisal and lower RNT predicted decreased negative and increased positive affect across the menstrual cycle (ps < 0.027). However, women using more favorable ER-strategies displayed stronger mood cyclicity, resulting in stronger mood deterioration in the late luteal phase, thereby resembling women with more unfavorable ER-strategies toward the end of the cycle. Lower mindfulness predicted lower cortisol in the menstrual phase.

Protective ER-strategies seem to be generally linked to better momentary mood in women with PMDD, but do not appear to protect affected women from premenstrual mood deterioration. Habitual mindfulness, in turn, seems to buffer blunted cortisol activity in women with PMDD, especially in the menstrual phase.

Multiple predictors have been associated with persistent somatic symptoms. However, previous studies problematically defined the persistence of symptoms, conflated participants' sex and gender, and focused on patient populations. Therefore, we studied associations between predictors, especially sex and gender, and longitudinal patterns of somatic symptoms in the general adult population. We also assessed whether predictors for persisting symptoms differ between sexes.

To identify developmental trajectories of somatic symptoms, assessed by the SCL-90 SOM, we used latent class trajectory modeling in the Dutch Lifelines Cohort Study [N = 150 494; 58.6% female; median time to follow-up: 46.0 (min–max: 22.0–123.0) months]. To identify predictors of trajectories, we applied multiple logistic regression analyses. Predictors were measured by surveys at baseline and a composite gender index was previously developed.

A five-class linear LCGA model fitted the data best: 93.7% of the population had a stable symptom trajectory, whereas 1.5% and 4.8% of the population had a consistently increasing or decreasing symptom trajectory, respectively. Female sex predicted severe, stable symptom severity (OR 1.74, 95% CI 1.36–2.22), but not increasing symptom severity (OR 1.15, 95% CI 0.99–1.40). Femininity was protective hereof (OR 0.60, 95% CI 0.44–0.82 and OR 0.66, 95% CI 0.51–0.85, respectively). Merely a few predictors of symptom severity, for instance hours of paid employment and physical functioning, differed in strength between sexes. Yet, effect sizes were small.

Female sex and femininity predict symptom trajectories. No large sex differences in the strength of additional predictors were found, thus it may not be clinically useful to distinguish between predictors specific to male or female patients of persistent somatic symptoms.

Individuals with depression often experience widespread and persistent cognitive deficits, which might be due to brain atrophy and cerebral small vessel disease (CSVD). We therefore studied the associations between depression, markers of brain atrophy and CSVD, and cognitive functioning.

We used cross-sectional data from the population-based Maastricht study (n = 4734; mean age 59.1 ± 8.6 years, 50.2% women), which focuses on type 2 diabetes. A current episode of major depressive disorder (MDD, n = 151) was assessed by the Mini-International Neuropsychiatric Interview. Volumes of cerebral spinal fluid, white matter, gray matter and white matter hyperintensities, presence of lacunar infarcts and cerebral microbleeds, and total CSVD burden were assessed by 3 T magnetic resonance imaging. Multiple linear and logistic regression analyses tested the associations between MDD, brain markers and cognitive functioning in memory, information processing speed, and executive functioning & attention, and presence of cognitive impairment. Structural equation modeling was used to test mediation.

In fully adjusted models, MDD was associated with lower scores in information processing speed [mean difference = −0.18(−0.28;−0.08)], executive functioning & attention [mean difference = −0.13(−0.25;−0.02)], and with higher odds of cognitive impairment [odds ratio (OR) = 1.60(1.06;2.40)]. MDD was associated with CSVD in participants without type 2 diabetes [OR = 1.65(1.06;2.56)], but CSVD or other markers of brain atrophy or CSVD did not mediate the association with cognitive functioning.

MDD is associated with more impaired information processing speed and executive functioning & attention, and overall cognitive impairment. Furthermore, MDD was associated with CSVD in participants without type 2 diabetes, but this association did not explain an impaired cognitive profile.

While adolescent-onset schizophrenia (ADO-SCZ) and adolescent-onset bipolar disorder with psychosis (psychotic ADO-BPD) present a more severe clinical course than their adult forms, their pathophysiology is poorly understood. Here, we study potentially state- and trait-related white matter diffusion-weighted magnetic resonance imaging (dMRI) abnormalities along the adolescent-onset psychosis continuum to address this need.

Forty-eight individuals with ADO-SCZ (20 female/28 male), 15 individuals with psychotic ADO-BPD (7 female/8 male), and 35 healthy controls (HCs, 18 female/17 male) underwent dMRI and clinical assessments. Maps of extracellular free-water (FW) and fractional anisotropy of cellular tissue (FAT) were compared between individuals with psychosis and HCs using tract-based spatial statistics and FSL's Randomise. FAT and FW values were extracted, averaged across all voxels that demonstrated group differences, and then utilized to test for the influence of age, medication, age of onset, duration of illness, symptom severity, and intelligence.

Individuals with adolescent-onset psychosis exhibited pronounced FW and FAT abnormalities compared to HCs. FAT reductions were spatially more widespread in ADO-SCZ. FW increases, however, were only present in psychotic ADO-BPD. In HCs, but not in individuals with adolescent-onset psychosis, FAT was positively related to age.

We observe evidence for cellular (FAT) and extracellular (FW) white matter abnormalities in adolescent-onset psychosis. Although cellular white matter abnormalities were more prominent in ADO-SCZ, such alterations may reflect a shared trait, i.e. neurodevelopmental pathology, present across the psychosis spectrum. Extracellular abnormalities were evident in psychotic ADO-BPD, potentially indicating a more dynamic, state-dependent brain reaction to psychosis.

It is not clear to what extent associations between schizophrenia, cannabis use and cigarette use are due to a shared genetic etiology. We, therefore, examined whether schizophrenia genetic risk associates with longitudinal patterns of cigarette and cannabis use in adolescence and mediating pathways for any association to inform potential reduction strategies.

Associations between schizophrenia polygenic scores and longitudinal latent classes of cigarette and cannabis use from ages 14 to 19 years were investigated in up to 3925 individuals in the Avon Longitudinal Study of Parents and Children. Mediation models were estimated to assess the potential mediating effects of a range of cognitive, emotional, and behavioral phenotypes.

The schizophrenia polygenic score, based on single nucleotide polymorphisms meeting a training-set p threshold of 0.05, was associated with late-onset cannabis use (OR = 1.23; 95% CI = 1.08,1.41), but not with cigarette or early-onset cannabis use classes. This association was not mediated through lower IQ, victimization, emotional difficulties, antisocial behavior, impulsivity, or poorer social relationships during childhood. Sensitivity analyses adjusting for genetic liability to cannabis or cigarette use, using polygenic scores excluding the CHRNA5-A3-B4 gene cluster, or basing scores on a 0.5 training-set p threshold, provided results consistent with our main analyses.

Our study provides evidence that genetic risk for schizophrenia is associated with patterns of cannabis use during adolescence. Investigation of pathways other than the cognitive, emotional, and behavioral phenotypes examined here is required to identify modifiable targets to reduce the public health burden of cannabis use in the population.

Psychosis is associated with a reasoning bias, which manifests as a tendency to ‘jump to conclusions’. We examined this bias in people at clinical high-risk for psychosis (CHR) and investigated its relationship with their clinical outcomes.

In total, 303 CHR subjects and 57 healthy controls (HC) were included. Both groups were assessed at baseline, and after 1 and 2 years. A ‘beads’ task was used to assess reasoning bias. Symptoms and level of functioning were assessed using the Comprehensive Assessment of At-Risk Mental States scale (CAARMS) and the Global Assessment of Functioning (GAF), respectively. During follow up, 58 (16.1%) of the CHR group developed psychosis (CHR-T), and 245 did not (CHR-NT). Logistic regressions, multilevel mixed models, and Cox regression were used to analyse the relationship between reasoning bias and transition to psychosis and level of functioning, at each time point.

There was no association between reasoning bias at baseline and the subsequent onset of psychosis. However, when assessed after the transition to psychosis, CHR-T participants showed a greater tendency to jump to conclusions than CHR-NT and HC participants (55, 17, 17%; χ2 = 8.13, p = 0.012). There was a significant association between jumping to conclusions (JTC) at baseline and a reduced level of functioning at 2-year follow-up in the CHR group after adjusting for transition, gender, ethnicity, age, and IQ.

In CHR participants, JTC at baseline was associated with adverse functioning at the follow-up. Interventions designed to improve JTC could be beneficial in the CHR population.

Substance use and psychiatric illness, particularly psychotic disorders, contribute to violence in emergency healthcare settings. However, there is limited research regarding the relationship between specific substances, psychotic symptoms and violent behaviour in such settings. We investigated the interaction between recent cannabinoid and stimulant use, and acute psychotic symptoms, in relation to violent behaviour in a British emergency healthcare setting.

We used electronic medical records from detentions of 1089 individuals under Section 136 of the UK Mental Health Act (1983 amended 2007), an emergency police power used to detain people for 24–36 h for psychiatric assessment. The relationship between recent cannabinoids and/or stimulant use, psychotic symptoms, and violent behaviour, was estimated using logistic regression.

There was evidence of recent alcohol or drug use in 64.5% of detentions. Violent incidents occurred in 12.6% of detentions. Psychotic symptoms increased the odds of violence by 4.0 [95% confidence intervals (CI) 2.2–7.4; p < 0.0001]. Cannabinoid use combined with psychotic symptoms increased the odds of violence further [odds ratios (OR) 7.1, 95% CI 3.7–13.6; p < 0.0001]. Recent use of cannabinoids with stimulants but without psychotic symptoms was also associated with increased odds of violence (OR 3.3, 95% CI 1.4–7.9; p < 0.0001).

In the emergency setting, patients who have recently used cannabinoids and exhibit psychotic symptoms are at higher risk of violent behaviour. Those who have used both stimulants and cannabinoids without psychotic symptoms may also be at increased risk. De-escalation protocols in emergency healthcare settings should account explicitly for substance use.

Major depressive disorder (MDD) is accompanied by alterations in grey matter volume. However, the biological processes associated with regional structural perturbations remain elusive.

We applied integrative omics analysis to investigate specialized transcriptome signatures and translational determinants associated with regional grey matter variations in 2737 MDD patients relative to 3098 controls by summarizing the results from gene co-expression network analysis of Allen human brain transcriptome profiles in six donors, enrichment analysis of gene-sets and cellular structure from rodents and mediation analysis of BrainSpan proteome profile in six donors.

We found convergent alterations of grey matter volume in MDD were associated with transcriptome profiles enriched for synaptic transmission, metabolism, immune processes and transmembrane transport. Genes with abnormal expression in post-mortem tissue in MDD were also associated with transcriptome signatures. Further gene co-expression network and enrichment analysis of MDD-related genes in these signatures revealed the modules with higher neuronal expression were enriched in the medial temporal cortex and temporo-parietal junction with genes differentially associated with neuronal development and metabolism. Also, the modules with higher non-neuronal (e.g. astrocyte and oligodendrocyte) expression were concentrated in the rostral and dorsal anterior cingulate cortex and were separately associated with immune response and transmembrane transport. Moreover, proteins as the gene expression products mediated the association between transcriptome signatures and brain volume changes in the visual and dorsolateral prefrontal cortex.

Our multidimensional analyses offer a novel approach to detect specific biological pathways that capture regional structural variations in MDD, which suggests structural endophenotypes associated with MDD.