Prior work has suggested that genetic influences on major depressive disorder (MDD) may be activated by the experience of negative life events. However, it is unclear whether these results persist when controlling for the possibility of confounding active gene–environment correlations (rGE).

We examined a sample of 1230 adopted and biological siblings between the ages of 10 and 20 years from the Sibling Interaction and Behavior Study. MDD was measured via a lifetime DSM-IV symptom count. Number of deaths experienced served as our environmental risk experience. Because this variable is largely independent of the individual's choices/behaviors, we were able to examine gene–environment interactions while circumventing possible rGE confounds.

Biometric analyses revealed pronounced linear increases in the magnitude of genetic influences on symptoms of MDD with the number of deaths experienced, such that genetic influences were estimated to be near-zero for those who had experienced no deaths but were quite large in those who had experienced two or more deaths (i.e. accounting for roughly two-thirds of the phenotypic variance). By contrast, shared and non-shared environmental influences on symptoms of MDD were not meaningfully moderated by the number of deaths experienced.

Such results constructively replicate prior findings of genetic moderation of depressive symptoms by negative life events, thereby suggesting that this effect is not a function of active rGE confounds. Our findings are thus consistent with the notion that exposure to specific negative life events may serve to activate genetic risk for depression during adolescence.

Many studies aggregate prescription opioid misuse (POM) and heroin use into a single phenotype, but emerging evidence suggests that their genetic and environmental influences may be partially distinct.

In total, 7164 individual twins (84.12% complete pairs; 59.81% female; mean age = 30.58 years) from the Australian Twin Registry reported their lifetime misuse of prescription opioids, stimulants, and sedatives, and lifetime use of heroin, cannabis, cocaine/crack, illicit stimulants, hallucinogens, inhalants, solvents, and dissociatives via telephone interview. Independent pathway models (IPMs) and common pathway models (CPMs) partitioned the variance of drug use phenotypes into general and drug-specific genetic (a), common environmental (c), and unique environmental factors (e).

An IPM with one general a and one general e factor and a one-factor CPM provided comparable fit to the data. General factors accounted for 55% (a = 14%, e = 41%) and 79% (a = 64%, e = 15%) of the respective variation in POM and heroin use in the IPM, and 25% (a = 12%, c = 8%, e = 5%) and 80% (a = 38%, c = 27%, e = 15%) of the respective variation in POM and heroin use in the CPM. Across both models, POM emerged with substantial drug-specific genetic influence (26–39% of total phenotypic variance; 69–74% of genetic variance); heroin use did not (0% of total phenotypic variance; 0% of genetic variance in both models). Prescription sedative misuse also demonstrated significant drug-specific genetic variance.

Genetic variation in POM, but not heroin use, is predominantly drug-specific. Misuse of prescription medications that reduce experiences of subjective distress may be partially influenced by sources of genetic variation separate from illicit drug use.

Social capital is thought to represent an environmental factor associated with the risk of psychotic disorder (PD). This study aims to investigate the association between neighbourhood-level social capital and clinical transitions within the spectrum of psychosis.

In total, 2175 participants, representative of a community-based population, were assessed twice (6 years apart) to determine their position within an extended psychosis spectrum: no symptoms, subclinical psychotic experiences (PE), clinical PE, PD. A variable representing change between baseline (T1) and follow-up (T2) assessment was constructed. Four dimensions of social capital (informal social control, social disorganisation, social cohesion and trust, cognitive social capital) were assessed at baseline in an independent sample, and the measures were aggregated to the neighbourhood level. Associations between the variable representing psychosis spectrum change from T1 to T2 and the social capital variables were investigated.

Lower levels of neighbourhood-level social disorganisation, meaning higher levels of social capital, reduced the risk of clinical PE onset (OR 0.300; z = −2.75; p = 0.006), persistence of clinical PE (OR 0.314; z = −2.36; p = 0.018) and also the transition to PD (OR 0.136; z = −2.12; p = 0.034). The other social capital variables were not associated with changes from T1 to T2.

Neighbourhood-level social disorganisation may be associated with the risk of psychosis expression. Whilst replication of this finding is required, it may point to level of social disorganisation as a public health target moderating population psychosis risk.

Maternal suicide attempts are associated with adverse psychosocial outcomes in children, but the association with chronic morbidity is poorly understood. We examined the relationship between maternal suicide attempt and risk of hospitalization for potentially preventable conditions in offspring.

We analyzed a longitudinal cohort of 1 032 210 children born in Quebec, Canada between 2006 and 2019. The main exposure measure was maternal suicide attempt before or during pregnancy. Outcomes included child hospitalizations for potentially preventable conditions, including infectious diseases, dental caries, atopy, and injury up to 14 years after birth. We used adjusted Cox proportional hazards regression models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of maternal suicide attempt with risk of hospitalization for these outcomes.

Compared with no suicide attempt, children whose mothers attempted suicide had an increased risk of hospitalization for infectious diseases (HR 1.11, 95% CI 1.06–1.16), dental caries (HR 1.31, 95% CI 1.15–1.48), and injury (HR 1.16, 95% CI 1.03–1.31). Risk of hospitalization for any of these outcomes was greater if mothers attempted suicide by hanging (HR 1.46, 95% CI 1.22–1.75), had their first attempt between the age of 25 and 34 years (HR 1.27, 95% CI 1.13–1.42), and had 3 or more attempts (HR 1.56, 95% CI 1.27–1.91). Maternal suicide attempts were more strongly associated with child hospitalization before 10 years of age.

Children whose mothers have a history of suicide attempt have an elevated risk of hospitalization for potentially preventable conditions.

Psychosis expression in the general population may reflect a behavioral manifestation of the risk for psychotic disorder. It can be conceptualized as an interconnected system of psychotic and affective experiences; a so-called ‘symptom network’. Differences in demographics, as well as exposure to adversities and risk factors, may produce substantial heterogeneity in symptom networks, highlighting potential etiological divergence in psychosis risk.

To explore this idea in a data-driven way, we employed a novel recursive partitioning approach in the 2007 English National Survey of Psychiatric Morbidity (N = 7242). We sought to identify ‘network phenotypes’ by explaining heterogeneity in symptom networks through potential moderators, including age, sex, ethnicity, deprivation, childhood abuse, separation from parents, bullying, domestic violence, cannabis use, and alcohol.

Sex was the primary source of heterogeneity in symptom networks. Additional heterogeneity was explained by interpersonal trauma (childhood abuse and domestic violence) in women and domestic violence, cannabis use, ethnicity in men. Among women, especially those exposed to early interpersonal trauma, an affective loading within psychosis may have distinct relevance. Men, particularly those from minority ethnic groups, demonstrated a strong network connection between hallucinatory experiences and persecutory ideation.

Symptom networks of psychosis expression in the general population are highly heterogeneous. The structure of symptom networks seems to reflect distinct sex-related adversities, etiologies, and mechanisms of symptom-expression. Disentangling the complex interplay of sex, minority ethnic group status, and other risk factors may help optimize early intervention and prevention strategies in psychosis.

Working memory (WM) deficits are seen as a core deficit in schizophrenia, implicated in the broad cognitive impairment seen in the illness. Here we examine the impact of WM storage of a single item on the operation of other cognitive systems.

We studied 37 healthy controls (HCS) and 43 people with schizophrenia (PSZ). Each trial consisted of a sequence of two potential target stimuli, T1 and T2. T1 was a letter presented for 100 ms. After delays of 100–800 ms, T2 was presented. T2 was a 1 or a 2 and required a speeded response. In one condition, subjects were instructed to ignore T1 but respond to T2. In another condition, they were required to report T1 after making their speeded response to T2 (i.e. to make a speeded T2 response while holding T1 in WM).

PSZ were dramatically slowed at responding to T2 when T1 was held in WM. A repeated measures ANOVA yielded main effects of group, delay, and condition with a group by condition interaction (p's < 0.001). Across delays, the slowing of the T2 response when required to hold T1 in memory, relative to ignoring T1, was nearly 3 times higher in PSZ than HCS (633 v. 219 ms).

Whereas previous studies have focused on reduced storage capacity, the present study found that PSZ are impaired at performing tasks while they are successfully maintaining a single item in WM. This may play a role in the broad cognitive impairment seen in PSZ.