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.

Many studies report an ethnic density effect whereby psychosis incidence among ethnic minority groups is higher in low co-ethnic density areas. It is unclear whether an equivalent density effect applies with other types of socioeconomic disadvantages.

We followed a population cohort of 2 million native Danes comprising all those born on 1st January 1965, or later, living in Denmark on their 15th birthday. Socioeconomic disadvantage, based on parents' circumstances at age 15 (low income, manual occupation, single parent and unemployed), was measured alongside neighbourhood prevalence of these indices.

Each indicator was associated with a higher incidence of non-affective psychosis which remained the same, or was slightly reduced, if neighbourhood levels of disadvantage were lower. For example, for individuals from a low-income background there was no difference in incidence for those living in areas where a low-income was least common [incidence rate ratio (IRR) 1.01; 95% confidence interval (CI) 0.93–1.10 v. those in the quintile where a low income was most common. Typically, differences associated with area-level disadvantage were the same whether or not cohort members had a disadvantaged background; for instance, for those from a manual occupation background, incidence was lower in the quintile where this was least v. most common (IRR 0.83; 95% CI 0.71–0.97), as it was for those from a non-manual background (IRR 0.77; 95% CI 0.67–0.87).

We found little evidence for group density effects in contrast to previous ethnic density studies. Further research is needed with equivalent investigations in other countries to see if similar patterns are observed.

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.

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.

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.

Extensive research has focused on the potential benefits of education on various mental and physical health outcomes. However, whether the associations reflect a causal effect is harder to establish.

To examine associations between educational duration and specific aspects of well-being, anxiety and mood disorders, and cardiovascular health in a sample of European Ancestry UK Biobank participants born in England and Wales, we apply four different causal inference methods (a natural policy experiment leveraging the minimum school-leaving age, a sibling-control design, Mendelian randomization [MR], and within-family MR), and assess if the methods converge on the same conclusion.

A comparison of results across the four methods reveals that associations between educational duration and these outcomes appears predominantly to be the result of confounding or bias rather than a true causal effect of education on well-being and health outcomes. Although we do consistently find no associations between educational duration and happiness, family satisfaction, work satisfaction, meaning in life, anxiety, and bipolar disorder, we do not find consistent significant associations across all methods for the other phenotypes (health satisfaction, depression, financial satisfaction, friendship satisfaction, neuroticism, and cardiovascular outcomes).

We discuss inconsistencies in results across methods considering their respective limitations and biases, and additionally discuss the generalizability of our findings in light of the sample and phenotype limitations. Overall, this study strengthens the idea that triangulation across different methods is necessary to enhance our understanding of the causal consequences of educational duration.

The utilisation of massed therapy for treating posttraumatic stress disorder (PTSD) is gaining strength, especially prolonged exposure. However, it is unknown whether massed prolonged exposure (MPE) is non-inferior to standard prolonged exposure (SPE) protocols in the long term. The current study aimed to assess whether MPE was non-inferior to SPE at 12 months post-treatment, and to ascertain changes in secondary measure outcomes.

A multi-site non-inferiority randomised controlled trial (RCT) compared SPE with MPE in 12 clinics. The primary outcome was PTSD symptom severity (CAPS-5) at 12 months post-treatment commencement. Secondary outcome measures included symptoms of depression, anxiety, anger, disability, and quality of life at 12 weeks and 12 months post-treatment commencement. Outcome assessors were blinded to treatment allocation. The intention-to-treat sample included 138 Australian military members and veterans and data were analysed for 134 participants (SPE = 71, MPE = 63).

Reductions in PTSD severity were maintained at 12 months and MPE remained non-inferior to SPE. Both treatment groups experienced a reduction in depression, anxiety, anger, and improvements in quality of life at 12 weeks and 12 months post-treatment commencement. Treatment effects for self-reported disability in the SPE group at 12 weeks were not maintained, with neither group registering significant effects at 12 months.

The emergence of massed protocols for PTSD is an important advancement. The current study provides RCT evidence for the longevity of MPE treatment gains at 12 months post-treatment commencement and demonstrated non-inferiority to SPE. Promisingly, both treatments also significantly reduced the severity of comorbid symptoms commonly occurring alongside PTSD.

Tightly connected symptom networks have previously been linked to treatment resistance, but most findings come from small-sample studies comparing single responder v. non-responder networks. We aimed to estimate the association between baseline network connectivity and treatment response in a large sample and benchmark its prognostic value against baseline symptom severity and variance.

N = 40 518 patients receiving treatment for depression in routine care in England from 2015–2020 were analysed. Cross-sectional networks were constructed using the Patient Health Questionnaire-9 (PHQ-9) for responders and non-responders (N = 20 259 each). To conduct parametric tests investigating the contribution of PHQ-9 sum score mean and variance to connectivity differences, networks were constructed for 160 independent subsamples of responders and non-responders (80 each, n = 250 per sample).

The baseline non-responder network was more connected than responders (3.15 v. 2.70, S = 0.44, p < 0.001), but effects were small, requiring n = 750 per group to have 85% power. Parametric analyses revealed baseline network connectivity, PHQ-9 sum score mean, and PHQ-9 sum score variance were correlated (r = 0.20–0.58, all p < 0.001). Both PHQ-9 sum score mean (β = −1.79, s.e. = 0.07, p < 0.001), and PHQ-9 sum score variance (β = −1.67, s.e. = 0.09, p < 0.001) had larger effect sizes for predicting response than connectivity (β = −1.35, s.e. = 0.12, p < 0.001). The association between connectivity and response disappeared when PHQ-9 sum score variance was accounted for (β = −0.28, s.e. = 0.19, p = 0.14). We replicated these results in patients completing longer treatment (8–12 weeks, N = 22 952) and using anxiety symptom networks (N = 70 620).

The association between baseline network connectivity and treatment response may be largely due to differences in baseline score variance.