Psychotic-like experiences (PLEs) are subclinical phenomena that often precede the onset of psychosis and occur in various mental disorders. Social determinants of psychosis and PLEs are important and have been operationalized within the social defeat (SD) hypothesis. The SD hypothesis posits that low social status and exposure to repeated humiliation can lead to imbalanced dopamine neuron activity, and thus increased risk of psychosis. We aimed to assess the role of dynamic interactions between SD components in shaping the occurrence of PLEs using a network analysis.

A total of 2241 non-clinical, young adults were assessed at baseline and invited for reassessment after a 6-month follow-up. Self-reports recording the occurrence of PLEs, aberrant salience (AS), depressive, and anxiety symptoms as well as SD characteristics (socioeconomic status, minority status, humiliation, perceived constraints, and domain control) were administered. Two networks were analyzed (the first one covering all baseline measures and the second one with the baseline SD components and follow-up measures of AS and psychopathology).

The SD components were not directly connected to the measures of PLEs in both networks. However, in both networks, SD components were connected to PLEs through a mediating effect of AS. Among SD components, humiliation had the highest bridge centrality across three predefined communities of variables (SD; depressive and anxiety symptoms; AS, and PLEs).

The findings indicate that SD might make individuals vulnerable to develop PLEs through the mediating effects of AS. Among SD components, humiliation might play the most important role in the development of PLEs.

The stressful minority position of transgender persons may result in a high risk of psychosis. Conflicting data suggest that the observed risk depends on setting of recruitment. We assessed the relative risk of non-affective psychotic disorder (NAPD) in a large, representative cohort of transgender persons.

This cohort was composed using: data on legal sex change from the Dutch population registry and data on dispensing of cross-sex hormones (route 1), and a registry of insurance claims from mental health care including persons with a diagnosis of gender identity disorder (DSM-IV) or gender dysphoria (DSM-5) (route 2). They were matched by sex at birth, calendar year and country of birth to controls from the general population. Transgender persons (N = 5564) and controls (N = 27 820), aged 16–60 years at 1 January 2011, were followed until the first insurance claim for NAPD in 2011–2019.

The incidence rate ratio (IRR) of NAPD for transgender persons selected exclusively through route 1 (N = 3859, IRR = 2.00, 95%-CI 1.52–2.63) was increased, but significantly lower than the IRRs for those selected exclusively through route 2 (N = 694, IRR = 22.15, 95%-CI 13.91–35.28) and for those found by both routes (N = 1011, IRR = 5.17, 95%-CI 3.57–7.49; p value for differences in IRR < 0.001).

This study supports the social defeat-hypothesis of NAPD. The results also show the presence of a substantial number of transgender persons with severe psychiatric problems who have not (yet) taken steps to gender-affirmative care.

Lesbian, bisexual, or gay individuals (LBGs) have an increased risk for mental health problems compared to heterosexuals, but this association has sparsely been investigated for psychotic disorders. The aim of this study was: (1) to examine whether LBG sexual orientation is more prevalent in individuals with a non-affective psychotic disorder (NAPD) than in people without a psychotic disorder; and if so, (2) to explore possible mediating pathways.

Sexual orientation was assessed in the 6-year follow-up assessment of the Dutch Genetic Risk and Outcome of Psychosis study (GROUP), a case–control study with 1547 participants (582 patients with psychotic disorder, 604 siblings, and 361 controls). Binary logistic regression analyses were used to calculate the risk of patients with a psychotic disorder being LBG, compared to siblings and controls. Perceived discrimination, history of bullying, childhood trauma (CT), and sexual identity disclosure were investigated as potential mediating variables.

The proportion of individuals with LBG orientation was 6.8% in patients (n = 40), 4.3% in siblings (n = 26), and 2.5% in controls (n = 10). The age- and gender-adjusted odds ratio of LBG for patients was 1.57 (95% CI 1.08–2.27; p = 0.019), compared to siblings and controls. Discrimination, bullying, and CT all partially mediated this association.

Adverse social experiences related to sexual minority status may increase the risk for NAPD. Sexual identity, behavior, and difficulties need more attention in everyday clinical practice.

Stressful life events play an important role in the aetiology of human mood disorders and are frequently modelled by chronic social defeat (SD) in rodents. Exploratory phenotype in rats is a stable trait that is likely related to inter-individual differences in reactivity to stress. The aim of the study was to confirm that low levels of exploratory activity (LE) are, in rodents, a risk factor for passive stress coping, and to clarify the role of medium (ME) and high (HE) exploratory disposition in the sensitivity to SD.

We examined the effect of SD on male Wistar rats with LE, ME, and HE activity levels as measured in the exploration box. After SD, the rats were evaluated in social preference, elevated zero maze, and open-field tests. Brain tissue levels of monoamines were measured by high-performance liquid chromatography.

Rats submitted to SD exhibited lower weight gain, higher sucrose consumption, showed larger stress-induced hyperthermia, lower levels of homovanillic acid in the frontal cortex, and higher levels of noradrenaline in the amygdala and hippocampus. Open-field, elevated zero maze, and social preference tests revealed the interaction between stress and phenotype, as only LE-rats were further inhibited by SD. ME-rats exhibited the least reactivity to stress in terms of changes in body weight, stress-induced hyperthermia, and sucrose intake.

Both low and high novelty-related activity, especially the former, are associated with elevated sensitivity to social stress. This study shows that both tails of a behavioural dimension can produce stress-related vulnerability.