There is evidence for a polygenic contribution to psychosis. One targetable mechanism through which polygenic variation may impact on individuals and interact with the social environment is stress sensitization, characterized by elevated reactivity to minor stressors in daily life. The current study aimed to investigate whether stress reactivity is modified by polygenic risk score for schizophrenia (PRS) in cases with enduring non-affective psychotic disorder, first-degree relatives of cases, and controls.

We used the experience sampling method to assess minor stressors, negative affect, positive affect and psychotic experiences in 96 cases, 79 first-degree relatives, i.e. siblings, and 73 controls at wave 3 of the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Genome-wide data were collected at baseline to calculate PRS.

We found that associations of momentary stress with psychotic experiences, but not with negative and positive affect, were modified by PRS and group (all pFWE<0.001). In contrast to our hypotheses, siblings with high PRS reported less intense psychotic experiences in response to momentary stress compared to siblings with low PRS. No differences in magnitude of these associations were observed in cases with high v. low level of PRS. By contrast, controls with high PRS showed more intense psychotic experiences in response to stress compared to those with low PRS.

This tentatively suggests that polygenic risk may operate in different ways than previously assumed and amplify reactivity to stress in unaffected individuals but operate as a resilience factor in relatives by attenuating their stress reactivity.

The attributional theory of paranoia suggests that paranoid beliefs may protect individuals from low self-esteem and distress (Bentall et al. 2001). The current study tested this theory by investigating a hypothesis that paranoid beliefs in combination with low perceived deservedness of persecution (poor-me beliefs) confer protection against the distress caused by social but not activity related stress.

Paranoid symptoms, perceived deservedness of persecution, self-esteem, mood, and stress levels of individuals diagnosed with schizophrenia spectrum disorders (N = 91) and healthy controls (N = 52) were assessed in the context of daily life using the experience sampling method.

Individuals holding poor-me beliefs (poor-me individuals) showed blunted sensitivity to social but not activity stress. In contrast, individuals holding paranoid beliefs in combination with high perceived deservedness of persecution (bad-me individuals) showed heightened sensitivity to social stress. No consistent differences in reactions to activity stress emerged. Although both poor-me and bad-me individuals reported low self-esteem, this disturbance was particularly characteristic of bad-me individuals.

The results suggest that poor-me paranoid beliefs may protect individuals against the distress associated with unpleasant social situations. The specificity of reactions to social stress is discussed in the context of wider literature. Future directions for research are suggested.

Childhood trauma is associated with higher risk for mental disorders, including psychosis. Heightened sensitivity to social stress may be a mechanism. This virtual reality study tested the effect of childhood trauma on level of paranoid ideations and distress in response to social stress, in interaction with psychosis liability and level of social stress exposure.

Seventy-five individuals with higher psychosis liability (55 with recent onset psychotic disorder and 20 at ultra-high risk for psychosis) and 95 individuals with lower psychosis liability (42 siblings and 53 controls) were exposed to a virtual café in five experiments with 0–3 social stressors (crowded, other ethnicity and hostility). Paranoid ideation was measured after each experiment. Subjective distress was self-rated before and after experiments. Multilevel random regression analyses were used to test main effects of childhood trauma and interaction effects.

Childhood trauma was more prevalent in individuals with higher psychosis liability, and was associated with higher level of (subclinical) psychotic and affective symptoms. Individuals with a history of childhood trauma responded with more subjective distress to virtual social stress exposures. The effects of childhood trauma on paranoia and subjective distress were significantly stronger when the number of virtual environmental stressors increased. Higher psychosis liability increased the effect of childhood trauma on peak subjective distress and stress reactivity during experiments.

Childhood trauma is associated with heightened social stress sensitivity and may contribute to psychotic and affective dysregulation later in life, through a sensitized paranoid and stress response to social stressors.

Evidence has accumulated that implicates childhood trauma in the aetiology of psychosis, but our understanding of the putative psychological processes and mechanisms through which childhood trauma impacts on individuals and contributes to the development of psychosis remains limited. We aimed to investigate whether stress sensitivity and threat anticipation underlie the association between childhood abuse and psychosis.

We used the Experience Sampling Method to measure stress, threat anticipation, negative affect, and psychotic experiences in 50 first-episode psychosis (FEP) patients, 44 At-Risk Mental State (ARMS) participants, and 52 controls. Childhood abuse was assessed using the Childhood Trauma Questionnaire.

Associations of minor socio-environmental stress in daily life with negative affect and psychotic experiences were modified by sexual abuse and group (all pFWE < 0.05). While there was strong evidence that these associations were greater in FEP exposed to high levels of sexual abuse, and some evidence of greater associations in ARMS exposed to high levels of sexual abuse, controls exposed to high levels of sexual abuse were more resilient and reported less intense negative emotional reactions to socio-environmental stress. A similar pattern was evident for threat anticipation.

Elevated sensitivity and lack of resilience to socio-environmental stress and enhanced threat anticipation in daily life may be important psychological processes underlying the association between childhood sexual abuse and psychosis.

It is well known that the hypothalamic–pituitary–adrenal (HPA) axis is compromised in major depression and bipolar disorder. There is increasing evidence that subtle HPA abnormalities, such as elevated cortisol levels, precede the development of an affective disorder. Interpersonal stress is also associated with the development of affective disorders. The present study sought to determine whether interpersonal chronic and episodic stress moderated the relationship between cortisol levels in the natural environment and risk status, defined as having a parent with bipolar disorder.

Sixty-two offspring of parents with bipolar disorder (OBD) and 60 offspring with no family history of affective disorders (OFH−), aged 19.48 years (s.d.=3.38, range 14–28), completed interviews assessing mental disorders and chronic and episodic stress, and provided saliva samples over 3 days.

Regression analyses revealed that the OBD who experienced high interpersonal chronic stress displayed a larger cortisol rise following awakening than the OBD reporting low interpersonal chronic stress. The same relationship was also found for levels of non-interpersonal chronic stress. The OBD who reported experiencing severe interpersonal episodic stress exhibited higher levels of daytime cortisol than the OBD reporting interpersonal episodic stress of mild severity. Importantly, none of the above relationships were detected in the OFH−. Each of the interactions between family history of affective disorders and stress remained after controlling for age, gender and offspring lifetime affective disorders and current non-affective disorders.

A biological sensitivity to stress may underlie the susceptibility to affective disorders among the OBD.