Polygenic risk, familial liability and stress reactivity in psychosis: an experience sampling study

Abstract

Background 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. Methods 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. Results 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. Conclusions 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.

Family environment and polygenic risk in the bipolar high‐risk context

“…That being said, some youth in our study who experienced high levels of conflict, rigidity, and low warmth may conceivably be experiencing FE that overlaps with maltreatment, which has been shown to have detrimental effects on health over the life course (Lippard & Nemeroff, 2020;Palmier-Claus et al, 2016;Stapp, Williams et al, 2020). Taken together, a small but converging body of evidence is consistent with the liability threshold model, in which lower genetic burden, in the presence of environmental stress (i.e., multifactorial), is associated with increased mood and psychotic disorder liability (Schick et al, 2022;Tonini et al, 2022). These findings are also somewhat consistent with studies demonstrating the importance of early adversity and parentchild relationship quality on differential stress responsivity and mood (Rudolph et al, 2020;Shakiba et al, 2020).…”

Thoughts falling apart: disorganized schizotypy specifically predicts both psychotic- and stress-reactivity in daily life

“…In line with this, individuals with a high risk of psychosis show increased distress-induced psychotic reactivity (i.e., behavioral sensitization (Collip et al, 2008)) compared to healthy controls (Klippel et al, 2017;Reininghaus et al, 2016). Additionally, a polygenic risk score for schizophrenia (PRS) predicted a stronger association between stress and psychotic experiences in healthy controls (Schick et al, 2022). However, in unaffected siblings of individuals diagnosed with schizophrenia, a higher PRS was related to reduced psychotic reactivity.…”

Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study

“…( 2016 ) found similar results: the PRS-SZ and childhood trauma history predicted both psychosis status, without interaction between these factors. To our knowledge, two other studies have looked for such interactions, that found a significant GxE interaction between the PRS-SZ and childhood trauma (Pries et al ., 2020 b ; Schick et al ., 2022 ). Another study using the PRS-SZ and conducted in adults looked for interaction with other environmental factors, i.e.…”

“…Two studies assessed the interaction between PRS-SZ and childhood trauma, but only one reported a significant interaction (Pries et al ., 2020 b ), whereas the other showed an independent (additive) effects of the PRS-SZ and the trauma without significant interaction (Trotta et al ., 2016 ). A recent study assessing the associations between momentary stress and subclinical psychotic symptoms showed that higher levels of PRS-SZ were associated with a higher intensity of symptoms after a momentary stress among controls (Schick et al ., 2022 ). In the fourth study, the authors assessed the interaction between PRS-SZ and smoking status, but did not show significant association (García-González et al ., 2020 ).…”