Polygenic liability for schizophrenia and childhood adversity influences daily‐life emotion dysregulation and psychosis proneness

Pries, Lotta-Katrin; Klingenberg, Boris; Menne-Lothmann, Claudia; Decoster, Jeroen; Winkel, Ruud van; Collip, Dina; Delespaul, Philippe; Hert, Marc De; Derom, Cathérine; Thiery, Evert; Jacobs, Nele; Wichers, Marieke; Cinar, Ozan; Lin, Bochao; Luykx, Jurjen J.; Rutten, Bart P. F.; Os, Jim van; Gülöksüz, Sinan

doi:10.1111/acps.13158

Cited by 40 publications

(41 citation statements)

References 78 publications

(82 reference statements)

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“…A recent study from the 1966 Northern Finland Birth Cohort showed that high birth weight, a risk factor for familial schizophrenia in this cohort, increased the association between PRS-SCZ and social anhedonia, suggesting a gene–environment interaction (Liuhanen et al ., 2018). Similarly, a study conducted in a general population twin cohort demonstrated that while PRS-SCZ was not independently associated with affective dysregulation and psychosis proneness, PRS-SCZ increased sensitivity to the effect of childhood adversities on affective dysregulation and psychosis proneness (Pries et al ., 2020 a ). Although not a direct test of gene–environment interaction, a study of healthy young males assessed during their compulsory military service showed that there was a negative association between PRS-SCZ and positive schizotypy at military induction (stressful condition) but not at follow-up, providing further support for the key role of environment in the phenotypic expression of schizotypy traits (Hatzimanolis et al ., 2018).…”

Section: Discussionmentioning

confidence: 99%

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum

Pries

Ferro

et al. 2020

Epidemiol Psychiatr Sci

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Aims Psychosis spectrum disorder has a complex pathoetiology characterised by interacting environmental and genetic vulnerabilities. The present study aims to investigate the role of gene–environment interaction using aggregate scores of genetic (polygenic risk score for schizophrenia (PRS-SCZ)) and environment liability for schizophrenia (exposome score for schizophrenia (ES-SCZ)) across the psychosis continuum. Methods The sample consisted of 1699 patients, 1753 unaffected siblings, and 1542 healthy comparison participants. The Structured Interview for Schizotypy-Revised (SIS-R) was administered to analyse scores of total, positive, and negative schizotypy in siblings and healthy comparison participants. The PRS-SCZ was trained using the Psychiatric Genomics Consortiums results and the ES-SCZ was calculated guided by the approach validated in a previous report in the current data set. Regression models were applied to test the independent and joint effects of PRS-SCZ and ES-SCZ (adjusted for age, sex, and ancestry using 10 principal components). Results Both genetic and environmental vulnerability were associated with case-control status. Furthermore, there was evidence for additive interaction between binary modes of PRS-SCZ and ES-SCZ (above 75% of the control distribution) increasing the odds for schizophrenia spectrum diagnosis (relative excess risk due to interaction = 6.79, [95% confidential interval (CI) 3.32, 10.26], p < 0.001). Sensitivity analyses using continuous PRS-SCZ and ES-SCZ confirmed gene–environment interaction (relative excess risk due to interaction = 1.80 [95% CI 1.01, 3.32], p = 0.004). In siblings and healthy comparison participants, PRS-SCZ and ES-SCZ were associated with all SIS-R dimensions and evidence was found for an interaction between PRS-SCZ and ES-SCZ on the total (B = 0.006 [95% CI 0.003, 0.009], p < 0.001), positive (B = 0.006 [95% CI, 0.002, 0.009], p = 0.002), and negative (B = 0.006, [95% CI 0.004, 0.009], p < 0.001) schizotypy dimensions. Conclusions The interplay between exposome load and schizophrenia genetic liability contributing to psychosis across the spectrum of expression provide further empirical support to the notion of aetiological continuity underlying an extended psychosis phenotype.

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Section: Discussionmentioning

confidence: 99%

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum

Pries

Ferro

et al. 2020

Epidemiol Psychiatr Sci

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“…For our primary analyses, we used the P -threshold of < .05, as this threshold explained most variation in the phenotype in the Psychiatric Genomics Consortium analysis 41 and was previously shown to perform well for the current phenotype of SF-36 mental health. 42 For details on the genotyping, see the supplementary material . Statistical analyses were adjusted for 3 principal components.…”

Section: Methodsmentioning

confidence: 99%

Do Current Measures of Polygenic Risk for Mental Disorders Contribute to Population Variance in Mental Health?

Marsman

Pries

Have

et al. 2020

Schizophrenia Bulletin

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The polygenic risk score (PRS) allows for quantification of the relative contributions of genes and environment in population-based studies of mental health. We analyzed the impact of transdiagnostic schizophrenia PRS and measures of familial and environmental risk on the level of and change in general mental health (Short-Form-36 mental health) in the Netherlands Mental Health Survey and Incidence Study-2 general population sample, interviewed 4 times over a period of 9 years, yielding 8901 observations in 2380 individuals. Schizophrenia PRS, family history, somatic pain, and a range of environmental risks and social circumstances were included in the regression model of level of and change in mental health. We calculated the relative contribution of each (group of) risk factor(s) to the variance in (change in) mental health. In the combined model, familial and environmental factors explained around 17% of the variance in mental health, of which around 5% was explained by age and sex, 30% by social circumstances, 16% by pain, 22% by environmental risk factors, 24% by family history, and 3% by PRS for schizophrenia (PRS-SZ). Results were similar, but attenuated, for the model of mental health change over time. Childhood trauma and gap between actual and desired social status explained most of the variance. PRS for bipolar disorder, cross-disorder, and depression explained less variance in mental health than PRS-SZ. Polygenic risk for mental suffering, derived from significance-testing in massive samples, lacks impact in analyses focusing on prediction in a general population epidemiological setting. Social-environmental circumstances, particularly childhood trauma and perceived status gap, drive most of the attributable variation in population mental health.

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“…24,42 We used a composite stress measure (row mean) consisting of items assessing eventrelated, activity-related and social stress to avoid multiple testing. 70,71 Event-related stress: Participants were asked to rate the most important event since the last beep on a 7-point Likert scale ranging from -3 (very unpleasant) to 3 (very pleasant). We recoded this item so that higher ratings indicate higher levels of stress (-3 recoded as 7 and 3 recoded as 1).…”

Section: Discussionmentioning

confidence: 99%

“…In line with previous studies we aggregated event-related, activity-related and social stress to a composite stress measure for each beep to reduce multiple testing. 70,71 Still, type I error should be taken into account when interpreting the results.…”

Section: Methodological Considerations/ Limitationsmentioning

confidence: 99%

Stress reactivity as a putative mechanism linking childhood trauma with clinical outcomes in individuals at ultra-high risk for psychosis: Findings from the EU-GEI High Risk Study

Pätzold¹,

Myin-Germeys²,

Schick³

et al. 2020

Preprint

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Childhood trauma is associated with an elevated risk for psychosis, but the psychological mechanisms involved remain largely unclear. This study aimed to investigate emotional and psychotic stress reactivity in daily life as a putative mechanism linking childhood trauma and clinical outcomes in individuals at ultra-high risk (UHR) for psychosis. Experience sampling methodology was used to measure momentary stress, affect and psychotic experiences in the daily life of N=79 UHR individuals in the EU-GEI High Risk study. The Childhood Trauma Questionnaire was used to assess self-reported childhood trauma. Clinical outcomes were assessed at baseline, 1- and 2-year follow-up. The association of stress with positive (β=-0.14, P=.010) and negative affect (β=0.11, P=.020) was modified by transition status such that stress reactivity was greater in individuals who transitioned to psychosis. Moreover, the association of stress with negative affect (β=0.06, P=.019) and psychotic experiences (β=0.05, P=.037) was greater in individuals exposed to high vs. low levels of childhood trauma. We also found evidence that decreased positive affect in response to stress was associated with reduced functioning at 1-year follow-up (B=6.29, P=.034). In addition, there was evidence that the association of childhood trauma with poor functional outcomes was mediated by stress reactivity (e.g. Bindirect effect =-2.13, P=.026), but no evidence that stress reactivity mediated the association between childhood trauma and transition (e.g. Bindirect effect=0.14, P=.506). Emotional and psychotic stress reactivity may be potential mechanisms linking childhood trauma with clinical outcomes in UHR individuals.

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Polygenic liability for schizophrenia and childhood adversity influences daily‐life emotion dysregulation and psychosis proneness

Cited by 40 publications

References 78 publications

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum

Examining the independent and joint effects of genomic and exposomic liabilities for schizophrenia across the psychosis spectrum

Do Current Measures of Polygenic Risk for Mental Disorders Contribute to Population Variance in Mental Health?

Stress reactivity as a putative mechanism linking childhood trauma with clinical outcomes in individuals at ultra-high risk for psychosis: Findings from the EU-GEI High Risk Study

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