Interaction between polygenic liability for schizophrenia and childhood adversity influences daily-life emotional dysregulation and psychosis proneness

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>The earliest stages of the pluripotent psychopathology on the pathway to psychotic disorders is represented by emotional dysregulation and subtle psychosis expression, which can be measured using the Ecological Momentary Assessment (EMA). However, it is not clear to what degree common genetic and environmental risk factors for psychosis contribute to variation in these early expressions of psychopathology.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>In this largest ever EMA study of a general population twin cohort including 593 adolescents and young adults between the ages of 15 and 35 years, we tested whether polygenic risk score for schizophrenia (PRS-S) interacts with childhood adversity (the Childhood Trauma Questionnaire score) and daily-life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress-sensitivity measures.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Both childhood adversity and daily-life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS-S was only associated with increased positive affect. No gene–environment correlation was detected. We have provided novel evidence for interaction effects between PRS-S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, 95% CI 0.01 to 0.13, <jats:italic>P</jats:italic> = 0.013), positive affect (b = −0.05, 95% CI −0.10 to −0.00, <jats:italic>P</jats:italic> = 0.043), and subtle psychosis expression (b = 0.11, 95% CI 0.03 to 0.19, <jats:italic>P</jats:italic> = 0.007)] and stress-sensitivity measures.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Exposure to childhood adversities, particularly in individuals with high PRS-S, is pleiotropically associated with emotional dysregulation and psychosis proneness.</jats:p></jats:sec>

Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia: results from the EUGEI study

“…A recent study demonstrated that intra‐uterine environment moderates the association between PRS‐SCZ and schizophrenia, and further revealed in the pathway analysis that genes involved in cellular stress response were the main drivers of the gene‐environment interaction. In our recent study of a general population twin cohort, we found evidence for positive interaction effects between PRS‐SCZ and exposure to childhood adversities to pleiotropically influence momentary emotional regulation and psychosis proneness. Further, a multimodal study combining genetics and imaging techniques reported that the association between PRS‐SCZ and cortical maturation in young male adults is moderated by early‐life exposure to cannabis.…”

Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene–environment interaction. The EUGEI study

“…Studies in healthy participants have shown inconsistent results (Hatzimanolis et al ., 2015; Jones et al ., 2016; Mistry et al ., 2017; Nivard et al ., 2017; Riglin et al ., 2017; Hatzimanolis et al ., 2018), one study notably reporting negative associations between polygenic risk and schizotypy, similar to the current results (Hatzimanolis et al ., 2018). Another recent general population study found a protective effect of PRS in that PRS predicted greater levels of positive affect in daily life (Pries et al ., 2019). It is likely that crucial variation may be occasioned by type of platform for genetic analysis and type of calculation of polygenic risk score.…”

TwinssCan — Gene-Environment Interaction in Psychotic and Depressive Intermediate Phenotypes: Risk and Protective Factors in a General Population Twin Sample

“…recent concepts of psychopathology acknowledge that the development of mental disorders is best understood when also looking at micro, complex, moment-to-moment dynamic changes (van Os, Verhagen et al, 2017). Therefore, Pries, Klingenberg et al (2019) investigated whether molecular genetic risk for schizophrenia interacted with CA and daily life stressors to influence moment-to-moment variations of mental states (i.e., negative affect, positive affect and subtle psychosis expression) and stress sensitivity. Molecular genetic vulnerability was expressed through polygenic risk score (PRS) for schizophrenia, which was calculated by summing weighted trait-alleles (EUGEI investigators, 2014;Purcell et al, 2009;Ripke et al, 2014).…”

“…They highlight the role of gene-environmental interaction focusing both on macro and micro levels of psychopathological changes, that is, changes occurring over month and years (Lecei et al, 2019;Pinckaers et al, 2019;Vaessen et al, 2017) and from moment to moment (Hasmi et al, 2017;Pries, Klingenberg et al, 2019;Vaessen et al, 2017), respectively. It is increasingly acknowledged that the development of pleiotropic psychopathology depends on a complex network of environmental exposures, that is, the exposome (Guloksuz et al, 2018;Pries, Lage Castellanos et al, 2019), and polygenic vulnerability (Guloksuz et al, 2019), which affect individuals throughout their life. Similarly, resilience is thought to dynamically change and can only be understood by prospectively evaluating different biological and psychological processes (Kalisch et al, 2017;Rutten et al, 2013;Snijders et al, 2018).…”

“…Similarly, resilience is thought to dynamically change and can only be understood by prospectively evaluating different biological and psychological processes (Kalisch et al, 2017;Rutten et al, 2013;Snijders et al, 2018). By benefitting from these recent developments, we recently calculated the exposome score (Pries, Lage-Castellanos et al, 2019), which we aim to apply to the TwinssCan population. Further, new features are under way.…”