Genetic susceptibility to the environment moderates the impact of childhood experiences on psychotic, depressive, and anxiety dimensions
BACKGROUND AND HYPOTHESIS: Gene-by-environment (GxE) studies in psychosis have exclusively focused on negative exposures. However, evidence supports the resilience-enhancing effect of positive factors on psychosis outcome. The Differential Susceptibility (DS) model proposes that common genetic varia...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Universitat Autònoma de Barcelona |
| Repositorio: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglés |
| OAI Identifier: | oai:ddd.uab.cat:318315 |
| Acceso en línea: | https://ddd.uab.cat/record/318315 https://dx.doi.org/urn:doi:10.1093/schbul/sbad130 |
| Access Level: | acceso abierto |
| Palabra clave: | Gene-Environment Interaction Schizotypy Psychosis Childhood adversity Risk factors Resilience Psychotic Disorders Schizotypal Personality Disorder |
| Sumario: | BACKGROUND AND HYPOTHESIS: Gene-by-environment (GxE) studies in psychosis have exclusively focused on negative exposures. However, evidence supports the resilience-enhancing effect of positive factors on psychosis outcome. The Differential Susceptibility (DS) model proposes that common genetic variants may confer not only disproportionate responsiveness to negative environments, but also greater sensitivity to positive, resilience-enhancing conditions. This study is the first to apply the DS model to the expression of subclinical psychosis, employing polygenic risk scores of environmental sensitivity (PRS-ES). PRS-ES were hypothesized to moderate, in a DS manner, associations between childhood adversity and psychosis, affective, and anxiety dimensions in young adults. An exploratory goal examined whether PRS for psychotic-like experiences (PRS-PLE) also showed DS patterns. STUDY DESIGN: PRS, schizotypy, PLE, depression, anxiety, and childhood adversity ratings were obtained for 197 nonclinical young adults. LEGIT software for testing competitive-confirmatory GxE models was employed. STUDY RESULTS: Results largely supported DS: Individuals high on PRS-ES showed increased subclinical psychosis, depression, and anxiety if they had experienced elevated childhood adversity, and lower symptoms if exposed to low levels of adversity as compared with those with low PRS-ES. Similarly, PRS-PLE moderated the effect of adversity on PLE, positive schizotypy, and depression following the DS model, but only PRS-ES moderation on PLE survived statistical correction. CONCLUSIONS: Our results suggest that genetic DS to the environment is relevant to psychosis, depression, and anxiety. Current debates on reconceptualization of genetic "risk" and resilience may benefit from this insight that support optimistic views on preventative efforts for early detection and intervention. |
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