The effect of polygenic risk score and childhood adversity on transdiagnostic symptom dimensions at first-episode psychosis: evidence for an affective pathway to psychosis

• Published in: Translational psychiatry 2024-10, Vol.14 (1), p.454-7, Article 454
• Main Authors: Alameda, Luis, Rodriguez, Victoria, Di Forti, Marta, Spinazzola, Edoardo, Trotta, Giulia, Arango, Celso, Arrojo, Manuel, Bernardo, Miguel, Bobes, Julio, de Haan, Lieuwe, Del-Ben, Cristina Marta, Gayer-Anderson, Charlotte, Sideli, Lucia, Jones, Peter B., Kirkbride, James B., La Cascia, Caterina, Tripoli, Giada, Ferraro, Laura, La Barbera, Daniele, Lasalvia, Antonio, Tosato, Sarah, Llorca, Pierre-Michel, Menezes, Paulo Rossi, van Os, Jim, Rutten, Bart P., Santos, Jose Luis, Sanjuán, Julio, Selten, Jean-Paul, Szöke, Andrei, Tarricone, Ilaria, Tortelli, Andrea, Velthorst, Eva, Jongsma, Hannah E., Vassos, Evangelos, Quattrone, Diego, Murray, Robin M., Aas, Monica
• Format: Article
• Language: English
• Subjects: 45; 45/23; 631/208/2489; 692/699/476/1799; Adolescent; Adult; Adverse childhood experiences; Adverse Childhood Experiences - psychology; Behavioral Sciences; Biological Psychology; Bipolar Disorder - genetics; Bipolar Disorder - psychology; Case-Control Studies; Childhood; Depressive Disorder, Major - genetics; Female; Gene-Environment Interaction; Genetic Predisposition to Disease; Genetic Risk Score; Humans; Male; Medicine; Medicine & Public Health; Middle Aged; Multifactorial Inheritance; Neurosciences; Pharmacotherapy; Psychiatry; Psychopathology; Psychosis; Psychotic Disorders - genetics; Psychotic Disorders - psychology; Risk Factors; Schizophrenia - genetics; Young Adult
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/s41398-024-03149-7

Childhood adversity is associated with various clinical dimensions in psychosis; however, how genetic vulnerability shapes the adversity-associated psychopathological signature is yet to be studied. We studied data of 583 First Episode Psychosis (FEP) cases from the EU-GEI FEP case-control study, including Polygenic risk scores for major depressive disorder (MDD-PRS), bipolar disorder (BD-PRS) and schizophrenia (SZ-PRS); childhood adversity measured with the total score of the Childhood Trauma Questionnaire (CTQ); and positive, negative, depressive and manic psychopathological domains from a factor model of transdiagnostic dimensions. Genes and environment interactions were explored as a departure from a multiplicative effect of PRSs and total CTQ on each dimension. Analyses were adjusted for age, sex, 10 PCA, site of recruitment and for medication. A childhood adversity and PRS multiplicative interaction was observed between A) the CTQ and MDD-PRS on the predominance of positive (β = 0.42, 95% CI = [0.155, 0.682], p = 0.004); and depressive (β = 0.33, 95% CI = [0.071, 0.591], p = 0.013) dimensions; B) between the CTQ and BD-PRS on the positive dimension (β = 0.45, 95% CI = [0.106, 0.798], p = 0.010), and C) with the CTQ and SZ-PRS on the positive dimension (β = −0.34, 95% CI = [−0.660, −0.015], p = 0.040). Bonferroni corrected p-value of significance was set at 0.0125. In conclusion, despite being underpowered, this study suggests that genetic liability for MDD and BD may have a moderating effect on the sensibility of childhood adversity on depressive and positive psychotic dimensions. This supports the hypothesis of an affective pathway to psychosis in those exposed to childhood adversity.