Translational Psychiatry (Oct 2024)

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

  • Luis Alameda,
  • Victoria Rodriguez,
  • Marta Di Forti,
  • Edoardo Spinazzola,
  • Giulia Trotta,
  • Celso Arango,
  • Manuel Arrojo,
  • Miguel Bernardo,
  • Julio Bobes,
  • Lieuwe de Haan,
  • Cristina Marta Del-Ben,
  • Charlotte Gayer-Anderson,
  • Lucia Sideli,
  • Peter B. Jones,
  • James B. Kirkbride,
  • Caterina La Cascia,
  • Giada Tripoli,
  • Laura Ferraro,
  • Daniele La Barbera,
  • Antonio Lasalvia,
  • Sarah Tosato,
  • Pierre-Michel Llorca,
  • Paulo Rossi Menezes,
  • Jim van Os,
  • Bart P. Rutten,
  • Jose Luis Santos,
  • Julio Sanjuán,
  • Jean-Paul Selten,
  • Andrei Szöke,
  • Ilaria Tarricone,
  • Andrea Tortelli,
  • Eva Velthorst,
  • Hannah E. Jongsma,
  • Evangelos Vassos,
  • Diego Quattrone,
  • Robin M. Murray,
  • Monica Aas

DOI
https://doi.org/10.1038/s41398-024-03149-7
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 7

Abstract

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Abstract 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.