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. 2023 Apr;53(5):1970-1978.
doi: 10.1017/S0033291721003664. Epub 2021 Sep 29.

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study

Monica Aas  1   2 , Luis Alameda  1   3   4   5 , Marta Di Forti  6 , Diego Quattrone  6 , Paola Dazzan  1 , Antonella Trotta  1 , Laura Ferraro  7 , Victoria Rodriguez  1 , Evangelos Vassos  6 , Pak Sham  8 , Giada Tripoli  1   7 , Caterina La Cascia  7 , Daniele La Barbera  7 , Ilaria Tarricone  9 , Roberto Muratori  10 , Domenico Berardi  11 , Antonio Lasalvia  12 , Sarah Tosato  12 , Andrei Szöke  13 , Pierre-Michel Llorca  14 , Celso Arango  15 , Andrea Tortelli  16 , Lieuwe de Haan  17 , Eva Velthorst  17   18 , Julio Bobes  19 , Miguel Bernardo  20 , Julio Sanjuán  21 , Jose Luis Santos  22 , Manuel Arrojo  23 , Cristina Marta Del-Ben  24 , Paulo Rossi Menezes  25 , Jean-Paul Selten  26 , Peter B Jones  27 , Hannah E Jongsma  28 , James B Kirkbride  28 , Bart P F Rutten  29 , Jim van Os  1   29 , Charlotte Gayer-Anderson  30 , Robin M Murray  1 , Craig Morgan  30
Affiliations

Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study

Monica Aas et al. Psychol Med. 2023 Apr.

Abstract

Background: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone.

Methods: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case-control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS - ORexposure - ORPRS + 1] with adjustment for potential confounders.

Results: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) -1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI -6.25 to 20.88).

Conclusions: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates.

Keywords: Childhood trauma; first-episode psychosis; interaction contrast ratio; polygenic risk; schizophrenia; synergistic effects.

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Conflict of interest statement

Dr Arango has been a consultant to or has received honoraria or grants from Acadia, Angelini, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. Dr Jones has consulted for Ricordatti and Janssen. Prof. Llorca has been a consultant to or has received honoraria or grants from Gedeon Richter, Janssen, Lundbeck, Otsuka, Roche, Sage, Sanofi and Teva. Prof. Paola Dazzan has received speaker's fees from Otsuka, Janssen and Lundbeck. Dr Bernardo has been a consultant to, received grant/research support or honoraria from, or been on the speakers/advisory board of ABBiotics, Adamed, Angelini, Casen Recordati, Janssen-Cilag, Menarini, Rovi and Takeda. The remaining authors declare no potential conflicts of interest.

Figures

Fig. 1.
Fig. 1.
Additive effects of childhood adverse events and polygenic risk on case–control status.
See this image and copyright information in PMC

References

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