Monica Aas1,2, Frank Bellivier3,4,5,6, Francesco Bettella1, Chantal Henry7,8,9,10, Sebastien Gard6,11, Jean-Pierre Kahn6,12, Trine V Lagerberg2, Sofie R Aminoff1,2, Ingrid Melle1,2, Marion Leboyer6,7,8,13, Stéphane Jamain13, Ole A Andreassen1,2,10, Bruno Etain3,4,5,6,10. 1. NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. 2. Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. 3. Université Paris Diderot, Paris, France. 4. INSERM U1144, Faculté de Pharmacie de Paris, Université Paris Descartes, Université Paris Diderot, Université Sorbonne Paris Cité, Paris, France. 5. AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Département de Psychiatrie et de Médecine Addictologique, Paris, France. 6. Fondation Fondamental, Créteil, France. 7. AP-HP, Pôle de Psychiatry, DHU Pepsy, Hôpitaux Universitaires Henri Monody, Créteil, France. 8. Université Paris-Est-Creteil-Val de Marne, Créteil, France. 9. Institut Pasteur, Unité Perception et Mémoire, Centre National de la Recherche Scientifique, Paris, France. 10. ENBREC, European Network of Bipolar Research Expert Centres (ENBREC), Paris, France. 11. Centre Expert Trouble Bipolaire, Service de psychiatrie adulte, Hôpital Charles Perrens, Bordeaux, France. 12. Service de Psychiatrie et Psychologie Clinique, Centre Psychothérapique de Nancy - Université de Lorraine, Nancy, France. 13. Inserm, U955, Equipe Psychiatrie Translationnelle, Créteil, France.
Abstract
BACKGROUND: Childhood maltreatment is a well-known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD. METHOD: We assigned a BD-polygenic risk score (BD-PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment. RESULTS: Cases who reported more severe childhood maltreatment had a lower BD-PRS (rho = -0.12, P = .01), especially when considering emotional abuse (rho = -0.16, P = .001). An interaction between BD-PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD-PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms). CONCLUSION: Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.
BACKGROUND: Childhood maltreatment is a well-known risk factor for developing a more severe and complex form of bipolar disorders (BD). However, knowledge is scarce about the interactions between childhood maltreatment and underlying genetic vulnerability on the clinical expression of BD. METHOD: We assigned a BD-polygenic risk score (BD-PRS), calculated from the Psychiatric Genomics Consortium, to each individual in a sample of 402 cases with BD. The lifetime clinical expression of BD was characterized using structured interviews and patients completed the Childhood Trauma Questionnaire (CTQ) to assess the severity of childhood maltreatment. RESULTS: Cases who reported more severe childhood maltreatment had a lower BD-PRS (rho = -0.12, P = .01), especially when considering emotional abuse (rho = -0.16, P = .001). An interaction between BD-PRS and childhood maltreatment was observed for the risk of rapid cycling (P = .01). No further interactions between BD-PRS and childhood maltreatment were observed for other clinical characteristics (age at onset, suicide attempts, number of mood episodes, mixed features, substance use disorders and psychotic symptoms). CONCLUSION: Our study is the first to show that less genetic risk may be needed to develop a more unstable form of BD when exposed to childhood maltreatment. Our study supports childhood trauma as an independent risk factor for BD.
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