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A three-factor model of common early onset psychiatric disorders: temperament, adversity, and dopamine

Abstract

Commonly comorbid early onset psychiatric disorders might reflect the varying expression of overlapping risk factors. The mediating processes remain poorly understood, but three factors show some promise: adolescent externalizing traits, early life adversity, and midbrain dopamine autoreceptors. To investigate whether these features acquire greater predictive power when combined, a longitudinal study was conducted in youth who have been followed since birth. Cohort members were invited to participate based on externalizing scores between 11 to 16 years of age. At age 18 (age 18.5 ± 0.6 y.o.), 52 entry criteria meeting volunteers had a 90-min positron emission tomography scan with [18F]fallypride, completed the Childhood Trauma Questionnaire, and were assessed with the Structured Clinical Interview for DSM-5. The three-factor model identified those with a lifetime history of DSM-5 disorders with an overall accuracy of 90.4% (p = 2.4 × 10−5) and explained 91.5% of the area under the receiver operating characteristic curve [95% CI: .824, 1.000]. Targeting externalizing disorders specifically did not yield a more powerful model than targeting all disorders (p = 0.54). The model remained significant when including data from participants who developed their first disorders during a three-year follow-up period (p = 3.5 × 10−5). Together, these results raise the possibility that a combination of temperamental traits, childhood adversity, and poorly regulated dopamine transmission increases risk for diverse, commonly comorbid, early onset psychiatric problems, predicting this susceptibility prospectively.

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Acknowledgements

We thank David Zald for feedback on an earlier version of this manuscript.

Funding

The project has been made possible with the financial support of Health Canada, through the Canada Brain Research Fund, an innovative partnership between the Government of Canada (through Health Canada) and Brain Canada, and the Montreal Neurological Institute, with further support from the Canadian Institutes for Health Research (CIHR) MOP-133537 (Leyton, Séguin, Boivin), MOP-44072 (Séguin) and MOP-97910 (Séguin, Parent); from the Fonds de Recherche du Québec—Santé (FRQS) numbers 981055, 991027 (Séguin) and 35282 (Castellanos-Ryan); Fonds de Recherche du Québec - Société et Culture numbers 2002-RS-79238, 2009-RG-124779 (Séguin, Boivin); and from the Social Sciences and Humanities Research Council of Canada numbers 410-99-1048 and 839-2000-1008 (Séguin, Boivin). Salary awards were provided by CIHR to Jaworska and Castellanos-Ryan and by FRQS to Tippler. The QLSCD cohort born 1997–1998 is led by the Institut de la Statistique du Québec in collaboration with several departments and agencies of the Government of Quebec and many collaborating researchers including the authors of this article. Project completion with QLSCD respondents was authorized by the QLSCD Steering Committee. The views expressed herein do necessarily represent the views of the Minister of Health or the Government of Canada.

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ML conceived of the study and designed it with JS and SMLC. MT, SMLC and NJ collected the data. MI, SMLC, NJ and NCR analyzed the data. MI, SMLC, NJ and ML interpreted the data and wrote the manuscript with input from the other authors (MT, SP, AD, FV, MRB, MB, ROP, SMC, RET, JRS).

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Correspondence to Jean R. Séguin or Marco Leyton.

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Iqbal, M., Cox, S.M.L., Jaworska, N. et al. A three-factor model of common early onset psychiatric disorders: temperament, adversity, and dopamine. Neuropsychopharmacol. 47, 752–758 (2022). https://doi.org/10.1038/s41386-021-01187-z

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