Developmental phenotypes of sequential comorbidity leading to major mood disorders

Uher, Rudolf, Fullerton, Janice, Zwicker, Alyson, Freeman, Kathryn, Serna, Elena de la, Castro-Fornieles, Josefina, van Haren, Neeltje, Hillegers, Manon, Rice, Frances ORCID: https://orcid.org/0000-0002-9484-1729, Thapar, Anita ORCID: https://orcid.org/0000-0002-3689-737X, Propper, Lukas, Hafeman, Danella, Birmaher, Boris, Mitchell, Philip, Alda, Martin and Nurnberger, John 2023. Developmental phenotypes of sequential comorbidity leading to major mood disorders. Biological Psychiatry 93 (9) , Supp1. 10.1016/j.biopsych.2023.02.176

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Abstract

Background The onset of major depressive disorder or bipolar disorder is typically not the first manifestations of psychopathology. We examine if sequential comorbidity with attention-deficit/hyperactivity disorder (ADHD) and anxiety disorders separates distinct phenotypes and predicts the onset of mood disorders in the context of family history. Methods Across 8 cohorts, 2,300 youth, including 1,082 (47%) biological offspring of parents with bipolar disorder, were followed up for an average of 7 years (until a mean age of 20, range 12 to 32) and repeatedly assessed with diagnostic interviews. Results By the end of follow-up, 407 (18%) youth were diagnosed with ADHD at a mean age of 9.5, 905 (39%) were diagnosed with anxiety disorders at a mean age of 11.7, 557 (24%) were diagnosed with a major depressive disorder at a mean age of 14.8, and 148 (6%) were diagnosed with a bipolar disorder at a mean age of 15.5. In a Cox proportional hazards model, prior ADHD (HR=1.33, 95%CI 1.10 to 1.61, p=0.003) and anxiety disorders (HR=3.02, 95%CI 2.54 to 3.59, p<0.001) predicted mood disorders independent of parent diagnosis, age, and sex. The combination of family history with both prior ADHD and anxiety disorders was associated with a 67% risk of a major mood disorder. While non-comorbid mood disorders were associated with polygenic scores for bipolar disorder, sequential comorbidity of anxiety and mood disorders was associated with polygenic scores for neuroticism. Conclusions We conclude that developmental phenotypes are linked to partially distinct genetic dispositions and make useful contribution to the prediction of mood disorders.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	Elsevier
ISSN:	0006-3223
Last Modified:	17 Jul 2024 16:15
URI:	https://orca.cardiff.ac.uk/id/eprint/169338

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