Do Common Genetic Factors Underlie Comorbidity Between Migraine and Major Depressive Disorder in Youth?

Alison K. Merikangas, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Lifespan Brain Institute of the Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: amerikangas@gmail.com.
Laura M. Schultz, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Lifespan Brain Institute of the Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania.
Kosha Ruparel, Lifespan Brain Institute of the Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Tarannum Lateef, Department of Neurology, Children's National Health System, George Washington University School of Medicine, Washington, District of Columbia; Genetic Epidemiology Research Branch, Intramural Research Program, National Institute of Mental Health, Bethesda, Maryland.
Raquel E. Gur, Lifespan Brain Institute of the Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Laura Almasy, Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; Lifespan Brain Institute of the Children's Hospital of Philadelphia and the University of Pennsylvania, Philadelphia, Pennsylvania.

Document Type

Journal Article

Publication Date

12-1-2025

Journal

Pediatric neurology

Volume

173

DOI

10.1016/j.pediatrneurol.2025.09.017

Keywords

Comorbidity; Depression; Migraine disorders; Polygenic score; Youth

Abstract

BACKGROUND: Migraine and major depressive disorder (MDD) are common, recurring conditions with comorbidity documented in clinical and community samples of both adults and youth. However, the etiology remains unknown. This study aims to (1) examine the prevalence and association between migraine and MDD in a large, diverse youth sample; (2) assess whether polygenic scores (PGSs) from adult genome-wide association studies are associated with these disorders in youth; and (3) evaluate shared genetic susceptibility underlying migraine-depression comorbidity. METHODS: The sample includes 8496 youth from the Philadelphia Neurodevelopmental Cohort (5239 of European-like Ancestry [EA]). Mental disorders and migraine were assessed using structured diagnostic tools aligned with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition and International Classification of Headache Disorders. In the EA subset, PGS from adult genome-wide association studies were used to examine genetic associations. RESULTS: In cross-sectional analyses, 7% of youth met migraine criteria and 12.5% met MDD criteria. Rates were similar across self-reported races. Migraine and depression were significantly associated (odds ratio = 2.05, P < 0.001). There were significant associations between the PGS for migraine and depression with those disorders in EA youth, but no cross-disorder genetic associations emerged. CONCLUSIONS: This is the first study to examine the genetic architecture of comorbid migraine and mood disorders in a large youth sample. PGS from adults were associated with migraine and depression in youth, but the lack of cross-disorder associations suggests limited shared genetic pathways. Future studies should include prospective data to examine potential mechanisms for migraine-depression comorbidity.

Department

Neurology

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