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OBJECTIVES: To examine patterns of associations between a broad range of mental and physical conditions by using a large, systematically obtained pediatric registry. METHODS: The sample included 9014 youth ages 8 to 21 years (4349 males and 4665 females; 3585 aged,13 years, 3678 aged 13 to 18 years, and 1751 aged 19 to 21 years) from the Philadelphia Neurodevelopmental Cohort identified through pediatric clinics at the Children's Hospital of Philadelphia health care network by the Center for Applied Genomics. Measures were as follows: physical condition based on electronic medical records and interview data on 42 physical conditions of 14 organ systems/specialties and mental disorders based on an abbreviated version of the structured Kiddie-Schedule for Affective Disorders and Schizophrenia psychiatric diagnostic interview. RESULTS: There was a direct association between the severity of the physical condition and most classes of mental disorders, as well as with functional impairment. Models adjusted for sociodemographic correlates, other physical and mental disorders, and false discovery and revealed broad patterns of associations between neurodevelopmental disorders with behavior disorders (odds ratio [OR]: 1.5; 95% confidence interval [CI]: 1.3-1.8; P < .004) and attention-deficit/hyperactivity disorder (OR: 3.1; 95% CI: 2.7-3.6; P < .0001), and neurologic/central nervous system conditions (OR: 1.3; 95% CI: 1.1-1.9; P < .05) with mood disorders and attention-deficit/hyperactivity disorder (OR: 1.3; 95% CI: 1.1-1.5; P < .001), and autoimmune/ inflammatory conditions with mood disorders (OR: 1.4; 95% CI: 1.1-1.8, P < .05). CONCLUSIONS: Findings show the strong overlap between physical and mental conditions and their impact on severity and functional impairment in youth. Specific patterns of comorbidity have important implications for etiology. Prospective tracking of cross-disorder morbidity will be important to establish more effective mechanisms for prevention and intervention. [ABSTRACT FROM AUTHOR]