Medical Multimorbidity in Patients With Treatment‐Resistant Psychosis and Rare Copy Number Variants: A Retrospective Case Series of 24 Patients

Neurodevelopmental disorder-risk copy number variations (NDD CNVs) are associated with complex neuropsychiatric phenotypes. These CNVs also confer risk for a host of medical outcomes in adults; yet, the long-term health consequences in the context of comorbid psychiatric illness have not been well documented. Twenty-four psychiatric inpatients with treatment-resistant psychosis were identified as carriers of NDD CNVs as part of a larger Pennsylvania State Hospital genomics study. Comprehensive life course phenotyping was performed through review of medical records, specialized neurobehavioral evaluation, and synthesis of data using the Human Phenotype Ontology. Phenotypes examined across the cohort indicated comorbid medical manifestations across multiple organ systems. Cardiovascular disorders were present in 96% of patients and motor disorders in 92%. All patients had multiple organ system involvement, and most organ systems (12/17 systems) were affected in 50% or more of patients, culminating in a high degree of individual-level multimorbidity. Comparing our observations to previously known CNV-associated phenotypes indicated several potentially novel health outcomes for individual CNV loci. Our descriptive case series supports a complex and multidimensional course of illness. Thorough reporting on the long-term implications of these variants is the first step toward advancing clinical care for these complex psychiatric patients carrying NDD CNVs.