Reconceptualizing Psychopathology for Genetic Studies using Hierarchical Dimensional Structural Models: The Example of Externalizing and AVPR1a

Recent trends in the psychopathology literature have reconceptualized psychopathology in terms of transdiagnostic or hierarchical dimensional perspectives. Despite these trends, the modal phenotypes used in psychiatric genetic... [ view full abstract ]

Recent trends in the psychopathology literature have reconceptualized psychopathology in terms of transdiagnostic or hierarchical dimensional perspectives. Despite these trends, the modal phenotypes used in psychiatric genetic studies (e.g., in GWASs of psychiatric disorders conducted through the Psychiatric Genetics Consortium) are single, specific psychiatric diagnoses. In this paper, I explore different conceptualizations of a higher-order Externalizing symptom dimension, as well as different analytic methods used to characterize this dimension, in its association with the Arginine Vasopressin 1a receptor gene (AVPR1a). I contrasted different models for characterizing the Externalizing symptom dimension with each other, as well as with models of its constituent diagnoses and symptom dimensions. In phenotypic analyses, data were available on parent ratings of DSM-IV symptoms of Attention Deficit Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), and Conduct Disorder (CD) from ~2800 children whereas in genetic analyses data were available from ~600 children, all aged 6-16 years old. In analyses of genetic association six SNPs in AVPR1a were used to characterize the gene in a series of gene-based tests. Comparisons of these phenotypic models used the percentage of variance explained and the relative fit of the alternative models to adjudicate among them. Results of these analyses highlight the benefits of construing psychopathology in terms of hierarchical dimensional models, as well as which conceptualizations and analytic methods are optimal.