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The hierarchical taxonomy of psychopathology as an approach to the psychiatric genetics of substance-related and addictive disorders in Vietnam-era twins

Pathological gambling and substance use disorders are highly prevalent and comorbid among veteran populations. These disorders also share genetic influences, although the underlying constructs and magnitude of their influence remain unclear. This project utilized the Hierarchical Taxonomy of Psychopathology (HiTOP) as a framework for modeling the underlying dimensions of psychopathology as latent factors and modeled genetic and environmental influences on substance use disorders and pathological gambling.
Study 1 examined the structure of psychopathology for 15 common mental disorders in a sample of Vietnam-era veteran twins from the Harvard Drug Study (nMZ = 3,748 and nDZ = 2,996) to determine the appropriate location for pathological gambling within the HiTOP framework. The best fitting model included internalizing and externalizing spectra and an illicit substance use subfactor. Pathological gambling (loading = .30) loaded onto the externalizing spectrum with legal substance use, conduct disorder, antisocial personality disorder, and a subfactor that subsumed all six illicit substance use disorders. The best fitting model in Study 1 did not support the existence of a ā€˜pā€™ factor underlying all psychopathology.
In Study 2, genetic and environmental components were modeled for the 15 disorders and 3 latent factors modeled in Study 1. Additive genetics explained from 10% (generalized anxiety disorder, panic disorder) to 49% (nicotine use) of the variance in specific disorders and from 24% (internalizing) to 46% (externalizing) of the variance of latent factors. Only cocaine use and conduct disorder demonstrated significant variance attributable to shared environment, the entirety of which occurred at the disorder-specific level. Only 9% of the genetic variance associated with alcohol use was shared across disorders, whereas 100% of genetic variance in cocaine and hallucinogen use was shared with latent factors. In total, 12% of the variance in risk for pathological gambling was associated with additive genetics, and 13% of that variance was shared via the externalizing spectrum.
Findings highlight shared risk among illicit substance use disorders and among other disorders on the externalizing spectrum. These findings suggest externalizing and illicit substance use as transdiagnostic targets for treatments aimed at individuals with comorbid substance use disorders, pathological gambling, and other externalizing disorders.

Identiferoai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/46361
Date16 June 2023
CreatorsCuthbert, Kristy N.
ContributorsLyons, Michael J.
Source SetsBoston University
Languageen_US
Detected LanguageEnglish
TypeThesis/Dissertation
RightsAttribution 4.0 International, http://creativecommons.org/licenses/by/4.0/

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