A Gene-Enviornment Approach To Predicting A Depressive Symptom Severity Phenotype Among Young Adults With A History Of Adverse Childhood Experiences

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Doctor of Philosophy (PhD)
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Lipsky, Rachele

Depressive and anxiety disorders in young adults are the leading causes of morbidity and mortality worldwide; and the high prevalence of these diagnoses contributes significantly to the global burden of disease. One of the most significant risk factors for the development of these disorders is known collectively as adverse childhood experiences (ACEs). However, not everyone with a history of ACEs goes on to develop psychopathology. There is a growing body of evidence that inter-individual factors, such as the type and amount ACEs, one’s proximal environmental milieu, and predisposing genetic variants, influence the prevalence of these disorders in young adulthood. Using a gene x environment framework, a secondary analysis of the National Longitudinal Study of Adolescent to Adult Health (Add Health) was conducted among young adults to examine: the cumulative ACE index and factor analytic approaches to measuring ACEs; the moderating role that genetic variants have between ACEs and depressive symptom severity, and; the genotype/phenotype combinations that increase the risk for and buffer against depressive symptom severity. Factor analysis yielded a three-factor solution, which resulted in greater predictive utility when estimating depression symptom severity as compared to the cumulative ACE index The moderation analyses revealed that no significant gene x environment interactions were found with either the candidate gene polymorphism, 5-HTTLPR, or the polygenic risk score (PRS) for major depressive disorder (MDD).Deep phenotyping, through the utilization of random forests and regression trees, revealed that the two most important variables that were used in the genotype/phenotype combinations to estimate depression symptom severity were perceived stress and neuroticism; and the intensity of these variables were the most pronounced among young adults with a history of ACEs who also had a genetic predisposition for depression (S/S genotype of 5-HTTLPR and/or a high PRS for MDD). Taken together, a precision health care approach that accounts for the type of ACE, one’s genotype, and the levels of perceived stress and neuroticism, may help to identify individuals who are at the greatest risk of depression symptom severity, and may help to reduce the individualized and worldwide symptom burden of depression.

Anne M. Teitelman
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