Neurocognitive and genetic influences on Eating Disorder and Substance Use Disorder comorbidity in individuals from families enriched with Substance Use Disorders

Abstract

Eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) have the highest mortality of all psychiatric disorders with no pharmacological treatment approved for AN in adults nor for any ED in children and adolescents. The prevalences of AN, BN, and BED range from 1-5% and differ between age groups, by sex, and between people of different races/ethnicities. Additionally, eating disorders are often comorbid with substance use disorders (SUDs), complicating treatment and increasing morbidity and mortality. The comorbidity of EDs and SUDs, which has been shown to be more likely in the case of EDs with binge behavior, suggests that other factors, such as neurocognitive, neurobiological, and genetic influences may underlie both disorders. However, no previous work has examined the influence of these factors together. This dissertation study aims to investigate the influence of neurophysiological and neuropsychological function as well as polygenic risk scores on the risk for EDs and co-occurring SUDs. This research will be carried out using data from the Collaborative Study on the Genetics of Alcoholism (COGA) (N= 15,221), a deeply characterized sample of families densely affected with AUD and community comparison families. Overall, the findings from this dissertation demonstrate the importance of considering epidemiological, neurocognitive, neurobiological, and genetic factors together when investigating influences of risk for EDs and co-occurring SUDs. These findings show that the comorbidity of EDs and AUD is especially likely in BN and BED across gender and racial groups, and that females and White individuals are at greater risk of to AN-AUD comorbidity. The necessity of screening Black individuals for developing EDs and comorbid AUD is highlighted, especially in the case of binge-type EDs, due to increased BED prevalence and seemingly equal risk of AUD comorbidity in this population. The findings suggest that AN symptoms may relate to better cognitive performance in specific areas of executive function, especially in females, and that decreased P3 amplitude and increased beta EEG coherence may serve as endophenotypes for the binge-type EDs. Increased beta coherence may be a factor underlying both EDs and SUDs, with males and females showing different coherence patterns. Finally, polygenic risk for EDs may relate to neurocognitive and neurophysiological differences seen in EDs, with more statistical genetic research necessary for BN and BED, and more representative samples needed for all EDs. This work points to the potential benefit of a neuropsychiatric approach, encompassing both epidemiological factors as well as assessment of executive function, P3 amplitude, and beta EEG coherence, in the screening for and management of EDs and comorbid SUDs.