Deep Phenotyping and Candidate Genetic Association Analysis of Problematic Sexual Behavior and Related Conditions
Creators: Jiang, Shui
Publisher: name: University of Alberta Library
Year: 2023

<p>Problematic sexual behavior (PSB) is defined by recurrent sexual behaviors that are difficult to control, causing social as well as functional impairments. The etiology of PSB is heterogeneous, and the mechanisms remain unknown. There is an ongoing scientific debate regarding whether PSB may be classified as a behavioral addiction. Thus, the prevalence, sociodemographic features, and nosology of the construct known as PSB in a diverse sample of adults in post-secondary education (“the university participants”) was investigated. My results show that screening positive for reward deficiency syndrome (RDS) related features, such as compulsive buying, personality disorders, obsessive-compulsive disorder (OCD), internet addiction, and attention-deficit/hyperactivity disorder (ADHD), as well as childhood trauma, a family history of PSB, and male gender, were associated with PSB. <br>
I then investigated the genetic association of a functional variant (the 3’ variable number tandem repeat, or VNTR) in the solute carrier family 6 member 3 (SLC6A3) gene encoding the dopamine transporter (a candidate owing to the prior literature associating this variant with various relevant phenotypes) with PSB in both the university participants and in patients with behavioral addictions. My hypothesis was that the genotypes of this variant associated with reward deficiency syndrome (RDS) would also be associated with PSB. My results firstly support an association between this variant and PSB, and secondly suggest that the variant may be associated with PSB differently in different groups.<br>
Previous research has shown that individuals with addictive disorders report high rates of NSSI and lifetime suicide attempt(s) (SA) compared to those without addictive disorders. Additionally, both NSSI and suicidal behavior may have addictive components. Furthermore, the relationship between NSSI and suicidality is a complex and debated issue. Thus, I investigated the sociodemographic aspects of NSSI and lifetime SA, as well as the relationship between NSSI and lifetime SA, and PSB, with hypotheses being that: NSSI may be associated with lifetime SA, and PSB may be a predictor of both NSSI and lifetime SA. My results showed that the interaction of PSB with gender (women), and with younger age (18-24 years old) was associated with NSSI and with lifetime SA, respectively. The findings emphasize that the link between PSB and NSSI or lifetime SA may vary by age and gender.<br>
    The 5-HTT-linked polymorphic region (5-HTTLPR) regulates gene transcription, and the short variant of the polymorphism is associated with reduced expression of the serotonin transporter. Previous research has shown that this variant can interact with stress, or family conflict, and is associated with violent behavior, depression, and suicidal behavior. Changes in serotonergic pathways have been linked to addictive disorders. Based on this, my hypothesis was that individuals with functional S/S genotype of the 5-HTTLPR, in combination with a family history of domestic violence, would be more likely to display PSB, NSSI, and lifetime SA. The results of my analysis supported this hypothesis, that the interaction of the 5-HTTLPR functional S/S genotype and a family history of domestic violence was associated with NSSI and with lifetime SA. Additionally, this gene-environment (G×E) interaction may be associated with PSB (in women). <br>
    To sum up, my results suggest that there are similarities between PSB and addictive disorders, with PSB being associated with RDS. In addition, different SLC6A3 3’ VNTR genotypes may be associated with different stages of PSB. These results are consistent with the three-stage model of addiction, which posits that impulsivity is often observed in the early stages of addiction, while other mechanisms become increasingly prominent as the condition progresses. My work also emphasizes that there are shared traits of individuals with PSB, NSSI, and lifetime SA, such as impulsivity, trust issues, dependency, being a loner, and difficulties in making and maintaining relationships. Of note, 5-HTTLPR functional S/S genotype and a family history of domestic violence were correlated with these personality traits and may be associated with PSB (in women), NSSI and lifetime SA, suggesting the potential existence of shared risk factors, including a G×E interaction effect for these three phenotypes. This is the first report of a genetic risk factor common to these three phenotypes.</p>