Objectives Problematic sexual behavior (PSB) is defined by recurrent sexual behaviors that are difficult to control, causing social and functional impairments. PSB can co-occur with reward deficiency syndrome (RDS), but this relationship remains unclear. RDS has been associated with the 10/10 genotype of 3’ variable number tandem repeat (VNTR) in the dopamine transporter gene SLC6A3, which is implicated in the reward pathway. This study investigates the genetic relationship between PSB and RDS, testing their association with SLC6A3 3’ VNTR genotype.

Methods PSB patients from addiction treatment facilities (n=454), and comparison participants (with PSB=82; without PSB, n=888) were recruited. PSB was measured by the Sexual Addiction Screening Test-Revised (SAST-R) Core and RDS was measured using a composite variable from a custom test battery. DNA was collected from saliva and buccal swabs. Genotyping was performed using polymerase chain reaction (PCR), and regression analyses were conducted to investigate the association of SLC6A3 3’ VNTR genotype with PSB and RDS.

Results The 10/10 genotype of SLC6A3 3’ VNTR was associated with RDS in a combined analysis of all groups, and with PSB only in comparison participants. In patients, rare SLC6A3 3’ VNTR genotypes (3-, 6-, 8-, 11-repeat alleles) were associated with PSB. No genotype showed relationships to RDS in only PSB patients.

Conclusions The link of the 10/10 genotype to RDS indicates that PSB could be a manifestation of RDS in non-clinical populations; rare genotypes might be associated with clinical forms of PSB, together with comorbid psychopathology.

While Dr Carnes was previously a Board member of the American Foundation for Addiction Research, he is no longer a member. Moreover, neither the Foundation nor any other of the funders played any role in study design, or in data analysis or interpretation thereof. All other authors declare no conflicts of interest.

The work herein was supported by an Alberta Centennial Addiction and Mental Health Research Chair and transitional funding (to KJA), Canada Foundation for Innovation (CFI), John R. Evans Leaders Fund (JELF) grant (32147 - Pharmacogenetic translational biomarker discovery), Alberta Innovation and Advanced Education Small Equipment Grants Program (to KJA), and a research grant and philanthropic support from the American Foundation for Addiction Research (to KJA). A Fulbright-Canada-Palix Foundation grant (to PC) assisted with his contributions to study design, project management, and collaborative working. SJ was supported by an Alberta Innovates Postdoctoral Recruitment Fellowship.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Quorum Review Institutional Review Board (Seattle, Washington; Protocol Number: 2016-001) and the University of Alberta Research Ethics Board (Protocol: Pro00066552) approved the study.

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All data produced in the present study are available upon reasonable request to the authors.