Serotonin system genes and obsessive-compulsive trait dimensions in a population-based, pediatric sample: a genetic association study.

Abstract

BACKGROUND:

Serotonin system genes are commonly studied in obsessive-compulsive disorder (OCD), but genetic studies to date have produced inconsistent results, possibly because phenotypic heterogeneity has not been adequately accounted for. In this paper, we studied candidate serotonergic genes and homogenous phenotypic subgroups as presented through obsessive-compulsive (OC) trait dimensions in a general population of children and adolescents. We hypothesized that different serotonergic gene variants are associated with different OC trait dimensions and, furthermore, that they vary by sex.

METHODS:

Obsessive-compulsive trait dimensions (Cleaning/Contamination, Counting/Checking, Symmetry/Ordering, Superstition, Rumination, and Hoarding) were examined in a total of 5,213 pediatric participants in the community using the Toronto Obsessive-Compulsive Scale (TOCS). We genotyped candidate serotonin genes (directly genotyping the 5-HTTLPR polymorphism in SLC6A4 for 2018 individuals and using single nucleotide polymorphism (SNP) array data for genes SLC6A4, HTR2A, and HTR1B for 4711 individuals). We assessed the association between variants across these genes and each of the OC trait dimensions, within males and females separately. We analyzed OC traits as both (a) dichotomized based on a threshold value and (b) quantitative scores.

RESULTS:

The [LG + S] variant in 5-HTTLPR was significantly associated with hoarding in males (p-value of 0.003 and 0.004 for categorical and continuous analyses, respectively). There were no significant findings for 5-HTTLPR in females. Using SNP array data, there were significant findings for rumination in males for HTR2A SNPs (p-value of 1.04e-6 to 5.20e-6).

CONCLUSIONS:

This represents the first genetic association study of OC trait dimensions in a community-based pediatric sample. Our strongest results indicate that hoarding and rumination may be distinct in their association with serotonin gene variants and that serotonin gene variation may be specific to sex. Future genetic association studies in OCD should properly account for heterogeneity, using homogenous subgroups stratified by symptom dimension, sex, and age group.

• Authors: Vanessa M Sinopoli, Lauren Erdman, Christie L Burton, Laura S Park, Annie Dupuis, Janet Shan, Tara Goodale, S-M Shaheen, Jennifer Crosbie, Russell J Schachar, Paul D Arnold
• Journal: Journal of child psychology and psychiatry, and allied disciplines (J Child Psychol Psychiatry) Vol. 60 Issue 12 Pg. 1289-1299 (12 2019) ISSN: 1469-7610 [Electronic] England
• PMID: 31321769 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 Association for Child and Adolescent Mental Health.

Chemical References

• HTR1B protein, human
• HTR2A protein, human
• Receptor, Serotonin, 5-HT1B
• Receptor, Serotonin, 5-HT2A
• SLC6A4 protein, human
• Serotonin Plasma Membrane Transport Proteins
• Serotonin

Topics

• Adolescent
• Child
• Compulsive Behavior (genetics)
• Female
• Genetic Association Studies
• Hoarding (genetics)
• Humans
• Male
• Obsessive Behavior (genetics)
• Obsessive-Compulsive Disorder (genetics)
• Personality (genetics)
• Polymorphism, Single Nucleotide
• Receptor, Serotonin, 5-HT1B (genetics)
• Receptor, Serotonin, 5-HT2A (genetics)
• Rumination, Cognitive (physiology)
• Serotonin (genetics)
• Serotonin Plasma Membrane Transport Proteins (genetics)
• Sex Characteristics