Related Experiment Video
Updated: Jun 12, 2026

An Unpredictable Chronic Mild Stress Protocol for Instigating Depressive Symptoms, Behavioral Changes and Negative Health Outcomes in Rodents
Published on: December 2, 2015
The association of 5-HTTLPR genotype and depressive symptoms is moderated by physical activity
Chad D Rethorst1, Daniel M Landers, Craig T Nagoshi
1Department of Psychiatry, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. chad.rethorst@utsouthwestern.edu
Abstract:
The s allele serotonin transporter polymorphic region (5-HTTLPR) is associated with a number of physiological mechanisms that may increase the risk of elevated depressive symptoms. However, reports of a relationship between serotonin transporter polymorphic region (5-HTTLPR) genotype and depressive symptoms have thus far been inconclusive. This heterogeneity of results suggests that other factors may be moderating the relationship between 5-HTTLPR and depressive symptoms. Higher levels of physical activity are associated with lower levels of depressive symptoms. Mechanisms responsible for this association include alterations of the serotonergic system and the hypothalamic-pituitary axis. The aim of the current study was to measure the moderating effect of physical activity on the relationship between 5-HTTLPR genotype and depressive symptoms. Participants, ages 18-23, provided a saliva sample for DNA analysis and completed questionnaires to assess depressive symptoms and physical activity. A hierarchical multiple regression analysis was conducted to examine the moderating effect of physical activity on the relationship between 5-HTTLPR genotype and depressive symptoms. Analysis revealed a significant interaction between 5-HTTLPR and physical activity (p = .010). At low levels of physical activity, individuals with at least one s allele had significantly higher levels of depressive symptoms compared to ll individuals (p = .011). This finding provides preliminary support for a moderating effect of physical activity on the relationship between 5-HTTLPR and depressive symptoms.
Related Concept Videos
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
Depressive Disorders: Etiology
Biological Factors in Depression
Biological predispositions significantly influence the risk of developing depressive disorders. Genetic studies highlight the role of variations in the serotonin transporter...
Depressive Disorders: MDD and Dysthymia
Huntington Disease l: Introduction
G-protein Coupled Receptors
Introduction to Stress and Lifestyle
