The serotonin transporter gene polymorphism (SLC6A4) and risk for psychiatric morbidity and comorbidity in the Baltimore ECA follow-up study

Background: The human serotonin transporter (SERT) gene polymorphism (5HTTLPR) has been associated with multiple psychiatric disorders, including major depression, anxiety disorders, and substance use disorders. This study investigated the association between 5HTTLPR and psychiatric morbidity and comorbidity in a psychiatrist-examined population sample. Methods: 628 participants, mean age 48.3 years old, were assessed by psychiatrists using the Schedules for Clinical Assessment in Neuropsychiatry. Associations between 5HTTLPR and the prevalence, comorbidity, and time-to-diagnoses for 16 psychiatric conditions were evaluated, using several analytical approaches. Results: The SERT S allele was significantly associated with an increased lifetime prevalence of panic disorder. There was a “protective” association between SERT gene S allele carrier status and the risk of obsessive-compulsive disorder (OCD) in time-to-event analysis. Carriers of the S allele had a significant increased risk of two specific comorbid disorder pairs: major depressive disorder (MDD) and social phobia, and MDD and agoraphobia. Overall, there was no increased risk of receiving an initial or an additional diagnosis for a mental disorder in the SERT S allele carriers Conclusions: The findings suggest that the S allele carrier status is associated with an increased prevalence of panic disorder in a community sample. There was an increased risk for comorbidity in a more homogeneous subgroup of cases with MDD and social phobia, as well as or agoraphobia. Our findings suggest a specific effect of the SERT promoter gene polymorphism on a subgroup of individuals identifiable by their comorbidity.