Effect of the 5-HTTLPR polymorphism in the serotonin transporter gene on major depressive disorder and related comorbid disorders.
OBJECTIVE
The serotonin transporter gene (5-HTT) has been proposed as a candidate gene for major depressive disorder (MDD). Association studies, however, have revealed inconsistent results. This could be because of the phenotypic heterogeneity of MDD, as it often presents with comorbid disorders such as generalized anxiety disorder (GAD), alcohol-related disorders, and dysthymia.


METHODS
In this exploratory study, we performed regression analyses with generalized estimating equations in patients with familial MDD (n=233) in order to explore whether a polymorphism in the serotonin transporter gene (5-HTTLPR) is differentially associated with MDD and a comorbid disorder compared with MDD without that particular comorbidity. As in general, GAD is more common in females and alcohol-related disorders are more common in males, the analyses were stratified for sex.


RESULTS
Comorbid dysthymia was less common in s-allele carriers with MDD (P<0.05) than in patients homozygous for the long allele. In the sex-specific analyses, an association between the 5-HTTLPR and comorbid alcohol use disorders was observed in females, with s-carriers reporting significantly less alcohol use disorders. The relationship with comorbid GAD differed by sex with male s-carriers reporting more comorbid GAD than female s-carriers.


CONCLUSIONS
The effect of the 5-HTTLPR polymorphism on MDD is co-dependent on the presence of comorbid disorders and sex. In this study, the s-allele of the 5-HTTLPR polymorphism was associated with significantly lower rates of particular lifetime comorbid disorders. Therefore, the presence of comorbid psychiatric disorders should be taken into account to clarify the association of the 5-HTTLPR polymorphism with MDD phenotypes.
Verhagen
Maaike
M
Department of Psychiatry, Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
van der Meij
Annemarie
A
Janzing
Joost G E
JG
Arias-Vásquez
Alejandro
A
Buitelaar
Jan K
JK
Franke
Barbara
B
D000293:Adolescent; D000328:Adult; D001008:Anxiety Disorders / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012727:Sex Characteristics
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins