Potential role of membrane-bound COMT gene polymorphisms in female depression vulnerability.
BACKGROUND
Several polymorphic variants within the catechol-O-methyltransferase (COMT) gene locus have been associated with a number of diverse psychiatric phenotypes including affective disorders. COMT enzyme participates in metabolic pathways involving brain catecholamines, as well as steroid hormones such as estrogens. Given the suggested mood enhancing role of estrogens and the higher prevalence of depression in women, we set out to investigate the potential impact of functional COMT genetic variants on depression and anxiety symptoms in a homogeneous female community sample.


METHODS
We genotyped three common polymorphisms within the COMT gene in a rural female population isolate (n=391) interviewed for the presence of lifetime major depression episodes and generalized anxiety disorder. Furthermore, well validated self-rated questionnaires were administered evaluating state depressive symptoms and neuroticism personality trait. Single-marker and haplotype association analyses were performed.


RESULTS
Two highly correlated markers located in the membrane-bound (MB) COMT promoter region (rs2020917, rs737865) were significantly associated with both self-rated and clinician-rated depressive symptomatology. We did not detect any robust association with generalized anxiety disorder or neuroticism. Exploratory haplotype analysis examining the two promoter markers in combination with the extensively studied val 158met polymorphism (rs4680) did not provide any further support for the contribution of this variant in depressive mood.


CONCLUSIONS
The relative small sample size should be considered a limitation of this study.


CONCLUSIONS
Our results provide promising evidence that MB-COMT specific genetic variation may represent an as yet unrecognized genetic factor that influences predisposition to depression amongst females.
University Mental Health Research Institute, Athens, Greece.
Alex
A
Hatzimanolis
Silia
S
Vitoratou
Laura
L
Mandelli
Chrysostomos
C
Vaiopoulos
Finiki A
FA
Nearchou
Costas N
CN
Stefanis
Alessandro
A
Serretti
Nicholas C
NC
Stefanis
D000328:Adult; D001008:Anxiety Disorders / Q000175:diagnosis / Q000235:genetics; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007406:Interview, Psychological; D008875:Middle Aged; D000075384:Neuroticism; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012423:Rural Health / Q000706:statistics & numerical data; D057566:Self Report; D012737:Sex Factors; D055815:Young Adult
D002394:Catechol O-Methyltransferase