Candidate gene polymorphisms in the serotonergic pathway: influence on depression symptomatology in an elderly population.
BACKGROUND
Depressed mood is a major concern in the elderly, with consequences for morbidity and mortality. Previous studies have demonstrated that genetic factors in depression and subsyndromal depressive symptoms are no less important in the elderly than during other life stages. Variations in genes included in the serotonin system have been suggested as risk factors for various psychiatric disorders but may also serve as candidates for normal variations in mood.


METHODS
This study included 684 elderly Danish twins to investigate the influence of 11 polymorphisms in 7 serotonin system genes on the mean level of depression symptomatology assessed over several years, reflecting individuals' underlying mood level.


RESULTS
A suggestive association of sequence variations in genes responsible for the synthesis (TPH), recognition (5-HTR2A), and degradation (MAOA) of serotonin with depression symptomatology was found, although the effect was generally restricted to men. We also found that a specific haplotype in VMAT2, the gene encoding the vesicular monoamine transporter, was significantly associated with depression symptoms in men (p= .007).


CONCLUSIONS
These results suggest that variations in genes encoding the components of serotonin metabolism may influence the basic mood level and that different genetic factors may apply in men and women.
Christiansen
Lene
L
Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, Denmark. lchristiansen@health.sdu.dk
Tan
Qihua
Q
Iachina
Maria
M
Bathum
Lise
L
Kruse
Torben A
TA
McGue
Matthew
M
Christensen
Kaare
K
D000339:Affect / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D003718:Denmark; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D004200:Diseases in Twins / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D005260:Female; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D008995:Monoamine Oxidase / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics; D012307:Risk Factors; D012701:Serotonin / Q000378:metabolism*; D012737:Sex Factors; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics
D044402:Receptor, Serotonin, 5-HT2A; C493452:SLC18A2 protein, human; D050493:Vesicular Monoamine Transport Proteins; D012701:Serotonin; D008995:Monoamine Oxidase; C023210:tyrosine phosphate hydrolase; D010744:Phosphoric Monoester Hydrolases