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 polymophisms 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 fect was generally restricted to men. We degradation (MAOA) of serotonin with depression symptomatology was found, although they also found that a specfic 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 serolonin metabolism may influence the basic mood level and that different genetic factors may apply in men and women.