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Modification by Two Genes of Associations Between General Somatic Health and Incident Depressive Syndrome in Older People

From the Department of Psychiatry and Depression Clinical Research Center, Chonnam National University Medical School, Kwangju, Korea (J.-M.K., S.-W.K., S.-J.Y., I.-S.S., J.-S.Y.); Institute of Psychiatry, King’s College London, London, United Kingdom (R.S.).

Address correspondence and reprint requests to Jin-Sang Yoon, Chonnam National University Medical School, Kwangju, Republic of Korea. E-mail: jsyoon{at}chonnam.ac.kr

Objective: To investigate the modifying effects of two candidate genes (serotonin transporter gene linked promoter region (5-HTTLPR) and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms) on the associations between general somatic morbidity and incidence of depression in an East Asian population with high frequencies of potential risk alleles.

Methods: With a 2-year prospective study of a community sample (N = 521) of older people (aged 65+), information on baseline number of health complaints, diagnosis of moderate/severe depressive syndrome (Geriatric Mental State), and genotypes for 5-HTTLPR and MTHFR C677T polymorphisms were ascertained. Interactions between somatic morbidity and the two genotypes were investigated for incident depression.

Results: Incident depression was present in 63 (12%) and was associated with worse somatic health. Significant interactions between number of somatic complaints and both genotypes were observed. For the 5-HTTLPR genotypes, the association between the number of somatic disorders and depression was significant in s/s homozygotes (² = 8.80 (1 df), p = .003) but not in heterozygotes (² = 0.23, p = .634) or l/l homozygotes (² = 0.04, p = .840). For the MTHFR genotypes, the association between the number of somatic disorders and depression was significant in T/T homozygotes (² = 4.97, p = .026) but not in C/T heterozygotes (² = 1.24, p = .265) or C/C homozygotes (² = 1.04, p = .307).

Conclusions: These findings suggest that associations between general somatic morbidity and late-life depression are modified by at least two genes, and that elders with particular genotypes are at greater risk for onset of depression in the presence of somatic ill health.

Key Words: chronic disease • genes • serotonin transporter • methylenetetrahydrofolate reductase • depression • gene-environment interaction

Abbreviations: 5-HTTLPR = serotonin transporter gene linked promoter region; GMS = Geriatric Mental State schedule; MTHFR = methylenetetrahydrofolate reductase; PCR = polymerase chain reaction.