Late-onset depression: Genetic, vascular and clinical contributions

I. Hickie*, E. Scott, S. Naismith, P. B. Ward, K. Turner, G. Parker, P. Mitchell, K. Wilhelm

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

121 Citations (Scopus)


Background. Neuropsychiatric research needs to examine the relationship between aetiological, genotypic and clinical risk factors and behavioural phenotypes. These relationships can now be examined in older patients with depressive disorders. Methods. Key behavioural features, clinical and vascular risk factors and putative genotypes for late-onset neurodegenerative disorders and/or vascular disease were recorded in 78 older patients with depression (mean age = 54.9 years, S.D. = 14.1) and 22 healthy control subjects (mean age = 55.5 years, S.D. = 9.6). Results. Two or more vascular risks were more common in older patients (65% v. 26% of control subjects, P < 0.01), and in patients with late-onset disorders (82% v. 57% in patients with early-onset disorders, P < 0.05). Patients with late-onset depression had a higher prevalence of the homozygous or heterozygous forms of the C677T mutation of the methylenetetrahydrofolate reductase enzyme (MTHFR)(74% v. 48% in patients with early-onset disorders, P < 0.05). In a multivariate model, only presence of the MTHFR gene mutation predicted late-onset depression (odds ratio = 3.8, 95% CI = 1.1-12.9). Neither apolipoprotein E epsilon 4 or epsilon 2 was associated with depression, late-onset depression, cognitive impairment, or psychomotor change. Patients with apolipoprotein E epsilon 4 were less likely to have psychotic forms of depression. Conclusions. Patients with late-onset depression had an increased rate of the C677T MTHFR gene mutation and other vascular risk factors. This suggests that a proportion of these patients may have genetically-determined and/or other vascular aetiologies. Patients at risk of these disorders may be assisted by currently-available preventative strategies.

Original languageEnglish
Pages (from-to)1403-1412
Number of pages10
JournalPsychological Medicine
Issue number8
Publication statusPublished - 2001
Externally publishedYes


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