Late-onset depression: genetic, vascular and clinical contributions

Psychol Med. 2001 Nov;31(8):1403-12. doi: 10.1017/s0033291701004731.


Background: Neuropsychiatric research needs to examine the relationships 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 = 549 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Apolipoproteins E / genetics
  • Cerebrovascular Disorders / complications*
  • Cerebrovascular Disorders / genetics*
  • Cognition Disorders / diagnosis
  • Cognition Disorders / etiology
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / etiology*
  • Depressive Disorder, Major / genetics
  • Depressive Disorder, Major / psychology*
  • Female
  • Gene Expression / genetics
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Phenotype
  • Psychiatric Status Rating Scales
  • Risk Factors


  • Apolipoproteins E