Late-onset depression: genetic, vascular and clinical contributions.
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.
Hickie
I
I
School of Psychiatry, University of New South Wales, Sydney, Australia.
Scott
E
E
Naismith
S
S
Ward
P B
PB
Turner
K
K
Parker
G
G
Mitchell
P
P
Wilhelm
K
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000523:psychology*; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D010641:Phenotype; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors
D001057:Apolipoproteins E