Homocysteine and depression in later life.
BACKGROUND
The prevalence of depression in later life increases with plasma total homocysteine concentration (tHcy). High tHcy accounts for about 15% of prevalent cases, but observational studies are prone to confounding and bias. Genetic association studies are not prone to the same sources of error and offer an opportunity to explore the consistency and external validity of this association.


OBJECTIVE
To determine if tHcy is causally related to depression in later life.


METHODS
Cross-sectional study (Health in Men Study), systematic review, and meta-analysis. Patients Community sample of 3752 men aged 70 years or older (Health in Men Study).


METHODS
Fifteen-Item Geriatric Depression Scale and self-reported past or current treatment for depression (Health in Men Study).


RESULTS
In the Health in Men Study, the odds ratio (OR) of prevalent depression increased 4% (OR, 1.04; 95% confidence interval [CI], 1.02-1.05) with every unit increase of tHcy (micromoles per liter). The tHcy was 0.19 mg/L higher among participants with the MTHFR C677T TT genotype compared with the CC genotype. The meta-analysis showed that older adults with high tHcy had increased risk of depression (OR, 1.70; 95% CI, 1.38-2.08) and TT carriers were 22% more likely than CC carriers to have current depression or a history of depression (OR, 1.22; 95% CI, 1.01-1.47).


CONCLUSIONS
The triangular association between the MTHFR genotype, tHcy, and depression implies that higher concentrations of tHcy increase the risk of depression and that lowering tHcy by 0.19 mg/L could reduce the odds of depression by about 20%. Confirmatory data from sufficiently powered randomized trials of homocysteine-lowering therapy are now required to test if the relationship between tHcy and depression is truly causal.
Almeida
Osvaldo P
OP
FRANZCP, Western Australian Centre for Health and Ageing, University of Western Australia, Mail Box M573, 35 Stirling Hwy, Crawley, WA 6009, Australia. osvaldo.almeida@uwa.edu.au
McCaul
Kieran
K
Hankey
Graeme J
GJ
Norman
Paul
P
Jamrozik
Konrad
K
Flicker
Leon
L
D000367:Age Factors; D000368:Aged; D015331:Cohort Studies; D003866:Depressive Disorder / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D005492:Folic Acid / Q000627:therapeutic use; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D016017:Odds Ratio; D010555:Personality Inventory; D011110:Polymorphism, Genetic / Q000235:genetics; D011736:Pyridoxine / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors; D014805:Vitamin B 12 / Q000627:therapeutic use
D006710:Homocysteine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D011736:Pyridoxine; D014805:Vitamin B 12