Relationship of homocysteine, folic acid and vitamin B12 with depression in a middle-aged community sample.
BACKGROUND
Case control studies have supported a relationship between low folic acid and vitamin B112 and high homocysteine levels as possible predictors of depression. The results from epidemiological studies are mixed and largely from elderly populations.


METHODS
A random subsample of 412 persons aged 60-64 years from a larger community sample underwent psychiatric and physical assessments, and brain MRI scans. Subjects were assessed using the PRIME-MD Patient Health Questionnaire for syndromal depression and severity of depressive symptoms. Blood measures included serum folic acid, vitamin B12, homocysteine and creatinine levels, and total antioxidant capacity. MRI scans were quantified for brain atrophy, subcortical atrophy, and periventricular and deep white-matter hyperintensity on T2-weighted imaging.


RESULTS
Being in the lowest quartile of homocysteine was associated with fewer depressive symptoms, after adjusting for sex, physical health, smoking, creatinine, folic acid and B12 levels. Being in the lowest quartile of folic acid was associated with increased depressive symptoms, after adjusting for confounding factors, but adjustment for homocysteine reduced the incidence rate ratio for folic acid to a marginal level. Vitamin B12 levels did not have a significant association with depressive symptoms. While white-matter hyperintensities had significant correlations with both homocysteine and depressive symptoms, the brain measures and total antioxidant capacity did not emerge as significant mediating variables.


CONCLUSIONS
Low folic acid and high homocysteine, but not low vitamin B12 levels, are correlates of depressive symptoms in community-dwelling middle-aged individuals. The effects of folic acid and homocysteine are overlapping but distinct.
Sachdev
Perminder S
PS
School of Psychiatry, University of New South Wales, Sydney, Australia. p.sachdev@unsw.edu.au
Parslow
Ruth A
RA
Lux
Ora
O
Salonikas
Chris
C
Wen
Wei
W
Naidoo
Daya
D
Christensen
Helen
H
Jorm
Anthony F
AF
D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D001315:Australia; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D015984:Causality; D003404:Creatinine / Q000097:blood; D003430:Cross-Sectional Studies; D003866:Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D005260:Female; D005492:Folic Acid / Q000097:blood; D005494:Folic Acid Deficiency / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D006305:Health Status Indicators; D006306:Health Surveys; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010552:Personality Assessment / Q000706:statistics & numerical data; D011237:Predictive Value of Tests; D011594:Psychometrics; D012016:Reference Values; D013223:Statistics as Topic; D014805:Vitamin B 12 / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000175:diagnosis / Q000453:epidemiology*
D000975:Antioxidants; D006710:Homocysteine; D005492:Folic Acid; D003404:Creatinine; D014805:Vitamin B 12