The folic acid endophenotype and depression in an elderly population.
OBJECTIVE
Folate status and/or genes have been linked to depression in a number of studies. This may be via a direct action (or actions) on neuronal membranes or indirect effects through the metabolism of methyl groups involved in neurotransmitter synthesis. This study examines folate and related thiol metabolism that might underpin either phenomenon.


METHODS
Cohort study describing the relationship between several genetic and nutritional aspects of folic acid homeostasis and depression assessed by the HADS psychometric index in an elderly cohort.


METHODS
New South Wales (Australia) retirement village.


METHODS
118 elderly participants (age 65-90 years).


RESULTS
Stepwise multiple regression was used to determine the best statistical model to predict depression; C677T-MTHFR (p=0.0103) was found to be positively associated with depression, while the thiol dipeptide Cys-Gly was negatively associated (p=0.0403). The statistical models used accounted for the major folate related indices (genetic and biochemical) that are most often evaluated in the context of health and disease. When only genetic data were examined for interactions, C677T-MTHFR was found to be negatively associated with the HADS Depression Index Score (p=0.0191).


CONCLUSIONS
The potential influence of Cys-Gly on this phenotype is novel, and of considerable interest given that it has been linked to altered spontaneous activity and sedation in an animal model. Cys-Gly is a recognised ligand at the N-methyl-D-aspartatic acid (NMDA) subclass of glutamate receptor, a system associated with depression. In addition, the C677T-MTHFR association adds further support to existing findings underscoring the potential role of folate in depression.
School of Environmental & Life Sciences, University of Newcastle, Ourimbah, NSW, Australia.
N
N
Naumovski
M
M
Veysey
X
X
Ng
L
L
Boyd
L
L
Dufficy
B
B
Blades
C
C
Travers
P
P
Lewis
J
J
Sturm
M
M
Townley-Jones
Z
Z
Yates
P
P
Roach
M
M
Lucock
D000368:Aged; D000369:Aged, 80 and over; D001315:Australia / Q000453:epidemiology; D015331:Cohort Studies; D003863:Depression / Q000097:blood / Q000453:epidemiology* / Q000235:genetics*; D004032:Diet; D004151:Dipeptides / Q000097:blood*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D005494:Folic Acid Deficiency / Q000453:epidemiology; D056726:Genetic Association Studies; D006706:Homeostasis; D016852:Housing for the Elderly; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D011795:Surveys and Questionnaires
D004151:Dipeptides; C028505:cysteinylglycine; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)