Background: Folate deficiency and low folate status have been linked in clinic studies to depression, persistent depressive symptoms, and poor antidepressant response. These relationships have not been demonstrated in general populations. This study examined associations between depression and folate status indicators in an ethnically diverse general US population sample aged 15–39 years. Methods: Healthy subjects whose red blood cell (RBC) folate concentrations had been measured were determined to have no depression (n = 2,526), major depression (n = 301 ), or dysthymia (n = 121) using a diagnostic interview schedule. Serum concentrations of folate and total homocysteine (tHcy) were also measured. Results: After adjustment for sociodemographic factors, serum vitamin B12 concentration, alcohol consumption over the past year and current status as to overweight and use of vitamin/mineral supplements, cigarettes and illegal drugs, subjects who met criteria for a lifetime diagnosis of major depression had folate concentrations in serum and RBCs that were lower than those of subjects who had never been depressed. Subjects who met criteria for dysthymia alone had lower RBC folate concentrations than never-depressed subjects, but the serum folate concentrations of the two groups were comparable. Serum tHcy concentration was not related to lifetime depression diagnoses. Low folate status was found to be most characteristic of recently recovered subjects, and a large proportion of such subjects were folate deficient. Conclusions: Low folate status was detectable in depressed members of the general US population. Folate supplementation may be indicated during the year following a depressive episode.

Keywords:
Affect, Depression, Dysthymicdisorder, Folic acid, Survey
1.
Alpert JE, Fava M: Nutrition and depression: The role of folate. Nutr Rev 1997;55:145–148.
2.
Alpert JE, Mischoulon D, Nierenberg AA, Fava M: Nutrition and depression: Focus on folate. Nutrition 2000;16:544–581.
3.
Bottiglieri T: Folate, vitamin B12, and neuropsychiatric disorders. Nutr Rev 1996;54:382–390.
4.
Smythies JR: Biochemistry of schizophrenia. Postgrad Med J 1963;39:26–33.
5.
Reynolds EH, Carney MWP, Toone BK: Methylation and mood (hypothesis). Lancet 1984;ii:196–198.
6.
Passeri M, Cucinotta D, Abate G, Senin U, Ventura A, Stramba Badiale M, Diana R, La Greca P, Le Grazie C: Oral 5′-methyltetrahydrofolic acid in senile organic mental disorders with depression: Results of a double-blind multicenter study. Aging (Milano) 1993;5:63–71.
7.
Guaraldi GP, Fava M, Mazzi F, la Greca P: An open trial of methyltetrahydrofolate in elderly depressed patients. Ann Clin Psychiatry 1993;5:101–105.
8.
Godfrey P, Crellin R, Toone BK, Flynn TG, Carney MW, Laundy M, Chanarin I, Bottiglieri T, Reynolds EH: Enhancement of recovery from psychiatric illness by methylfolate. Br J Psychiatry 1992;161:126–127.
9.
Coppen A, Bailey JE: Enhancement of the antidepressant action of fluoxetine by folic acid: A randomised, placebo controlled trial. J Affect Disord 2000;60:121–130.
10.
American Psychiatric Association: Diagnostic and Statistical Manual for Mental Disorders, ed 3. Washington, American Psychiatric Press, 1987.
11.
National Center for Health Statistics: Third National Health and Nutrition Examination Survey (NHANES III, 1988–94) Reference Manuals and Reports (CD-ROM). Hyattsville, US Department of Health and Human Services, 1996.
12.
Robins LN, Helzer JE, Croughan J, et al: The National Institute of Mental Health Diagnostic Interview Schedule: Its history, characteristics, and validity. Arch Gen Psychiatry 1981;38:381–389.
13.
Metz J: Appropriate use of tests for folate and vitamin B12 deficiency. Aust Prescrib 1999;22:16–18.
14.
Klee GG: Cobalamin and folate evaluation: Measurement of methylmalonic acid and homocysteine vs. vitamin B12 and folate. Clin Chem 2000 Aug;46:1277–1283.
15.
Wright AJ, Finglas PM, Southon S: Erythrocyte folate analysis: A cause for concern? Clin Chem 1998;44:1886–1891.
16.
Refsum H, Ueland PM, Nygard O, Vollset SE: Homocysteine and cardiovascular disease. Annu Rev Med 1998;49:31–62.
17.
Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MW, Reynolds EH: Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry. 2000 Aug;69:228–232.
18.
Fava M, Borus JS, Alpert JE, Nierenberg AA, Rosenbaum JF, Bottiglieri T: Folate, vitamin B12, and homocysteine in major depressive disorder. Am J Psychiatry 1997;154:426–428.
19.
Jacques PF, Rosenberg IH, Rogers G, Selhub J, Bowman BA, Gunter EW, Wright JD, Johnson CL: Serum total homocysteine concentrations in adolescent and adult Americans: Results from the third National Health and Nutrition Examination Survey. Am J Clin Nutr 1999;69:482–489.
20.
Israelsson B, Brattstrom L, Refsum H: Homocysteine in frozen plasma samples. A short cut to establish hyperhomocysteinaemia as a risk factor for arteriosclerosis? Scand J Clin Lab Invest 1993;53:465–469.
21.
Araki A, Sako Y: Determination of free and total homocysteine in human plasma by high-performance liquid chromatography with fluorescence detection. J Chromatogr 1987;422:43–52.
22.
The SAS system for Windows, Version 6.12. Cary, SAS Institute, 1996.
23.
Shah BV, Barnwell BG, Bieler GS: SUDAAN User’s manual, Release 7.0. Research Triangle Park, Research Triangle Institute, 1996.
24.
Gibson RS: Principles of Nutritional Assessment. New York, Oxford University Press, 1990.
25.
Penninx BW, Guralnik JM, Ferrucci L, et al: Vitamin B12 deficiency and depression in physically disabled older women: Epidemiologic evidence from the Women’s Health and Aging Study. Am J Psychiatry 2000;157:715–721.
26.
Lindeman RD, Romero LJ, Koehler KM, Liang HC, LaRue A, Baumgartner RN, Garry PJ: Serum vitamin B12, C and folate concentrations in the New Mexico Elder Health Survey: Correlations with cognitive and affective functions. J Am Coll Nutr 2000 Feb;19:68–76.
27.
Bell IR, Edman JS, Morrow FD, Marby DW, Mirages S, Perrone G, Kayne HL, Cole JO: B complex vitamin patterns in geriatric and young adult inpatients with major depression. J Am Geriatr Soc 1991;39:252–257.
28.
Spillman M, Fava M: S-adenosylmethionine in psychiatric disorders: Historical perspective and current status. CNS Drugs 1996;6:416–425.
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2003
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