Diet and mental health, does nutrition have a role in the prevention of depression?

Background
While depression is one of the most important health problems in western countries, there are only few studies about the role of nutrition in prevention of depression. Most of these studies have been published on the relationship between folate and depression and between omega-3 fatty acids and depression. Patients with major depression have had lower serum or erythrocyte levels of folate in a number of case-control studies. Also, low blood levels of folate have been linked to a poor response to antidepressant treatment. In some studies there has also been an inverse relationship between blood folate levels and the severity of depression.

Folate, cobalamin and depression, possible mechanisms behind the association The association between the blood concentrations of these vitamins and depression has been explained by their ability to decrease the serum total homocysteine (tHcy) levels and by their connection with monoamine metabolism in the central nervous system. Thus, a deficiency of folate and cobalamin results in an increase in tHcy, which in turn may aggravate depression. Bottiglieri et al (2000) found that in psychiatric inpatients high concentrations of tHcy were associated with more severe depression measured with the Hamilton Depression Rating Scale. Recently, Bjelland and co-workers found an increased risk of depression in the general population in subjects with high plasma levels of tHcy. However, the results are inconsistent.
	Two nutrition- epidemiologists under the palm tree, just taking care of their mental health...

Still unsolved questions:
Although there are reports of earlier cross-sectional and case-control studies and clinical trials, no studies have been published on the relationship between dietary folate and the incidence of depression. In fact, it is not known whether the association between low levels of folate and depression is caused by a low intake, poor absorption or higher need of folate - or whether low blood levels of folate are the result of a poor appetite as a symptom of depression.

Our results and research interests
These results are part of MD, psychiatrist Tommi Tolmunen's doctoral thesis and have been done in co-operation with Department of Psychiatry, University of Kuopio.

…Cross-sectional analyses
At the moment, we have studied the association between dietary intake of folate, cobalamin, pyridoxine and riboflavin and serum levels of folate and tHcy with depressive symptoms. These analyses have made of both cross-sectional and prospective study designs of the KIHD Study. First we investigated the association between dietary folate, cobalamin, pyridoxine and riboflavin and current depressive symptoms in a cross-sectional analysis of 2682 male participants of the KIHD Study. Those who had a previous history of psychiatric disorder were excluded (5.6% of the cohort). Depressive symptoms were assessed with the 18-item Human Population Laboratory Depression Scale. Those who scored 5 or more at baseline were considered to have elevated depressive symptoms (9.3% of the cohort). The participants were grouped into thirds according to their dietary folate intake. Those in the lowest third of energy-adjusted folate intake had a 67% higher risk of being depressed than those in the highest folate intake third. This excess risk remained significant after adjustment for smoking habits, alcohol consumption, appetite, body mass index, marital status, education, adulthood socioeconomic status and total fat consumption. There were no associations between the intake of cobalamin, pyridoxine or riboflavin and depression.

…Prospective analyses
We studied the association between dietary folate and cobalamin and the incidence of severe depression requiring hospitalization using prospective study design. The participants were classified into 2 categories according to the median intake of dietary folate. Those below the median of energy adjusted folate intake had increased risk of becoming hospitalized due to depression during the follow-up period compared with those in the higher folate intake group.

…About homocysteine and depression
We have also studied the association between serum folate and tHcy with the current depressive symptoms using the KIHD Study 4-year re-examination study population. These results are not published yet.

…What about the genes?
Present research interest in homocysteine-folate metabolism and the risk of depression is to study interaction of folate and homocysteine with genes and risk of depression. Genes available for these analyses are cystathione -synthetase (CBS ile278thr), 5,10-methylenetetrahydrofolate reductase (MTHFR ala223val) genes and three mutations in PON1 genes and one in PON2 gene. Material available for these analyses is KIHD Study 4-year visit cohort, n=1038 men. Gene-nutrient interactions are a part of nutritionist Anu Ruusunen's doctoral thesis.

Taken together:
Our results indicate that the nutrition may have a role in the prevention of depression. We can not fully exclude the possibility that the relation between depression and dietary folate could be explained by other healthy features of a folate-rich diet. For example, folate-rich vegetables and grains contain little saturated fat. However, adjustment for intake of total fat, fiber and vitamin C did not change the results significantly in our studies. It could also be that poor eating habits, low physical activity, smoking and excess alcohol consumption cluster in same people, who in any case would be at risk of mental health problems - either because of their lifestyle or despite it. However, adjustment for several possible risk factors associated with lifestyle did not change the main results in our studies.

More information
tommi.tolmunen@kuh.fi, anu.ruusunen@uku.fi, sari.voutilainen@uku.fi

References

Bottiglieri T, Laundy M, Crellin R, Toone BK, Carney MWP, Reynolds EH. Homocysteine, folate, methylation, and monoamine metabolism in depression. J Neurol Neurosurg Psychiatry 2000;69:228-232.

Bjelland I, Tell GS, Vollset SE, Refsum H, Ueland PM. Folate, vitamin B12, homocysteine and the MTHFR 677C T polymorphism in anxiety and depression. Arch Gen Psychiatry 2003;60:618-626.

Penninx BW, Guralnik JM, Ferucci L, Fried LP, Allen RH, Stabler SP. 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.

Alpert JE, Mischoulon D, Nierenberg MD, Fava M. Nutrition and depression: focus on folate. Nutrition 2000;16:544-581.

Alpert JE, Fava M. Nutrition and depression: the role of folate. Nutr Rew 1997;55:145-9.

Morris SM, Fava M, Jacques PF, Selhub J, Rosenberg IW. Depression and folate status in the US population. Psychoter Psychosom 2003;72;80-87.

Coppen A, Bailey J. Enhancement of the antidepressant action of fluoxetine by folic acid: a randomised, placebo controlled trial. J Affective Disord 2000;60:121-130.

For further information, please contact Sari Voutilainen (sari.voutilainen@uku.fi)