Study Title:

Folic Acid, B12, and Risk of Depression

Study Abstract


An association between low blood folate levels and depressive symptoms (DS) has been reported in several epidemiological studies, but no studies have examined folate intake in melancholic or non-melancholic DS in population-based samples.


The aim of the study was to evaluate folate intake in DS with or without melancholic characteristics as a part of the Finnish diabetes prevention program (FIN-D2D). Altogether, 4500 randomly selected subjects aged 45–74years were selected from the National Population Register. The study population (N=2806, participation rate 62%) consisted of 1328 men and 1478 women. The health examinations were carried out in 2007 according to the WHO MONICA project. The assessment of DS was based on the Beck Depression Inventory (BDI, cut-off≥10 points). A summary score of melancholic items in the BDI was used in dividing the participants with DS (N=429) into melancholic (N=138) and non-melancholic DS (N=291) subgroups. Folate intake was assessed using a validated food frequency questionnaire (FFQ).


DS associated linearly with gender specific tertiles of folate intake (p for linearity=0.003). The OR for melancholic DS was 0.55 (95%CI 0.34 to 0.90) for the high tertile of folate intake versus the low (p for linearity=0.018), while the ORs for non-melancholic DS were nonsignificant.


Assessment of DS was based on a self-rating scale, and the population was in advanced middle-aged.


A low folate intake was associated with DS through its effect on melancholic DS.

From press release:

(Nov. 26, 2012) — A low intake of folate and vitamin B12 increases the risk of melancholic depressive symptoms, according to a study among nearly 3,000 middle-aged and elderly Finnish subjects. On the other hand, non-melancholic depressive symptoms are associated with an increased risk for the metabolic syndrome. Based on these new observations, melancholic and non-melancholic depression may be separate depressive subtypes with different etiologies in terms of proinflammation and diet. The study was the first to look at these depressive sub-types separately.

"The findings have practical implications in the care of patients with depressive symptoms. For example, it may be wise to avoid medication causing weight gain among patients with non-melancholic depression, whereas melancholic depressive symptoms may call for a closer look at the quality of the patient's diet," says Mr Jussi Seppälä, MD, Chief of the Department of Psychiatry of the Hospital District of Southern Savo.

Melancholic depression involves typical depressive symptoms, such as a depressed mood. Non-melancholic depression is characterized by other types of symptoms, such as low self-esteem and feelings of worry and anxiety.

Among subjects with the highest folate intake, the risk for melancholic depressive symptoms was almost 50 per cent lower than among those with the lowest intake. In addition, among those with the highest vitamin B12 levels, the risk for melancholic depressive symptoms was almost three times lower than among those with the lowest levels. Both findings are new. A similar association with non-melancholic depressive symptoms was not observed.

Another novel observation is that the risk for the metabolic syndrome was twofold among those with non-melancholic depressive symptoms, as compared to those with melancholic symptoms or those with no depressive symptoms.

Mr Seppälä's doctoral thesis "Depressive symptoms, metabolic syndrome and diet" was published at the University of Eastern Finland. The study was conducted as part of the Finnish Type 2 Diabetes Prevention Programme. The findings were originally published in Journal of Affective Disorders.

Study Information

Jussi Seppälä, Hannu Koponen, Hannu Kautiainen, Johan G. Eriksson, Olli Kampman, Satu Männistö, Pekka Mäntyselkä, Heikki Oksa, Yrjö Ovaskainen, Merja Viikki, Mauno Vanhala.
Association between folate intake and melancholic depressive symptoms. A Finnish population-based study.
Journal of Affective Disorders
2012 May
Department of Psychiatry of the Hospital District of Southern Savo, Finland.

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