Preliminary communicationAssociation between folate intake and melancholic depressive symptoms. A Finnish population-based study
Introduction
Depression is a global public health problem in developed countries. Recently, the World Health Organization estimated that unipolar depressive disorder remains one of the leading causes of total disability adjusted life years (DALY's) worldwide (World Health Organization, 2003). It accounts for 8% of total DALY's in the Americas and 6% in Europe (Ustun et al., 2004). Overall, 12-month and lifetime prevalence rates of depression are approximately 12% and 24% among U.S. men and women, respectively (Kessler et al., 1994).
A wide array of etiological hypotheses has been suggested to underlie depression. Of the biological hypotheses the monoamine hypothesis proposes an important etiological role for serotoninergic or noradrenergic dysfunction in depression (Stahl and Muntner, 2008). Since several of the key enzymes in the 1-carbon cycle are folate-dependent in their activity, folate plays an important role in single carbon transfer methylation reactions needed for the production of several neurotransmitters, including dopamine, noradrenalin, and serotonin (Bottiglieri, 1996, Coppen et al., 1989, Fava and Mischoulon, 2009). This forms a biologically plausible link between folate and mood (Reynolds and Carney, 1984), and may also indicate that the association between depression and folate could be mediated through monoamine synthesis.
Most studies examining the association between folate and depressive symptoms (DS) have been based upon serum folate levels. Many cross-sectional studies have shown that low levels of folate are associated with the risk of depression or elevated depressive symptoms in adults (Beydoun et al., 2010a, Beydoun et al., 2010b, Lee et al., 1998, Sanchez-Villegas et al., 2009, Tiemeier et al., 2002), which has been confirmed in a longitudinal study in an older Korean population (Kim et al., 2008). However, the findings have not been consistent since no association between folate levels and DS was detected in a longitudinal study among young women registered in general practices in England (Kendrick et al., 2008). In addition, the associations between depressive symptoms or depression and folate levels may be confounded by different subtypes of DS, as in a clinical study in which subjects with low folate levels were more likely to have melancholic depression (Fava et al., 1997).
Only a few cross-sectional studies have examined the association between folate intake and DS or depression. An association has been reported between a low folate intake and depression in university graduates (Sanchez-Villegas et al., 2009), and a connection between low folate intake and DS in boys and girls (Murakami et al., 2010). Furthermore, a population-based Finnish study demonstrated an association between low folate intake and DS among men (Tolmunen et al., 2003).
Of the three published prospective studies, a Finnish population-based study reported a 3-fold increased risk of depression in men with a low folate intake (Tolmunen et al., 2004). A low folate intake may also increase the risk of recurrent depression among middle-aged men (Astorg et al., 2008). On the other hand, a recent U.S. population-based study reported that the intake of folate was not associated with DS (Skarupski et al., 2010).
As the relationship between folate intake and subtypes of DS has not been thoroughly evaluated, we examined the association between folate intake and DS in groups with predominantly melancholic or non-melancholic characteristics in a large Finnish population-based study comprising middle-aged and elderly individuals.
Section snippets
Study population
The Finnish type 2 diabetes (FIN-D2D) survey was the implementation project of a national program for the prevention of type 2 diabetes covering a population of 1.5 million between the years 2003–2008 (Saaristo et al., 2007). The specific aims were to improve the screening of people at risk of diabetes and the detection of undiagnosed diabetes.
The study population comprised a random sample of 4500 subjects aged 45–74 years, stratified according to gender in 10-year age groups (45–54, 55–64, and
Results
The study population (N = 2806) included 429 subjects with a BDI score ≥ 10. These subjects were divided into groups with predominantly melancholic (N = 138) and non-melancholic DS (N = 291). Table 1 presents the general characteristics of the two subgroups with BDI scores of < 10 or ≥ 10. Participants with elevated DS were less educated, more likely to be older or female, and to have a higher BMI, be unmarried, unemployed and less physically active. Their also used less alcohol than their less depressed
Discussion
The novel finding in our study is that after taking into account a large number of potential confounders (age, BMI, LTPA, alcohol use, smoking, marital status, years of education and chronic diseases) the folate intake was associated with melancholic DS but not with non-melancholic DS. This result is in line with the monoamine hypothesis of depressive disorders connecting a low folate intake with diminished serotonin synthesis (Stahl and Muntner, 2008). No previous studies have evaluated the
Role of funding source
FIN-D2D was supported by financing from the hospital districts of Pirkanmaa, Southern Ostrobothnia, North Ostrobothnia, Central Finland and Northern Savo, the Finnish National Public Health Institute, the Finnish Diabetes Association, the Ministry of Social Affairs and Health in Finland and Finland's Slot Machine Association. Funding for the study had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to
Conflict of interest
None.
Acknowledgments
FIN-D2D was supported by funding from the hospital districts of Pirkanmaa, Southern Ostrobothnia, North Ostrobothnia, Central Finland and Northern Savo, the National Institute for Health and Welfare, the Finnish Diabetes Association, the Ministry of Social Affairs and Health in Finland and Finland's Slot Machine Association in cooperation with the FIN-D2D Study Group, and the Steering Committee: J. Huttunen, A. Kesäniemi, S. Kiuru, L. Niskanen, H. Oksa, J. Pihlajamäki, J. Puolakka, P. Puska, T.
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