As far as we know, there have been no previous studies that have suggested a positive relationship between the vitamin B12
level and the treatment outcome in patients with major depressive disorder who generally have normal or high serum vitamin B12
levels. Previous research has focused on possible associations between a low vitamin B12
level and a poor treatment response [9
]. A low vitamin B12
level was less common in our sample than has been previously reported in patients with major depression [21
]. We found no correlation between the severity of depression and the level of vitamin B12
at baseline, although the folate level and severity of depression displayed a weak positive correlation. Engström et al. [22
] found no correlation between the levels of folate or B12
and the severity of depression, but an inverse relationship between the level of folate and severity of depression has been reported in some other studies [3
A low folate level was relatively common (18%) among our patients with major depressive disorder, which is in accordance with previous studies [23
]. Nevertheless, a low folate level was not detected in German or Chinese patients with major depression [24
]. We observed only weak indications that a low erythrocyte folate level might be associated with the poor treatment outcome, which is contradictory to some previous studies [4
]. It could be that culturally defined dietary habits influence the relationship between the folate status and depression in different societies [25
]. Recently it was reported that low dietary folate and depressive symptoms are associated in middle-aged Finnish men [26
]. Moreover, our study included only young and middle-aged outpatients with moderate depression, which may have influenced the results. The association between folate and depression may be more prominent in elderly subjects, among whom folate deficiency has been relatively common in some studies [27
Poor appetite and inappropriate food intake as symptoms of depression could result in low levels of vitamin B12
and especially low levels of folate. However, we found no connection between BMI, HDRS items relating to gastrointestinal symptoms and weight loss, and blood vitamin levels. Why some depressed people have lower levels of these vitamins could be a topic for further investigation. It might reflect to a lower intake of vitamins from food or assimilation from the gastrointestinal track, or a higher rate of metabolism of these vitamins. Depression may also affect the quality of food in the diet. Morris and co-workers [7
] found that levels of blood folate had decreased after an episode of depression. However, loss of appetite, weight loss and being underweight were not related to folate levels.
There are several theories concerning potential associations between depression and levels of vitamin B12
and folate. Vitamin B12
and folate are connected with the synthesis of monoamines and are involved in single carbon transfer methylation reactions connected with the production of monoamine neurotransmitters [28
]. Low levels of 5-hydroxyindole acetic acid (5-HIAA) in cerebrospinal fluid (CSF) have been found in depressed patients with folate deficiency [29
]. However, Engström et al. [22
] found no correlation between levels of 5-HIAA in the CSF and vitamin B12
or folate levels.
deficiency may also result in the accumulation of homocysteine, which has been suggested to lead to exito-toxic reactions and may enhance depression [30
]. Bottiglieri et al. [32
] found raised levels of homocysteine in 52% of depressed inpatients. Vitamin B12
is also required in the synthesis of S-adenosylmethionine (SAM), which is needed as a methyl donor in many methylation reactions in the brain. It has been also suggested to have antidepressant properties [33
We observed no correlation between vitamin B12
and folate levels and the mean corpuscular volume, red blood cell count or hematocrit, which is in line with previous studies [5
]. Haematological indices did not predict the treatment outcome, either. This indicates that haematological indices have no value in assessing depressed patients, while the levels of vitamin B12
in serum and folate in erythrocytes may have.
Multivariate analyses adjusted for age, sex, the family history of depression, the duration of the illness, severity of depression at baseline and treatment variables during the follow-up period supported the existence of an independent relationship between the vitamin B12 level and decline in the HDRS score. This was, however, a naturalistic follow-up study, and sociodemographic and clinical and treatment variables were not controlled a priori. This is the main shortcoming of our study. We suggest further studies with controlled illness and treatment variables to confirm or to refute our findings.
Our sample included more women (61%) than men, only one subject was aged over 65 years and 87% had only been treated as outpatients. All these variables may influence the results. Men and women may have different dietary habits. A low folate intake is common among Finnish men [26
]. A low vitamin B12
level and B12
deficiency have been found to be common among older women [5
], but elderly men may have even lower B12
]. Finally, patients with psychotic depression may have lower B12
levels than non-psychotic depressives [35
]. Psychotic depression is a common indication for inpatient treatment. For all these reasons one should be careful about generalizing these findings to all groups of depressive patients.
The mean level of vitamin B12
on follow-up was lower than at baseline, which may indicate some deterioration of the samples during freezing. Previously, Kirke et al. have reported that levels of folate may decline by approximately 20% during six years of freezing [36
]. The length of the storage had little effect on this deterioration. Another explanation is that depression may also affect the quality of food in the diet which lowers levels of blood vitamins during an episode of depression [7
]. Nevertheless, baseline and follow-up levels of vitamin B12
in the present study correlated significantly and both also associated highly significantly with the decline in the HDRS level during the follow-up, which supports our findings.