A longitudinal study of blood folate levels and depressive symptoms among young women in the Southampton Women's Survey

Background: Lower blood folate levels have been associated with depression in cross-sectional surveys, but no studies have examined the relationship prospectively to determine whether the relationship is causal. A follow-up study was designed to examine whether lower blood folate levels predict incident depressive symptoms. Method: Women aged 20-34 years registered in general practices in Southampton, UK, were asked to participate. Baseline assessment included the general health questionnaire (GHQ-12) measure of anxiety and depression, and socioeconomic factors, diet, smoking and alcohol intake. Two years later, participants' general practice ( GP) records were examined for evidence of incident symptoms of depression. Results: At baseline, 5051 women completed the GHQ-12 and had red cell folate levels measured, of whom 1588 (31.4%) scored above the threshold for case level symptoms of anxiety and depression on the GHQ-12. Two years later, GP records for 3996 (79.1%) were examined, but 1264 with baseline evidence of depression were excluded from follow-up analysis. Incident depressive symptoms were recorded for 307 (11.2%) of the remaining 2732. Lower red cell folate levels were associated with caseness on the GHQ-12 ( adjusted prevalence ratio 0.99 per 100 nmol/l red cell folate, 95% CI 0.98 to 1.00). No relationship was found between red cell folate levels and incident depressive symptoms over 2 years ( adjusted hazard ratio 1.00, 95% CI 0.97 to 1.03). Conclusions: Low folate levels were not associated with subsequent depressive symptoms. This suggests that lower blood folate levels may be a consequence rather than a cause of depressive symptoms.