Observational studies examining the relationship between folate status and risk of depression
| Study | Design | Population | Case definition | Controls | Definition of low folate | Confounders and adjustment | Unadjusted OR (>1 = association) | Adjusted OR (>1 = association) |
|---|---|---|---|---|---|---|---|---|
| BMI, body mass index; CCF, congestive cardiac failure; CES-D, Center for Epidemiologic Studies—Depression; DSM, Diagnostic and Statistical Manual for mental disorders; GDS, Geriatric Depression Scale; HAD, Hospital Anxiety and Depression; HPL, Human Population Laboratory; ICD, International Classification of Diseases; NA, not applicable; SES, socioeconomic status. | ||||||||
| Abou-Saleh and Coppen 39 | Case–control | Consecutive psychiatric inpatients and day-hospital patients with depression | ICD-9 major depression (n = 95) | Laboratory and hospital staff with no depression (n = 60) | Serum folate | None | OR 12.74 (95% CI 2.97 to 113.48) | NA |
| <2.5 ng/ml | ||||||||
| <5.67 nmol/l | ||||||||
| Carney et al37 | Case–control | Consecutive inpatient psychiatric admissions | Depression diagnosed by a psychiatrist (n = 152) | Euthymic controls (n = 42) | Red cell folate | None | OR 3.93 (95% CI 0.63 to 24.61) | NA |
| <150 ng/ml | ||||||||
| <337 nmol/l | ||||||||
| Lee et al38 | Case–control | Consecutive inpatient psychiatric admissions aged 15–87 years | DSM-III-R major depression (n = 117) | Hospital staff with no history of depression (n = 72) | Red cell folate | None | OR 0.77 (95% CI 0.24 to 2.57) | NA |
| <150 ng/ml | ||||||||
| <337.8 nmol/l | ||||||||
| Lindeman29 | Cross-sectional survey | Hispanic males and females aged ⩾65 years | GDS score >6 (n = 74) | Not currently depressed and from the same population (n = 709) | Serum folate | None | OR 1.51(95% CI 0.82 to 2.71 ) | NA |
| <5 ng/ml | ||||||||
| <11.1 nmol/l | ||||||||
| Tiemeier et al31 | Cross-sectional survey | Patients >55 years from a population survey | DSM-IV depression or dysthymia (n = 112) | Randomly selected non-depressed people from the same population (n = 416) | Serum folate | Age, gender, education, smoking, alcohol intake, cognitive functioning | OR 1.52 (95% CI 0.85 to 2.71) | OR 1.49 (95% CI 0.83 to 2.67) |
| <5.03 ng/ml <11.4 nmol/l | ||||||||
| Plus raised homocysteine (>13.9 nmol/L) | ||||||||
| Pennix et al32 | Cross-sectional survey | Women ⩾65 years from a Population survey | Severe depression on the GDS score ⩾14 (n = 122) | Non-depressed people from the same population, GDS score ⩽9 (n = 478) | Serum folate | Age, race education; income; BMI serum creatinine; CCF; diabetes; disability; cancer | OR 0.78 (95% CI 0.22 to 2.73) | OR 0.90 (95% CI 0.24 to 3.36) |
| <5.03 ng/ml | ||||||||
| <11.4 nmol/l | ||||||||
| and raised homocysteine (>13.9 nmol) | ||||||||
| Bjelland et al33 | Cross-sectional survey | Men and women aged 46–49 and 70–74 years from a population cohort study | High score on HAD >8 (n = 243) | Non-depressed people from the same population (n = 5705) | Serum folate | Age, sex, smoking status, educational level | OR 1.48 (95% CI 0.93 to 2.37) | OR 1.31 (95% CI 0.82 to 2.11) |
| <1.68 ng/ml | *Least adjusted–adjusts only for age and sex | |||||||
| <3.8 nmol/l | ||||||||
| Tolmunen et al30 | Cross-sectional survey | Middle-aged Finnish men 42–60 years from a population cohort | High score on HPL scale ⩾5 (n = 228) | Non-depressed people from the same population (n = 2215) | Ascertained from dietary records. Lowest third tertile of folate intake (daily intake <201.9 (SD 52) μg/day | Age, sex, smoking, alcohol, appetite, BMI, living alone, education, SES, fat consumption | OR 1.67 (95% CI 1.19 to 2.35) | OR 1.46 (1.01 to 2.12) |
| *Least-adjusted for age and examination years | ||||||||
| Tolmunen et al40 | Cohort study | Middle-aged Finnish men 42–60 years from population cohort | Hospital discharge diagnosis of ICD major depression during 15-year follow-up (n = 47) | No ICD diagnosis of depression during 15-year follow-up (n = 2313) | Ascertained from dietary records. Below median folate intake (256 μg/day) | Age and examination year, SES, baseline depression score, daily intake of fibre, vitamin C and fat | OR 3.04 (95% CI 1.58 to 5.86) | OR 2.53 (95% CI 1.17 to 5.48) |
| *OR approximated directly from reported RR | *Cohort reports the same subjects as the above study,30 so prospective data rather than cross-sectional data included in meta-analysis only | |||||||
| Morris et al34 | Cross-sectional study | Males and females aged 15–39 years from a US National Population Nutrition Survey | Lifetime risk of DSM-III major depression (n = 301) and dysthymia (n = 121) ascertained by diagnostic interview (total n = 422) | Ethnically diverse members from the same population (n = 2526) | Red cell folate below 25th centile in the population* Cut-off provided by author | Gender age, race, income, education, alcohol use, drug use, weight and nutritional status | OR 1.7 (95% CI 1.1 to 2.6) | OR 2.4 (95% CI 1.3 to 4.4) |
| <196 ng/ml | †Least adjusted–adjusts only for age, sex and ethnicity | |||||||
| <445 nmol/l | Based upon unpublished data from author. | |||||||
| Ramos et al35 | Cross-sectional study | Elderly Latino males (n = 627) and females (n = 883) aged ⩾60 years | CES-D score >15 (n = 385) | Depression score ⩽15 from the same population (n = 1125) | Serum folate in lowest tertile* | Age, education, B12 status, homocysteine levels, use of folate supplements, use of anti-depressants and alcohol consumption | Overall OR 0.96 (95% CI 0.56 to 1.65) | Overall OR 75 (95% CI 0.42 to 1.33) |
| <11.2 ng/ml | Folate*sex interaction, so analysis also presented separately for men and women. | Folate*sex interaction, so analysis also presented separately for men and women. | ||||||
| <25.4 nmol/l | Men OR 0.96 (95% CI 0.56 to 1.65) | Men OR 0.74 (95% CI 0.40 to 1.35) | ||||||
| Study conducted post-fortification | Women OR 2.08 (95% CI 1.47 to 2.95) | Women OR 2.04 (95% CI 1.38 to 3.02) | ||||||