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Dietary Folate and Depression: A Prospective Study

Dietary Folate and Depression: A Prospective Study. 張宜平 3/4/2005. INTRODUCTION. Potential Mechanisms. Neurotransmitter (serotonin) synthesis: - S-adenosylmethionine (SAM) in the one-carbon cycle - tetrahydrobiopterin (BH 4 ) in the biopterin metabolic pathway

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Dietary Folate and Depression: A Prospective Study

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  1. Dietary Folate and Depression: A Prospective Study 張宜平 3/4/2005

  2. INTRODUCTION

  3. Potential Mechanisms • Neurotransmitter (serotonin) synthesis: - S-adenosylmethionine (SAM) in the one-carbon cycle - tetrahydrobiopterin (BH4) in the biopterin metabolic pathway • Accumulated homocysteine - neurotoxic effect: metabolized to S-denosylhomocysteine (SAH) and inhibit the monoamine and phospholipid methylation requiring SAM - excitotoxic effect: on the N-methyl-D-aspartate receptors in the central nervous system

  4. One-Carbon Cycle Vit B 2

  5. Neurotransmitter Synthesis

  6. Biopterin Pathway

  7. Population-Based Research • Depression associated with folate but not with vitamin B12 status: - the third US National Health and Nutrition Examination Survey (NHANES III): younger American adults - Kuopio Ischemic Heart Disease Risk Factor Study: middle-aged Finnish men - Hordaland Health Study: middle-aged Norwegian women • Associated with vitamin B12 but not with folate status: - Women’s Health and Aging Study: physically disabled older American women - Rotterdam Study: older Dutch adults • Associated with neither folate nor vitamin B12 status: - New Mexico Elder Health Survey: older Hispanic and non-Hispanic white adults - Hordaland Health Study: Norwegian middle-aged men and older adults

  8. METHODS

  9. Subjects • Kuopio Ischaemia Heart Disease Study • 2,313 middle-aged (42-60 yo) men: Kuopio, Eastern Finland • Baseline: 1984.3. - 1989.12. • Follow-up: till the end of2000 (mean: 13 yr)

  10. Baseline Assessment • 4-day food record - nutrient content: analyzed by Nutrica - vitamin intake: adjusted for energy intake - supplements: not calculated ∵ only 13% of the sample used antixidants, folate not commonly used in the 1980s • Questionnaire - Human Population Laboratory Depression Scale (exclusion criteria) - demographics - smoking, drinking • BMI (ht, wt)

  11. Human Population Laboratory Depression Scale • Screening general population samples • Exclusion criteria : score > 5 (n = 287) • 18-items, measuring: - mood disturbance - problems with eating and sleeping - a negative self-concept - trouble with concentration - loss of energy - psychomotor retardation or agitation • Validity: highly correlated with the Beck Depression Inventory score • Reliability: Cronbach’s alpha = 0.71

  12. Follow-Up Assessment • Outcome discharge diagnosis of depressive disorders • Source national hospital discharge register • Diagnosis criteria ICD-8 (years 1985-86) ICD-9 (years 1987-95) ICD-10 (years 1996-2000)

  13. Statistical Analysis • RR of depression: Cox ‘proportional hazards’ model - model 1: adjusted for age, examination years - model 2: adjusted for age, examination years, SES, depression score, energy–adjusted daily intake of fiber and vitamin C, total fat intake • Differences in baseline characteristics b/w subjects with and without depression during the follow-up period: - Student t test - Mann-Whitney U test - X2 test

  14. RESULTS

  15. RR of Depression According to Energy-Adjusted Mean Intake of Folate • Further adjustment for marital status, education, smoking, alcohol consumption: RR = 2.51 (1.16-5.45), p = 0.020 • Excluding subjects with depression during the first 2 years of follow-up: (→ 44 cases) - model 1: RR = 3.13 (1.58-6.19), p=0.001 - model 2: RR = 2.57 (1.16-5.70), p=0.021 • Excluding subjects with a mental disorder before the baseline: (→ 40 cases) - model 1: RR = 3.16 (1.54-6.48), p=0.002 - model 2: RR = 2.53 (1.17-5.48), p=0.019

  16. RR of Depression According to Energy-Adjusted Mean Intake of Folate • Adjustment for total energy intake: - model 1: RR = 3.01 (1.56-5.82), p=0.001 • Excluding subjects with history of cancer or CVD: (→ 35 cases) - model 1: RR = 2.82 (1.35-5.89), p=0.006 - model 2: RR = 2.51 (1.06-5.95), p=0.036

  17. DISCUSSION

  18. Discussion • No correlation b/w B12 intake and depression: Finnish diets – dairy products, meat • Higher energy intake in depressed subjects: no difference in appetite, BMI Morris et al. (2003) – overweight among depressed subjects

  19. Limitations of the Study • Other health features of a folate-rich diet might explain the relationship b/w dietary folate and depression • Changes in eating habits during the follow-up period: folate intake↓by 7.1% (268 → 248 ug/d) during 11 years of follow-up • Age & gender difference • No national register of out-patients with depression • Many depressed people do not seek treatment

  20. APPLICATION TO OUR STUDY

  21. Consistent results • Prevalence of folate deficiency - Finland study: 25% reached RDI - Taiwan study: deficiency – none borderline deficiency – 18% in men 12% in women - Mexican American study: deficiency < 1%

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