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1 2013, Vol. 21, No. 3, Advances in Psychological Science DOI: /SP.J * n-3 系多元不饱和脂肪酸对抑郁症的影响及其机制 ( 1, ) ( 2, ) 越来越多的实验证据表明, n-3 系多元不饱和脂肪酸 (n-3pufa) 与抑郁症之间存在联系, 二十二碳六烯酸 (DHA) 和二十碳五烯酸 (EPA) 可能具有预防和治疗抑郁症的作用回顾国内外关于 n-3pufa 与抑郁症之间存在的负性关系的研究并介绍其主要的研究结果和现状, 解释 n-3pufa 引起的抗抑郁效果可能涉及的神经机制, 包括神经传递葡萄糖的新陈代谢促炎细胞因子的分泌 5- 羟色胺 (5-HT) 以及脑源性神经营养因子 (BDNF) 的水平还有神经元的凋亡等的变化并且总结现有研究中存在的一些问题, 例如使用的 n-3pufa 种类和剂量问题, DHA 或 EPA 是否对于不同种类的抑郁症均有效, 单独作用还是共同作用才能引起抗抑郁效果等等, n-3pufa 对抑郁症病理机制的具体影响可能是未来的研究方向 n-3pufa; DHA; EPA; 抑郁症 ; 神经机制 ; 5-HT; BDNF B845 1 引言 (Depressive Disorder),,,, 2001,, 2020, (Major Depressive Disorder, MDD) n-3 (polyunsaturated fatty acid, PUFA),, 16-22, : * (BBA100016) :, renj@zjnu.cn, PUFA n-3 n-6 n-7 n-9, n-3 n-6 n-3pufa ( ω 3PUFA), α- (alfa-linolenic acid, ALA) (eicosapentaenoic acid, EPA) (docospentaenoic acid, DPA) (docosahexaenoic acid, DHA); n-6pufa ( ω 6PUFA),, (linoleic acid, LA) γ- (gamma-linolenic acid, GLA) -γ- (double high gamma-linolenic acid, DHGLA) (arachidonic acid, AA) n-3 n-6pufa,,,, n-3 n-6pufa,, n-6pufa n-6/n-3pufa, n-3pufa 458

2 3 : n (Simopoulos, 2008) n-3pufa (Arab, 2003), PUFA n-3pufa, (Simopoulos, 2002; Young & Conquer, 2005) EPA DHA n-3pufa,,, DHA EPA,,,, DHA EPA EPA (Narayan, Miyashita, &Hosakawa, 2006) DHA, DHA 15%, (McNamara et al., 2008) DHA, DHA (Carver, Benford, Han, & Cantor, 2001) DHA - (Coti, O Kusky, & Innis, 2006; Yavin, Himovichi, & Eilam, 2009), DHA 80, DHA EPA, n-3pufa (Ellis & Sanders 1977; Fehily, Bowey, Ellis, Meade, & Dickerson, 1981) n-3pufa, (Bourre, 2007; Colangelo, He, Whooley, Daviglus, & Liu, 2009; Riemer, Maes, Christophe, & Rief, 2009) n-3pufa, n-3,, n-3pufa, n-3pufa DHA EPA n-3pufa, n-3pufa,, n-3pufa DHA EPA 2 n-3pufa 与抑郁症关联的主要证据, n-3pufa, 2.1 临床观察方面的证据典型案例研究 n-3pufa n-3pufa gEPA 2gDHA, 20mg,, (Chiu, Huang, Shen, & Su, 2003), Sontrop, n-3pufa, n-6pufa, (Sontrop & Campbell, 2006),,,,, 调查研究 n-3pufa, Hibbeln Lancet (Hibbeln, 1998); 22 ( ), 16

3 DHA, EPA (Hibbeln, 2003), Noaghiul Hibbeln (Noaghiul & Hibbeln, 2003), DHA (Mamalakis, Tornaritis, & Kafatos, 2002),, (Tanskanen et al., 2001a,b; Silvers, & Scott, 2002) 865 n-3pufa (Miyake et al., 2006), Crowe 36, (Crowe, Skeaff, Green, & Gray, 2007) 771, EPA DHA (Suzuki et al., 2004) Sublette 2, DHA n-3 n-6pufa (n-3 n-6) (Sublette, Hibbeln, Galfalvy, Oquendo, & Mann, 2006) 8 n-3pufa 0.10%, (Astorg et al., 2008) 29,133 50~69 n-3pufa, (Hakkarainen et al., 2004a, b);, Browne n-3pufa, n-3pufa (Browne, Scott, & Silvers, 2006), n-3pufa n-3pufa,,,,, n-3pufa n-3pufa n-3pufa,,, 2.2 实验研究方面的证据, n-3pufa,, n-3pufa, 人类实验研究, n-3pufa, n-3pufa,, DHA EPA 8 (randomized clinical trial, RCT), 22, 6.6gEPA+DHA,, n-3pufa 21 (HAM-D), (Su, Huang, Chiu, &

4 3 : n Shen, 2003), Jazaiery 48, mg EPA, 20mg (fluoxetine), EPA, (Jazaiery et al., 2008) Frangou 75 1g EPA 2g EPA 12, EPA, (Frangou, Lewis, & McCrone, 2006), 24 RCT, Su 8 3.4g n-3pufa, n-3pufa 6 8 HAM-D, ; (Su et al., 2008) Marangell , 4 (DSM-IV), 6 2g DHA, (Marangell et al., 2003) g, Silvers (Silvers, Woolley, Hamilton, Watts, & Watson, 2005), Rogers n-3pufa RCT, gEPA+DHA n-3pufa, (DASS) (Rogers et al., 2008), Llorente, 4 200mgDHA, DHA DHA (Llorente et al., 2003) Keck 4, 6g EPA (Keck et al., 2006) Doornbos DHA, DHA 16 3 (220 mg/d) DHA (220 mg/d) DHA ( 220 mg/d), DHA (Doornbos et al., 2009) n-3pufa n-3pufa, (heterogeneity) (Lin, Huang, & Su, 2010; Bloch, & Hannestad, 2012),, n-3pufa, ; n-3pufa 动物实验研究 n-3pufa, n-3pufa Levant Long- Evans DHA DHA, (brain-derived neurotrophic factor, BDNF) 5- (5-hydroxytryptamine, 5-HT) DHA, BDNF DHA (Levant et al., 2008) n-3pufa, BDNF (Venna et al., 2009) ( DHA EPA) (modified forced swimming test, MFST) (, ), n-3pufa (Ferraz

5 et al., 2011) 93M EPA+DHA 0% 0.5% 1%, SD ( 8 )12, n-3pufa, -6 (IL-6) (cyclic AMP, camp) (cyclic AMPresponsive element binding protein CREB), 5-HT CREB, (Park, Moon, & Kim, 2012) 5-HT 5-HT 1A n-3pufa, n-3pufa BDNF 5-HT 1A BDNF n-3pufa 5- (Vines et al., 2012) 3 n-3pufa 抗抑郁的机理解释 n-3pufa, 50, (NE) 5- (5-HT) (DA), (Aan het Rot, Mathew, & Charney, 2009),,,,,, - - (hypothalamuspituitary-adrenal, HPA) - - (hypothalamic-pituitary-thyroid, HPT), 5-HT,, n-3pufa,,,, BDNF, (Logan, 2003),, n-3pufa,, 5-HT, BDNF, 3.1 解释一 :n-3pufa 对 5- 羟色胺系统的影响, n-3pufa 5-5-HT, 5-HT,, 5-HT 1A,,, 5-HT 1A (Savitz, Lucki, & Drevets, 2009) n-3pufa, n-3 5-HT DHA, 5-HT 5HT 2A DHA (Logan, 2003) 1998, Hibbeln n-3pufa 5-HT, DHA 5-HT, 5-HT (Hibbeln et al., 1998); EPA DHA 5-HT (Branchey, Branchey, & Hibbeln, 2011) 5-HT 1A 30% 5-HT,, 5-HT, (Richardson-Jones et al., 2010), 5-HT

6 3 : n n-3pufa n-3/n-6 (Borsonelo, & Galduroz, 2008) Vines 5-HT 5-HT 1A n-3pufa, n-3pufa 5- (Vines et al., 2012) 3.2 解释二 :n-3pufa 对免疫系统 ( 促炎细胞因子 proinflammatory cytokines) 的影响 n-3pufa (Maes, Smith, & Scharpe, 1995; Smith, 1991), (Miller, Maletic, & Raison, 2009; Dowlati et al., 2010), -1β (IL-1β), -2 (IL-2), -6 (IL-6) γ- -α (TNF- α) (Raison, Capuron, & Miller, 2006), -, mrna C, (Maes et al., 2011); α, (Bonaccorso et al., 2001); (Logan, 2003; Liperoti, Landi, Fusco, Bernabei, & Onder, 2009),, EPA DHA (Su, 2012) (Simopoulos, 2002) n-3pufa 15, DHA (Liperoti et al., 2009) n-3pufa, n-6 n-3, (Dinan et al., 2009) n-3pufa 3.3 解释三 :n-3pufa 对脑源性神经营养因子的影响,,,, BDNF, BDNF (Kim et al., 2007; Krishnan & Nestler, 2008; Castrén, Võikar, & Rantamäki, 2007) BDNF (De Foubert et al., 2004),, BDNF (Lee, Kim, H., Park, & Kim, Y. K., 2007) BDNF,, BDNF (Dwivedi, 2009) BDNF n-3pufa BDNF, BDNF (Molteni, Barnard, Ying, Roberts, & Gómez-Pinilla, 2002; Wu, Molteni, Ying, & Gomez- Pinilla, 2003) n-3pufa BDNF ; DHA BDNF (Rao et al., 2007) n-3pufa BDNF (Levant et al., 2008) n-3pufa,, BDNF (Venna et al., 2009) EPA DHA CREB BDNF (Park et al., 2012) 4 问题与展望,,

7 n-3pufa,, n-3pufas, n-3pufa n-3pufa EPA DHA EPA DHA (Grenyer et al., 2007),, n-3pufa n-3pufa,, EPA DHA, EPA DHA,,, EPA DHA,,,,, n-3pufa,, n-3pufa, n-3pufa, D2,,,, BDNF, (Sinclair, Begg, Mathai, Weisinger, & Richard, 2007), BDNF 5-,, ; BDNF 5-, n-3pufa BDNF 5-HT, n-3pufa, n-3pufa, n-3pufa Aan het Rot, M., Mathew, S. J., & Charney, D. S. (2009). Neurobiological mechanisms in major depressive disorder. Canadian Medical Association Journal, 180, Arab, L. (2003). Biomarkers of fat and fatty acid intake. Nutrition, 133, 925S 932S. Astorg, P., Couthouis, A., Bertrais, S., Arnault, N., Meneton, P., & Guesnet, P., Hercberg, S. (2008). Association of fish and long-chain n-3 polyunsaturated fatty acid intakes with the occurrence of depressive episodes in middle-aged French men and women. Prostaglandins, Leukotrienes and Essential Fatty Acids, 78, Bloch, M. H., & Hannestad, J. (2012). Omega-3 fatty acid for the treatment of depression: Systematic review and meta-analysis. Molecular Psychiatry, 17, Bonaccorso, S., Puzella, A., Marino, V., Pasquini, M., Biondi, M., Artini, M., Maes, M. (2001). Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms. Psychiatry Research, 105, Borsonelo, E. C., & Galduróz, J. C. (2008). The role of polyunsaturated fatty acids (PUFAs) in development, aging and substance abuse disorders: Review and propositions. Prostaglandins, Leukotrienes and Essential Fatty Acids, 78, Bourre, J. M. (2007). Dietary omega-3 fatty acids for women. Biomedicine & Pharmacotherapy, 61, Branchey, L. B., Branchey, M., & Hibbeln, J. R. (2011). Higher n-3 fatty acids are associated with more intense fenfluramine-induced ACTH and cortisol responses among cocaine-abusing men. Psychiatry Research, 188, Browne, J. C., Scott, K. M., & Silvers, K. M. (2006). Fish consumption in pregnancy and omega-3 status after birth are not associated with postnatal depression. Journal of Affective Disorders, 90(2-3), Carver, J. D., Benford, V. J., Han, B., & Cantor, A. B. (2001). The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects. Brain Research Bulletin, 56(2), Castrén, E., Võikar, V., & Rantamäki, T. (2007). Role of neurotrophic factors in depression. Current Opinion in Pharmacology, 7(1), Chiu, C. C., Huang, S. Y., Shen, W. W., & Su, K. P. (2003). Omega-3 fatty acids for depression in pregnancy. Psychiatry, 160, 385. Colangelo, L. A., He, K., Whooley, M. A., Daviglus, M. L., & Liu, K. (2009). Higher dietary intake of long-chain ω-3 polyunsaturated fatty acids is inversely associated with

8 3 : n depressive symptoms in women. Nutrition, 25, Coti, B. P., O Kusky, J. R., & Innis, S. M. (2006). Maternal dietary (n-3) fatty acid deficiency alters neurogenesis in the embryonic rat brain. Nutrition, 136, Crowe, F. L., Skeaff, C. M., Green, T. J., & Gray, A. R. (2007). Serum phospholipid n-3 long-chain polyunsaturated fatty acids and physical and mental health in a population-based survey of New Zealand adolescents and adults. Clinical Nutrition, 86, De Foubert, G., Carney, S. L., Robinson, C. S., Destexhe, E. J., Tomlinson, R., Hicks, C. A., Zetterström, T. S. C. (2004). Fluoxetine-induced change in rat brain expression of brain-derived neurotrophic factor varies depending on length of treatment. Neuroscience, 128, Dinan, T., Siggins, L., Scully, P., O Briena, S., Ross, P., & Stanton, C. (2009). Investigating the inflammatory phenotype of major depression: Focus on cytokines and polyunsaturated fatty acids. Journal of Psychiatric Research, 43, Doornbos, B., Goor, S. A., Dijck-Brouwer, D. A. J., Schaafsma, A., Korf, J., & Muskiet, F. A. J. (2009). Supplementation of a low dose of DHA or DHA+AA does not prevent peripartum depressive symptoms in a small population based sample. Progress in Neuro- Psychopharmacology & Biological Psychiatry, 33, Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E. K., & Lanctôt, K. L. (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry, 67, Dwivedi, Y. (2009). Brain derived neurotrophic factor: Role in depression and suicide. Neuropsychiatric Disease and Treatment, 5, Ellis, F. R., & Sanders, T. A. (1977). Long chain polyunsaturated fatty acids in endogenous depression. Journal of Neurology, Neurosurgery & Psychiatry, 40, Fehily, A. M., Bowey, O. A., Ellis, F. R., Meade, B. W., & Dickerson, J. W. (1981). Plasma and erythrocyte membrane long chain polyunsaturated fatty acids in endogenous depression. Neurochemistry International, 3, Ferraz, A. C., Delattre, A. M., Almendra, R. G., Sonagli, M., Borges C., Araujo P. Lima, M. M. S. (2011). Chronic ω-3 fatty acids supplementation promotes beneficial effects on anxiety, cognitive and depressive-like behaviors in rats subjected to a restraint stress protocol. Behavioural Brain Research, 219, Frangou, S., Lewis, M., & McCrone, P. (2006). Efficacy of ethyl-eicosapentaenoic acid in bipolar depression: Randomised double-blind placebo-controlled study. Psychiatry, 188, Grenyer, B. F. S., Crowe, T., Meyer, B., Owen, A. J., Grigonis-Deane, E. M., Caputi, P., & Howe, P. R. C. (2007). Fish oil supplementation in the treatment of major depression: A randomised double-blind placebo-controlled trial. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31, Hakkarainen, R., Partonen, T., Haukka, J., Virtamo, J., Albanes, D., & Lonnqvist, J. (2004a). Food and nutrient intake in relation to mental wellbeing. Nutrition, 3, 14. Hakkarainen, R., Partonen, T., Haukka, J., Virtamo, J., Albanes, D., & Lonnqvist, J. (2004b). Is low dietary intake of omega-3 fatty acids associated with depression? Psychiatry, 161, Hibbeln, J. R. (1998). Fish consumption and major depression. Lancet, 351, Hibbeln, J. R. (2003). Seafood consumption, the DHA content of mothers' milk and prevalence rates of postpartum depression: A cross-national, ecological analysis. Journal of Affective Disorders, 69, Hibbeln, J. R., Linnoila, M., Umhau, J. C., Rawlings, R., George, D.T., & Salem, N., Jr. (1998). Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biological Psychiatry, 44, Jazaiery, S., Tehrani-Doost, M., Keshavarz, S. A., Hosseini, M., Djazayery, A., Amini, H., Peet, M. (2008). Comparison of therapeutic effects of omega-3 fatty acid eicosapentaenoic acid and fluoxetine, separately and in combination, in major depressive disorder. Psychiatry, 42, Keck, P. E., Jr., Mintz, J., McElroy, S. L., Freeman, M. P., Suppes, T., & Frye, M. A., Post, R. M. (2006). Double-blind, randomized, placebo-controlled trials of ethyl-eicosapentanoate in the treatment of bipolar depression and rapid cycling bipolar disorder. Biological Psychiatry, 60, Kim, Y. K., Lee, H. P., Won, S. D., Park, E. Y., Lee, H. Y., Lee, B. H.,... Choi, S. H. (2007). Low plasma BDAF is associated with suicidal behavior in major depression. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 31, Krishnan, V., & Nestler, E. J. (2008). The molecular neurobiology of depression. Nature, 455, Lee, B. H., Kim, H., Park, S. H., & Kim, Y. K. (2007). Decreased plasma BDNF level in depressive patients. Journal of Affective Disorders, 101, Levant, B., Ozias, M. K., Davis, P. F., Winter, M., Russell, K. L., Carlson, S. E., Mccarson, K. E. (2008). Decreased brain docosahexaenoic acid content produces neurobiological effects associated with depression: Interactions with reproductive status in female rats. Psychoneuroendocrinology, 33, Lin, P. Y., Huang, S. Y., & Su, K. P. (2010). A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biological Psychiatry, 68,

9 Liperoti, R., Landi, F., Fusco, O., Bernabei, R., & Onder, G. (2009). Omega-3 polyunsaturated fatty acids and depression: A review of the evidence. Current Pharmaceutical Design, 15, Llorente, A. M., Jensen, C. L., Voigt, R. G., Fraley, J. K., Berretta, M. C., & Heird, W. C. (2003). Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing. American Journal of Obstetrics and Gynecology, 188, Logan, A. C. (2003). Neurobehavioral aspects of omega-3 fatty acids: Possible mechanisms and therapeutic value in major depression. Alternative Medicine Review, 8, Maes, M., Leonard, B., Fernandez, A., Kubera, M., Nowak, G., Veerhuis, R.,... Berk, M. (2011). (Neuro)inflammation and neuroprogression as new pathways and drug targets in depression: from antioxidants to kinase inhibitors. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 35, Maes, M., Smith, R. S., & Scharpe, S. (1995). The monocyte-t-lymphocyte hypothesis of major depression. Psychoneuroendocrinology, 20, Mamalakis, G., Tornaritis, M., & Kafatos, A. (2002). Depression and adipose essential polyunsaturated fatty acids. Prostaglandins, Leukotrienes and Essential Fatty Acids, 67, Marangell, L. B., Martinez, J. M., Zboyan, H. A., Kertz, B., Kim, H. F., & Puryear, L. J. (2003). A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. The American Journal of Psychiatry, 160, McNamara, R. K., Jandacek, R., Rider, T., Tso, P., Stanford, K. E., Hahn, C. G., & Richtand, N. M. (2008). Deficits in docosahexaenoic acid and associated elevations in the metabolism of arachidonic acid and saturated fatty acids in the postmortem orbitofrontal cortex of patients with bipolar disorder. Psychiatry Research, 160, Miller, A. H., Maletic, V., & Raison, C. L. (2009). Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biological Psychiatry, 65, Miyake, Y., Sasaki, S., Yokoyama, T., Tanaka, K., Ohya, Y., Fukushima, W., Hirota, Y. (2006). Risk of postpartum depression in relation to dietary fish and fat intake in Japan: The Osaka Maternal and Child Health Study. Psychological Medicine, 36, Molteni, R., Barnard, R. J., Ying, Z., Roberts, C. K., & Gómez-Pinilla, F. (2002). A high-fat, refined sugar diet reduces hippocampal brain-derived neurotrophic factor, neuronal plasticity, and learning. Neuroscience, 112, Narayan, B., Miyashita, K., & Hosakawa, M. (2006).Physiological effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)-A review. Food Reviews International, 22(3), Noaghiul, S., & Hibbeln, J. R. (2003). Cross-national comparisons of seafood consumption and rates of bipolar disorders. The American Journal of Psychiatry, 160, Park, Y., Moon, H. J., & Kim, S. H. (2012). N-3 polyunsaturated fatty acid consumption produces neurobiological effects associated with prevention of depression in rats after the forced swimming test. Journal of Nutritional Biochemistry, 23, Raison, C. L., Capuron, L., & Miller, A. H. (2006). Cytokines sing the blues: Inflammation and the pathogenesis of depression. Trends in Immunology, 27, Rao, J. S., Ertley, R. N., Lee, H. J., De Mar, J. C., Jr., Arnold, J. T., Rapoport, S. I., & Bazinet, R. P. (2007). n-3 polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism. Molecular Psychiatry, 12, Richardson-Jones, J. W., Craige, C. P., Guiard, B. P., Stephen, A., Metzger, K. L., Kung, H. F., Leonardo, E. D. (2010). 5-HT1A autoreceptor levels determine vulnerability to stress and response to antidepressants. Neuron, 65, Riemer, S., Maes, M., Christophe, A., & Rief, W. (2009). Lowered omega-3 PUFAs are related to major depression, but not to somatization syndrome. Journal of Affective Disorders, 123, Rogers, P. J., Appleton, K. M., Kessler, D., Peters, T. J., Gunnell, D., Hayward, R. C., Ness, A. R. (2008). No effect of n-3 long-chain polyunsaturated fatty acid (EPA and DHA) supplementation on depressed mood and cognitive function: A randomised controlled trial. Nutrition, 99, Savitz, J., Lucki, I., & Drevets, W. C. (2009). 5-HT 1A receptor function in major depressive disorder. Progress in Neurobiology, 88, Silvers, K. M., & Scott, K. M. (2002). Fish consumption and self-reported physical and mental health status. Public Health Nutrition, 5, Silvers, K. M., Woolley, C. C., Hamilton, F. C., Watts, P. M., & Watson, R. A. (2005). Randomised double-blind placebo-controlled trial of fish oil in the treatment of depression. Prostaglandins, Leukotrienes and Essential Fatty Acids, 72, Simopoulos, A. P. (2002). Omega-3 fatty acids in inflammation and autoimmune diseases. Journal of the American College of Nutrition, 21, Simopoulos, A. P. (2008). The importance of the omega-6/ omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Experimental Biology and Medicine, 233, Sinclair, A. J., Begg, D., Mathai, M., & Weisinger, R. S. (2007). Omega 3 fatty acids and the brain: Review of

10 3 : n studies in depression. Asia Pacific Journal of Clinical Nutrition, 16, Smith, R. S. (1991). The macrophage theory of depression. Medical Hypotheses, 35, Sontrop, J., & Campbell, M. K. (2006). ω-3 polyunsaturated fatty acids and depression: A review of the evidence and a methodological critique. Preventive Medicine, 42(1), Su, K. P. (2012). Inflammation in psychopathology of depression: Clinical, biological, and therapeutic implications. BioMedicine, 2, Su, K. P, Huang, S. Y., Chiu, T. H., Huang, K. C, Huang, C. L, Chang, H. C., & Pariante, C. M. (2008). Omega-3 fatty acids for major depressive disorder during pregnancy: Results from a randomized, double-blind, placebo-controlled trial. Journal of Clinical Psychiatry, 69, Su, K. P., Huang, S. Y., Chiu, C. C., & Shen, W. W. (2003). Omega-3 fatty acids in major depressive disorder: A preliminary double-blind, placebo-controlled trial. European Neuropsychopharmacology, 13, Sublette, M. E, Hibbeln, J. R, Galfalvy, H., Oquendo, M. A., & Mann, J. J. (2006). Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. The American Journal of Psychiatry, 163, Suzuki, S., Akechi, T., Kobayashi, M., Taniguchi, K., Goto, K., Sasaki, S., Uchitomi, Y. (2004). Daily omega-3 fatty acid intake and depression in Japanese patients with newly diagnosed lung cancer. British Journal of Cancer, 90, Tanskanen, A., Hibbeln, J. R., Hintikka, J., Haatainen, K., Honkalampi, K., & Viinamaki, H. (2001a). Fish consumption, depression, and suicidality in a general population. Archives of General Psychiatry, 58, Tanskanen, A., Hibbeln, J. R., Tuomilehto, J., Uutela, A., Haukkala, A., Viinamaki, H., Vartiainen, E. (2001b). Fish consumption and depressive symptoms in the general population in Finland. Psychiatric Services, 52, Venna, V. R., Deplanque, D., Allet, C., Belarbi, K., Hamdane, M., & Bordet, R. (2009). PUFA induce antidepressant-like effects in parallel to structural and molecular changes in the hippocampus. Psychoneuroendocrinology, 34, Vines, A., Delattre, A. M., Lima, M. M. S., Rodrigues, L. S., Suchecki, D., Machado, R. B., Ferraz, A. C. (2012). The role of 5-HT 1A receptors in fish oil-mediated increased BDNF expression in the rat hippocampus and cortex: A possible antidepressant mechanism. Neuropharmacology, 62, Wu, A., Molteni, R., Ying, Z., & Gomez-Pinilla, F. (2003) A saturated-fat diet aggravates the outcome of traumatic brain injury on hippocampal plasticity and cognitive function by reducing brain-derived neurotrophic factor. Neuroscience, 119, Yavin, E., Himovichi, E., & Eilam, R. (2009). Delayed cell migration in the developing rat brain following maternal omega-3 alpha-linolenic acid dietary deficiency. Neuroscience, 162, Young, G., & Conquer, J. (2005). Omega-3 fatty acids and neuropsychiatric disorders. Reproduction Nutrition Development, 45, The Effect of n-3 Polyunsaturated Fatty Acids on Depressive Disorder and Its Mechanism GUO Xiaoyue 1 ; REN Jun 1 ; GUO Jianyou 2 ( 1 College of Teacher Education, Zhejiang Normal University, Jinhua , China) ( 2 Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing , China) Abstract: A growing body of evidence suggests that n-3 polyunsaturated fatty acid (n-3pufa) is associated with depressive disorder, and supplementation of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), which are the most common PUFA in the brain, may be of value in the prevention and treatment of depression. The purpose of this article is to review studies in this emerging area, identify and evaluate available evidence of a negative correction between n-3pufa intake and depression, and propose mechanisms that could explain such relationship. n-3pufa may play an etiological role in serotonergic transmission, glucose metabolism, and release of pro-inflammatory cytokines, brain-derived neurotrophic factor (BDNF) level, and neuronal apoptosis. Future studies are needed to examine the dosage response functions of n-3pufa, the specific roles of DHA or EPA in different clusters of depressive symptoms, whether DHA or EPA is effective in antidepressant treatments independently or coefficiently, as well as the potential clinical value of n-3pufa in major depression. Key words: n-3pufa; DHA; EPA; depression; neural mechanism; 5-HT; BDNF

专注于数字营养的移动健康公司解决一个吃的健康的问题中粮数字健康科技有限公司 COFCO Digital Health Technology Co. Ltd By Hong Bill Xu COFCO Group Tel:86(1

专注于数字营养的移动健康公司解决一个吃的健康的问题中粮数字健康科技有限公司 COFCO Digital Health Technology Co. Ltd By Hong Bill Xu COFCO Group Tel:86(1 专注于数字营养的移动健康公司解决一个吃的健康的问题中粮数字健康科技有限公司 COFCO Digital Health Technology Co. Ltd By Hong Bill Xu COFCO Group Tel:86(10)8500-6419 Fax:86(10)8561-5955 Email:xuh@cofco.com