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UND Life Sciences
13800 Fairhill Road, no. 321
Shaker Heights, OH 44120
E-mail: undurti{at}hotmail.com
Dear Sir:
The conclusion of the recent meta-analysis by Appleton et al (1) that depression is more likely in those whose intakes of long-chain polyunsaturated fatty acids (LCPUFAs), especially of n–3 fatty acids, are low suggests that depression could be a disorder of low-grade systemic inflammatory condition because LCPUFAs modulate proinflammatory events.
Recent studies showed that proinflammatory cytokines might cause depressive illness. This conclusion is based on the observations that 1) activation of the immune system and administration of endotoxin (lipopolysaccharide; LPS) or interleukin-1 (IL-1) to experimental animals induces sickness behavior that resembles depression (2); 2) activation of the immune system is observed in many depressed patients (3); 3) depression is more frequent in those with medical disorders associated with immune dysfunction (4); 4) treatment of patients with cytokines can produce symptoms of depression (4); 5) chronic treatment with antidepressants inhibits sickness behavior induced by LPS (5); 6) pro-inflammatory cytokines activate the hypothalamo-pituitary-adrenocortical axis (HPAA), which is activated in depressed patients (2); 7) cytokines activate cerebral noradrenergic systems, which is known to occur in depressed patients (4); and 8) several proinflammatory cytokines activate brain serotonergic systems, which have been implicated in major depressive illness and its treatment (6, 7). These results suggest that depression could be a low-grade systemic inflammatory condition.
The central nervous system regulates the production of the proinflammatory cytokines: tumor necrosis factor, IL-1, high mobility group-1, IL-6, and macrophage migration inhibitory factor through the efferent vagus nerve (8, 9). Acetylcholine, the principal vagal neurotransmitter, inhibits the production of proinflammatory cytokines through a mechanism dependent on the 7 nicotinic acetylcholine receptor subunit. Because vagal nerve stimulation (VNS) is of benefit in depression, I proposed that the beneficial effect of VNS in depression is due to its inhibitory action on the production of proinflammatory cytokines (10).
A significant decrease in n–3 fatty acids in plasma or in the membranes of red blood cells has been reported in subjects with depression (11–13). n–3 Fatty acids suppress the production of IL-1ß, IL-2, IL-6, and TNF-; therefore, n–3 fatty acids could play a major role in depression through their role in maintaining membrane fluidity, which influences neurotransmission, and in modulating the production of proinflammatory cytokines (14). In addition, antidepressants exhibit an immunoregulating effect by reducing the release of proinflammatory cytokines, by increasing the release of endogenous antagonists of proinflammatory cytokines such as IL-10 and, finally, by acting like inhibitors of cyclooxygenase (15). Double-blind placebo-controlled and other studies have shown that consumption of the n–3 fatty acids eicosapentaenoic acid and docosahexaenoic acid is associated with a longer period of remission in depressed patients (16–18). Thus, epidemiologic, experimental, and clinical data favor the idea that polyunsaturated fatty acids could play a role in the pathogenesis and treatment of depression. Well-planned larger trials with adequate power to detect clinically important benefits are required to determine the relevant dose of fatty acids to be used for the treatment of depression.
ACKNOWLEDGMENTS
The author had no conflict of interest to declare.
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