Phospholipid Hypothesis of Depression: From Molecular Biology, Neuroimaging to Behaviour

Overview

With the dissatisfaction of monoamine-based pharmacotherapy and the high comorbidity of physical illness in depression, the serotonin hypothesis seems to fail in approaching the etiology of depression. Based upon the evidence from epidemiological data, case-control studies of PUFAs compositions, and antidepressant effects in clinical trials, phospholipid polyunsaturated fatty acids (PUFAs) is enlightening a promising path to discover the unsolved of depression.

There are several important questions to answer regarding phospholipid polyunsaturated fatty acids (PUFAs) hypothesis of depression. Firstly, although case-control studies revealed that depressive patients had lower levels of omega-3 PUFAs, the abnormal findings in individual PUFA of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) or arachidonic acid (AA) are not consistent. Secondly, the deficits in n-3 PUFAs are related to their metabolic enzymes. However, the association study of polymorphisms of PUFA-metabolism related genes in depression is limited. Thirdly, the active component of antidepressant effect in n-3 PUFAs is still in debate. Fourthly, the molecular mechanisms of n-3 PUFAs' antidepressant effects have yet to be elucidated in human brain functional neuroimaging or in cellular models. This 3-year proposal is divided into 2 clinical studies. In study 1, the investigators aim to test the clinical and biological effects of n-3 PUFAs (EPA: 3.5 g/d and DHA: 1.75 g/d versus placebo: high oleic oil) for depressive symptoms in a 12-week, double-blind, placebo-controlled trial of patients with drug-free MDD. In study 2, the investigators will measure the biological and neuroimaging markers to investigate the biological mechanisms of EPA (3.5 g/d) versus DHA (1.75 g/d) in 12-week, double-blind, randomized-controlled trial with patients with drug-free major depression disorder (MDD).

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