Inflammation in psychopathology of depression: Clinical, biological, and therapeutic implications

Increasing evidence suggests that inflammation responses play an important role in the pathophysiology of depression. Clinically depressed patients manifest higher levels of inflammatory biomarkers, while proinflammatory cytokines induce neuropsychiatric symptoms (sickness behavior) as well as major depressive episode. Mechanisms that might be responsible for inflammation-mediated neuropsychiatric and depressive symptoms are vital in understanding “mind-body” interface; these have been studied in clinical and animal models (e.g., interferon-α-induced depression in patients with chronic hepatitis C, one of the most notable clinical models for testing inflammation theory of depression and an excellent approach to investigate development of depression in a prospective manner). Furthermore, the anti-inflammatory pathway has become a hot topic in looking for new antidepressant therapies. Recently, omega-3 polyunsaturated fatty acids (omega-3 PUFAs or n-3 PUFAs) have gained more attention as a promising treatment for depression. raEicosapentanoic acid and docosahexanoic acid, major bioactive components of omega-3 PUFAs, are both natural anti-inflammatory and antidepressant agents. Here, we review recent epidemiological studies, cross-sectional and longitudinal case-controlled studies, interventional clinical trials, as well as basic animal and cellular studies to prove the linkage among omega-3 PUFAs, inflammation, and depression.