Background: Animals show seasonal changes in the endocrine and immune system in response to vvinter stressors. Even though increased inflammation has been implicated in the pathophysiology of depression, whether immune disorder is a key mediator in seasonal affective depression (SAD) is unknown. Here, we hypothesized that short photoperiods in vvinter may induce inflammatory response, which contributes to SAD, and that light treatments should normalize immune function and improve depressive symptoms. Methods.: Twenty patients vvith a diagnosis of SAD, and a score on the HAM 29 of 20 or higher were recruited for this study. Twenty-one healthy subjects with no personal and family history of psychiatric disorder were matched to patients according to age and sex. Patients and controls were sampled during winter between November and January, inclusive. A subset of SAD patients (N= 13) was re-sampled after 4 weeks of light therapy. Blood samples were assayed for macrophage activity, lymphocyte proliferation and cytokine release. Results: SAD patients showed significantly higher macrophage activity and lower lymphocyte proliferation in winter compared to healthy subjects. The concentrations of macrophage-produced proinflammatory cytokines interleukin-1 beta and tumour necrosis factor-alpha, and T-helper (Th)-1 produced cytokine, interferon-y were all significantly increased. In contrast, no significant changes in Th2-produced cytokines were observed. Light therapy significantly improved depressive scores, which was associated with attenuation of decreased lymphocyte functions, increased macrophage activity and level of proinflammatory cytokines. Conclusion: SAD patients have increased macrophage and Thl type responses in winter, and light therapy normalized immune functions and depressive symptoms. These results support an inflammatory hypothesis for SAD and an immunomodulatory role of light Lherapy. (C) 2015 Elsevier B.V. All rights reserved.