Does neuroimmune dysfunction mediate seasonal mood changes in winter depression?

BACKGROUND: Animal studies have demonstrated seasonal changes in immune function mediated by nocturnal melatonin duration as a biological signal for photoperiod. Recent research has highlighted the potential role of neuroimmune dysfunction in depressive disorders. The etiology of winter depression (seasonal affective disorder, or SAD) is not known, but a number of studies have provided support for both photoperiod and neurotransmitter hypotheses. HYPOTHESIS: A new hypothesis is presented that links the SAD data on melatonin, photoperiod, and neurotransmitters by proposing that seasonal increases in proinflammatory cytokines are critical in the pathophysiology of winter SAD. TESTING THE HYPOTHESIS: In SAD patients, but not healthy subjects: proinflammatory cytokines will be increased and the Th1/Th2 balance will be shifted to the left in winter compared to summer; neuroimmune function will be correlated with nocturnal melatonin duration in SAD patients; and light treatment will correct neuroimmune dysfunction. IMPLICATIONS OF THE HYPOTHESIS: Diagnostic tests for SAD may be developed using cytokine assays; neuroimmune dysfunction may be predictors of response to treatments; new treatments for SAD (immune or anti-inflammatory treatment) may be developed.