Immunological Parameters and fMRI in SAD

Major depressive disorder (MDD) is a common and often seriously debilitating mental disorder. It goes along with structural changes in certain brain regions and alterations in brain functioning that can be detected by functional magnetic resonance imaging (fMRI). While the pathogenesis of the disorder still has not been completely understood, there is increasing evidence from multiple studies for a dysregulation of the immune system with systemic inflammation and consecutive neuroinflammation in MDD. Increased immune responses have also been demonstrated in fall-winter depression (seasonal affective disorder, SAD), which is a subtype of MDD or bipolar disorder with regularly occurring depressive episodes during fall and winter followed by remission or in the case of a bipolar course of illness hypomanic (seldom manic) episodes during the subsequent spring-summer period. Studies using fMRI have also reported correlates of altered brain function in SAD patients and several studies have substantiated altered immune functions and increased levels of inflammation in SAD. Bright artificial full-spectrum visible light (bright light therapy) has been termed the treatment of choice for SAD. However, about half of the patients do not respond to light therapy, experience side effects or object against the use for logistic reasons. Therefore, it is necessary to develop psychopharmacological alternatives for these patients. Intriguingly, omega-3 polyunsaturated fatty acids have been shown to possess anti-inflammatory properties and certain omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have antidepressant effects. Within this study we aim to examine the influence of a treatment with EPA and DHA on brain function assessed by fMRI and blood immunological parameters. We therefore propose a double-blind, randomized, controlled clinical trial of omega-3 fatty acids, specifically EPA 1.5 g and DHA 0.5 g per day, or placebo over 8 weeks in 40 depressive SAD patients and 40 healthy controls. Resting-state fMRI together with a facial discrimination task will be conducted 3 times at baseline and at weeks 4 and 8 in all subjects with concurrent tests of proinflammatory and anti-inflammatory immunological blood parameters. This will be the first study to explore the association of immune function and altered brain function in SAD patients and to assess the effects of treatment with omega-3 fatty acids on these parameters.