The Role of Brain Structure and Function in the Association Between Inflammation and Depressive Symptoms: A Systematic Review

Objective Major depressive disorder and related symptoms have been shown to be associated with inflammation, and this association is likely to be mediated through changes in brain structure and function. This article provides a systematic review of studies that have used brain imaging techniques to identify neural mechanisms linking inflammation and depressive symptoms. Methods A systematic search of online databases identified 26 studies that fulfilled the inclusion and exclusion criteria. Results In general, increased peripheral inflammation was associated with differences in function in several subcortical regions, as well as medial and ventral prefrontal regionsboth at rest (7 studies) and during exposure to emotional stimuli (14 studies). Also, increased activation in some of these regions was associated with depression (18 studies). Too few studies have measured neuroinflammation markers (three) or brain structure (three), so generalizations about these mechanisms cannot yet be made. Conclusions This review supports the view that peripheral inflammation is an etiological process that may influence depression via effects on brain function. Several methodological inconsistencies in the extant literature need to be addressed, most notably a lack of formal mediational testing in longitudinal designs and inconsistencies across imaging methods and inflammation induction and measurement techniques. Further work is also required to establish the mechanisms by which basal inflammation levels influence brain function and depressive symptoms in both healthy and clinical samples.