ObjectiveEstablish whether inflammatory biomarkersserum amyloid A (SAA), C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor- (TNF-)are related to key symptoms of depression, including anxiety and fatigue, in a cross-sectional, out-patient setting to identify biomarkers that reflect psychiatric symptomatology in a naturalistic, real-life population. MethodsWe measured SAA, CRP, IL-6, and TNF- in plasma samples from 89 adult psychiatric out-patients by multiplex, high-sensitivity electrochemiluminescent assays. Psychiatric symptoms were evaluated using the Hamilton Depression Rating Scale (HAMD-17), the Patient Health Questionnaire (PHQ-9), and the Center for Epidemiological Studies Depression Scale (CES-D). ResultsPlasma SAA was most robustly associated with depressive symptoms across diagnostic boundaries in this cohort of out-patients. Elevated SAA was significantly associated with higher total scores on the HAMD-17 scale and correlated with multiple scale items that rated symptoms of fatigue and depressed mood, but not with anxiety-related items. ConclusionsSAA might constitute a cross-diagnostic marker indicative of depressed mood and fatigue in a naturalistic patient setting. Because SAA activates Toll-like receptors 2 and 4, present on macrophages and glial cells, its association with depression severity could also implicate this inflammatory mediator in the pathogenesis of mood disorders.