Ebrahim Haroon, M.D.

Assistant Professor of Psychiatry and Behavioral Sciences, Emory University School of Medicine

Inflammatory biotype of depression is characterized by symptoms such as anhedonia and psychomotor slowing resulting from disrupted neurotransmitter dynamics in regions associated with mood and cognition. Our previous studies have demonstrated that increased concentrations of the excitatory neurotransmitter glutamate in the basal ganglia regions during immune activation was associated with anhedonia and psychomotor slowing. Herein, we will present new data profiling neural and network level dysfunction that mediate the association between inflammation, glutamate and depressive symptoms. Concentrations of the inflammatory marker c-reactive protein (CRP) in the plasma and estimates of glutamate (Glu) in the basal ganglia (obtained using magnetic resonance spectroscopy, MRS) were combined using a hierarchical clustering algorithm to subdivide 41-unmedicated depressed subjects into High CRP-Glu (n=22) or Low CRP-Glu (n=19) groups. Measures of local/regional activity, functional connectivity, network integrity were obtained using resting state brain-oxygen-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) and compared between the High and Low CRP-Glu groups. Reductions in the measure of homogenous local activity (regional homogeneity, ReHo) in the basal ganglia region used for MRS were associated with High CRP-Glu group status. Similar decreases in ReHo were also noted in a distributed network of brain regions involved in reward processing, salience and psychomotor functions - including striatal, ventral medial prefrontal, superior frontal, insular, anterior and posterior cingulate regions. The local activity and connectivity between these regions were linked to the severity of anhedonia and depression. The clinical and neurobiological significance of the findings will be discussed.