Increased inflammation is associated with increased glutamate in the basal ganglia of depressed patients

Abstract

Previous work by our group has demonstrated that administration of the inflammatory cytokine interferon (IFN)-alpha increases glutamate in the left basal ganglia and dorsal anterior cingulate cortex (dACC). IFN-alpha-induced increases in glutamate were in turn associated with depressive symptoms. We therefore assessed the impact of inflammatory status on CNS glutamate in patients with major depression. Proton magnetic resonance spectroscopy (MRS) was used to estimate absolute glutamate concentrations in the left basal ganglia and dACC of 44 medication-free depressed patients, and inflammation was assessed by measures of plasma c-reactive protein (CRP). Increased CRP was associated with increased left basal glutamate in both a linear and stepwise fashion (r = 0.43, p = 0.004 and F(2,43) = 4.42, p = 0.012 respectively). In turn, basal ganglia glutamate was positively correlated with scores of anhedonia and measures of simple reaction time and negatively correlated with scores on the Digit Symbol Substitution Task and the finger tapping test (all p<0.05). CRP was not associated with glutamate concentrations in the dACC. These data provide the first evidence that increased inflammation in major depression is associated with increased glutamate in the basal ganglia which in turn is associated with alterations in motivation and psychomotor activity. These data also suggest that therapeutic strategies targeting glutamate may be preferentially effective in depressed patients with increased inflammation.