IFN-alpha-induced cortical and subcortical glutamate changes assessed by magnetic resonance spectroscopy.
Level 3 - non-randomized controlled study
Non-randomized controlled cohort study
PubMed 24481242 · doi:10.1038/npp.2014.25
What was done
Single-voxel magnetic resonance spectroscopy (MRS) was used to measure glutamate concentrations normalized to creatine (Glu/Cr) in the dorsal anterior cingulate cortex (dACC) and basal ganglia in 31 patients with hepatitis C. Patients were evaluated before and after approximately 1 month of either no treatment (n = 14) or treatment with IFN-alpha (n = 17). Depressive symptoms and fatigue were measured using the Inventory of Depressive Symptoms-Clinician Rating (IDS-C) and the Multidimensional Fatigue Inventory.
What was found
IFN-alpha was associated with a significant increase in Glu/Cr in the dACC and left basal ganglia, with no changes found in the right basal ganglia (the abstract reports no exact numerical values, effect sizes, or p-values). Increases in dACC Glu/Cr positively correlated with IDS-C scores across the entire group, but not in either group individually. Glu/Cr increases in the left basal ganglia correlated with decreased motivation across the whole sample and within the IFN-alpha group alone. No significant correlations were found between Glu/Cr and inflammatory markers.
Why it matters
This study provides human in vivo evidence that systemic inflammatory cytokines like IFN-alpha can elevate glutamate levels in specific corticolimbic regions, suggesting a neurochemical pathway connecting inflammation to depression and reduced motivation.
Limits
The study had a small sample size (n = 31), non-randomized allocation, and lacked reporting of exact numerical values or confidence intervals in the abstract. The correlation between dACC glutamate and depressive symptoms was not significant within the treatment cohort alone.
Cited by
- supports Studies on interferon show that inflammatory molecules preferentially alter brain activity in the dorsal anterior cingulate cortex and default mode/rumination regions.