Treatments for
Cocaine Use Disorder (CUD) are variably effective, and there are no FDA-approved medications. One approach to developing new treatments for CUD may be to investigate and target poor prognostic signs. One such sign is
anhedonia (i.e. a loss of pleasure or interest in non-drug rewards), which predicts worse outcomes in existing CUD treatments.
Inflammation is thought to underlie
anhedonia in many other disorders, but the relationship between
anhedonia and
inflammation has not been investigated in CUD. Therefore, we assessed peripheral genome-wide gene expression in n = 48 individuals with CUD with high (n = 24) vs. low (n = 24) levels of
anhedonia, defined by a median split of self-reported
anhedonia. Our hypothesis was that individuals with high
anhedonia would show differential gene expression in inflammatory pathways. No individual genes were significantly different between the low and high
anhedonia groups when using t-tests with a stringent false discovery rate correction (FDR-corrected p < 0.05). However, an exploratory analysis identified 166 loci where t-tests suggested group differences at a nominal p < 0.05. We used DAVID, a bioinformatics tool that provides functional interpretations of complex lists of genes, to examine representation of this gene list in known pathways. It confirmed that mechanisms related to immunity were the top significant associations with
anhedonia in the sample. Further, the two top differentially expressed genes in our sample, IRF1 and GBP5, both have primary
inflammation and immune functions, and were significantly negatively correlated with total scores on our self-report of
anhedonia across all 48 subjects. These results suggest that prioritizing development of anti-inflammatory medications for CUD may pay dividends, particularly in combination with treatment-matching strategies using either phenotypic measures of
anhedonia or
biomarkers of inflammatory gene expression to individualize treatment.