High Levels of Inflammation and Blood Glucose May Contribute to Anhedonia in MDD

High blood glucose levels coupled with low tyrosine metabolism may identify patients with depression who have increased inflammation and higher rates of anhedonia.

High blood glucose levels coupled with low tyrosine metabolism may identify patients with depression, who have increased inflammation and higher rates of anhedonia, according to a study published in Brain, Behavior, and Immunity. Additionally, the study reported that anhedonia with high C-reactive protein (CRP), a marker for inflammation, may involve immunometabolic shifts as well as reduced availability of dopamine precursors in patients in major depressive disorder (MDD).

A total of 93 patients with a primary diagnosis of MDD (n=88) and bipolar disorder-current episode depressed (n=5) were enrolled. All participants were unmedicated and had stable MDD. A Gene Set Enrichment Analysis (GSEA) was performed in 62 participants to assess functional enrichment of gene pathways, whereas data from all participants were used for a linear regression analysis. The researchers examined whether or not patients had increased inflammation, as determined by high (>3mg/L) plasma CRP. Self-reported phenotypes of high (33rd percentile; n=30) vs low (67th percentile; n=32) anhedonia were also identified.

In patients with high CRP, the researchers observed significant enrichment of 13 Kyoto Encyclopedia of Genes and Genomes pathways in those with high (n=10) vs low (n=9) anhedonia (FDR <0.25). These pathways included those related to glucose metabolism, cancer, and inflammation. In patients with low CRP, enrichment of the extracellular matrix-receptor interaction pathway was observed in high (n=20) vs low (n=23) anhedonia (FDR <0.25).

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In the group of patients with high CRP, insulin signaling was the primary pathway associated with high anhedonia (normalized enrichment score [NES], 2.00; FDR q, 0.01; P <.001). Among patients with high CRP in GSEA, the insulin signaling pathway was the primary enriched pathway in patients with high (n=10) vs low (n=9) anhedonia, expressed mainly by circulating monocytes (z, 2.95; P <.01). The tyrosine metabolism pathway was reduced in patients with high (n=20) vs low (n=10) CRP within the group with high anhedonia (NES, -1.87; FDR q, 0.085; P =.001).

Limitations of the study included the small sample sizes following stratification by CRP and anhedonia, as well as the subjective nature of the self-reported anhedonia assessment.

According to the investigators, a greater understanding of the “causal relationships among inflammation, glucose metabolism and anhedonia may reveal novel therapeutic approaches targeting immunometabolism for motivational deficits in psychiatric and medical illnesses.”


Bekhbat M, Treadway M, Goldsmith DR, et al. Gene signatures in peripheral blood immune cells related to insulin resistance and low tyrosine metabolism define a sub-type of depression with high CRP and anhedonia [published online March 17, 2020]. Brain Behav Immun. doi:10.1016/j.bbi.2020.03.015.