A Modest Increase in 11C-PK11195-Positron Emission Tomography TSPO Binding in Depression Is Not Associated With Serum C-Reactive Protein or Body Mass Index

BACKGROUND: Immune mechanisms have been implicated in the pathogenesis of depression. Translocator protein (TSPO)-targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to 1) test the hypothesis of significant case-control differences in TSPO binding in the anterior cingulate cortex, prefrontal cortex, and insula regions; and 2) explore the relationship between cerebral TSPO binding and peripheral blood C-reactive protein (CRP) concentration. METHODS: A total of 51 depressed subjects with Hamilton Depression Rating Scale score >13 (median 17; interquartile range, 16-22) and 25 healthy control subjects underwent dynamic brain C-11-PK11195 PET and peripheral blood immune marker characterization. Depressed subjects were divided into high CRP (>3 mg/L; n = 20) and low CRP (>3 mg/L; n = 31). RESULTS: Across the three regions, TSPO binding was significantly increased in depressed versus control subjects (eta(2) p = .09; F-1,F-71 = 6.97, p = .01), which was not influenced by body mass index. The case-control difference was greatest in the anterior cingulate cortex (d = 0.49; t(74) = 2.00, p = .03) and not significant in the prefrontal cortex or insula (d = 0.27 and d = 0.36, respectively). Following CRP stratification, significantly higher TSPO binding was observed in low-CRP depression compared with controls (d = 0.53; t(54) = 1.96, p = .03). These effect sizes are comparable to prior major depressive disorder case-control TSPO PET data. No significant correlations were observed between TSPO and CRP measures. CONCLUSIONS: Consistent with previous findings, there is a modest increase in TSPO binding in depressed patients compared with healthy control subjects. The lack of a significant correlation between brain TSPO binding and blood CRP concentration or body mass index poses questions about the interactions between central and peripheral immune responses in the pathogenesis of depression.

Automated summary

In patients with depression, there is a significant increase in TSPO binding in the anterior cingulate cortex, and depressed patients with low CRP levels show significantly higher TSPO binding compared to controls. However, there is no significant correlation between brain TSPO binding and blood CRP concentration or body mass index.