A modest increase in 11C-PK11195-PET TSPO binding in depression is not associated with serum C-reactive protein or body mass index

Abstract:

ABSTRACT

BACKGROUND

Immune mechanisms have been implicated in the pathogenesis of depression, and translocator-protein (TSPO) targeted positron emission tomography (PET) has been used to assess neuroinflammation in major depressive disorder. We aimed to: (i) test the prior hypothesis of significant case-control differences in TSPO binding in anterior cingulate (ACC), prefrontal (PFC) and insular (INS) cortical regions; and (ii) explore the relationship between cerebral TSPO binding and peripheral blood concentration of C-reactive protein (CRP).

METHODS

51 depressed cases with Hamilton Depression Rating Scale score > 13 (median 17; IQR 16-22) and 25 healthy matched controls underwent dynamic brain 11 C-PK11195 PET and peripheral blood immune marker characterisation. Depressed cases were divided into high CRP (>3mg/L;N=20) and low CRP (<3mg/L;N=31).

RESULTS

Across the three regions, TSPO binding was significantly increased in cases vs controls ( ; F(1,71)=6.97, P =0.01). which was not influenced by differences in body mass index (BMI). The case-control difference was greatest in ACC (d=0.49; t(74)=2.00, . P =0.03) and not significant in PFC or INS (d=0.27; d=0.36). Following CRP stratification, significantly higher TSPO binding was observed in low CRP depression compared to controls (d=0.53; t(54)=1.96, P=0.03). These effect sizes are comparable to prior MDD 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 cases compared to healthy controls. The lack of a significant correlation between brain TSPO binding and blood CRP concentration or BMI poses questions about the interactions between central and peripheral immune responses in the pathogenesis of depression.