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

Abstract

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 ¹¹C-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 (η²_p = .09; F_1,71 = 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; t₇₄ = 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; t₅₄ = 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.

Keywords: C-reactive protein; Depression; Inflammation; Microglia; PET; TSPO.

Figure 1

(A) Case-control differences in mean ¹¹C-PK11195 binding potential measurements in anterior cingulate cortex (ACC), prefrontal cortex (PFC), and insula (INS) regions between healthy control and depressed subjects. Error bars represent SE. The analyses are corrected for age, sex, and body mass index. Significant differences (p < .05) are indicated by an asterisk. (B) Forest plot summarizing the current results in the context of previous translocator protein positron emission tomography results from case-control studies of depression in the ACC, frontal lobe regions, and INS regions. BP_ND, relative binding potential.

Figure 2

Case-control differences in mean ¹¹C-PK11195 binding potential measurements in the anterior cingulate cortex (ACC), prefrontal cortex (PFC), and insula (INS) regions between healthy control subjects (HC), low C-reactive protein (CRP) depression, high-CRP depression, and all depressed subjects (DS). Error bars represent SE. Analyses are corrected for age, sex, and body mass index. Significant differences (p < .05) are indicated by an asterisk. BP_ND, relative binding potential.

Figure 3

Scatterplots of ¹¹C-PK11195 binding potential measurements (y-axis) for the anterior cingulate cortex (ACC), prefrontal cortex (PFC), and insula (INS) regions vs. (A) serum C-reactive protein (CRP) concentration (mg/L), (B) Hamilton Depression Rating Scale (HDRS) and (C) body mass index (BMI, kg/m²) in depressed subjects.