Elevated translocator protein in anterior cingulate in major depression and a role for inflammation in suicidal thinking: a positron emission tomography study

Background: Major Depressive Disorder (MDD) is associated with raised peripheral inflammatory markers. Mounting evidence also suggests that inflammation is involved in suicidal behavior. However, the involvement of inflammation in the brains of depressed individuals, and its association with suicidal ideation, needs further clarification. Translocator protein (TSPO), which is upregulated in activated glia, predominantly microglia, can be measured as an indication of neuroinflammation in-vivo using Positron Emission Tomography (PET) and TSPO-specific radioligands.
Methods: We used [¹¹C](R)-PK11195 PET to compare TSPO availability in anterior cingulate cortex (ACC), prefrontal cortex (PFC) and insula between fourteen medication-free patients in a major depressive episode (MDE) of at least moderate severity and thirteen matched healthy controls. In a post-hoc analysis, we also compared TSPO availability between patients with and without suicidal thoughts.
Results: Multivariate analysis of variance indicated significantly higher TSPO in patients compared to controls (p=0.005). The elevation was of large effect size and significant in ACC (p=0.022; Cohen’s d=0.95), with smaller, non-significant elevations in PFC (p=0.342; Cohen’s d=0.38) and insula (p=0.466; Cohen’s d=0.29). TSPO was not elevated in patients without suicidal thinking, but was significantly increased in those with suicidal thoughts compared to those without, most robustly in ACC (p=0.008) and insula (p=0.023).
Conclusions: We confirm evidence for increased TSPO availability, suggestive of predominantly microglial activation, in the ACC during a moderate to severe MDE. Our findings provide further incentive for evaluating anti-inflammatory therapies in MDD.