Neuroinflammation in Major Depressive Disorder: A Review of PET Imaging Studies Examining the 18-kDa Translocator Protein

Background: Major Depressive Disorder (MDD) is a severe psychiatric disorder whose pathological mechanisms are largely unknown. In the field of immunopsychiatry, several evidences suggested a prominent role of inflammation in MDD not only in peripheral immune system but also in the brain. To date, brain inflammation is traceable in vivo with Positron Emission Tomography (PET), through the quantification of the expression of 18-kda Translocator Protein (TSPO) by active microglia. In this context, this review aimed to summarize the results of all in vivo PET imaging studies that evaluated microglia activation in MDD. Methods: A bibliographic search in PubMed up to June 2020 was performed. A total of 9 studies that used first and second generation TSPO radiotracers met our inclusion criteria. Results: Overall the results suggested the presence of TSPO upregulation in MDD, especially in anterior cingulate cortex, prefrontal cortex, hippocampal formation and insula. Notably, from a therapeutic point of view, results suggested that the symptoms amelioration, caused by both antidepressant medication and cognitive behavioural therapy, may be accompanied by reduced inflammatory status in the brain. Finally, a positive effect of the anti-inflammatory treatment with a cyclooxygenase inhibitor has also been observed. Limitations: The heterogeneity across the studies in experimental designs, sample selection and methods limited the studies comparison. Conclusions: These findings supported the presence of neuroinflammation in MDD, suggesting that microgliosis may be an important pathophysiological mechanism that merits further investigation as a potential target for novel treatment strategies.

Automated summary

A review of in vivo PET imaging studies found upregulation of TSPO in specific regions of the brain in patients with MDD. Treatment with antidepressants and cognitive behavioral therapy may lead to reduced brain inflammation. Additionally, anti-inflammatory treatment with cyclooxygenase inhibitors showed positive effects.