Assessing brain immune activation in psychiatric disorders: clinical and preclinical PET imaging studies of the 18-kDa translocator protein

Abstract

Accumulating evidence from different lines of research suggests an involvement of the immune system in the pathophysiology of several psychiatric disorders. During recent years, a series of positron emission tomography (PET) studies have been published using radioligands for the translocator protein (TSPO) to study microglia activation in schizophrenia, bipolar I disorder, major depression, autism spectrum disorder, and drug abuse. The results have been somewhat conflicting, which could be due to differences both in patient sample characteristics and in PET methods. In particular, further work is needed to address both methodological and biological sources of variability in TSPO levels, a process in which the use of animal models and small animal PET systems can be a valuable tool. Given this development, PET studies of immune activation have the potential to further increase our understanding of disease mechanisms in psychiatric disorders, which is a requisite in the search for new treatment approaches. Furthermore, molecular imaging could become an important clinical tool for identifying specific subgroups of patients or disease stages that would benefit from treatment targeting the immune system.

Keywords: Microglia; Neuroinflammation; PET; Psychiatry; TSPO.

Fig. 1

Cross-species TSPO imaging using [¹¹C]PBR28: SUV images of a mouse b rat, and c a healthy human subject. All PET images are overlaid over MR images. Courtesy of the PET centre, Karolinska Institutet