Positron Emission Tomography Studies of the Glial Cell Marker Translocator Protein in Patients With Psychosis: A Meta-analysis Using Individual Participant Data

Abstract

BACKGROUND: Accumulating evidence suggests that the immune system may be an important target for new treatment approaches in schizophrenia. Positron emission tomography and radioligands binding to the translocator protein (TSPO), which is expressed in glial cells in the brain including immune cells, represents a potential method for patient stratification and treatment monitoring. This study examined whether patients with first-episode psychosis and schizophrenia had altered TSPO levels compared with healthy control subjects. METHODS: PubMed was searched for studies comparing patients with psychosis with healthy control subjects using second-generation TSPO radioligands. The outcome measure was total distribution volume (V T ), an index of TSPO levels, in frontal cortex, temporal cortex, and hippocampus. Bayes factors (BFs) were applied to examine the relative support for higher, lower, or no difference in patients' TSPO levels compared with healthy control subjects. RESULTS: Five studies, with 75 participants with first-episode psychosis or schizophrenia and 77 healthy control subjects, were included. BFs showed strong support for lower V T in patients relative to no difference (all BFs .

Regional heterogeneity in gene expression, regulation and coherence in hippocampus and dorsolateral prefrontal cortex across development and in schizophrenia

“…These results in total suggest largely unique differentially expressed genes and processes associated with schizophrenia in the HIPPO compared with DLPFC and underscore the incompleteness of the molecular pathology associated with schizophrenia based on only DLPFC or HIPPO. The enrichment of immune processes in genes relatively decreased in expression in schizophrenia echoes several recent studies that have not confirmed earlier proposals of an upregulated immune response in the brain of patients with this illness (Birnbaum et al, 2018;Plavén-Sigray et al, 2018) .…”

TSPO expression and brain structure in the psychosis spectrum

“…A recent study, however, reported a significantly lower TSPO expression in first-episode psychosis as compared to healthy volunteer using [ 11 C]PBR28 16 . Supporting this, a recent meta-analysis of PET studies with second-generation radioligands in psychosis suggests an overall reduction of TSPO expression in psychosis 22 .…”

“…Also, in the study by Holmes and colleagues, increase in TSPO expression was only observed in medicated schizophrenia, not in drug-naïve patients 18 . It is noteworthy that a recent meta-analysis of individual data of previous PET studies with second-generation radioligands in psychosis suggests an overall reduction of TSPO expression in psychosis 22 .…”

Brain glial activation in fibromyalgia – A multi-site positron emission tomography investigation

“…For instance, previous work showed no differences in TSPO PET signal in cocaine dependence (Narendran et al, 2014), and decreased signal in alcohol dependence (Hillmer et al, 2017; Kalk et al, 2017). In patients with psychosis, initial studies with first generation TSPO tracers showed an increase, whereas recent studies using second-generation radioligands are supportive of a decrease in TSPO levels (Plaven-Sigray et al, 2018). Thus, further work is needed to better assess the potential usefulness of TSPO as a means to image neuroinflammation, and the meaning of the observed TSPO signal changes, particularly in certain pathologies.…”