Abstract
Several lines of evidence are indicative of a role for immune activation in the pathophysiology of schizophrenia. Nevertheless, studies using positron emission tomography (PET) and radioligands for the translocator protein (TSPO), a marker for glial activation, have yielded inconsistent results. Whereas early studies using a radioligand with low signal-to-noise in small samples showed increases in patients, more recent studies with improved methodology have shown no differences or trend-level decreases. Importantly, all patients investigated thus far have been on antipsychotic medication, and as these compounds may dampen immune cell activity, this factor limits the conclusions that can be drawn. Here, we examined 16 drug-naive, first-episode psychosis patients and 16 healthy controls using PET and the TSPO radioligand [11C]PBR28. Gray matter (GM) volume of distribution (VT) derived from a two-tissue compartmental analysis with arterial input function was the main outcome measure. Statistical analyses were performed controlling for both TSPO genotype, which is known to affect [11C]PBR28 binding, and gender. There was a significant reduction of [11C]PBR28 VT in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM VT and clinical or cognitive measures after correction for multiple comparisons. The observed decrease in TSPO binding suggests reduced numbers or altered function of immune cells in brain in early-stage schizophrenia.
Highlights
Schizophrenia is a severe mental disorder for which currently available treatment is satisfactory only in a minority of cases
Initial translocator protein 18kDA (TSPO) positron emission tomography (PET) studies in small samples have shown increased binding in patients with schizophrenia as compared with controls;[11,12] a radioligand with low signal-to-noise ratio was used, as well as an outcome measure generally shown to be less reliable.[13]
The aim of the present study was to overcome the critical drawback of previous investigations by measuring TSPO binding in antipsychotic-naive, first-episode psychotic patients, as compared with age-matched control subjects
Summary
Schizophrenia is a severe mental disorder for which currently available treatment is satisfactory only in a minority of cases. Cognitive impairments, such as memory dysfunction and reduced speed of processing, are present already at an early stage of the disease, and are difficult to ameliorate.[1] The development of new, improved treatment approaches is presently hampered by a lack of understanding of the pathophysiology of the disease. More recent studies using novel TSPO radioligands have failed to replicate these findings
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