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 .
Here, we examined reproducibility of [ 11 C]PBR28 binding in healthy subjects as quantified on a regional and voxel-by-voxel basis. In addition, a preliminary analysis of diurnal changes in TSPO availability was performed. MethodsTwelve subjects were examined with HRRT PET and [ 11 C]PBR28, six in the morning and afternoon on the same day, and six in the morning of two separate days. Regional Volume of distribution (V T ) values were derived using a region-of-interest based two-tissue compartmental analysis (2TCM), as well as a parametric approach. Metabolite-corrected arterial plasma was used as input function. ResultsFor the whole sample, the mean absolute variability of V T in gray matter (GM) was 18.3 ± 12.7 %. Intraclass Correlation Coefficient values in GM regions ranged from 0.90 to 0.94. Reducing the time of analysis from 91 to 63 minutes yielded a variability of 16.9 ± 14.9%. There was a strong correlation between the parametric and 2TCM-derived GM values (r=0.99). A significant increase in GM V T was observed between morning and afternoon examinations when using secondary methods of quantification (p=0.028). For the subjects examined at the same time of the day, the absolute variability was 15.9 ± 12.2 % for the 91 minute 2TCM data. [15,16], the study was designed so that six subjects were examined in the morning and afternoon on the same day, and six subjects at the same time point on two different days. Conclusions Methods SubjectsThe study was conducted at the Karolinska University Hospital, Solna, Sweden and was approved by the regional Ethics Committee in Stockholm and the Radiation Safety Committee at the Karolinska University Hospital, Stockholm.Subjects were recruited by advertisement and provided written informed consent. They were healthy according to medical history, clinical examination and routine laboratory tests in blood and urine. All subjects were assessed by a senior psychiatrist (K.C.), using the Mini International Neuropsychiatric Interview (MINI) for psychiatric diagnoses. None of the subjects had previously been exposed to psychopharmacological medication. Furthermore, a negative illegal drug screening test was ascertained in all subjects, prior to PET examination. None of the subjects were on any medication at the time of the study. No brain abnormality was detected on magnetic resonance imaging (MRI), as evaluated by a neuroradiologist at the MR-centre, Karolinska University Hospital, Solna.As demonstrated both in vitro and in vivo, [ 11 C]PBR28 binding is influenced by an identified single point mutation in the TSPO gene [8,17]. At screening, a blood sample was collected and genotyping was performed according to the description below. In total, 15 subjects were recruited. Of these, one was a low affinity binder (LAB) and was therefore excluded from the analysis. Two additional subjects were excluded due to technical issues with the PET measurements. The remaining twelve subjects were six men and six women, with a mean age of 23.9 SD ± 3.1 years. Six were high affinity binders ...
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 [C]PBR28. Gray matter (GM) volume of distribution (V) 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 [C]PBR28 binding, and gender. There was a significant reduction of [C]PBR28 V in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM V 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.
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