Lower levels of the glial cell marker TSPO in drug-naive first-episode psychosis patients as measured using PET and [11C]PBR28

被引:82
作者
Collste, K. [1 ]
Plaven-Sigray, P. [1 ]
Fatouros-Bergman, H. [1 ]
Victorsson, P. [1 ]
Schain, M. [1 ,2 ]
Forsberg, A. [1 ]
Amini, N. [1 ]
Aeinehband, S. [3 ]
Erhardt, S. [4 ]
Halldin, C. [1 ]
Flyckt, L. [1 ,5 ]
Farde, L. [1 ]
Cervenka, S. [1 ,6 ]
机构
[1] Karolinska Inst, Ctr Psychiat Res, Dept Clin Neurosci, Stockholm, Sweden
[2] Columbia Univ, Dept Psychiat, Mol Imaging & Neuropathol Div, New York, NY USA
[3] Karolinska Univ Hosp, Karolinska Inst, Dept Clin Neurosci, Neuroimmunol Unit, Stockholm, Sweden
[4] Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden
[5] Karolinska Inst, Astrazeneca PET Sci Ctr, Personalised Healthcare & Biomarkers, Stockholm, Sweden
[6] Univ Cambridge, Dept Psychiat, Cambridge, England
关键词
CONSENSUS COGNITIVE BATTERY; RECENT-ONSET SCHIZOPHRENIA; KDA TRANSLOCATOR PROTEIN; IN-VIVO; BENZODIAZEPINE-RECEPTORS; RADIOLIGAND BINDING; HUMAN-BRAIN; NEUROINFLAMMATION; QUANTIFICATION; ACTIVATION;
D O I
10.1038/mp.2016.247
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-11]PBR28. Gray matter (GM) volume of distribution (V-T) 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-11]PBR28 binding, and gender. There was a significant reduction of [C-11]PBR28 V-T in patients compared with healthy controls in GM as well as in secondary regions of interest. No correlation was observed between GM V-T 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.
引用
收藏
页码:850 / 856
页数:7
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