Department of Psychiatry and Behavioural Sciences, The University of Texas Health Science Center at Houston, Houston, TX 77054, USA; Psychiatric Imaging Group, MRC Clinical Sciences Centre, Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital, London, W12 0NN, UK.
Psychiatric Imaging Group, MRC Clinical Sciences Centre, Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital, London, W12 0NN, UK.
Schizophr Res. 2018 May;195:206-214. doi: 10.1016/j.schres.2017.08.063. Epub 2017 Oct 12.
Patients with schizophrenia show whole brain and cortical gray matter (GM) volume reductions which are progressive early in their illness. Microglia, the resident immune cells in the CNS, phagocytose neurons and synapses. Some post mortem and in vivo studies in schizophrenia show evidence for elevated microglial activation compared to matched controls. However, it is currently unclear how these results relate to changes in cortical structure.
Fourteen patients with schizophrenia and 14 ultra high risk for psychosis (UHR) subjects alongside two groups of age and genotype matched healthy controls received [C]PBR28 PET scans to index TSPO expression, a marker of microglial activation and a 3T MRI scan. We investigated the relationship between the volume changes of cortical regions and microglial activation in cortical GM (as indexed by [C]PBR28 distribution volume ratio (DVR).
The total cortical GM volume was significantly lower in SCZ than the controls [mean (SD)/cm: SCZ=448.83 (39.2) and controls=499.6 (59.2) (p=0.02) but not in UHR (mean (SD)=503.06 (57.9) and controls=524.46 (45.3) p=0.3). Regression model fitted the total cortical GM DVR values with the cortical regional volumes in SCZ (r=0.81; p<0.001) and in UHR (r=0.63; p=0.02). We found a significant negative correlation between the TSPO signal and total cortical GM volume in SCZ with the highest absolute correlation coefficient in the right superior-parietal cortex (r=-0.72; p=0.006).
These findings suggest that microglial activity is related to the altered cortical volume seen in schizophrenia. Longitudinal investigations are required to determine whether microglial activation leads to cortical gray matter loss.
精神分裂症患者表现出全脑和皮质灰质(GM)体积减少,这些减少在疾病早期就呈进行性发展。小胶质细胞是中枢神经系统中的固有免疫细胞,吞噬神经元和突触。一些精神分裂症的死后和体内研究表明,与匹配的对照相比,小胶质细胞的激活升高。然而,目前尚不清楚这些结果与皮质结构的变化有何关系。
14 名精神分裂症患者和 14 名超高风险精神病(UHR)患者以及两组年龄和基因型匹配的健康对照者接受了 [C]PBR28 PET 扫描,以评估 TSPO 表达,这是小胶质细胞激活的标志物,以及 3T MRI 扫描。我们研究了皮质 GM 中皮质区域体积变化与小胶质细胞激活之间的关系(以 [C]PBR28 分布容积比(DVR)表示)。
SCZ 的总皮质 GM 体积明显低于对照组[平均值(标准差)/cm:SCZ=448.83(39.2)和对照组=499.6(59.2)(p=0.02),但 UHR 中则没有(平均值(标准差)=503.06(57.9)和对照组=524.46(45.3)(p=0.3)。在 SCZ 中,回归模型拟合了总皮质 GM DVR 值与皮质区域体积(r=0.81;p<0.001),在 UHR 中,回归模型拟合了总皮质 GM DVR 值与皮质区域体积(r=0.63;p=0.02)。我们发现,在 SCZ 中,TSPO 信号与总皮质 GM 体积之间存在显著的负相关,其中右侧上顶叶皮质的绝对相关系数最高(r=-0.72;p=0.006)。
这些发现表明,小胶质细胞活性与精神分裂症中观察到的皮质体积变化有关。需要进行纵向研究,以确定小胶质细胞的激活是否导致皮质灰质的丢失。