首发精神分裂症及临床高危人群脑神经生化代谢物异常

Abnormal neurobiochemical metabolites in the first-episode schizophrenia and clinical high-risk population

目的:探索首发精神分裂症(first-episode schizophrenia,FES)及临床高危(clinical high risk,CHR)人群内侧前额叶(medial prefrontal cortex,mPFC)神经生化代谢物的特点。方法:应用质子磁共振波谱(^(1)H magnetic resonance spectroscopy,^(1)H-MRS)检测满足入组标准的46例FES患者、49例CHR者、61例遗传高危(genetic high risk,GHR)者及56例健康对照者(healthy control,HC)的m PFC N-乙酰天门冬酰胺复合物(N-acetylaspartylglutamate+Nacetylaspartate=total NAA,tNAA)、胆碱复合物(choline,Cho)、谷氨酸类复合物[glutamate (Glu)+glutamine (Gln)=Glx]、肌醇(myo-inositol,MI)的绝对含量并比较其差异,评估FES组及CHR组的临床症状,并使用持续性操作测验(continuous performance test,CPT)评估4组的视觉和听觉反应时间及正确率。结果:4组之间Glx、tNAA、MI水平差异有统计学意义(P<0.05),其中FES组的MI及Glx水平明显低于HC组(P<0.05),CHR组的Glx和tNAA水平明显低于GHR组(P<0.05),FES组的视觉及听觉正确率明显低于HC组(P<0.05)。FES组的Glx含量与视觉反应时间呈负相关(r=-0.41,P=0.05)。结论:FES患者MI及Glx水平降低,提示患者在疾病早期就可能存在神经胶质细胞功能障碍和谷氨酸能递质失调;而GHR个体可能存在代谢物水平的代偿性增高,这是罹患精神分裂症的保护因素。

Objective: To explore the metabolite characteristics in medial prefrontal cortex(mPFC) by ^(1)H magnetic resonance spectroscopy(^(1)H-MRS) in the first-episode schizophrenia(FES) and clinical high-risk(CHR) people.Methods: A total of 46 patients with the first-episode schizophrenia(FES), 49 people with clinical high risk(CHR), 61 people with genetic high risk(GHR), and 58 healthy controls(HC) were enrolled. The levels of N-acetylaspartylglutamate+N-acetylaspartate(tNAA),choline-containing compounds(Cho) and myo-inositol(MI), glutamate+glutamine(Glx) in medial prefrontal cortex were measured by single-voxel ^(1)H-MRS. The clinical symptoms were evaluated in the FES group and the CHR group. Continuous performance test(CPT)were carried out to assess the visual and auditory accuracy and reaction time in the 4 groups.Results: There were significant differences in Glx, tNAA, and MI concentrations among 4 groups(all P<0.05). Compared with the HC group, the FES group showed lower level of MI and Glx. The levels of Glx and tNAA in the CHR group were significantly lower than those in the GHR group(all P<0.05). The visual and auditory accuracies of CPT in the FES group were significantly lower than those in the HC group(P<0.05). In the FES group, Glx was negatively correlated with the reaction time of vision(r=-0.41, P=0.05).Conclusion: The decreased levels of MI and Glx in the FES patients suggest that there may be glial functional damage and glutamatergic transmitter dysfunction in the early stage of the disease. The compensatory increase of metabolites may be a protective factor for schizophrenia in the genetic individuals.