Kessler Robert M, Woodward Neil D, Riccardi Patrizia, Li Rui, Ansari M Sib, Anderson Sharlett, Dawant Benoit, Zald David, Meltzer Herbert Y
Department of Radiology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Biol Psychiatry. 2009 Jun 15;65(12):1024-31. doi: 10.1016/j.biopsych.2008.12.029. Epub 2009 Feb 28.
Studies in schizophrenic patients have reported dopaminergic abnormalities in striatum, substantia nigra, thalamus, anterior cingulate, hippocampus, and cortex that have been related to positive symptoms and cognitive impairments.
[(18)F]fallypride positron emission tomography studies were performed in off-medication or never-medicated schizophrenic subjects (n = 11, 6 men, 5 women; mean age of 30.5 +/- 8.0 [SD] years; 4 drug-naive) and age-matched healthy subjects (n = 11, 5 men, 6 women, mean age of 31.6 +/- 9.2 [SD]) to examine dopamine D(2) receptor (DA D(2)r) levels in the caudate, putamen, ventral striatum, medial thalamus, posterior thalamus, substantia nigra, amygdala, temporal cortex, anterior cingulate, and hippocampus.
In schizophrenic subjects, increased DA D(2)r levels were seen in the substantia nigra bilaterally; decreased levels were seen in the left medial thalamus. Correlations of symptoms with ROI data demonstrated a significant correlation of disorganized thinking/nonparanoid delusions with the right temporal cortex ROI (r = .94, p = .0001), which remained significant after correction for multiple comparisons (p < .03). Correlations of symptoms with parametric images of DA D(2)r levels revealed no significant clusters of correlations with negative symptoms but significant clusters of positive correlations of total positive symptoms, delusions and bizarre behavior with the lateral and anterior temporal cortex, and hallucinations with the left ventral striatum.
The results of this study demonstrate abnormal DA D(2)r-mediated neurotransmission in the substantia nigra consistent with nigral dysfunction in schizophrenia and suggest that both temporal cortical and ventral striatal DA D(2)r mediate positive symptoms.
对精神分裂症患者的研究报告称，纹状体、黑质、丘脑、前扣带回、海马体和皮质中存在多巴胺能异常，这些异常与阳性症状和认知障碍有关。
对未服药或从未服药的精神分裂症患者（n = 11，6名男性，5名女性；平均年龄30.5±8.0[标准差]岁；4名未用过药）和年龄匹配的健康受试者（n = 11，5名男性，6名女性，平均年龄31.6±9.2[标准差]）进行[(18)F]氟哌利多正电子发射断层扫描研究，以检测尾状核、壳核、腹侧纹状体、内侧丘脑、后丘脑、黑质、杏仁核、颞叶皮质、前扣带回和海马体中的多巴胺D(2)受体（DA D(2)r）水平。
在精神分裂症患者中，双侧黑质的DA D(2)r水平升高；左侧内侧丘脑的水平降低。症状与感兴趣区（ROI）数据的相关性表明，思维紊乱/非偏执性妄想与右侧颞叶皮质ROI显著相关（r = 0.94，p = 0.0001），在进行多重比较校正后仍具有显著性（p < 0.03）。症状与DA D(2)r水平参数图像的相关性显示，与阴性症状无显著相关簇，但总阳性症状、妄想和怪异行为与外侧和颞叶前部皮质存在显著正相关簇，幻觉与左侧腹侧纹状体存在显著正相关簇。
本研究结果表明，黑质中存在异常的DA D(2)r介导的神经传递，这与精神分裂症中的黑质功能障碍一致，并提示颞叶皮质和腹侧纹状体的DA D(2)r均介导阳性症状。
