From the Clinical and Translational Neuroscience Branch, NIMH-Intramural Research Program (IRP), the Magnetic Resonance Spectroscopy Core, NIMH-IRP, and the Program on Pediatric Imaging and Tissue Sciences, National Institute of Child Health and Human Development-IRP, Bethesda, Md.; the Lieber Institute for Brain Development, Baltimore; the Departments of Psychiatry, Neurology, and Neuroscience and the Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore.
Am J Psychiatry. 2016 May 1;173(5):527-34. doi: 10.1176/appi.ajp.2015.15020190. Epub 2016 Jan 22.
The authors sought to compare GABA levels in treated and untreated patients with psychosis with levels in their unaffected siblings and healthy control subjects, and to assess the effects of antipsychotic medications on GABA levels.
GABA+ levels (i.e., including signal from unrelated proteins or macromolecules) referenced to creatine or water were studied with J-edited proton spectroscopy in the dorsal anterior cingulate cortex of 289 individuals: 184 healthy control subjects, 83 treated patients with psychosis, 25 untreated patients, 31 unaffected siblings, and 17 patients studied both while off all medications and while on a single antipsychotic.
GABA+ levels in the dorsal anterior cingulate did not differ between untreated patients and healthy controls. For treated patients, levels were modestly lower for GABA+/creatine but did not differ for GABA+/water compared with healthy controls. For both GABA+ measures, unaffected siblings had significantly lower levels compared with controls. GABA+/creatine showed a modest degree of familiality (intraclass correlation=0.36). Antipsychotic dosage was negatively correlated with GABA+ levels, but the on-off medication studies indicated no difference in GABA+ levels on antipsychotics compared with off antipsychotics.
GABA+/creatine in the dorsal anterior cingulate may constitute an intermediate phenotype with low effect size for psychosis, but GABA+/water measures do not fully support this conclusion. Low GABA+ levels in unaffected siblings could suggest a genetic association, but the failure to find consistent evidence of this phenotype in the patients themselves weakens genetic inference on risk for psychosis. Replication in independent samples of siblings is warranted to confirm the potential genetic risk association.
作者旨在比较治疗和未治疗精神病患者与未受影响的兄弟姐妹和健康对照者的 GABA 水平，并评估抗精神病药物对 GABA 水平的影响。
使用 J 编辑质子谱研究了 289 个人的背侧前扣带皮层中的 GABA+水平（即包括与无关蛋白质或大分子相关的信号）：184 名健康对照者、83 名接受精神病治疗的患者、25 名未接受治疗的患者、31 名未受影响的兄弟姐妹和 17 名同时接受抗精神病药物治疗的患者。
未治疗的患者与健康对照组的背侧前扣带皮层中的 GABA+水平没有差异。对于治疗的患者，GABA+/肌酸水平略低，但与健康对照组相比，GABA+/水水平没有差异。对于两种 GABA+测量方法，未受影响的兄弟姐妹的水平明显低于对照组。GABA+/肌酸显示出适度的家族性（组内相关系数=0.36）。抗精神病药物剂量与 GABA+水平呈负相关，但开-关药物研究表明，与停药相比，抗精神病药物治疗对 GABA+水平没有影响。
背侧前扣带皮层中的 GABA+/肌酸可能构成精神病的中间表型，但其效应大小较低，但 GABA+/水的测量方法并不能完全支持这一结论。未受影响的兄弟姐妹中的低 GABA+水平可能表明存在遗传关联，但未能在患者自身中找到一致的证据，削弱了对精神病风险的遗传推断。有必要在独立的兄弟姐妹样本中进行复制，以确认这种潜在的遗传风险关联。
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