Matosin Natalie, Fernandez-Enright Francesca, Frank Elisabeth, Deng Chao, Wong Jenny, Huang Xu-Feng, Newell Kelly A
The Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Illawarra Health and Medical Research Institute, Wollongong, New South Wales, and Schizophrenia Research Institute, Sydney, New South Wales, Australia.
The Faculty of Science, Medicine and Health, University of Wollongong, New South Wales, Illawarra Health and Medical Research Institute, Wollongong, New South Wales, Schizophrenia Research Institute, Sydney, New South Wales, and School of Psychology, Faculty of Social Science, University of Wollongong, New South Wales, Australia.
J Psychiatry Neurosci. 2014 Nov;39(6):407-16. doi: 10.1503/jpn.130242.
Metabotropic glutamate receptors 2/3 (mGluR2/3) and 5 (mGluR5) are novel therapeutic targets for major depression (MD), bipolar disorder (BD) and schizophrenia. We aimed to determine whether mGluR2/3 and mGluR5 binding in the anterior cingulate cortex (ACC), a brain region essential for the regulation of mood, cognition and emotion, were differentially altered in these pathologies.
Using postmortem human brains derived from 2 cohorts, [(3)H]LY341495 binding to mGluR2/3 and [(3)H]MPEP binding to mGluR5 were measured by receptor autoradiography in the ACC. The first cohort comprised samples from individuals who had MD with psychosis (MDP), MD without psychosis (MDNP) and matched controls (n = 11-12 per group). The second cohort comprised samples from individuals who had MDNP, BD, schizophrenia and matched controls (n = 15 per group).
No differences in mGluR2/3 or mGluR5 binding were observed in the MDP, MDNP, BD or schizophrenia groups compared with the control group (all p > 0.05). Importantly, there were also no differences in binding densities between the psychiatric disorders (p > 0.05). We did, however, observe age-related effects, with consistent negative associations between mGluR2/3 and age in the control group (r < -0.575, p < 0.025) and the psychotic disorder groups (MDP and schizophrenia: r = -0.765 to -0.515, p < 0.05), but not in the mood disorder groups (MDNP, BD).
Replication in larger independent cohorts and medication-naive individuals would strengthen these findings.
Our findings suggest that mGluRs are unaltered in the ACC; however, the presence of altered receptor function cannot be discounted and requires further investigation. Taken together with previous studies, which report differential changes in mGluR2, 3 and 5 across these disorders, we suggest mGluRs may be affected in a brain region-specific manner.
代谢型谷氨酸受体2/3（mGluR2/3）和5（mGluR5）是重度抑郁症（MD）、双相情感障碍（BD）和精神分裂症的新型治疗靶点。我们旨在确定在调节情绪、认知和情感至关重要的脑区——前扣带回皮质（ACC）中，mGluR2/3和mGluR5的结合在这些疾病中是否存在差异改变。
使用来自2个队列的尸检人脑，通过受体放射自显影术测量ACC中与mGluR2/3结合的[(3)H]LY341495和与mGluR5结合的[(3)H]MPEP。第一个队列包括来自患有精神病性重度抑郁症（MDP）、非精神病性重度抑郁症（MDNP）的个体以及匹配对照的样本（每组n = 11 - 12）。第二个队列包括来自患有MDNP、BD、精神分裂症的个体以及匹配对照的样本（每组n = 15）。
与对照组相比，在MDP、MDNP、BD或精神分裂症组中未观察到mGluR2/3或mGluR5结合的差异（所有p > 0.05）。重要的是，精神疾病之间的结合密度也没有差异（p > 0.05）。然而，我们确实观察到了与年龄相关的效应，在对照组（r < -0.575，p < 0.025）以及精神病性障碍组（MDP和精神分裂症：r = -0.765至-0.515，p < 0.05）中，mGluR2/3与年龄之间存在一致的负相关，但在情绪障碍组（MDNP、BD）中未观察到。
在更大的独立队列和未用药个体中进行重复研究将加强这些发现。
我们的研究结果表明，ACC中的代谢型谷氨酸受体未发生改变；然而，受体功能改变的可能性不能排除，需要进一步研究。结合先前报告这些疾病中mGluR2、3和5存在差异变化的研究，我们认为代谢型谷氨酸受体可能以脑区特异性方式受到影响。
