INM-4, Forschungszentrum Jülich GmbH, Wilhelm-Johnen-Straße, Institute of Neuroscience and Medicine, Jülich, Germany.
Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany.
Hum Brain Mapp. 2020 Jul;41(10):2762-2781. doi: 10.1002/hbm.24976. Epub 2020 Mar 9.
Consistent findings postulate disturbed glutamatergic function (more specifically a hypofunction of the ionotropic NMDA receptors) as an important pathophysiologic mechanism in schizophrenia. However, the role of the metabotropic glutamatergic receptors type 5 (mGluR5) in this disease remains unclear. In this study, we investigated their significance (using [ C]ABP688) for psychopathology and cognition in male patients with chronic schizophrenia and healthy controls. In the patient group, lower mGluR5 binding potential (BP ) values in the left temporal cortex and caudate were associated with higher general symptom levels (negative and depressive symptoms), lower levels of global functioning and worse cognitive performance. At the same time, in both groups, mGluR5 BP were significantly lower in smokers (F = 15.500; p = .001), but without significant differences between the groups. Our findings provide support for the concept that the impaired function of mGluR5 underlies the symptoms of schizophrenia. They further supply a new perspective on the complex relationship between tobacco addiction and schizophrenia by identifying glutamatergic neurotransmission-in particularly mGluR5-as a possible connection to a shared vulnerability.
一致的研究结果假设谷氨酸能功能障碍(更具体地说是离子型 NMDA 受体的功能低下)是精神分裂症的重要病理生理机制。然而,代谢型谷氨酸能受体 5(mGluR5)在这种疾病中的作用仍不清楚。在这项研究中,我们使用 [C]ABP688 研究了它们在男性慢性精神分裂症患者和健康对照组的精神病理学和认知功能中的意义。在患者组中,左侧颞皮质和尾状核的 mGluR5 结合潜能(BP)值较低与一般症状水平(阴性和抑郁症状)较高、整体功能水平较低以及认知表现较差相关。与此同时,在两组中,吸烟者的 mGluR5 BP 值均显著降低(F = 15.500;p =.001),但两组之间无显著差异。我们的研究结果为 mGluR5 功能障碍是精神分裂症症状的基础这一概念提供了支持。通过确定谷氨酸能神经传递——特别是 mGluR5——作为与共同易感性的可能联系,为烟草成瘾和精神分裂症之间复杂的关系提供了新的视角。