Mäki-Marttunen Verónica, Andreassen Ole A, Espeseth Thomas
Department of Psychology, University of Oslo, Postboks 1094, Blindern, 0317 Oslo, Norway.
CoE NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, Building 49, P.O. Box 4956 Nydalen, N-0424 Oslo, Norway.
Neurosci Biobehav Rev. 2020 Nov;118:298-314. doi: 10.1016/j.neubiorev.2020.07.038. Epub 2020 Aug 5.
Several lines of evidence have suggested for decades a role for norepinephrine (NE) in the pathophysiology and treatment of schizophrenia. Recent experimental findings reveal anatomical and physiological properties of the locus coeruleus-norepinephrine (LC-NE) system and its involvement in brain function and cognition. Here, we integrate these two lines of evidence. First, we review the functional and structural properties of the LC-NE system and its impact on functional brain networks, cognition, and stress, with special emphasis on recent experimental and theoretical advances. Subsequently, we present an update about the role of LC-associated functions for the pathophysiology of schizophrenia, focusing on the cognitive and motivational deficits. We propose that schizophrenia phenomenology, in particular cognitive symptoms, may be explained by an abnormal interaction between genetic susceptibility and stress-initiated LC-NE dysfunction. This in turn, leads to imbalance between LC activity modes, dysfunctional regulation of brain network integration and neural gain, and deficits in cognitive functions. Finally, we suggest how recent development of experimental approaches can be used to characterize LC function in schizophrenia.
几十年来，有几条证据线索表明去甲肾上腺素（NE）在精神分裂症的病理生理学和治疗中发挥作用。最近的实验结果揭示了蓝斑-去甲肾上腺素（LC-NE）系统的解剖学和生理学特性及其在脑功能和认知中的作用。在此，我们整合这两条证据线索。首先，我们回顾LC-NE系统的功能和结构特性及其对功能性脑网络、认知和应激的影响，特别强调最近的实验和理论进展。随后，我们介绍关于LC相关功能在精神分裂症病理生理学中的作用的最新情况，重点关注认知和动机缺陷。我们提出，精神分裂症的症状表现，尤其是认知症状，可能是由遗传易感性与应激引发的LC-NE功能障碍之间的异常相互作用所解释的。这反过来又导致LC活动模式之间的失衡、脑网络整合和神经增益的功能失调以及认知功能缺陷。最后，我们建议如何利用实验方法的最新进展来表征精神分裂症中的LC功能。
