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.

数十年的证据表明，去甲肾上腺素（NE）在精神分裂症的病理生理和治疗中发挥了作用。最近的实验发现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。在这里，我们整合了这两种证据。首先，我们回顾了LC-NE系统的功能和结构特性及其对功能性大脑网络，认知和压力的影响，其中特别强调了最近的实验和理论进展。随后，我们介绍有关LC相关功能在精神分裂症的病理生理中的作用的更新，重点是认知和动机缺陷。我们建议精神分裂症的现象学，尤其是认知症状，遗传易感性与压力引发的LC-NE功能障碍之间的异常相互作用可能解释了这一现象。反过来，这会导致LC活动模式之间的失衡，大脑网络整合和神经增益的功能失调以及认知功能的缺陷。最后，我们建议如何使用最新的实验方法来表征精神分裂症的LC功能。