The role of norepinephrine in the pathophysiology of schizophrenia

•LC-NE system is involved in motivation and cognition in humans.•This system participates in mechanisms of stress response.•LC-NE system may be connected to the cognitive and motivational deficits of SCZ.•A combination of methodological approaches is proposed to answer open questions. Several lines...

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Published inNeuroscience and biobehavioral reviews Vol. 118; pp. 298 - 314
Main Authors Mäki-Marttunen, Verónica, Andreassen, Ole A., Espeseth, Thomas
Format Journal Article
LanguageEnglish
Published United States Elsevier Ltd 01.11.2020
Subjects
Cognition
Dopamine
Locus coeruleus
Norepinephrine
Schizophrenia
Schizophrenia
Norepinephrine
Cognition
Dopamine
Locus coeruleus
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Summary:•LC-NE system is involved in motivation and cognition in humans.•This system participates in mechanisms of stress response.•LC-NE system may be connected to the cognitive and motivational deficits of SCZ.•A combination of methodological approaches is proposed to answer open questions. 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.
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ISSN:0149-7634
1873-7528
DOI:10.1016/j.neubiorev.2020.07.038