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      Brain mechanisms of insomnia: new perspectives on causes and consequences.

      1
      Physiological reviews
      American Physiological Society
      anxiety, depression, insomnia, locus coeruleus, plasticity

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          Abstract

          While insomnia is the second most common mental disorder, progress in our understanding of underlying neurobiological mechanisms has been limited. The present review addresses the definition and prevalence of insomnia and explores its subjective and objective characteristics across the 24-hour day. Subsequently, the review extensively addresses how the vulnerability to develop insomnia is affected by genetic variants, early life stress, major life events, and brain structure and function. Further supported by the clear mental health risks conveyed by insomnia, the integrated findings suggest that the vulnerability to develop insomnia could rather be found in brain circuits regulating emotion and arousal than in circuits involved in circadian and homeostatic sleep regulation. Finally, a testable model is presented. The model proposes that in people with a vulnerability to develop insomnia, the locus coeruleus is more sensitive to-or receives more input from-the salience network and related circuits, even during rapid eye movement sleep, when it should normally be sound asleep. This vulnerability may ignite a downward spiral of insufficient overnight adaptation to distress, resulting in accumulating hyperarousal, which, in turn, impedes restful sleep and moreover increases the risk of other mental health adversity. Sensitized brain circuits are likely to be subjectively experienced as "sleeping with one eye open". The proposed model opens up the possibility for novel intervention studies and animal studies, thus accelerating the ignition of a neuroscience of insomnia, which is direly needed for better treatment.

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          Author and article information

          Journal
          Physiol Rev
          Physiological reviews
          American Physiological Society
          1522-1210
          0031-9333
          Jul 01 2021
          : 101
          : 3
          Affiliations
          [1 ] Department of Sleep and Cognition, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands; Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research, Amsterdam Neuroscience, Vrije Universiteit University Amsterdam, Amsterdam, The Netherlands; and Amsterdam UMC, Vrije Universiteit, Psychiatry, Amsterdam Neuroscience, Amsterdam, The Netherlands.
          Article
          10.1152/physrev.00046.2019
          32790576
          1c0dabe2-5f51-4511-a18e-ae53247172cd
          History

          locus coeruleus,plasticity,insomnia,anxiety,depression
          locus coeruleus, plasticity, insomnia, anxiety, depression

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