TY - JOUR
T1 - Brain mechanisms of insomnia
T2 - new perspectives on causes and consequences
AU - Van Someren, Eus J W
PY - 2021
Y1 - 2021
N2 - 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 gene variants, early life stress and 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 REM sleep, when it should normally be sound asleep. This vulnerability may ignite a downwards 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.
AB - 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 gene variants, early life stress and 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 REM sleep, when it should normally be sound asleep. This vulnerability may ignite a downwards 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.
U2 - 10.1152/physrev.00046.2019
DO - 10.1152/physrev.00046.2019
M3 - Article
C2 - 32790576
SN - 0031-9333
VL - 101
SP - 995
EP - 1046
JO - Physiological Reviews
JF - Physiological Reviews
ER -