Insomnia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Insomnia is a sleep disorder characterized by an inability to sleep and/or inability to remain asleep for a reasonable period. It might occur as a standalone condition or along with existing physical or mental comorbidities.
Pathophysiology
Physiology
Although sleep is influenced by a myriad of conditions, both physical and environmental, most sleep patterns follow a circadian rhythm which is in turn regulated by a number of compounds in the body.[1]
- These compounds are broadly divided into either sleep-promoting or wake-promoting.[2]
- Examples of sleep-promoting compounds are melatonin, adenosine, serotonin, etc.
- Wake-promoting compounds include catecholamines, histamine, etc.
- Although all cases of insomnia cannot be explained by an imbalance between sleep-promoting and wake-promoting compounds, an imbalance or an excess of either points to sleep-wake disorder of some kind.
- Comorbid conditions like GERD, restless leg syndrome, anxiety disorder can result in chronic insomnia.
- Local sleep theory proposed by Krueger et al, defines sleep as a "fundamental emergent property of highly interconnected neurons"[3]. This theory states that in insomnia, compounds which regulate sleep act locally at the site of neurons and influence sleep-wake regulation.
Pathogenesis
It is thought that insomnia is mediated by[4]:
- Molecular Mechanism
- Hormones causing wakefulness: Catecholamine, Histamine, Orexin
- Hormones promoting sleep: Adenosine, serotonin, GABA, melatonin, Prostaglandin D2
- Hyperarousal model
- Cognitive
- Physiologic
- Cortical
- Genetic: ApoE4, PER3, 5HTTLPR, Single Nucleotide Polymorphism, CLOCK gene, HLA DQI*002
- Sleep switch Model (Orexin mediated)
- Sleep promoting areas:Ventrolateral Preoptic and Median preoptic Nucleus
- Wake promoting areas: Tuberomammillary nucleus, dorsal raphe, Locus coeruleus
- Cognitive and Behavioural Model(3P model): This model of insomnia helps to explain how acute insomnia becomes chronic and aids in assessing insomnia in individual patients
- Precipitating factors
- Predisposing factors
- Perpetuating factors
Although sleep is influenced by a myriad of conditions, both physical and environmental, most sleep patterns follow a circadian rhythm which is in turn regulated by a number of compounds in the body.[1]
- These compounds are broadly divided into either sleep-promoting or wake-promoting.[2]
- Examples of sleep-promoting compounds are melatonin, adenosine, serotonin, etc.
- Wake-promoting compounds include catecholamines, histamine, etc.
- Although all cases of insomnia cannot be explained by an imbalance between sleep-promoting and wake-promoting compounds, an imbalance or an excess of either points to sleep-wake disorder of some kind.
- Comorbid conditions like GERD, restless leg syndrome, anxiety disorder can result in chronic insomnia.
- Local sleep theory proposed by Krueger et al, defines sleep as a "fundamental emergent property of highly interconnected neurons"[3]. This theory states that in insomnia, compounds which regulate sleep act locally at the site of neurons and influence sleep-wake regulation.
It is thought that insomnia is mediated by[4]:
- Molecular Mechanism
- Hormones causing wakefulness: Catecholamine, Histamine, Orexin
- Hormones promoting sleep: Adenosine, serotonin, GABA, melatonin, Prostaglandin D2
- Hyperarousal model
- Cognitive
- Physiologic
- Cortical
- Genetic: ApoE4, PER3, 5HTTLPR, Single Nucleotide Polymorphism, CLOCK gene, HLA DQI*002
- Sleep switch Model (Orexin mediated)
- Sleep promoting areas:Ventrolateral Preoptic and Median preoptic Nucleus
- Wake promoting areas: Tuberomammillary nucleus, dorsal raphe, Locus coeruleus
- Cognitive and Behavioural Model(3P model): This model of insomnia helps to explain how acute insomnia becomes chronic and aids in assessing insomnia in individual patients
- Precipitating factors
- Predisposing factors
- Perpetuating factors
Genetics
A gene is reported to be responsible for insomnia, called human circadian clock gene CRY1.[5]
References
- ↑ 1.0 1.1 Ban HJ, Kim SC, Seo J, Kang HB, Choi JK (2011). "Genetic and metabolic characterization of insomnia". PLoS One. 6 (4): e18455. doi:10.1371/journal.pone.0018455. PMC 3071826. PMID 21494683.
- ↑ 2.0 2.1 Griffith LC (2013). "Neuromodulatory control of sleep in Drosophila melanogaster: integration of competing and complementary behaviors". Curr Opin Neurobiol. 23 (5): 819–23. doi:10.1016/j.conb.2013.05.003. PMC 3783581. PMID 23743247.
- ↑ 3.0 3.1 Krueger JM, Rector DM, Roy S, Van Dongen HP, Belenky G, Panksepp J (2008). "Sleep as a fundamental property of neuronal assemblies". Nat Rev Neurosci. 9 (12): 910–9. doi:10.1038/nrn2521. PMC 2586424. PMID 18985047.
- ↑ 4.0 4.1 "Sleep Medicine: Insomnia and Sleep - PubMed".
- ↑ Patke A, Murphy PJ, Onat OE, Krieger AC, Özçelik T, Campbell SS, Young MW (April 2017). "Mutation of the Human Circadian Clock Gene CRY1 in Familial Delayed Sleep Phase Disorder". Cell. 169 (2): 203–215.e13. doi:10.1016/j.cell.2017.03.027. PMC 5479574. PMID 28388406.