Sleep Medicine and Psychophysiology (수면정신생리)

KOREAN ACADEMY OF SLEEP MEDICINE (대한수면의학회)
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Brain Metabolite Changes in Insomnia and Obstructive Sleep Apnea

수면장애에서 나타나는 뇌 대사물질의 변화 : 불면증과 폐쇄수면무호흡증을 중심으로

  • 홍혜진 (이화여자대학교 뇌융합과학연구원) ;
  • 이향원 (이화여자대학교 뇌융합과학연구원) ;
  • 윤수정 (이화여자대학교 뇌융합과학연구원) ;
  • 김정윤 (이화여자대학교 뇌융합과학연구원)
  • Received : 2021.04.19
  • Accepted : 2021.06.12
  • Published : 2021.06.30
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Abstract

Sleep is essential to brain function and mental health. Insomnia and obstructive sleep apnea (OSA) are the two most common sleep disorders, and are major public health concerns. Proton magnetic resonance spectroscopy (1H-MRS) is a non-invasive method of quantifying neurometabolite concentrations. Therefore, 1H-MRS studies on individuals with sleep disorders may enhance our understanding of the pathophysiology of these disorders. In this article, we reviewed 1H-MRS studies in insomnia and OSA that reported changes in neurometabolite concentrations. Previous studies have consistently reported insomnia-related reductions in γ-aminobutyric acid (GABA) levels in the frontal and occipital regions, which suggest that changes in GABA are important to the etiology of insomnia. These results may support the hyperarousal theory that insomnia is associated with increased cognitive and physiological arousal. In addition, the severity of insomnia was associated with low glutamate and glutamine levels. Previous studies of OSA have consistently reported reduced N-acetylaspartate (NAA) levels in the frontal, parieto-occipital, and temporal regions. In addition, OSA was associated with increased myo-inositol levels. These results may provide evidence that intermittent hypoxia induced by OSA may result in neuronal damage in the brain, which can be related to neurocognitive dysfunction in patients with OSA. The current review summarizes findings related to neurochemical changes in insomnia and OSA. Future well-designed studies using 1H-MRS have the potential to enhance our understanding of the pathophysiology of sleep disorders including insomnia and OSA.

Keywords

Acknowledgement

이 논문은 한국연구재단을 통한 교육부의 중점연구소지원사업(2020R1A6A1A03043528), 과학기술정보통신부의 기초연구사업(2020R1F1A1077421), 과학기술정보통신부의 뇌질환극복연구사업(2020M3E5D9080555)의 연구비 지원으로 수행되었습니다.

References

  1. Alchanatis M, Deligiorgis N, Zias N, Amfilochiou A, Gotsis E, Karakatsani A, et al. Frontal brain lobe impairment in obstructive sleep apnoea: a proton MR spectroscopy study. Eur Resp J 2004;24:980-986. https://doi.org/10.1183/09031936.04.00127603
  2. Algin O, Gokalp G, Ocakoglu G, Ursavas A, Taskapilioglu O, Hakyemez B. Neurochemical-structural changes evaluation of brain in patients with obstructive sleep apnea syndrome. Eur J Radiol 2012;81:491-495. https://doi.org/10.1016/j.ejrad.2010.12.092
  3. Alkan A, Sharifov R, Akkoyunlu ME, Kilicarslan R, Toprak H, Aralasmak A, et al. MR spectroscopy features of brain in patients with mild and severe obstructive sleep apnea syndrome. Clin Imaging 2013;37:989-992. https://doi.org/10.1016/j.clinimag.2013.07.010
  4. Baglioni C, Nanovska S, Regen W, Spiegelhalder K, Feige B, Nissen C, et al. Sleep and mental disorders: a meta-analysis of polysomnographic research HHS public access author manuscript. Psychol Bull 2017;42:969-990.
  5. Bartlett DJ, Rae C, Thompson CH, Byth K, Joffe DA, Enright T, et al. Hippocampal area metabolites relate to severity and cognitive function in obstructive sleep apnea. Sleep Med 2004;5:593-596. https://doi.org/10.1016/j.sleep.2004.08.004
  6. Benson KL, Bottary R, Schoerning L, Baer L, Gonenc A, Jensen JE, et al. 1H MRS measurement of cortical GABA and glutamate in primary insomnia and major depressive disorder: relationship to sleep quality and depression severity. J Affect Disord 2020;274:624-631. https://doi.org/10.1016/j.jad.2020.05.026
  7. Bonnet MH, Arand DL. Hyperarousal and insomnia. Sleep Med Rev 1997;1:97-108. https://doi.org/10.1016/S1087-0792(97)90012-5
  8. Cappuccio FP, D'Elia L, Strazzullo P, Miller MA. Quantity and quality of sleep and Incidence of Type 2 Diabetes: a systematic review and meta-analysis. Diabetes Care 2010;33:414-420. https://doi.org/10.2337/dc09-1124
  9. Castillo M, Kwock L, Mukherji SK. Clinical applications of proton MR spectroscopy. AJNR Am J Neuroradiol 1996;17:1-15.
  10. Cross NE, Lagopoulos J, Duffy SL, Cockayne NL, Hickie IB, Lewis SJ, et al. Sleep quality in healthy older people: relationship with 1H magnetic resonance spectroscopy markers of glial and neuronal integrity. Behav Neurosci 2013;127:803. https://doi.org/10.1037/a0034154
  11. Decary A, Rouleau I, Monplaisir J. Cognitive deficits associated with sleep apnoea syndrome: a proposed neuropsychological test battery. Sleep 2000;23:369-381.
  12. Desseilles M, Dang-Vu T, Schabus M, Sterpenich V, Maquet P, Schwartz S. Neuroimaging insights into the pathophysiology of sleep disorders. Sleep 2008;31:777-794. https://doi.org/10.1093/sleep/31.6.777
  13. Engelman HM, Kingshot RN, Martin SE, Douglas NJ. Cognitive function in the sleep apnoea/hypopnoea syndrome (SAHS). Sleep 2000;23:s102-s108.
  14. Goldstein AN, Walker MP. The role of sleep in emotional brain function. Annu Rev Clin Psychol 2014;10:679-708. https://doi.org/10.1146/annurev-clinpsy-032813-153716
  15. Govindaraju V, Young K, Maudsley AA. Proton NMR chemical shifts and coupling constants for brain metabolites. NMR in Biomedicine 2000;13:129-153. https://doi.org/10.1002/1099-1492(200005)13:3<129::AID-NBM619>3.0.CO;2-V
  16. Halbower AC, Degaonkar M, Barker PB, Earley CJ, Marcus CL, Smith PL, et al. Childhood obstructive sleep apnea associates with neuropsychological deficits and neuronal brain injury. PLoS Med 2006;3:e301. https://doi.org/10.1371/journal.pmed.0030301
  17. Hatton SN, Lagopoulos J, Hermens DF, Naismith SL, Bennett MR, Hickie IB. Correlating anterior insula gray matter volume changes in young people with clinical and neurocognitive outcomes: an MRI study. BMC Psychiatry 2012;12:1-10. https://doi.org/10.1186/1471-244X-12-1
  18. Kamba M, Suto Y, Ohta Y, Inoue Y, Matsuda E. Cerebral metabolism in sleep apnea: evaluation by magnetic resonance spectroscopy. Am J Respir Crit Care Med 1997;156:296-298. https://doi.org/10.1164/ajrccm.156.1.9611063
  19. Kamba M, Inoue Y, Higami S, Suto Y, Ogawa T, Chen W. Cerebral metabolic impairment in patients with obstructive sleep apnoea: an independent association of obstructive sleep apnoea with white matter change. J Neurol Neurosurg Psychiatry 2001;71:334-339. https://doi.org/10.1136/jnnp.71.3.334
  20. Kang J, Tian Z, Li M. Changes in insular cortex metabolites in patients with obstructive sleep apnea syndrome. Neuroreport 2018;29:981-986. https://doi.org/10.1097/WNR.0000000000001065
  21. Kantarci KJCJ, Jack CR, Xu YC, Campeau NG, O'Brien PC, Smith GE, et al. Regional metabolic patterns in mild cognitive impairment and Alzheimer's disease: a 1H MRS study. Neurology 2000;55:210-217. https://doi.org/10.1212/WNL.55.2.210
  22. Kapeller P, Ropele S, Enzinger C, Lahousen T, Strasser-Fuchs S, Schmidt R, et al. Discrimination of white matter lesions and multiple sclerosis plaques by short echo quantitative 1H-magnetic resonance spectroscopy. J Neurol 2005;252:1229-1234. https://doi.org/10.1007/s00415-005-0847-3
  23. Khazaie H, Veronese M, Noori K, Emamian F, Zarei M, Ashkan K, et al. Functional reorganization in obstructive sleep apnoea and insomnia: a systematic review of the resting-state fMRI. Neurosci Biobehav Rev 2017;77:219-231. https://doi.org/10.1016/j.neubiorev.2017.03.013
  24. Kizilgoz V, Aydin H, Tatar IG, Hekimoglu B, Ardic S, Firat H, et al. Proton magnetic resonance spectroscopy of periventricular white matter and hippocampus in obstructive sleep apnea patients. Pol J Radiol 2013;78:7.
  25. Korenic SA, Klingaman EA, Wickwire EM, Gaston FE, Chen H, Wijtenburg SA, et al. Sleep quality is related to brain glutamate and symptom severity in schizophrenia. J Psychiatr Res 2020;120:14-20. https://doi.org/10.1016/j.jpsychires.2019.10.006
  26. Krause AJ, Simon EB, Mander BA, Greer SM, Saletin JM, Goldstein-Piekarski AN, et al. The sleep-deprived human brain. Nat Rev Neurosci 2017;18:404-418. https://doi.org/10.1038/nrn.2017.55
  27. Levy P, Kohler M, McNicholas WT, Barbe F, McEvoy RD, Somers VK, et al. Obstructive sleep apnoea syndrome. Nat Rev Dis Primers 2015;1:1-21.
  28. Meyerhoff DJ, Mon A, Metzler T, Neylan TC. Cortical gammaaminobutyric acid and glutamate in posttraumatic stress disorder and their relationships to self-reported sleep quality. Sleep 2014;37:893-900. https://doi.org/10.5665/sleep.3654
  29. Miller CB, Rae CD, Green MA, Yee BJ, Gordon CJ, D'Rozario AL, et al. An objective short sleep insomnia disorder subtype is associated with reduced brain metabolite concentrations in vivo: a preliminary magnetic resonance spectroscopy assessment. Sleep 2017;40:zsx148.
  30. Miller EK. The prefontral cortex and cognitive control. Nat Rev Neurosci 2000;1:59-65. https://doi.org/10.1038/35036228
  31. Morgan PT, Pace-Schott EF, Mason GF, Forselius E, Fasula M, Valentine GW, et al. Cortical GABA levels in primary insomnia. Sleep 2012;35:807-814. https://doi.org/10.5665/sleep.1880
  32. Morin CM, Drake CL, Harvey AG, Krystal AD, Manber R, Riemann D, et al. Insomnia disorder. Nat Rev Dis Primers 2015;1:1-18.
  33. Nagai M, Hoshide S, Kario K. Sleep duration as a risk factor for cardiovascular disease: a review of the recent literature. Curr Cardiol Rev 2010;6:54-61. https://doi.org/10.2174/157340310790231635
  34. Nofzinger EA. What can neuroimaging findings tell us about sleep disorders? Sleep Med 2004;5:S16-S22. https://doi.org/10.1016/S1389-9457(04)90003-2
  35. O'Donoghue FJ, Wellard RM, Rochford PD, Dawson A, Barnes M, Ruehland WR, et al. Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment. Sleep 2012;35:41-48. https://doi.org/10.5665/sleep.1582
  36. Ohayon MM. Epidemiology of insomnia: what we know and what we still need to learn. Sleep Med Rev 2002;6:97-111. https://doi.org/10.1053/smrv.2002.0186
  37. Oppenheimer SM, Gelb A, Girvin JP, Hachinski VC. Cardiovascular effects of human insular cortex stimulation. Neurology 1992;42:1727-1732. https://doi.org/10.1212/WNL.42.9.1727
  38. Plante DT, Jensen JE, Schoerning L, Winkelman JW. Reduced γ-aminobutyric acid in occipital and anterior cingulate cortices in primary insomnia: a link to major depressive disorder? Neuropsychopharmacology 2012a;37:1548-1557. https://doi.org/10.1038/npp.2012.4
  39. Plante DT, Jensen JE, Winkelman JW. The role of GABA in primary insomnia. Sleep 2012b;35:741-742. https://doi.org/10.5665/sleep.1854
  40. Rosenzweig I, Glasser M, Polsek D, Leschziner GD, Williams SC, Morrell MJ. Sleep apnoea and the brain: a complex relationship. Lancet Respir Med 2015;3:404-414. https://doi.org/10.1016/S2213-2600(15)00090-9
  41. Ross B, Michaelis T. Clinical applications of magnetic resonance spectroscopy. Magn Reson Q 1994;10:191-247.
  42. Rudkin TM, Arnold DL. Proton magnetic resonance spectroscopy for the diagnosis and management of cerebral disorders. Arch Neurol 1999;56:919-926. https://doi.org/10.1001/archneur.56.8.919
  43. Sarchielli P, Presciutti O, Alberti A, Tarducci R, Gobbi G, Galletti F, et al. A 1H magnetic resonance spectroscopy study in patients with obstructive sleep apnea. Eur J Neurol 2008;15:1058-1064. https://doi.org/10.1111/j.1468-1331.2008.02244.x
  44. Sharma SK, Sinha S, Danishad KA, Sharma U, Sharma H, Mishra HK, et al. Proton magnetic resonance spectroscopy of brain in obstructive sleep apnoea in north Indian Asian subjects. Indian J Med Res 2010;132:278-286.
  45. Sivertsen B, Krokstad S, Overland S, Mykletun A. The epidemiology of insomnia: associations with physical and mental health: the HUNT-2 study. J Psychosom Res 2009;67:109-116. https://doi.org/10.1016/j.jpsychores.2009.05.001
  46. Spiegelhalder K, Regen W, Nissen C, Feige B, Baglioni C, Riemann D, et al. Magnetic resonance spectroscopy in patients with insomnia: a repeated measurement study. PLoS One 2016;11:e0156771. https://doi.org/10.1371/journal.pone.0156771
  47. Stradling JR. Davies RJ. Sleep 1: obstructive sleep apnoea/hypopnoea syndrome: definitions, epidemiology, and natural history. Thorax 2004;59:73-78. https://doi.org/10.1136/thx.2003.007161
  48. Tonon C, Vetrugno R, Lodi R, Gallassi R, Provini F, Iotti S, et al. Proton magnetic resonance spectroscopy study of brain metabolism in obstructive sleep apnoea syndrome before and after continuous positive airway pressure treatment. Sleep 2007;30:305-311. https://doi.org/10.1093/sleep/30.3.305
  49. Urrila AS, Hakkarainen A, Castaneda A, Paunio T, Marttunen M, Lundbom N. Frontal cortex Myo-inositol is associated with sleep and depression in adolescents: a proton magnetic resonance spectroscopy study. Neuropsychobiology 2017;75:21-31. https://doi.org/10.1159/000478861
  50. Vgontzas AN, Kales A. Sleep and its disorders. Annu Rev Med 1999;50:387-400. https://doi.org/10.1146/annurev.med.50.1.387
  51. Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H. GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol 2002;213:1-47. https://doi.org/10.1016/S0074-7696(02)13011-7
  52. Winkelman JW, Buxton OM, Jensen JE, Benson KL, O'Connor SP, Wang W, et al. Reduced brain GABA in primary insomnia: preliminary data from 4T proton magnetic resonance spectroscopy. Sleep 2008;31:1499-1506. https://doi.org/10.1093/sleep/31.11.1499
  53. Xia Y, Fu Y, Xu H, Guan J, Yi H, Yin S. Changes in cerebral metabolites in obstructive sleep apnea: a systemic review and meta-analysis. Sci Rep 2016;6:1-8. https://doi.org/10.1038/s41598-016-0001-8
  54. Xu S, Yang J, Shen J. Measuring N-acetylaspartate synthesis in vivo using proton magnetic resonance spectroscopy. J Neurosci Methods 2008;172:8-12. https://doi.org/10.1016/j.jneumeth.2008.04.001
  55. Yadav SK, Kumar R, Macey PM, Woo MA, Yan-Go FL, Harper RM. Insular cortex metabolite changes in obstructive sleep apnea. Sleep 2014;37:951-958. https://doi.org/10.5665/sleep.3668
  56. Zhu H, Barker PB. MR spectroscopy and spectroscopic imaging of the brain. Methods Mol Biol 2011;711:203-226. https://doi.org/10.1007/978-1-61737-992-5_9