수면장애에서 나타나는 뇌 대사물질의 변화 : 불면증과 폐쇄수면무호흡증을 중심으로
Brain Metabolite Changes in Insomnia and Obstructive Sleep Apnea
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본 종설에서는 불면증과 OSA 환자에서 뇌 대사물질의변화가 관찰되고 이러한 변화가 수면장애 증상과 연관성을가진다는 점을 확인하였다. 불면증 환자를 대상으로 한 대부분의 기존 연구에서 불면증 환자가 대조군에 비해 후두부피질, 전대상피질 등의 영역에서 GABA가 감소되어 있었고, GABA 농도가 감소할수록 수면의 질이 악화됨을 보고하였다. 이러한 결과는 불면증이 인지 및 생리학적 증가된 각성으로 인해 발생한다는기존 이론을 뒷받침하며, GABA 농도가 불면증의 발생 및유지와 주요한 연관성이 있음을 시사한다. 또한 불면증 환자에서 전대상피질, 배외측 전전두피질 등의 전두엽 영역과후두엽 영역에서 glutamine과 glutamate 농도 감소가 관찰되었고, 해당 농도가 감소할수록 수면의 질이 감소하는 연관성을 보고하였다. 해당 결과는 GABA 합성에 중요한 전구체이자 신경전달물질의 활동을 조절하는 glutamine과glutamate의 농도 변화 역시 불면증에서 각성 수준을 나타내는 지표임을 시사한다. OSA를 대상으로 한 대부분의 기존 연구에서는 OSA 환자가 대조군에 비해 주로 전두엽 영역에서의 NAA의 감소를 보고하였으며, NAA 농도가 감소할수록 수면장애 정도가 증가하는 상관관계를 확인하였다. 이러한 NAA의 감소는 심장질환이나 심혈관계 위험 요인이 없는 OSA 환자에서도 동일하게 관찰되었으며, 심각한 단계가 아닌 최근 OSA 를 진단받은 환자에서도 NAA의 감소가 보고되었다. 또한전두엽뿐만 아니라 두정, 후두, 측두피질에서도 NAA 농도의 감소와 이에 따른 수면의 질 감소가 함께 관찰되었다. 해당 결과는 OSA 환자에서 간헐적 저산소증에 의한 축삭 손실 및 기능장애와 신경변성의 증거를 나타낸다. 본 종설은 불면증과 OSA에서 나타나는 신경화학적 변화에 대한 근거를 제시하며, 비침습적으로 뇌 내 대사물질을 측정할 수 있는 1H-MRS가 수면장애의 병태생리에 대한 심층적 이해를 위한 유용한 도구로 활용될 수 있음을 제안한다. 불면증과 OSA에서 MRS를 활용한 연구는 다른 구조적및 기능적 뇌영상 연구에 비해 매우 적은 편이며, 수면장애에서 나타나는 대사물질의 변화와 여러 증상 간의 관계를명확히 규명하기 위해서는 좀더 많은 수의 연구가 필요하다. 또한, 수면장애의 심각도, 동반 질환, 연령, 성별 등 다양한 환자 상태에서 대사물질 변화를 측정하고, 인지 및 행동적 변화와의 관련성을 확인하며, 이에 대해 반복 검증하는연구가 추가적으로 이루어져야 할 것이다.
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, parietooccipital, 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.
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