Winkelman John W, Buxton Orfeu M, Jensen J Eric, Benson Kathleen L, O'Connor Shawn P, Wang Wei, Renshaw Perry F
Division of Sleep Medicine, Brigham & Women's Hospital, Harvard Medical School, 1505 Commonwealth Avenue, Brighton, MA 02135, USA.
Sleep. 2008 Nov;31(11):1499-506. doi: 10.1093/sleep/31.11.1499.
Both basic and clinical data suggest a potential significant role for GABA in the etiology and maintenance of primary insomnia (PI). Proton magnetic resonance spectroscopy (1H-MRS) can non-invasively determine GABA levels in human brain. Our objective was to assess GABA levels in unmedicated individuals with PI, using 1H-MRS.
Matched-groups, cross-sectional study conducted at two university-based hospitals.
Sixteen non-medicated individuals (8 women) with PI (mean age = 37.3 +/- 8.1) and 16 (7 women) well-screened normal sleepers (mean age = 37.6 +/- 4.5).
PI was established with an unstructured clinical interview, a Structured Clinical Interview for DSM-IV (SCID), sleep diary, actigraphy and polysomnography (PSG). 1H-MRS data were collected on a Varian 4 Tesla magnetic resonance imagingl spectroscopy scanner. Global brain GABA levels were averaged from samples in the basal ganglia, thalamus, and temporal, parietal, and occipital white-matter and cortex.
Average brain GABA levels were nearly 30% lower in patients with PI (.18 +/- .06) compared to controls (.25 +/- .11). GABA levels were negatively correlated with wake after sleep onset (WASO) on two independent PSGs (r = -0.71, p = 0.0024 and -0.70, p = 0.0048).
Our preliminary finding of a global reduction in GABA in non-medicated individuals with PI is the first demonstration of a neurochemical difference in the brains of those with PI compared to normal sleeping controls. 1H-MRS is a valuable tool to assess GABA in vivo, and may provide a means to shed further light on the neurobiology of insomnia.
基础研究和临床数据均表明，γ-氨基丁酸（GABA）在原发性失眠（PI）的病因及维持机制中可能发挥重要作用。质子磁共振波谱（1H-MRS）能够无创测定人脑内的GABA水平。我们的目的是利用1H-MRS评估未用药的PI患者的GABA水平。
在两家大学附属医院开展的匹配组横断面研究。
16名未用药的PI患者（8名女性）（平均年龄=37.3±8.1岁）和16名（7名女性）经过充分筛查的正常睡眠者（平均年龄=37.6±4.5岁）。
通过非结构化临床访谈、《精神疾病诊断与统计手册》第四版（DSM-IV）结构化临床访谈、睡眠日记、活动记录仪及多导睡眠图（PSG）确诊PI。1H-MRS数据在Varian 4特斯拉磁共振成像/波谱扫描仪上采集。从基底神经节、丘脑、颞叶、顶叶、枕叶白质及皮质的样本中计算全脑GABA水平的平均值。
与对照组（0.25±0.11）相比，PI患者的平均脑内GABA水平低近30%（0.18±0.06）。在两项独立的PSG检查中，GABA水平与睡眠后觉醒时间（WASO）呈负相关（r=-0.71，p=0.0024；r=-0.70，p=0.0048）。
我们初步发现未用药的PI患者全脑GABA水平降低，这首次证明了PI患者大脑与正常睡眠对照组相比存在神经化学差异。1H-MRS是一种评估体内GABA的有价值工具，可能为进一步阐明失眠的神经生物学机制提供一种方法。
