Bravi Beatrice, Bollettini Irene, Di Pasquasio Camilla, Falini Andrea, Colombo Cristina, Zanardi Raffaella, Poletti Sara, Benedetti Francesco
Psychiatry & Clinical Psychobiology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy.
Psychiatry & Clinical Psychobiology, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milano, Italy; C.E.R.M.A.C. (Centro di Eccellenza Risonanza Magnetica ad Alto Campo), Vita-Salute San Raffaele University, Milan, Italy.
Psychiatry Res Neuroimaging. 2022 Oct;326:111534. doi: 10.1016/j.pscychresns.2022.111534. Epub 2022 Aug 27.
Bipolar disorder (BD) is associated with alterations in white matter (WM) microstructure, glutamatergic neurotransmission, and glia activity. Previous studies showed higher concentrations of glutamate (Glu), glutamate+glutamine (Glx), and reduced N-acetyl-aspartate (NAA) in BD. We investigated brain concentrations of Glu, Glx, NAA, mI as indirect marker of microglia activation, and Glx/NAA ratio as index of neuronal damage through H-MR, and WM integrity with Tract-Based Spatial Statistics in 93 depressed BD patients and 58 healthy controls (HC). We tested for linear effects of cited spectroscopic metabolites on DTI measures of WM integrity with general linear models for each group, then performing a conjunction analysis of Glx/NAA and mI concentration on the same measures. Statistical analyses (whole sample) revealed higher concentration of Glx/NAA, Glx and mI in BD patients compared to HC, and a positive association between mI and the ratio. DTI analyses (87 BD and 35 HC) showed a significant association of Glx/NAA ratio, and mI with WM microstructure. Conjunction analysis revealed a joint negative association between Glx/NAA and mI with fractional anisotropy. This is the first study showing an association between brain metabolites involved in neuronal damage, and glial activation and the alterations in WM consistently reported in BD.
双相情感障碍（BD）与白质（WM）微观结构、谷氨酸能神经传递及胶质细胞活性改变有关。既往研究显示，BD患者体内谷氨酸（Glu）、谷氨酸+谷氨酰胺（Glx）浓度较高，而N-乙酰天门冬氨酸（NAA）浓度降低。我们通过氢磁共振波谱（H-MR）研究了93例抑郁发作的BD患者和58例健康对照（HC）脑内Glu、Glx、NAA、作为小胶质细胞激活间接标志物的肌醇（mI）以及作为神经元损伤指标的Glx/NAA比值，并采用基于纤维束的空间统计学方法研究了WM完整性。我们用一般线性模型检验了上述波谱代谢物对每组WM完整性扩散张量成像（DTI）测量值的线性效应，然后对相同测量值进行Glx/NAA和mI浓度的联合分析。统计分析（全样本）显示，与HC相比，BD患者的Glx/NAA、Glx和mI浓度更高，且mI与该比值呈正相关。DTI分析（87例BD患者和35例HC）显示，Glx/NAA比值和mI与WM微观结构存在显著关联。联合分析显示，Glx/NAA和mI与各向异性分数呈联合负相关。这是第一项表明BD中一直报道的神经元损伤、胶质细胞激活及WM改变所涉及的脑代谢物之间存在关联的研究。
