Department of Psychiatry and Behavioural Neurosciences and Medicine, McMaster University, Hamilton, Ontario, Canada.
Transl Psychiatry. 2012 Nov 13;2(11):e187. doi: 10.1038/tp.2012.107.
There is increasing recognition that mitochondrial dysfunction may have a critical role in the pathophysiology of major psychiatric illnesses. Patients with mitochondrial disorders offer a unique window through which we can begin to understand the association between psychiatric symptoms and mitochondrial dysfunction in vivo. Using proton magnetic resonance spectroscopy ((1)H-MRS), we investigated metabolic indices in mitochondrial patients in regions of the brain that have been implicated in psychiatric illness: the caudate, cingulate cortex and hippocampus. In all, 15 patients with mitochondrial disorders and 15 age- and sex-matched controls underwent a comprehensive psychiatric assessment, including the administration of standardized psychiatric rating scales, followed by single voxel (1)H-MRS of the caudate, cingulate cortex and hippocampus to measure N-acetyl aspartate (NAA), creatine (Cr), glycerophosphocholine (GPC), myoinositol and glutamate+glutamine (Glx). Pearson's correlation coefficients were used to determine correlations between metabolites and the psychiatric rating scales. Anxiety symptoms in these patients correlated with higher GPC, Glx, myoinositol and Cr in the hippocampus. Impaired level of function as a result of psychiatric symptoms correlated with higher Glx and GPC in the cingulate cortex. In summary, we found remarkably consistent, and statistically significant, correlations between anxiety and metabolic indices in the hippocampus in patients with mitochondrial disorders, while overall impairment of functioning due to psychiatric symptoms correlated with metabolic markers in the cingulate cortex. These findings lend support to the notion that mitochondrial dysfunction in specific brain regions can give rise to psychiatric symptoms. In particular, they suggest that metabolic processes in the hippocampus may have an important role in the neurobiology of anxiety.
越来越多的人认识到，线粒体功能障碍可能在主要精神疾病的病理生理学中起着关键作用。线粒体疾病患者为我们提供了一个独特的窗口，通过这个窗口我们可以开始理解精神症状与体内线粒体功能障碍之间的关联。我们使用质子磁共振波谱（1H-MRS）研究了大脑中与精神疾病有关的区域（尾状核、扣带回皮质和海马体）的代谢指标。共有 15 名线粒体疾病患者和 15 名年龄和性别匹配的对照组患者接受了全面的精神评估，包括使用标准化精神评定量表进行评估，然后对尾状核、扣带回皮质和海马体进行单体素 1H-MRS 以测量 N-乙酰天冬氨酸（NAA）、肌酸（Cr）、甘油磷酸胆碱（GPC）、肌醇和谷氨酸+谷氨酰胺（Glx）。Pearson 相关系数用于确定代谢物与精神评定量表之间的相关性。这些患者的焦虑症状与海马体中的 GPC、Glx、肌醇和 Cr 呈正相关。由于精神症状导致的功能水平受损与扣带回皮质中的 Glx 和 GPC 呈正相关。总之，我们发现线粒体疾病患者的焦虑症与海马体代谢指标之间存在显著的、一致的、统计学上显著的相关性，而由于精神症状导致的整体功能障碍与扣带皮层中的代谢标志物相关。这些发现支持了这样一种观点，即特定脑区的线粒体功能障碍可能会导致精神症状。特别是，它们表明海马体中的代谢过程可能在焦虑症的神经生物学中具有重要作用。
