Coplan Jeremy D, Mathew Sanjay J, Mao Xiangling, Smith Eric L P, Hof Patrick R, Coplan Paul M, Rosenblum Leonard A, Gorman Jack M, Shungu Dikoma C
Department of Psychiatry, Division of Neuropsychopharmacology, State University of New York, Downstate Medical Center, Brooklyn, 11023, USA.
Psychiatry Res. 2006 Jun 30;147(1):27-39. doi: 10.1016/j.pscychresns.2005.12.011. Epub 2006 Jun 22.
We have demonstrated, using proton magnetic resonance spectroscopy imaging ((1)H-MRSI), elevations of N-acetyl-aspartate/creatine (NAA/CR) in right dorsolateral prefrontal cortex (DLPFC) in patients with generalized anxiety disorder (GAD) in comparison to healthy volunteers. A recent study indicates that the volume of prefrontal cortical white matter may be disproportionately increased in man in comparison to other primate species, with evolutionary implications. We therefore re-analyzed the identical scans with a specific focus on the centrum semiovale (CSO) as a representative region of interest of cerebral white matter. The central hypothesis was, in accordance with our gray matter findings, that patients with GAD, in comparison to healthy controls, would exhibit either an increase in NAA in CSO, or alternatively demonstrate reductions in concentrations of choline (CHO)-containing compounds and/or creatine+phosphocreatine (CR). MRSI scans that were obtained from an earlier [Mathew, S.J., Mao, X., Coplan, J.D., Smith, E.L., Sackeim, H.A., Gorman, J.M., Shungu, D.C., 2004. Dorsolateral prefrontal cortical pathology in generalized anxiety disorder: a proton magnetic resonance spectroscopic imaging study. American Journal of Psychiatry 161, 1119-1121] sample of 15 patients with GAD [6 with early trauma (ET)] and 15 healthy age- and sex-matched volunteers were analyzed further for CSO metabolite alterations. Self-reported worry was scored using the Penn State Worry Questionnaire (PSWQ) and intelligence was assessed using the Wechsler Abbreviated Scale of Intelligence (WASI). Serial multislice/multivoxel MRSI scans had been performed on a 1.5-T MRI. Using absolute quantification methods for metabolite concentrations, we examined NAA, CHO and CR. GAD patients without ET exhibited bilaterally decreased concentrations of CHO and CR in CSO in comparison to healthy volunteers, whereas GAD patients with ET were indistinguishable from controls. In patients with GAD, high IQ was paired with greater worry, whereas in healthy volunteers, high IQ was associated with less worry. In all subjects, IQ inversely predicted left and right CSO CHO concentrations, independent of age, sex, group assignment and PSWQ scores. The CSO may therefore represent a neural substrate that exhibits reductions in CHO and CR metabolite concentrations that are inversely associated with GAD symptomatology and, in the case of CHO, with intelligence. These conclusions are deemed preliminary due to small sample size, with further study of cerebral WM in anxiety disorders suggested.
我们通过质子磁共振波谱成像（(1)H-MRSI）证明，与健康志愿者相比，广泛性焦虑症（GAD）患者右侧背外侧前额叶皮质（DLPFC）中的N-乙酰天门冬氨酸/肌酸（NAA/CR）升高。最近一项研究表明，与其他灵长类物种相比，人类前额叶皮质白质的体积可能会不成比例地增加，这具有进化意义。因此，我们重新分析了相同的扫描结果，特别关注半卵圆中心（CSO），将其作为脑白质的一个代表性感兴趣区域。核心假设是，与我们在灰质方面的发现一致，与健康对照组相比，GAD患者在CSO中要么表现出NAA增加，要么表现出含胆碱（CHO）化合物和/或肌酸+磷酸肌酸（CR）浓度降低。对从早期[Mathew, S.J., Mao, X., Coplan, J.D., Smith, E.L., Sackeim, H.A., Gorman, J.M., Shungu, D.C., 2004. 广泛性焦虑症的背外侧前额叶皮质病理学：一项质子磁共振波谱成像研究。《美国精神病学杂志》161, 1119 - 1121]样本中选取的15名GAD患者[6名有早期创伤（ET）]和15名年龄及性别匹配的健康志愿者的MRSI扫描结果进一步分析CSO代谢物变化。使用宾夕法尼亚州立大学忧虑问卷（PSWQ）对自我报告的忧虑进行评分，并使用韦氏简易智力量表（WASI）评估智力。在1.5-T MRI上进行了系列多层/多体素MRSI扫描。使用代谢物浓度的绝对定量方法，我们检测了NAA、CHO和CR。与健康志愿者相比，无ET的GAD患者CSO中CHO和CR的浓度双侧降低，而有ET的GAD患者与对照组无差异。在GAD患者中，高智商与更多忧虑相关，而在健康志愿者中，高智商与较少忧虑相关。在所有受试者中，智商与左右CSO中CHO浓度呈负相关，与年龄、性别、分组及PSWQ评分无关。因此，CSO可能代表一种神经基质，其CHO和CR代谢物浓度降低，且与GAD症状呈负相关，就CHO而言，还与智力呈负相关。由于样本量小，这些结论被认为是初步的，建议对焦虑症中的脑白质进行进一步研究。
