Leckman J F, Chittenden E H
Département de Psychiatrie, Faculté de Médecine de l'Université de Yale, New Haven, Connecticut 06510.
Encephale. 1990 Jul-Aug;16 Spec No:321-3.
Family aggregation and twin studies suggest that Gilles de La Tourette's syndrome (TS) and some forms of obsessive-compulsive disorder (OCD) are etiologically related. Neuroanatomically, the structures of the basal ganglia, thalamus and cortex have also been implicated in both TS and OCD suggesting a common neural substrate for these disorders. Neurochemical and neuropharmacological studies have provided less compelling data concerning this heuristically important association. Clinical studies have largely focused on the role of the nigrostriatal, mesolimbic and mesocortical dopaminergic systems in the pathophysiology of TS. In the case of OCD, serotoninergic systems originating in the raphe nuclei and projecting rostrally, have received considerable attention. Recent neuropathological studies of TS have implicated the endogenous opioid peptide, dynorphin, in the pathophysiology of TS. Animal studies have shown that dynorphin can modulate both dopaminergic and serotonergic systems. We have undertaken a cerebrospinal fluid (CSF) study to determine if abnormalities in dynorphin A concentration can be observed in drug-free TS and OCD patients. Preliminary results from this study suggest: 1) that TS patients have an elevated level of CSF dynorphin A (1-8) compared to normal controls; 2) that their level of CSF dynorphin is correlated with the severity of their OCD symptoms; 3) that some, but not all, OCD patients also have high levels of this neuropeptide in their CSF.
家系聚集研究和双胞胎研究表明,抽动秽语综合征(TS)与某些形式的强迫症(OCD)在病因上相关。从神经解剖学角度来看,基底神经节、丘脑和皮质的结构在TS和OCD中均有涉及,这表明这些疾病存在共同的神经基础。神经化学和神经药理学研究提供的关于这种具有启发性重要关联的数据说服力较弱。临床研究主要集中在黑质纹状体、中脑边缘和中脑皮质多巴胺能系统在TS病理生理学中的作用。就OCD而言,起源于中缝核并向前投射的5-羟色胺能系统受到了相当多的关注。最近对TS的神经病理学研究表明,内源性阿片肽强啡肽与TS的病理生理学有关。动物研究表明,强啡肽可以调节多巴胺能和5-羟色胺能系统。我们进行了一项脑脊液(CSF)研究,以确定在未用药的TS和OCD患者中是否能观察到强啡肽A浓度异常。这项研究的初步结果表明:1)与正常对照组相比,TS患者脑脊液中强啡肽A(1-8)水平升高;2)他们脑脊液中强啡肽水平与OCD症状的严重程度相关;3)一些(但不是所有)OCD患者脑脊液中这种神经肽水平也较高。