McDougle C J, Barr L C, Goodman W K, Price L H
Indiana University School of Medicine, Department of Psychiatry, Indianapolis 46202, USA.
Psychoneuroendocrinology. 1999 Jan;24(1):1-24. doi: 10.1016/s0306-4530(98)00046-8.
The most consistent finding in clinical research of obsessive compulsive disorder (OCD) is the significant treatment advantage of potent serotonin uptake inhibitors (SUIs) over other classes of antidepressant and antianxiety drugs. Clinical neurobiological studies of OCD, however, have yielded limited and inconsistent evidence for significant fundamental abnormalities in monoamine systems including serotonin, norepinephrine and dopamine. Furthermore, one-third to one-half of OCD patients do not experience a clinically meaningful improvement with SUI treatment. Investigation beyond the monoamine systems may be necessary in order to more fully understand the pathophysiology of obsessive-compulsive symptoms and develop improved treatments. Evidence from preclinical studies suggests that neuropeptides may have important influences on memory acquisition, maintenance and retrieval; grooming, maternal, sexual and aggressive behavior; fixed action patterns; and stereotyped behavior; these phenomena may relate to some features of OCD. In addition, extensive interactions have been identified in the brain between neuropeptidergic and monoaminergic systems, including co-localization among specific populations of neurons. The purpose of this review is to present the current knowledge of the role of neuropeptides in the clinical neurobiology of children, adolescents and adults with OCD focusing primarily on results from pharmacological challenge and cerebrospinal fluid studies. Where evidence exists, developmentally regulated differences in neuropeptide function between children and adolescents versus adults with OCD will be emphasized; these data are intended to underscore the potential importance of establishing the age of symptom onset (childhood versus adult) in individual patients with OCD participating in clinical neurobiological investigations. Likewise, where information is available, differences in measures of neuropeptides between patients with non-tic-related OCD versus tic-related OCD will be highlighted; these data will demonstrate the critical value of diagnostic precision, as these two particular subtypes of OCD may have different neurochemical underpinnings.
强迫症（OCD）临床研究中最一致的发现是，强效5-羟色胺摄取抑制剂（SUIs）相较于其他抗抑郁和抗焦虑药物具有显著的治疗优势。然而，OCD的临床神经生物学研究在包括5-羟色胺、去甲肾上腺素和多巴胺在内的单胺系统存在显著基本异常方面，所获证据有限且不一致。此外，三分之一至二分之一的OCD患者在接受SUIs治疗后并未出现具有临床意义的改善。为了更全面地理解强迫症状的病理生理学并开发更好的治疗方法，可能有必要对单胺系统之外展开研究。临床前研究的证据表明，神经肽可能对记忆的获取、维持和提取；梳理行为、母性行为、性行为和攻击行为；固定行为模式；以及刻板行为有重要影响；这些现象可能与OCD的某些特征相关。此外，已确定在大脑中神经肽能系统和单胺能系统之间存在广泛的相互作用，包括特定神经元群体之间的共定位。本综述的目的是介绍目前关于神经肽在患有OCD的儿童、青少年和成人临床神经生物学中作用的知识，主要关注药理学激发试验和脑脊液研究的结果。如有证据，将强调患有OCD的儿童和青少年与成人在神经肽功能上的发育调节差异；这些数据旨在强调在参与临床神经生物学研究的OCD个体患者中确定症状起始年龄（儿童期与成年期）的潜在重要性。同样，如有可用信息，将突出非抽动相关OCD患者与抽动相关OCD患者在神经肽测量方面的差异；这些数据将证明诊断精确性的关键价值，因为这两种特定的OCD亚型可能具有不同的神经化学基础。
