Erritzoe David, Talbot Peter, Frankle W Gordon, Abi-Dargham Anissa
Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, 1051 Riverside Drive, Unit 31, New York, NY 10032, USA.
Neuroimaging Clin N Am. 2003 Nov;13(4):817-32. doi: 10.1016/s1052-5149(03)00089-3.
We reviewed findings from PET and SPECT studies that have contributed to our understanding of the pathophysiology and treatment of schizophrenia. The most robust set of findings pertains to imaging of presynaptic dopaminergic function in the striatum. The results of these studies have been consistent in showing that schizophrenia, at least during episodes of illness exacerbation, is associated with increased activity of DA neurons; this increased presynaptic activity is associated with positive symptoms and good therapeutic response. Studies of cortical DA function are less numerous and less consistent. In the future, technical advances in PET instrumentation and radioligand development should contribute to a clarification of the role of prefrontal DA in the cognitive impairment that is presented by these patients. An important drawback of the literature in this field is the generally low number of subjects that are included in studies (typically less than 20 per group). Small samples are necessitated by the cost of these investigations, but also, in some instances, to the difficulty in recruiting appropriate clinical subjects (such as drug-free patients who have schizophrenia). In conditions that are characterized by marked heterogeneity, such as major depressive disorders, this factor is bound to yield divergent results across studies. Another source of discrepancy is the variety of technical approaches to data acquisition and analysis. For example, analytical methods range from "empirical" or "semiquantitative" (typically a region of interest to a region of reference ratio measured at one time point) to model-based methods that use an arterial input function. The limitations that are associated with empirical analytical methods might account for artifactual results, especially when the effect size of the between-group difference and the number of subjects are small [149]. In addressing these limitations it will be important to increase the availability of these techniques beyond a few academic centers, to promote multi-center studies in well-characterized populations, and to standardize analytical methods. Until recently, SPECT was the only widely available technique, and SPECT studies have provided a substantial contribution to this field. With the current increase in PET camera availability, the development of [18F]-based molecular imaging probes will provide unique opportunities for further dissemination of these techniques. The article reviewed seminal findings obtained with PET and SPECT molecular imaging of schizophrenia. These techniques do not play a major role in the diagnosis and treatment of this disorder, remain essentially research tools. The results that have been produced by this field to date suggest that PET will significantly contribute to unraveling the biologic bases of psychiatric disorders and may contribute to their clinical management. Moreover, it is foreseeable that PET will become increasingly involved in the development of new psychiatric medications. Expanding the availability of PET and the current radiopharmaceutical portfolio will be critical for these predictions to become reality.
我们回顾了正电子发射断层扫描(PET)和单光子发射计算机断层扫描(SPECT)研究的结果,这些研究有助于我们理解精神分裂症的病理生理学和治疗方法。最有力的一组研究结果与纹状体中突触前多巴胺能功能的成像有关。这些研究结果一致表明,精神分裂症至少在病情加重期间,与多巴胺(DA)神经元活动增加有关;这种突触前活动增加与阳性症状及良好的治疗反应相关。关于皮质DA功能的研究数量较少且结果不太一致。未来,PET仪器和放射性配体开发方面的技术进步应有助于阐明前额叶DA在这些患者所表现出的认知障碍中的作用。该领域文献的一个重要缺点是研究中纳入的受试者数量普遍较少(每组通常少于20人)。这些研究成本高,导致样本量小,但在某些情况下,也是因为招募合适的临床受试者(如未服用药物的精神分裂症患者)存在困难。在以显著异质性为特征的疾病中,如重度抑郁症,这一因素必然会导致不同研究结果出现差异。另一个差异来源是数据采集和分析的技术方法多种多样。例如,分析方法从“经验性”或“半定量”(通常是在一个时间点测量感兴趣区域与参考区域的比值)到使用动脉输入函数的基于模型的方法。与经验性分析方法相关的局限性可能导致人为结果,尤其是当组间差异的效应大小和受试者数量较小时[149]。为解决这些局限性,增加这些技术在少数几个学术中心以外的可及性、促进在特征明确的人群中开展多中心研究以及使分析方法标准化将很重要。直到最近,SPECT还是唯一广泛可用的技术,SPECT研究为该领域做出了重大贡献。随着目前PET相机可及性的提高,基于[18F]的分子成像探针的开发将为这些技术的进一步推广提供独特机会。本文回顾了通过PET和SPECT分子成像获得的关于精神分裂症的开创性研究结果。这些技术在该疾病的诊断和治疗中并不起主要作用,本质上仍是研究工具。该领域迄今为止产生的结果表明,PET将对揭示精神疾病的生物学基础做出重大贡献,并可能有助于其临床管理。此外,可以预见PET将越来越多地参与新精神药物的研发。扩大PET的可及性和当前放射性药物的种类对于这些预测成为现实至关重要。