Kestler L P, Walker E, Vega E M
Emory University, Atlanta, Georgia 30322, USA.
Behav Pharmacol. 2001 Sep;12(5):355-71. doi: 10.1097/00008877-200109000-00007.
Controversy surrounds the question of whether there are dopamine (DA) receptor abnormalities in the brains of schizophrenia patients; in particular, whether DA receptors of the D2 family are elevated in density. Methodological factors and sample characteristics have been postulated to account for differences in study outcome, but there has been no systematic analysis of the contribution of these factors to study effect sizes. This meta-analysis of the research findings sought to determine the influence of methodologic factors and sample characteristics on the magnitude of diagnostic group differences in DA D2 density (Bmax) and affinity (Kd). The analysis suggests at least moderate effects, such that schizophrenia patients show an elevation in both values when compared to controls. These effects are amplified in medicated patients, but not solely attributable to antipsychotics. The group differences in DA D2 receptor density and affinity increase with age among nonmedicated patients. The use of a butyrophenone ligand also yields larger effects. It is concluded that a subgroup of schizophrenia patients manifests increased DA D2 receptor density and decreased receptor affinity. In the absence of medication, these changes may become more pronounced with age. Differences in study outcome are also partially due to methodologic factors, including the ligand.
围绕精神分裂症患者大脑中是否存在多巴胺(DA)受体异常这一问题存在争议;尤其是D2家族的DA受体密度是否升高。有人推测方法学因素和样本特征可以解释研究结果的差异,但尚未对这些因素对研究效应大小的贡献进行系统分析。这项对研究结果的荟萃分析旨在确定方法学因素和样本特征对DA D2密度(Bmax)和亲和力(Kd)诊断组差异大小的影响。分析表明至少有中等程度的效应,即与对照组相比,精神分裂症患者的这两个值均升高。这些效应在接受药物治疗的患者中更为明显,但并非完全归因于抗精神病药物。在未接受药物治疗的患者中,DA D2受体密度和亲和力的组间差异随年龄增加。使用丁酰苯类配体也会产生更大的效应。得出的结论是,一部分精神分裂症患者表现出DA D2受体密度增加和受体亲和力降低。在未用药的情况下,这些变化可能会随着年龄增长而更加明显。研究结果的差异也部分归因于方法学因素,包括配体。