Striatal Presynaptic Dopamine in Schizophrenia, Part I: Meta-Analysis of Dopamine Active Transporter (DAT) Density
Striatal Presynaptic Dopamine in Schizophrenia, Part I: Meta-Analysis of Dopamine Active Transporter (DAT) Density
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DOI：
10.1093/schbul/sbr111
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发表时间：
2013-01-01
影响因子：
6.6
通讯作者：
Meyer-Lindenberg, Andreas
中科院分区：
文献类型：
--
作者：
Fusar-Poli, Paolo;Meyer-Lindenberg, Andreas
背景资料：纹状体多巴胺能神经传递被认为是精神分裂症关键症状（如精神病症状）出现的基础，并且是目前可用的多巴胺能药物的靶向。纹状体中突触前多巴胺神经元完整性的特异性标志物，纹状体多巴胺终末的密度，可以通过多巴胺活性转运蛋白（DAT）的分子神经成像来定量。然而，目前使用这种方法治疗精神分裂症的结果并不一致。研究方法：13项单光子发射断层扫描或正电子发射断层扫描（PET）研究调查了精神分裂症患者和匹配对照组纹状体中的DAT密度，这些研究被纳入定量荟萃分析。从每篇出版物中提取纹状体、尾状核和壳核的结合电位以及人口统计学、临床和方法学变量。Hedges' g被用作效应量的量度。结果：整个数据库包含202名精神分裂症患者和147名对照者，在社会人口学变量方面匹配良好。纹状体DAT密度在患者和对照组之间没有显著差异。在壳核和尾状核中区域性确认了类似的阴性结果。外部因素没有调节作用。结论：我们的荟萃分析没有发现任何证据表明精神分裂症患者纹状体多巴胺终末密度改变。此外，纹状体DAT密度似乎不受抗精神病药物或疾病持续时间的影响。我们的数据表明，纹状体多巴胺能突触的完整性改变是不是精神分裂症的出现或治疗的关键。这些发现将有助于进一步完善精神分裂症的多巴胺能假说。
Background: Striatal dopaminergic neurotransmission has been postulated to be fundamental to the emergence of key symptoms of schizophrenia, such as psychotic symptoms, and is targeted by currently available dopaminergic drugs. A specific marker of the integrity of presynaptic dopamine neurons in the striatum, the density of striatal dopamine terminals, can be quantified through molecular neuroimaging of the dopamine active transporter (DAT). However, the currently available results using this approach in schizophrenia are inconsistent. Methods: Thirteen Single Photon Emission Tomography or Positron Emission Tomography (PET) studies investigating DAT density in the striatum of schizophrenic patients and matched controls were included in a quantitative meta-analysis. Binding potentials in the striatum, caudate, and putamen, as well as demographic, clinical, and methodological variables, were extracted from each publication. Hedges' g was used as a measure of effect size. Results: The overall database contained 202 subjects with schizophrenia and 147 controls, well matched with respect to sociodemographic variables. Striatal DAT density was not significantly different between patients and controls. Similar negative findings were regionally confirmed in the putamen and caudate. There was no moderating effect for external factors. Conclusions: Our meta-analysis uncovered no evidence indicating altered density of striatal dopamine terminals in schizophrenia. Moreover, striatal DAT density did not seem to be influenced by antipsychotic medication or illness duration. Our data suggest that altered integrity of striatal dopaminergic synapses is not critical for the emergence of schizophrenia or its treatment. These findings should be useful in further refining dopaminergic hypotheses of schizophrenia.