Booij Jan, van Amelsvoort Thérèse
Department of Nuclear Medicine, University of Amsterdam, Amsterdam, The Netherlands.
Handb Exp Pharmacol. 2012(212):299-337. doi: 10.1007/978-3-642-25761-2_12.
The results of imaging studies have played an important role in the formulation of hypotheses regarding the etiology of psychosis and schizophrenia, as well as in our understanding of the mechanisms of action of antipsychotics. Since this volume is primarily directed to molecular aspects of psychosis and antipsychotics, only the results of molecular imaging techniques addressing these topics will be discussed here.One of the most consistent findings of molecular imaging studies in schizophrenia is an increased uptake of DOPA in the striatum, which may be interpreted as an increased synthesis of L-DOPA. Also, several studies reported an increased release of dopamine induced by amphetamine in schizophrenia patients. These findings played an important role in reformulating the dopamine hypothesis of schizophrenia. To study the roles of the neurotransmitters γ-aminobutyric acid (GABA) and glutamate in schizophrenia, SPECT as well as MR spectroscopy have been used. The results of preliminary SPECT studies are consistent with the hypothesis of NMDA receptor dysfunction in schizophrenia. Regarding the GABA deficit hypothesis of schizophrenia, imaging results are inconsistent. No changes in serotonin transporters were demonstrated in imaging studies in schizophrenia, but studies of several serotonin receptors showed conflicting results. The lack of selective radiotracers for muscarinic receptors may have hampered examination of this system in schizophrenia as well as its role in the induction of side effects of antipsychotics. Interestingly, preliminary molecular imaging studies on the cannabinoid-1 receptor and on neuroinflammatory processes in schizophrenia have recently been published. Finally, a substantial number of PET/SPECT studies have examined the occupancy of receptors by antipsychotics and an increasing number of studies is now focusing on the effects of these drugs using techniques like spectroscopy and pharmacological MRI.
影像学研究结果在关于精神病和精神分裂症病因的假说形成中，以及在我们对抗精神病药物作用机制的理解中都发挥了重要作用。由于本卷主要关注精神病和抗精神病药物的分子方面，这里仅讨论针对这些主题的分子成像技术的结果。
精神分裂症分子成像研究最一致的发现之一是纹状体中多巴摄取增加，这可能被解释为左旋多巴合成增加。此外，多项研究报告称，精神分裂症患者中苯丙胺诱导的多巴胺释放增加。这些发现对重新阐述精神分裂症的多巴胺假说起到了重要作用。为了研究神经递质γ-氨基丁酸（GABA）和谷氨酸在精神分裂症中的作用，已使用单光子发射计算机断层扫描（SPECT）以及磁共振波谱（MR spectroscopy）。初步SPECT研究结果与精神分裂症中N-甲基-D-天冬氨酸（NMDA）受体功能障碍的假说一致。关于精神分裂症的GABA缺乏假说，成像结果并不一致。精神分裂症的成像研究未显示5-羟色胺转运体有变化，但对几种5-羟色胺受体的研究结果相互矛盾。缺乏针对毒蕈碱受体的选择性放射性示踪剂可能阻碍了对精神分裂症中该系统的检查及其在抗精神病药物副作用诱导中的作用的研究。有趣的是，最近发表了关于精神分裂症中大麻素-1受体和神经炎症过程的初步分子成像研究。最后，大量正电子发射断层扫描（PET）/SPECT研究检查了抗精神病药物对受体的占有率，现在越来越多的研究正使用波谱学和药物磁共振成像等技术关注这些药物的作用。
