Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria.
Neuroimage. 2012 Oct 15;63(1):447-59. doi: 10.1016/j.neuroimage.2012.07.001. Epub 2012 Jul 10.
The highly diverse serotonergic system with at least 16 different receptor subtypes is implicated in the pathophysiology of most neuropsychiatric disorders including affective and anxiety disorders, obsessive compulsive disorder, post-traumatic stress disorder, eating disorders, sleep disturbance, attention deficit/hyperactivity disorder, drug addiction, suicidal behavior, schizophrenia, Alzheimer, etc. Alterations of the interplay between various pre- and postsynaptic receptor subtypes might be involved in the pathogenesis of these disorders. However, there is a lack of comprehensive in vivo values using standardized procedures. In the current PET study we quantified 3 receptor subtypes, including the major inhibitory (5-HT(1A) and 5-HT(1B)) and excitatory (5-HT(2A)) receptors, and the transporter (5-HTT) in the brain of healthy human subjects to provide a database of standard values. PET scans were performed on 95 healthy subjects (age=28.0 ± 6.9 years; 59% males) using the selective radioligands [carbonyl-(11)C]WAY-100635, [(11)C]P943, [(18)F]altanserin and [(11)C]DASB, respectively. A standard template in MNI stereotactic space served for region of interest delineation. This template follows two anatomical parcellation schemes: 1) Brodmann areas including 41 regions and 2) AAL (automated anatomical labeling) including 52 regions. Standard values (mean, SD, and range) for each receptor and region are presented. Mean cortical and subcortical binding potential (BP) values were in good agreement with previously published human in vivo and post-mortem data. By means of linear equations, PET binding potentials were translated to post-mortem binding (provided in pmol/g), yielding 5.89 pmol/g (5-HT(1A)), 23.5 pmol/g (5-HT(1B)), 31.44 pmol/g (5-HT(2A)), and 11.33 pmol/g (5-HTT) being equivalent to the BP of 1, respectively. Furthermore, we computed individual voxel-wise maps with BP values and generated average tracer-specific whole-brain binding maps. This knowledge might improve our interpretation of the alterations taking place in the serotonergic system during neuropsychiatric disorders.
5-羟色胺能系统高度多样化，至少包含 16 种不同的受体亚型，与大多数神经精神疾病的病理生理学有关，包括情感障碍和焦虑障碍、强迫症、创伤后应激障碍、饮食障碍、睡眠障碍、注意缺陷/多动障碍、药物成瘾、自杀行为、精神分裂症、阿尔茨海默病等。各种突触前和突触后受体亚型之间相互作用的改变可能与这些疾病的发病机制有关。然而，目前缺乏使用标准化程序进行全面的体内评估。在目前的 PET 研究中，我们对 95 名健康受试者的 3 种受体亚型（包括主要抑制性（5-HT（1A）和 5-HT（1B））和兴奋性（5-HT（2A））受体以及转运体（5-HTT）进行了量化，为标准值提供了数据库。使用选择性放射性配体[羰基-（11）C]WAY-100635、[（11）C]P943、[（18）F]altanserin 和[（11）C]DASB，分别对 95 名健康受试者（年龄=28.0±6.9 岁；59%为男性）进行了 PET 扫描。基于 MNI 立体定向空间的标准模板用于感兴趣区域的勾画。该模板遵循两种解剖分区方案：1）布罗德曼区，包括 41 个区域；2）AAL（自动解剖标记），包括 52 个区域。呈现了每个受体和区域的标准值（平均值、标准差和范围）。每个受体和区域的平均皮质和皮质下结合潜能（BP）值与先前发表的人体体内和死后数据非常吻合。通过线性方程，将 PET 结合潜能转化为死后结合（以 pmol/g 表示），得到 5.89pmol/g（5-HT（1A））、23.5pmol/g（5-HT（1B））、31.44pmol/g（5-HT（2A））和 11.33pmol/g（5-HTT）分别与 1 的 BP 相当。此外，我们还计算了个体体素水平的 BP 值图，并生成了平均示踪剂特异性全脑结合图。这些知识可能会提高我们对神经精神疾病期间 5-羟色胺能系统发生变化的解释能力。
