5-HT(1A) receptor function in major depressive disorder.
5-HT(1A) receptor function in major depressive disorder.
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DOI：
10.1016/j.pneurobio.2009.01.009
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发表时间：
2009-05
影响因子：
6.7
通讯作者：
Drevets WC
中科院分区：
文献类型：
--
作者：
Savitz J;Lucki I;Drevets WC
血清素 1A 受体 (5-HT1A) 功能障碍可能在重度抑郁症 (MDD) 的发生中发挥作用。在这里，我们回顾了支持这一说法的药理学、尸检、正电子发射断层扫描 (PET) 和遗传证据。我们还简要介绍了两种与 MDD 相关的表型：认知障碍和躯体疼痛。 5-HT1A 受体激动剂的药理学挑战研究结果表明抑郁症患者的内分泌反应减弱。锂、丙戊酸、选择性血清素再摄取抑制剂 (SSRI)、三环类抗抑郁药 (TCA) 和其他治疗，如电惊厥休克疗法 (ECT)，都会通过直接或间接作用增加突触后 5-HT1A 受体信号传导。一些自杀受害者的尸检研究报告称，体细胞树突和突触后 5-HT1A 受体数量或亲和力减少，这一结果与重复性良好的 PET 分析一致，表明中缝背侧、内侧前额叶皮层 (mPFC)、杏仁核和海马等不同区域的 5-HT1A 受体结合潜力降低。 5-HT1A 受体敲除 (KO) 小鼠表现出更多的焦虑相关行为，与野生型小鼠不同，这种行为无法通过 AD 治疗来挽救。据报道，在人类中，5-HT1A 受体基因（HTR1A；rs6295）中的单核苷酸多态性 (SNP) 的 G 等位基因消除了 Deaf-1 和 Hes5 的转录因子结合位点，据报道在 MDD 病例中出现过多。相反，C 等位基因与 AD 药物的更好反应有关。我们提出这样一种可能性：5-HT1A 受体功能障碍代表了 MDD 和其他压力相关疾病的一种潜在机制。
Dysfunction of the serotonin 1A receptor (5-HT1A) may play a role in the genesis of major depressive disorder (MDD). Here we review the pharmacological, post-mortem, positron-emission tomography (PET), and genetic evidence in support of this statement. We also touch briefly on two MDD-associated phenotypes, cognitive impairment and somatic pain. The results of pharmacological challenge studies with 5-HT1A receptor agonists are indicative of blunted endocrine responses in depressed patients. Lithium, valproate, selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other treatment, such as electroconvulsive shock therapy (ECT), all increase post-synaptic 5-HT1A receptor signaling through either direct or indirect effects. Reduced somatodendritic and postsynaptic 5-HT1A receptor numbers or affinity have been reported in some post-mortem studies of suicide victims, a result consistent with well-replicated PET analyses demonstrating reduced 5-HT1A receptor binding potential in diverse regions such as the dorsal raphe, medial prefrontal cortex (mPFC), amygdala and hippocampus. 5-HT1A receptor knockout (KO) mice display increased anxiety-related behavior, which, unlike in their wild-type counterparts, cannot be rescued with AD treatment. In humans, the G allele of a single nucleotide polymorphism (SNP) in the 5-HT1A receptor gene (HTR1A; rs6295), which abrogates a transcription factor binding site for Deaf-1 and Hes5, has been reported to be over-represented in MDD cases. Conversely, the C allele has been associated with better response to AD drugs. We raise the possibility that 5-HT1A receptor dysfunction represents one potential mechanism underpinning MDD and other stress-related disorders.
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