Dysfunction of the serotonin 1A receptor (5-HT(1A)) 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-HT(1A) 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-HT(1A) receptor signaling through either direct or indirect effects. Reduced somatodendritic and postsynaptic 5-HT(1A) 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-HT(1A) receptor binding potential in diverse regions such as the dorsal raphe, medial prefrontal cortex (mPFC), amygdala and hippocampus. 5-HT(1A) receptor knockout (KO) mice display increased anxiety-related behavior, which, unlike in their wild-type counterparts, cannot be rescued with antidepressant drug (AD) treatment. In humans, the G allele of a single nucleotide polymorphism (SNP) in the 5-HT(1A) receptor gene (HTR1A; rs6295), which abrogates a transcription factor binding site for deformed epidermal autoregulatory factor-1 (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-HT(1A) receptor dysfunction represents one potential mechanism underpinning MDD and other stress-related disorders.

中文翻译：

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5-HT(1A) 受体在重度抑郁症中的功能。

5-羟色胺 1A 受体 (5-HT(1A)) 的功能障碍可能在重度抑郁症 (MDD) 的发生中起作用。在这里，我们回顾了支持该声明的药理学、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 MDD 相关的表型，认知障碍和躯体疼痛。使用 5-HT(1A) 受体激动剂进行药理学激发研究的结果表明抑郁症患者的内分泌反应迟钝。锂、丙戊酸盐、选择性血清素再摄取抑制剂 (SSRIs)、三环抗抑郁药 (TCA) 和其他治疗，如电休克疗法 (ECT)，都通过直接或间接作用增加突触后 5-HT(1A) 受体信号传导. 一些自杀受害者的尸检研究报告了躯体树突和突触后 5-HT(1A) 受体数量或亲和力降低，这一结果与重复性良好的 PET 分析一​​致，表明不同区域的 5-HT(1A) 受体结合潜力降低如中缝背、内侧前额叶皮层 (mPFC)、杏仁核和海马体。5-HT(1A) 受体敲除 (KO) 小鼠表现出增加的焦虑相关行为，这与野生型小鼠不同，不能通过抗抑郁药物 (AD) 治疗来挽救。在人类中，5-HT(1A) 受体基因 (HTR1A; rs6295) 中单核苷酸多态性 (SNP) 的 G 等位基因取消了变形表皮自动调节因子-1 (Deaf-1) 的转录因子结合位点和据报道，Hes5 在 MDD 案例中的比例过高。反过来，C 等位基因与对 AD 药物的更好反应有关。我们提出了 5-HT(1A) 受体功能障碍代表一种支持 MDD 和其他压力相关疾病的潜在机制的可能性。