Serotonin receptors and suicide, major depression, alcohol use disorder and reported early life adversity.,Translational Psychiatry

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Serotonin receptors and suicide, major depression, alcohol use disorder and reported early life adversity.
Translational Psychiatry ( IF 5.8 ) Pub Date : 2018-Dec-14 , DOI: 10.1038/s41398-018-0309-1
Mark D Underwood _{1,

2} , Suham A Kassir ₂ , Mihran J Bakalian ₂ , Hanga Galfalvy _{1,

2,

3} , Andrew J Dwork _{1,

2,

4,

5} , J John Mann _{1,

2} , Victoria Arango _{1,

2}

Affiliation

Serotonin neurotransmitter deficits are reported in suicide, major depressive disorder (MDD) and alcohol use disorder (AUD). To compare pathophysiology in these disorders, we mapped brain serotonin transporter (SERT), 5-HT_1A, and 5-HT_2A receptor binding throughout prefrontal cortex and in anterior cingulate cortex postmortem. Cases and controls died suddenly minimizing agonal effects and had a postmortem interval ≤24 h to avoid compromised brain integrity. Neuropathology and toxicology confirmed absence of neuropathology and psychotropic medications. For most subjects (167 of 232), a DSM-IV Axis I diagnosis was made by psychological autopsy. Autoradiography was performed in right hemisphere coronal sections at a pre-genual level. Linear model analyses included sex and age with group and Brodmann area as interaction terms. SERT binding was lower in suicides (p = 0.004) independent of sex (females < males, p < 0.0001), however, the lower SERT binding was dependent on MDD diagnosis (p = 0.014). Higher SERT binding was associated with diagnosis of alcoholism (p = 0.012). 5-HT_1A binding was greater in suicides (p < 0.001), independent of MDD (p = 0.168). Alcoholism was associated with higher 5-HT_1A binding (p < 0.001) but only in suicides (p < 0.001). 5-HT_2A binding was greater in suicides (p < 0.001) only when including MDD (p = 0.117) and alcoholism (p = 0.148) in the model. Reported childhood adversity was associated with higher SERT and 5-HT_1A binding (p = 0.004) in nonsuicides and higher 5-HT_2A binding (p < 0.001). Low SERT and more 5-HT_1A and 5-HT_2A binding in the neocortex in depressed suicides is dependent on Axis I diagnosis and reported childhood adversity. Findings in alcoholism differed from those in depression and suicide indicating a distinct serotonin system pathophysiology.

中文翻译：

血清素受体与自杀、重度抑郁症、酒精使用障碍和报道的早年逆境。

据报道，自杀、重度抑郁症 (MDD) 和酒精使用障碍 (AUD) 中存在血清素神经递质缺陷。为了比较这些疾病的病理生理学，我们在死后绘制了大脑血清素转运蛋白 (SERT)、5-HT _1A和 5-HT _2A受体在整个前额叶皮层和前扣带皮层中的结合情况。病例和对照突然死亡，最大限度地减少了临终效应，尸检间隔≤24小时，以避免大脑完整性受损。神经病理学和毒理学证实不存在神经病理学和精神药物。对于大多数受试者（232 名受试者中的 167 名），DSM-IV Axis I 诊断是通过心理尸检做出的。在膝前水平的右半球冠状切片上进行放射自显影。线性模型分析包括性别和年龄以及群体和布罗德曼面积作为交互项。自杀者的 SERT 结合较低 (p = 0.004)，与性别无关（女性 < 男性，p < 0.0001），但是，较低的 SERT 结合取决于 MDD 诊断 (p = 0.014)。较高的 SERT 结合与酒精中毒的诊断相关（p = 0.012）。 5-HT _1A结合在自杀者中更高 (p < 0.001)，与 MDD 无关 (p = 0.168)。酗酒与较高的 5-HT _1A结合有关 (p < 0.001)，但仅与自杀有关 (p < 0.001)。仅当模型中包含 MDD (p = 0.117) 和酗酒 (p = 0.148) 时，自杀者中 5-HT _2A结合才较高 (p < 0.001)。报告的童年逆境与非自杀者较高的 SERT 和 5-HT _1A结合 (p = 0.004) 以及较高的 5-HT _2A结合 (p < 0.001) 相关。抑郁症自杀患者新皮质中的低 SERT 和更多 5-HT _1A和 5-HT _2A结合取决于 Axis I 诊断和报告的童年逆境。酗酒的研究结果与抑郁症和自杀的研究结果不同，表明血清素系统的病理生理学不同。

更新日期：2019-01-26

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