Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, L.S. Skaggs Hall, Room 3916, 30 S 2000 E, Salt Lake City, UT, 84112, USA.
Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
Eur Arch Psychiatry Clin Neurosci. 2023 Mar;273(2):411-425. doi: 10.1007/s00406-022-01480-y. Epub 2022 Sep 12.
Antisocial behavior (ASB) is characterized by frequent violations of the rights and properties of others, as well as aggressive conduct. While ample evidence points to a critical role of serotonin in the emotional modulation of social responses, the implication of this neurotransmitter in ASB is unclear. Here, we performed the first-ever postmortem analysis of serotonergic markers in the orbitofrontal cortex (OFC) of male subjects with ASB (n = 9). We focused on this brain region, given its well-recognized role in social response and ASB pathophysiology. Given that all individuals also had a substance use disorder (SUD) diagnosis, two age-matched control groups were used: SUD only and unaffected controls. Tissues were processed for immunoblotting analyses on eight key serotonergic targets: tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of brain serotonin synthesis; serotonin transporter (SERT), the primary carrier for serotonin uptake; monoamine oxidase A (MAOA), the primary enzyme for serotonin catabolism; and five serotonin receptors previously shown to influence social behavior: 5-HT, 5-HT, 5-HT, 5-HT, and 5-HT. Our analyses documented a significant increase in 5-HT receptor levels in the ASB + SUD group compared to SUD-only controls. Furthermore, TPH2 levels were significantly reduced in the SUD group (including SUD only and ASB + SUD) compared to unaffected controls. No difference was detected in the expression of any other serotonergic target. These results are in keeping with previous evidence showing high 5-HT receptor binding in the OFC of pathologically aggressive individuals and point to this molecule as a potential target for ASB treatment.
反社会行为（ASB）的特征是频繁侵犯他人权利和财产，以及具有攻击性。虽然大量证据表明 5-羟色胺在调节社会反应的情绪方面起着关键作用，但这种神经递质与 ASB 的关系尚不清楚。在这里，我们首次对患有 ASB（n=9）的男性受试者的眶额叶皮层（OFC）中的 5-羟色胺能标记物进行了死后分析。我们专注于这个大脑区域，因为它在社会反应和 ASB 病理生理学中具有公认的作用。鉴于所有个体也有物质使用障碍（SUD）诊断，我们使用了两个年龄匹配的对照组：仅 SUD 和未受影响的对照组。对组织进行了八项关键 5-羟色胺能靶标的免疫印迹分析：色氨酸羟化酶 2（TPH2），脑 5-羟色胺合成的限速酶；5-羟色胺转运体（SERT），5-羟色胺摄取的主要载体；单胺氧化酶 A（MAOA），5-羟色胺分解代谢的主要酶；以及先前显示影响社会行为的五种 5-羟色胺受体：5-HT、5-HT、5-HT、5-HT 和 5-HT。我们的分析记录了 ASB+SUD 组与仅 SUD 对照组相比，5-HT 受体水平显著增加。此外，与未受影响的对照组相比，SUD 组（包括仅 SUD 和 ASB+SUD）的 TPH2 水平显著降低。未检测到其他 5-羟色胺能靶标的表达差异。这些结果与先前的证据一致，表明病理性攻击性个体的 OFC 中存在高 5-HT 受体结合，并指出该分子是 ASB 治疗的潜在靶点。
