Role of the amygdala and possible biomarkers in psychiatric disorders

Gonzalo Flores a 1, Sebastian Reyes-Lizaola a, Leonardo Aguilar-Hernández a, Alicia Gil-Velazco a, Hiram Tendilla-Beltrán a, Julio C. Morales-Medina b

a Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla (BUAP), Puebla, Mexico

b Centro de Investigación en Reproducción Animal, CINVESTAV-Universidad Autónoma de Tlaxcala, Tlaxcala, Mexico

Received 29 October 2024, Revised 15 November 2024, Accepted 22 November 2024, Available online 6 December 2024, Version of Record 15 January 2025.

https://doi.org/10.1016/j.neumar.2024.100032

Abstract

In the early 1800s, the "cerebral amygdala" was described as an almond-shaped structure within the temporal lobe. A century later, the role of amygdala in modulating behavior became evident, specifically in social and emotional features. This discovery established the amygdala as a critical component of the limbic system and essential for emotion regulation. Its connections with the hippocampus, prefrontal cortex, and hypothalamus highlight its role in controlling fear, anxiety, and stress, all of which are risk factors for psychiatric diseases. Consequently, multiple efforts have been made to understand the amygdala’s role in the pathophysiology of these conditions. The basolateral amygdala, a key part of the amygdala, is composed of glutamatergic pyramidal neurons that project excitatory signals to the prefrontal cortex, hippocampus, and reward-related regions. It also receives inputs from various systems, including dopaminergic, serotoninergic, and cholinergic pathways. These extensive connections with other brain areas contribute to its role in regulating emotions and its involvement in psychiatric conditions such as schizophrenia, depression, and Alzheimer’s disease. This review explores the role of the amygdala, with a focus on the particularly the basolateral amygdala, in various conditions, including depression (a stress-related disorder), schizophrenia (a neurodevelopmental disorder), dementia (an age-related neurodegenerative disorder), physiological aging, and other psychiatric conditions such as obsessive-compulsive disorder and substance use disorder (including ethanol, hallucinogens, cannabis, stimulants, opioids, and nicotine). The data discussed include potential biomarkers for structural changes in the amygdala documented from clinical studies, as well as animal models relevant to the study of each condition.

杏仁核在精神疾病中的作用和可能的生物标记物

摘要

19 世纪初，“大脑杏仁核 ”被描述为颞叶内的一个杏仁状结构。一个世纪后，杏仁核在调节行为，特别是社交和情感特征方面的作用变得显而易见。这一发现确定了杏仁核是边缘系统的重要组成部分，对情绪调节至关重要。杏仁核与海马、前额叶皮质和下丘脑的联系突出了它在控制恐惧、焦虑和压力方面的作用，而所有这些都是精神疾病的危险因素。因此，人们一直在努力了解杏仁核在这些疾病的病理生理学中的作用。基底外侧杏仁核是杏仁核的关键部分，由谷氨酸能锥体神经元组成，可向前额叶皮质、海马和奖赏相关区域投射兴奋信号。它还接收来自不同系统的输入，包括多巴胺能、血清素能和胆碱能通路。这些与其他脑区的广泛联系有助于它在调节情绪方面发挥作用，并与精神分裂症、抑郁症和阿尔茨海默病等精神疾病有关。这篇综述探讨了杏仁核在各种疾病中的作用，尤其是在基底外侧杏仁核中的作用，包括抑郁症（一种与压力有关的疾病）、精神分裂症（一种神经发育障碍）、痴呆症（一种与年龄有关的神经退行性疾病）、生理衰老以及其他精神疾病，如强迫症和药物使用障碍（包括乙醇、致幻剂、大麻、兴奋剂、阿片类药物和尼古丁）。讨论的数据包括临床研究中记录的杏仁核结构变化的潜在生物标志物以及与每种疾病研究相关的动物模型。