Role of the amygdala and possible biomarkers in psychiatric disorders

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.