Role of the Amygdala in the Complex Relationship Between Sleep and Anxiety

This review explores the multifaceted roles of the amygdala, focusing on its structural components, projections, physiological aspects, and key functions in emotional processing and fear conditioning. Beyond traditional roles, it examines the amygdala's involvement in sleep architecture during the NREM and REM phases. In NREM sleep, the amygdala is involved in memory replay and encoding. During REM sleep, it is highly active, contributing to the emotional content of dreams. This state is characterized by increased cerebral blood flow to the amygdaloid complexes and the generation of Ponto-Geniculo-Occipital (PGO) waves, which are linked to vivid visual imagery and emotional experiences. The review establishes a critical link between the amygdala and the cycle of anxiety disorders and sleep disturbances. It explores anxiety disorders' specific impact on the amygdala and their influence on sleep patterns. Additionally, the review discusses how medications for anxiety disorders and sleep disturbances act on the amygdala. Selective serotonin reuptake inhibitors (SSRIs) regulate amygdala function, affecting emotional responses and connectivity patterns, improving anxiety, and potentially enhancing sleep quality over time. Trazodone, a serotonin antagonist and reuptake inhibitor (SARI), improves sleep by blocking serotonin receptors and is effective in treating post-traumatic stress disorder (PTSD) related sleep disturbances. Benzodiazepines and zolpidem affect sleep architecture and anxiety by selectively enhancing the actions of both endogenous and exogenous GABA through GABA-A receptors. At the same time, agomelatine, an antidepressant with anxiolytic properties, improves sleep quality without disrupting REM sleep and treats insomnia associated with various conditions, including alcohol dependence. The aim of this review is to summarize amygdala functions, with a focus on their role in regulating sleep and affective responses. Moreover, it discusses possible therapeutic targets in the amygdala for anxiety and sleep disorders.