From the Guidelines
The serotonergic system is the neurotransmitter system in the amygdala most commonly associated with the regulation of anxiety. This is based on the strongest and most recent evidence, which suggests that serotonergic function plays a key role in modulating fear, worry, and stress, as well as facilitating cognitive processing of those emotions 1. The effectiveness of selective serotonin reuptake inhibitors (SSRIs) in treating anxiety disorders provides strong evidence for the serotonergic system's central role in anxiety regulation.
Some of the key points that support the serotonergic system's role in anxiety regulation include:
- The ability of SSRIs to increase the availability of serotonin at the synaptic cleft, which leads to a downregulation of inhibitory serotonin autoreceptors and eventually heightens the serotonergic neuronal firing rate 1
- The substantial empirical support for the effectiveness and safety of the SSRI class of medications for the treatment of anxiety 1
- The fact that medications from the SSRI class, such as citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline, and vilazodone, are commonly used to treat anxiety disorders, despite not having specific FDA approval for this indication 1
While other neurotransmitter systems, such as the GABAergic and dopaminergic systems, also contribute to anxiety regulation, the serotonergic system is considered the most directly involved in the modulation of anxiety responses, based on the most recent and highest quality study 1.
From the Research
Neurotransmitter Systems in the Amygdala
The amygdala plays a crucial role in the regulation of emotional processes, including anxiety. Several neurotransmitter systems are involved in this regulation, including:
- GABAergic neurotransmission, which inhibits the amygdala and prevents inappropriate emotional and behavioral responses 2
- Serotonergic neurotransmission, which is widely supported as playing a role in anxiety 3
- Norepinephrine neurotransmission, which may also contribute to the symptoms of anxiety 3
Regulation of Anxiety in the Amygdala
The regulation of anxiety in the amygdala is a complex process involving multiple neurotransmitter systems.
- GABAergic neurotransmission is thought to play a crucial role in inhibiting the amygdala and preventing anxiety 2
- Abnormal serotonergic neurotransmission is widely supported as contributing to anxiety 3
- Norepinephrine neurotransmission may also contribute to anxiety, although its role is less clear 3
- Benzodiazepines, which enhance GABAergic neurotransmission, are commonly used to treat anxiety disorders 4, 5
Most Commonly Associated Neurotransmitter System
Based on the available evidence, the GABAergic neurotransmission system is most commonly associated with the regulation of anxiety in the amygdala 2. This system inhibits the amygdala and prevents inappropriate emotional and behavioral responses, and its dysfunction has been implicated in anxiety disorders.