From the Guidelines
The serotonin neurotransmitter system is primarily implicated in the pathophysiology of Generalized Anxiety Disorder (GAD). This is based on the most recent evidence from 2020, which suggests that serotonergic function plays a key role in the ability of the brain to modulate fear, worry, and stress as well as to facilitate cognitive processing of those emotions 1. The effectiveness of selective serotonin reuptake inhibitors (SSRIs) in treating GAD further supports the involvement of the serotonin system.
Some key points to consider include:
- The SSRI medication class inhibits the presynaptic reuptake of serotonin in the brain, thereby increasing availability of serotonin at the synaptic cleft 1.
- This blockade over time is believed to lead to a downregulation of inhibitory serotonin autoreceptors, which eventually heightens the serotonergic neuronal firing rate, leading to increased serotonin release 1.
- Although other neurotransmitter systems, such as the noradrenergic system, may also play a role in GAD, the serotonin system is the most directly implicated in the pathophysiology of the disorder 1.
- The complex interplay between different neurotransmitter systems, including serotonin, norepinephrine, and others, contributes to the varied presentation and treatment responses seen in GAD.
In terms of treatment, SSRIs are a preferred option for long-term management of GAD, due to their efficacy and relatively favorable side effect profile compared to other options like benzodiazepines 1. However, the choice of a specific SSRI should be governed by considerations such as pharmacokinetics, pharmacodynamics, and individual patient factors.
From the Research
Neurotransmitter Systems Implicated in GAD
The pathophysiology of Generalized Anxiety Disorder (GAD) is complex and involves multiple neurotransmitter systems. The primary neurotransmitter system implicated in GAD is:
- GABA (Gamma-aminobutyric acid) system, which is the primary inhibitory neurotransmitter in the brain 2, 3, 4, 5, 6
Role of GABA in GAD
The GABA system plays a crucial role in regulating anxiety, and dysregulation of this system has been implicated in the pathophysiology of GAD. Studies have shown that:
- GABAergic agents, such as benzodiazepines and tiagabine, have anxiolytic properties and can be effective in reducing symptoms of GAD 2, 3, 5
- The GABAB receptor is a therapeutic candidate for depression and anxiety disorders, including GAD 6
Interactions with Other Neurotransmitter Systems
The GABA system interacts with other neurotransmitter systems, including: