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Serotonin (5-hydroxytryptamine, 5-HT) is a neurotransmitter primarily found in the central nervous system (CNS) and the gastrointestinal tract. It plays a vital role in mood regulation, fear processing, and anxiety modulation.
Serotonin is synthesized from L-tryptophan via the enzyme tryptophan hydroxylase (TPH).
The raphe nuclei in the brainstem are the primary source of serotonin projections to various brain regions involved in anxiety:
Amygdala (fear and emotional processing)
Prefrontal cortex (cognitive control over emotions)
Prefrontal cortex (cognitive control over emotions)
Serotonin exerts its effects through 14 different receptor subtypes (5-HT1–5-HT7).
The 5-HT1A receptor is the most critical in anxiety regulation.
Agonism (activation) of 5-HT1A leads to reduced fear responses and anxiety (e.g., buspirone, a 5-HT1A agonist, is used as an anxiolytic).
Deficiency in 5-HT1A receptors has been linked to increased anxiety in animal models.
Human and animal studies show that low serotonin levels or dysfunctional 5-HT receptors lead to exaggerated stress responses.
Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, sertraline) enhance serotonergic neurotransmission, reducing anxiety symptoms by increasing serotonin availability in the synaptic cleft.
Genetic studies: Variations in the serotonin transporter gene (5-HTTLPR) are associated with anxiety sensitivity and stress response.
The hypothalamic-pituitary-adrenal (HPA) axis, which controls the body's stress response, is regulated by serotonin.
Low serotonin levels are linked to increased cortisol release, contributing to heightened anxiety and stress sensitivity
Dopamine plays a key role in anxiety by influencing motivation, reward processing, and emotional regulation. While often associated with pleasure and motivation, dopamine imbalances—either too low or too high—can contribute to anxiety. Low dopamine levels can lead to excessive worry, difficulty handling stress, and a lack of motivation, making it harder to regulate anxious thoughts. On the other hand, excessive dopamine activity, particularly in certain brain regions, can heighten alertness and fear responses, worsening anxiety symptoms. Managing dopamine through balanced nutrition, exercise, stress management, and healthy sleep patterns can help regulate anxiety and improve overall emotional well-being.
Anxiety is more than just a mental state—it’s a neurochemical event, and noradrenaline plays a central role in how it feels in the body and brain. Understanding this link helps explain symptoms like a racing heart, restlessness, and constant worry.
Noradrenaline (norepinephrine) is both a neurotransmitter and a stress hormone. It’s produced in the locus coeruleus in the brainstem and the adrenal glands. It prepares your body for "fight or flight" by:
Increasing heart rate and blood pressure
Heightening alertness and focus
Preparing muscles for quick response
Suppressing digestion and rest functions
The adrenal glands release adrenaline during stress or danger. It increases heart rate, blood pressure, and energy.
When you're anxious, your body may produce too much adrenaline, triggering physical symptoms like rapid heartbeat, sweating, and shakiness — classic "fight or flight" responses.
GABA is the brain’s main calming chemical. It inhibits excessive brain activity and helps relax the nervous system.
Low levels of GABA are commonly linked to anxiety, racing thoughts, and restlessness. It’s like the brakes are failing in your brain.
DHEA is a hormone produced by the adrenal glands, acting as a precursor to sex hormones and playing a role in mood, immunity, and stress resilience.
Healthy DHEA levels can buffer the negative effects of cortisol (stress hormone). Low DHEA is often associated with poor stress tolerance and higher anxiety.
Cortisol is released by the adrenal glands in response to stress. It helps regulate blood sugar, inflammation, metabolism, and memory.
Chronically high cortisol keeps the body in a state of stress, leading to anxiety, sleep problems, and even panic attacks. Low cortisol (due to burnout/adrenal fatigue) can also affect emotional balance.
Glutamate is the brain’s primary excitatory neurotransmitter, essential for activating neurons, learning, and memory.
Glutamate is the brain’s primary excitatory neurotransmitter, essential for activating neurons, learning, and memory.
This hyperactivity especially affects the amygdala (the brain’s fear center) and the prefrontal cortex, contributing to:
Heightened fear response
Heightened fear response
Racing thoughts
Overreactions to stress
Chronic anxiety can create a feedback loop:
Chronic anxiety can create a feedback loop:
Elevated glutamate increases neural firing
This amplifies anxiety symptoms, keeping the brain in a “threat” state
Research has shown:
People with anxiety disorders often have elevated glutamate levels in specific brain regions (like the anterior cingulate cortex and insula).
Overactivation of NMDA receptors (stimulated by glutamate) can worsen anxious thoughts and hyperarousal.
Glial cell dysfunction or inflammation can prevent proper glutamate clearance, prolonging excitatory signals and contributing to persistent anxiety.