Physiological Causes of Anxiety: A Current Evidence Summary

Neural Circuit Dysregulation

Three brain regions work together to generate anxiety. The amygdala handles emotional processing, the bed nucleus of the stria terminalis (BNST) sustains the prolonged state of anxiety, and the lateral habenula amplifies negative emotional signals. Importantly, anxiety differs from fear , fear is a rapid response to an immediate threat, while anxiety is a sustained, anticipatory state tied to vague or future-oriented concerns. Each involves different circuitry. nihnih

HPA Axis & Cortisol Dysregulation

The brain's stress hormone system is a core driver. When it misfires — producing too much or too little cortisol, it disrupts mood, cognition, and arousal across the board. CRH neuronal circuits interact bidirectionally with the serotonergic and noradrenergic systems, both of which are critically involved in anxiety disorders. nih

Neurotransmitter Imbalance

Three systems are most implicated. GABA, the brain's primary "brake," becomes depleted in anxious states. Serotonin, norepinephrine, and dopamine have all been identified in the pathogenesis of anxiety disorders. And when GABA is low, glutamate, the main excitatory signal — goes unchecked, keeping the nervous system in a state of overactivation. MDPI

The Microbiota-Gut-Brain Axis

The gut plays a more direct role than once thought. Anxiety involves not only brain neurochemistry but also changes in gut microbiota, with the gut-brain axis operating bidirectionally through neural, endocrine, and immune pathways. Disrupted gut flora reduces serotonin, activates the kynurenine pathway, and weakens the blood-brain barrier, all of which feed back into anxious brain states. nih

Neuroinflammation

Chronic inflammation in the brain is now recognized as a common thread linking the other mechanisms. Microglial activation and elevated inflammatory cytokines impair the amygdala and prefrontal cortex, undermining the top-down regulation that normally keeps anxious arousal in check.

Clinical Takeaway

Anxiety is a multi-system phenomenon — not simply a serotonin or GABA deficiency. Current evidence points to overlapping dysregulation across brain circuits, stress hormones, neurotransmitters, gut microbiota, and neuroinflammation. 

Effective treatment increasingly reflects that complexity.

Sources: International Journal of Molecular Sciences (2025), Frontiers in Neural Circuits (2025), Current Psychiatry Reports (2025), Frontiers in Neuroscience (2024–2025)

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