Neurotransmitter dysregulation in depression, anxiety, and suicidality: From synaptic dysfunction to cellular
Angu Bala Ganesh K S V1, Amit Kumar Verma2, Shreha S A3
1Department of Anatomy, Gujarat Adani Institute of Medical Sciences, Gujarat, India.
Psychiatry Research
|April 2, 2026
Summary
Neurotransmitter dysregulation triggers cellular damage in affective disorders like depression and anxiety. A unified model emphasizes promoting cellular resilience and rebuilding brain circuits for future treatments.
Area of Science:
- Neuroscience
- Psychiatry
- Cellular Biology
Background:
- Affective disorders, including depression and anxiety, are significant global health concerns.
- The traditional "chemical imbalance" theory is being updated to include broader cellular changes.
- Neurotransmitter systems (serotonergic, noradrenergic, dopaminergic, GABAergic, glutamatergic) are implicated in stress response and neural circuit disruption.
Purpose of the Study:
- To propose a unified model of affective disorder pathogenesis.
- To integrate neurochemical and cellular evidence for a comprehensive understanding.
- To explore therapeutic implications and future directions in precision psychiatry.
Main Methods:
- Review and integration of existing research on neurotransmitter dysfunction and cellular changes.
- Development of a unified model of pathogenesis.
- Analysis of therapeutic strategies targeting cellular resilience and circuit repair.
Main Results:
- Neurotransmitter dysregulation leads to oxidative stress, excitotoxicity, neuroinflammation, and reduced trophic support.
- Common pathways include reduced brain-derived neurotrophic factor (BDNF) signaling, dendritic retraction, synapse loss, and apoptosis.
- These cellular changes manifest as amygdala hyperactivity and structural atrophy in the hippocampus and prefrontal cortex, leading to clinical symptoms.
Conclusions:
- A unified model highlights neurotransmitter dysregulation as a driver of cellular damage in affective disorders.
- Therapeutic strategies may involve SSRIs, SNRIs, ketamine, and novel drugs targeting cellular pathways.
- Developing biomarkers for oxidative damage and neuroinflammation is crucial for precision psychiatry, shifting focus to cellular resilience and circuit rebuilding.
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