Neurotransmitter dysregulation in depression, anxiety, and suicidality: From synaptic dysfunction to cellular pathogenesis - PubMed
19 hours ago
- #Cellular Pathogenesis
- #Neurotransmitter Dysregulation
- #Affective Disorders
- The article reviews neurotransmitter dysregulation in depression, anxiety, and suicidality, moving beyond the traditional 'chemical imbalance' theory to include cellular changes.
- Dysregulation in serotonergic, noradrenergic, dopaminergic, GABAergic, and glutamatergic systems leads to oxidative stress, excitotoxicity, neuroinflammation, and reduced trophic support.
- This cascade results in reduced BDNF signaling, dendritic retraction, synapse loss, and apoptosis, causing amygdala hyperactivity and structural atrophy in the hippocampus and prefrontal cortex.
- Clinical symptoms include rumination, fear, anhedonia, cognitive impairment, and suicidal ideation due to circuit failure.
- A unified model of pathogenesis is proposed, emphasizing neurotransmitter dysregulation as a driver of cellular damage.
- Therapeutic implications reassess SSRIs/SNRIs, rapid synaptic repair by ketamine (an NMDA antagonist), and new drugs targeting oxidative stress, inflammation, and glutamate subtypes.
- Future directions highlight the need for biomarkers in oxidative damage and neuroinflammation to advance precision psychiatry.
- The paradigm shift aims to focus on cellular resilience and brain circuit rebuilding rather than just neurotransmitter regulation.