Neurotransmitter dysregulation in depression, anxiety, and suicidality: From synaptic dysfunction to cellular pathogenesis.
Level 5 - mechanism / opinion, no new human data
Narrative review and theoretical framework without systematic review methodology or new human data
PubMed 41924767 · doi:10.1016/j.psychres.2026.117120
What was done
The authors conducted a narrative review synthesizing literature across neurochemical, cellular, and circuit domains to propose a unified pathophysiological model for depression, anxiety, and suicidality. The paper maps how multi-system neurotransmitter dysregulation interacts with cellular cascades, neuroplasticity mechanisms, and therapeutic responses to conventional and rapid-acting agents.
What was found
The abstract provides no empirical quantitative data, statistical metrics, or effect sizes. Mechanistically, it links disruption across serotonergic, noradrenergic, dopaminergic, GABAergic, and glutamatergic systems to oxidative stress, excitotoxicity, neuroinflammation, and reduced BDNF signaling. These cellular changes correspond to synaptic loss, amygdala hyperactivity, prefrontal and hippocampal atrophy, and clinical manifestations including anhedonia, rumination, cognitive deficits, and suicidality.
Why it matters
The paper frames affective disorders beyond simple neurotransmitter deficits, arguing that therapeutic progress requires interventions that enhance cellular resilience, repair synaptic connections, and target oxidative or inflammatory pathways.
Limits
As a narrative review, the paper provides no systematic literature search protocol, inclusion/exclusion criteria, or quantitative synthesis. No primary clinical or preclinical data are presented in the abstract, precluding independent assessment of bias or effect precision.
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