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February 2, 2026American Journal of Psychiatry5 citations

Brain Neuroplasticity Mechanisms in Psychiatric Illnesses and in the Development of Novel Treatments

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POPatricio O’DonnellAEAmit EtkinHMHusseini Manji

Key Points

  • To explore the relationship between neuroplasticity and psychiatric illnesses, and how it informs treatment development.
  • Assessment of synaptic responses to measure neuroplasticity.
  • Behavioral changes were observed as indicators of learning and memory.
  • Use of neuroimaging to assess functional and structural connectivity.
  • Postmortem analyses of neuronal and glial structures were conducted.
  • Altered neuroplasticity is implicated in psychiatric disorders.
  • Behavioral changes indicate responses to treatment interventions.
  • Neuroplasticity potential is shown to be reversible but deserves cautious interpretation.

Abstract

Neuroplasticity-the brain's capacity to modify synaptic strength and connectivity-likely underlies both the pathophysiology of psychiatric disorders and the mechanisms through which treatments exert therapeutic effects. Direct assessment of plasticity requires measuring changes in synaptic responses, which remains technically challenging in humans. The most proximal human indicators are behavioral changes reflecting learning and memory, or physiological responses to neurostimulation paradigms that engage cortical circuits. More commonly, plasticity is inferred indirectly through postmortem analyses of neuronal and glial structure or via neuroimaging measures such as functional and structural connectivity. Together, these approaches suggest that altered and potentially reversible plasticity is central to understanding and treating psychiatric illness, but the field needs to be cautious about what is, what could be, and what is not plasticity.

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Cite This Study

O’Donnell et al. (2026) studied this question.

synapsesocial.com/papers/6980fb97c1c9540dea80d5a6https://doi.org/10.1176/appi.ajp.20251212
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