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

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Am J Psychiatry. 2026 Feb 1;183(2):98-107. doi: 10.1176/appi.ajp.20251212. Epub 2026 Feb 1.

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.

PMID:41620807 | DOI:10.1176/appi.ajp.20251212

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