Editorial: Retuning the Adolescent Brain: Esketamine and Rapid Structural Change in the rACC

Document Type

Article

Publication Date

3-17-2026

Publication Title

Journal of the American Academy of Child and Adolescent Psychiatry

Abstract

Adolescent major depressive disorder (MDD) is a leading cause of disability worldwide and a major, modifiable risk factor for suicide, which remains the second leading cause of death in this age group.1 For 30% to 50% of patients who fail to achieve remission despite multiple treatment steps, the clinical and psychosocial consequences are substantial.2 Although selective serotonin-reuptake inhibitors are widely used as first-line treatments, their therapeutic effects typically require several weeks to emerge, and a substantial proportion of adolescents do not respond to an initial antidepressant trial. Together, the delayed efficacy and incomplete response contribute to a critical treatment gap during which vulnerable youth remain at elevated risk. These limitations have driven growing interest in rapid-acting interventions such as the N-methyl-D-aspartate (NMDA) receptor antagonist esketamine. Multiple pieces of evidence suggest that esketamine can produce faster symptom relief than conventional antidepressants,2 including efficacy as a monotherapy in treatment-resistant depression3; however, its neural mechanisms remain incompletely understood. A clearer understanding of how esketamine acts on the developing brain is necessary to guide clinical use and to inform more targeted prevention strategies.

PubMed ID

41856246

ePublication

ePub ahead of print

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