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Abstract <p>Understanding hippocampal neurostructural alterations at baseline and following antidepressant treatment in high-risk youth, particularly within distinct subregions, is critical for elucidating bipolar disorder (BD) pathophysiology and treatment planning. In this prospective randomized clinical trial, 105 high-risk youth with a first-degree BD-I relative(s) and moderate to severe depression and/or anxiety disorder, along with 51 healthy controls (HCs), were recruited. All participants underwent baseline structural MRI and clinical evaluations for depression, anxiety, and adverse events. High-risk youth were then randomized to receive psychotherapy and with either escitalopram or placebo. After 4 weeks of treatment, high-risk youth underwent repeated structural MRI and clinical assessments. These clinical assessments continued biweekly over the remaining 12 weeks of treatment (up to week 16). Volumetric measurements of hippocampal subregions were analyzed at baseline and 4 weeks. Compared to HCs, high-risk youth had significant baseline volume increases in the right cornu ammonis (CA)3, bilateral CA4, bilateral granule cell and molecular layers of the dentate gyrus (GC-ML-DG), and bilateral molecular layer, but reduced volumes in the bilateral fimbria and left parasubiculum. Volume reduction in the left hippocampal tail after 4 weeks of escitalopram treatment was associated with improvements in disinhibition and impulsivity symptoms from baseline to 4 weeks, and this association remained significant from baseline to 16 weeks. CA3-4 and GC-ML-DG enlargement may reflect adaptive changes, while fimbria and parasubiculum atrophy indicate vulnerabilities in BD-risk youth. Escitalopram-related volume reduction in the left hippocampal tail may reflect neural plasticity associated with emotional symptom improvement in BD high-risk youth.</p> Clinical trial registration information <p>Mechanism of Antidepressant-Related Dysfunctional Arousal in High-Risk Youth; <a href="https://clinicaltrials.gov/">https://clinicaltrials.gov/</a>; NCT02553161.</p>

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Hippocampal subregion volume alterations at baseline and following antidepressant treatment in youth at high risk for bipolar disorder

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月1日

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  • Biqiu Tang,
  • L. Rodrigo Patino,
  • Thomas J. Blom,
  • Jeffrey A. Welge,
  • Jeffrey R. Strawn,
  • Kaitlyn M. Bruns,
  • Wenjing Zhang,
  • Su Lui,
  • Manpreet K. Singh,
  • Melissa P. DelBello

摘要

Abstract

Understanding hippocampal neurostructural alterations at baseline and following antidepressant treatment in high-risk youth, particularly within distinct subregions, is critical for elucidating bipolar disorder (BD) pathophysiology and treatment planning. In this prospective randomized clinical trial, 105 high-risk youth with a first-degree BD-I relative(s) and moderate to severe depression and/or anxiety disorder, along with 51 healthy controls (HCs), were recruited. All participants underwent baseline structural MRI and clinical evaluations for depression, anxiety, and adverse events. High-risk youth were then randomized to receive psychotherapy and with either escitalopram or placebo. After 4 weeks of treatment, high-risk youth underwent repeated structural MRI and clinical assessments. These clinical assessments continued biweekly over the remaining 12 weeks of treatment (up to week 16). Volumetric measurements of hippocampal subregions were analyzed at baseline and 4 weeks. Compared to HCs, high-risk youth had significant baseline volume increases in the right cornu ammonis (CA)3, bilateral CA4, bilateral granule cell and molecular layers of the dentate gyrus (GC-ML-DG), and bilateral molecular layer, but reduced volumes in the bilateral fimbria and left parasubiculum. Volume reduction in the left hippocampal tail after 4 weeks of escitalopram treatment was associated with improvements in disinhibition and impulsivity symptoms from baseline to 4 weeks, and this association remained significant from baseline to 16 weeks. CA3-4 and GC-ML-DG enlargement may reflect adaptive changes, while fimbria and parasubiculum atrophy indicate vulnerabilities in BD-risk youth. Escitalopram-related volume reduction in the left hippocampal tail may reflect neural plasticity associated with emotional symptom improvement in BD high-risk youth.

Clinical trial registration information

Mechanism of Antidepressant-Related Dysfunctional Arousal in High-Risk Youth; https://clinicaltrials.gov/; NCT02553161.