Hippocampal subregion volume alterations at baseline and following antidepressant treatment in youth at high risk for bipolar disorder.
11 affiliations
- 1Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
- 2Psychoradiology Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
- 3Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China.
- 4Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
- 5Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, West China Hospital of Sichuan University, Chengdu, Sichuan, China. [email protected].
- 6Psychoradiology Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China. [email protected].
- 7Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China. [email protected].
- 8Department of Radiology, Huaxi MR Research Center (HMRRC), Institute of Radiology and Medical Imaging, West China Hospital of Sichuan University, Chengdu, Sichuan, China. [email protected].
- 9Psychoradiology Key Laboratory of Sichuan Province, West China Hospital of Sichuan University, Chengdu, Sichuan, China. [email protected].
- 10Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, Sichuan, China. [email protected].
- 11Department of Psychiatry and Behavioral Sciences, University of California Davis School of Medicine, Sacramento, California, USA.
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.
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BibTeX
@article{tang2026hippocampal,
title = {{Hippocampal subregion volume alterations at baseline and following antidepressant treatment in youth at high risk for bipolar disorder.}},
author = {Biqiu Tang and L Rodrigo Patino and Thomas J Blom and Jeffrey A Welge and Jeffrey R Strawn and Kaitlyn M Bruns and Wenjing Zhang and Su Lui and Manpreet K Singh and Melissa P DelBello},
journal = {Translational psychiatry},
year = {2026},
month = aug,
doi = {10.1038/s41398-026-04314-w},
url = {https://europepmc.org/article/MED/42957641},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Hippocampal subregion volume alterations at baseline and following antidepressant treatment in youth at high risk for bipolar disorder.
AU - Biqiu Tang
AU - L Rodrigo Patino
AU - Thomas J Blom
AU - Jeffrey A Welge
AU - Jeffrey R Strawn
AU - Kaitlyn M Bruns
AU - Wenjing Zhang
AU - Su Lui
AU - Manpreet K Singh
AU - Melissa P DelBello
PY - 2026
DA - 2026/08/01
JO - Translational psychiatry
DO - 10.1038/s41398-026-04314-w
UR - https://europepmc.org/article/MED/42957641
AB - 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.
SN - 2158-3188
ER -