Neural markers of working memory and emotional regulation are predictors of future depression severity in at risk young adults: a replication study
- 1Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA USA
- 2Department of Statistics, University of Pittsburgh School of Arts and Sciences, Pittsburgh, PA USA
Abstract
Objective neural markers that reflect the underlying pathophysiological mechanisms of affective disorders are needed to facilitate early identification of individuals most at risk of future affective disorders and ultimately provide neural targets to guide therapeutic interventions. Using an emotional n-back paradigm designed to examine working memory (WM) and emotional regulation (ER) capacity, we previously showed that WM-related elevated left dlPFC activity (a key node of the central executive network (CEN)) and elevated right precuneus activity (a key node of the default mode network (DMN)), as well as ER-related elevated left dlPFC activity were positively associated with future depression severity in young adults at risk for affective disorders. We now aimed to replicate and extend these previous longitudinal findings by examining relationships among right precuneus activity and left dlPFC activity during WM and ER tasks and future depression severity in a new independent young adult sample (n = 77: 50 female, age = 24.68), and a larger combined sample (n = 121: 83 female, age = 23.81) comprising the original and new samples. The Hamilton Rating Scale for Depression (HAM-D) and Young Mania Rating Scale (YMRS) were measured at 12 months post scan to assess future depression and mania/hypomania severity respectively. In the new sample, we showed patterns of left dlPFC activity and right precuneus activity during WM, and left dlPFC activity during ER that were consistent with the original sample. In both the new and combined samples, future depression severity was robustly predicted by WM-related left dlPFC activity and right precuneus activity, and ER-related left dlPFC activity (all ps < 0.05 qFDR). These findings were specific to future depression severity. The effect sizes (pseudo R-squared values) for the full models including all IVs in the new and combined samples ranged from approximately 25–43%, with left dlPFC and right precuneus activity during WM explaining 15.59% of variance in future depression severity in the new sample; and left dlPFC activity during ER explaining 14.63% of variance in future depression severity in the combined sample. These replicated, longitudinal findings provide candidate neural markers to guide risk identification and targeting of new interventions for individuals with and those at risk for future affective disorders.
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BibTeX
@article{afriyieagyemang2026neural,
title = {{Neural markers of working memory and emotional regulation are predictors of future depression severity in at risk young adults: a replication study}},
author = {Yvette Afriyie-Agyemang and Michele A. Bertocci and Satish Iyengar and Richelle S. Stiffler and Lisa K. Bonar and Haris A. Aslam and Simona Graur and Genna Bebko and Osasumwen Benjamin and Yiming Wang and Henry W. Chase and Mary L. Phillips},
journal = {Molecular Psychiatry},
year = {2026},
month = jul,
doi = {10.1038/s41380-026-03771-5},
url = {https://doi.org/10.1038/s41380-026-03771-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neural markers of working memory and emotional regulation are predictors of future depression severity in at risk young adults: a replication study
AU - Yvette Afriyie-Agyemang
AU - Michele A. Bertocci
AU - Satish Iyengar
AU - Richelle S. Stiffler
AU - Lisa K. Bonar
AU - Haris A. Aslam
AU - Simona Graur
AU - Genna Bebko
AU - Osasumwen Benjamin
AU - Yiming Wang
AU - Henry W. Chase
AU - Mary L. Phillips
PY - 2026
DA - 2026/07/31
JO - Molecular Psychiatry
DO - 10.1038/s41380-026-03771-5
UR - https://doi.org/10.1038/s41380-026-03771-5
AB - Objective neural markers that reflect the underlying pathophysiological mechanisms of affective disorders are needed to facilitate early identification of individuals most at risk of future affective disorders and ultimately provide neural targets to guide therapeutic interventions. Using an emotional n-back paradigm designed to examine working memory (WM) and emotional regulation (ER) capacity, we previously showed that WM-related elevated left dlPFC activity (a key node of the central executive network (CEN)) and elevated right precuneus activity (a key node of the default mode network (DMN)), as well as ER-related elevated left dlPFC activity were positively associated with future depression severity in young adults at risk for affective disorders. We now aimed to replicate and extend these previous longitudinal findings by examining relationships among right precuneus activity and left dlPFC activity during WM and ER tasks and future depression severity in a new independent young adult sample (n = 77: 50 female, age = 24.68), and a larger combined sample (n = 121: 83 female, age = 23.81) comprising the original and new samples. The Hamilton Rating Scale for Depression (HAM-D) and Young Mania Rating Scale (YMRS) were measured at 12 months post scan to assess future depression and mania/hypomania severity respectively. In the new sample, we showed patterns of left dlPFC activity and right precuneus activity during WM, and left dlPFC activity during ER that were consistent with the original sample. In both the new and combined samples, future depression severity was robustly predicted by WM-related left dlPFC activity and right precuneus activity, and ER-related left dlPFC activity (all ps < 0.05 qFDR). These findings were specific to future depression severity. The effect sizes (pseudo R-squared values) for the full models including all IVs in the new and combined samples ranged from approximately 25–43%, with left dlPFC and right precuneus activity during WM explaining 15.59% of variance in future depression severity in the new sample; and left dlPFC activity during ER explaining 14.63% of variance in future depression severity in the combined sample. These replicated, longitudinal findings provide candidate neural markers to guide risk identification and targeting of new interventions for individuals with and those at risk for future affective disorders.
SN - 1359-4184
SN - 1476-5578
ER -