Age-related differences in neurometabolite concentrations during early infancy: A cross-sectional analysis of the HBCD Release 1.0
- 1The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Abstract
Background: Developmental trajectories of low-concentration neurometabolites such as the neurotransmitter {gamma}-aminobutyric acid (GABA), and the antioxidants glutathione (GSH) and ascorbate (Asc) across early infancy remain unexplored. Advances in spectral editing enabled the measurement of these key molecules together with high-concentration metabolites like N-acetylaspartate (NAA) and glutamate (Glu) in the HEALthy Brain and Child Development (HBCD) study, the largest longitudinal study of early brain development in the United States. Purpose: To determine the age-associated trajectories of 14 key neurometabolites during early infancy from a cross-sectional 1H-MRS dataset. Materials and Methods: HBCD utilizes ISTHMUS, an integrated MRS sequence that includes both an unedited short-echo-time PRESS acquisition and an advanced 4-step Hadamard-encoded sequence, HERCULES to enable measurement of both high- and low-concentration metabolites. Metabolite quantification was carried out by the HBCD Data Coordinating Center (HDCC) using an automated Osprey pipeline, with data from 201 infants ages 0 - 10 weeks adjusted age included in the tabular imaging results in HBCD data release 1.0. After excluding preterm born infants and data with poor linewidth or model quality metric, we tested for linear associations with adjusted age for each metabolite. Results: Concentration estimates of total NAA (tNAA), total creatine (tCr) and glutamate (Glu) as well as the combined sum of glutamate and glutamine (Glx) significantly increased across ages 0 - 10 weeks, while myo-inositol (mI) decreased. GABA and GSH showed age-related trends, but did not reach significance. Levels of the lipid precursor phosphorylethanolamine (PE) and Asc are higher in the first months than established adult values. Conclusion: Multiple metabolites showed significant age-related changes during early infancy. While GABA and GSH did not, future work will establish whether the trends suggested here contribute to linear or non-linear patterns across the first years of life.
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BibTeX
@misc{muralimanohar2026agerelated,
title = {{Age-related differences in neurometabolite concentrations during early infancy: A cross-sectional analysis of the HBCD Release 1.0}},
author = {S. Murali-Manohar and H. J. Zoellner and C. W. Davies-Jenkins and A. T. Gudmundson and S. C. N. Hui and Y. Song and G. L. Simegn and Z. Shams and A. Gad and B. Gagoski and M. D. Tisdall and M. G. Saleh and R. Noeske and S. K. Ganji and G. Gilbert and Y. Zhao and T. J. Hendrickson and E. G. Lee and W. T. Clarke and D. C. Dean and M. B. Nebel and C. D. Smyser and D. A. Fair and H. E. Volk and G. Oeltzschner and J. L. Wisnowski and R. A. E. Edden},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748552},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748552v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Age-related differences in neurometabolite concentrations during early infancy: A cross-sectional analysis of the HBCD Release 1.0
AU - S. Murali-Manohar
AU - H. J. Zoellner
AU - C. W. Davies-Jenkins
AU - A. T. Gudmundson
AU - S. C. N. Hui
AU - Y. Song
AU - G. L. Simegn
AU - Z. Shams
AU - A. Gad
AU - B. Gagoski
AU - M. D. Tisdall
AU - M. G. Saleh
AU - R. Noeske
AU - S. K. Ganji
AU - G. Gilbert
AU - Y. Zhao
AU - T. J. Hendrickson
AU - E. G. Lee
AU - W. T. Clarke
AU - D. C. Dean
AU - M. B. Nebel
AU - C. D. Smyser
AU - D. A. Fair
AU - H. E. Volk
AU - G. Oeltzschner
AU - J. L. Wisnowski
AU - R. A. E. Edden
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748552
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748552v1
AB - Background: Developmental trajectories of low-concentration neurometabolites such as the neurotransmitter {gamma}-aminobutyric acid (GABA), and the antioxidants glutathione (GSH) and ascorbate (Asc) across early infancy remain unexplored. Advances in spectral editing enabled the measurement of these key molecules together with high-concentration metabolites like N-acetylaspartate (NAA) and glutamate (Glu) in the HEALthy Brain and Child Development (HBCD) study, the largest longitudinal study of early brain development in the United States. Purpose: To determine the age-associated trajectories of 14 key neurometabolites during early infancy from a cross-sectional 1H-MRS dataset. Materials and Methods: HBCD utilizes ISTHMUS, an integrated MRS sequence that includes both an unedited short-echo-time PRESS acquisition and an advanced 4-step Hadamard-encoded sequence, HERCULES to enable measurement of both high- and low-concentration metabolites. Metabolite quantification was carried out by the HBCD Data Coordinating Center (HDCC) using an automated Osprey pipeline, with data from 201 infants ages 0 - 10 weeks adjusted age included in the tabular imaging results in HBCD data release 1.0. After excluding preterm born infants and data with poor linewidth or model quality metric, we tested for linear associations with adjusted age for each metabolite. Results: Concentration estimates of total NAA (tNAA), total creatine (tCr) and glutamate (Glu) as well as the combined sum of glutamate and glutamine (Glx) significantly increased across ages 0 - 10 weeks, while myo-inositol (mI) decreased. GABA and GSH showed age-related trends, but did not reach significance. Levels of the lipid precursor phosphorylethanolamine (PE) and Asc are higher in the first months than established adult values. Conclusion: Multiple metabolites showed significant age-related changes during early infancy. While GABA and GSH did not, future work will establish whether the trends suggested here contribute to linear or non-linear patterns across the first years of life.
ER -