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Traumatic stress load and stressor reactivity score associated with accelerated gray matter maturation in youths indexed by normative models

Molecular Psychiatry volume 28, pages 1137–1145 (2023)Cite this article

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Abstract

Understanding how traumatic stress affects typical brain development during adolescence is critical to elucidate underlying mechanisms related to both maladaptive functioning and resilience after traumatic exposures. The current study aimed to map deviations from normative ranges of brain gray matter for youths with traumatic exposures. For each cortical and subcortical gray matter region, normative percentiles of variations were established using structural MRI from typically developing youths without any traumatic exposure (n = 245; age range = 8–23) from the Philadelphia Neurodevelopmental Cohort (PNC). The remaining PNC participants with neuroimaging data (n = 1129) were classified as either within the normative range (5–95%), delayed (>95%) or accelerated (<5%) maturational ranges for each region using the normative model. An averaged quantile regression index was calculated across all regions. Mediation models revealed that high traumatic stress load was positively associated with poorer cognitive functioning and greater psychopathology, and these associations were mediated by accelerated gray matter maturation. Furthermore, higher stressor reactivity scores, which represent a less resilient response under traumatic stress, were positively correlated with greater acceleration of gray matter maturation (r = 0.224, 95% CI = [0.17, 0.28], p < 0.001), suggesting that more accelerated maturation was linked to greater stressor response regardless of traumatic stress load. We conclude that traumatic stress is a source of deviation from normative brain development associated with poorer cognitive functioning and more psychopathology in the long run.

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Fig. 1: Schematic Workflow for Calculating Quantile Regression Index (QRI).
Fig. 2: Accelerated brain maturation mediated the relationship between traumatic stress load and functioning composite score.
Fig. 3: Accelerated brain maturation was associated with stressor reactivity score.

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Acknowledgements

We thank Allyson P. Mackey for her critical comments on the early draft of the manuscript. This study was supported by grants MH107235, MH119219, MH089983, and MH096891 from the NIMH; the Dowshen Neuroscience fund; and the Lifespan Brain Institute of Children’s Hospital of Philadelphia and Penn Medicine, University of Pennsylvania. KSLY has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 777084 (DynaMORE project), and from the Deutsche Forschungsgemeinschaft (DFG grant CRC 1193, subproject Z03).

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Authors and Affiliations

  1. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Ting Yat Wong, Tyler M. Moore, Jakob Seidlitz, Kosha Ruparel, Ran Barzilay, Monica E. Calkins, Aaron F. Alexander-Bloch, Theodore D. Satterthwaite, Raquel E. Gur & Ruben C. Gur

  2. Lifespan Brain Institute, Perelman School of Medicine and Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Tyler M. Moore, Jakob Seidlitz, Ran Barzilay, Monica E. Calkins, Aaron F. Alexander-Bloch, Theodore D. Satterthwaite, Raquel E. Gur & Ruben C. Gur

  3. Department of Child and Adolescent Psychiatry and Behavioral Science, The Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Jakob Seidlitz, Ran Barzilay, Aaron F. Alexander-Bloch & Raquel E. Gur

  4. Focus Program Translational Neuroscience, Neuroimaging Center, Johannes Gutenberg University Medical Center, Mainz, Germany

    Kenneth S. L. Yuen

  5. Leibniz Institute for Resilience Research, Mainz, Germany

    Kenneth S. L. Yuen

  6. Penn Lifespan Informatics and Neuroimaging Center (PennLINC), Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Theodore D. Satterthwaite

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Contributions

TYW: Conceptualization, methodology, software, formal analysis, data curation, writing—original draft, writing—review & editing, visualization. TMM: Data curation, formal analysis, writing—review & editing. JS: Formal analysis, writing—review & editing. KSLY: Writing—review & editing. KR: Resources, data curation, writing—review & editing. RB: Writing—review & editing. MEC: Writing—review & editing. AFA-B: Writing—review & editing. TDS: Resources, writing—review & editing. REG: Resources, writing—review & editing, supervision, project administration, funding acquisition. RCG: Conceptualization, resources, writing—review & editing, supervision, project administration, funding acquisition.

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Correspondence to Ting Yat Wong.

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Supplementary information

Appendix. Abbreviation table for key variables

Appendix. Abbreviation table for key variables

Key Variable

Abbreviation

Brief Description

Traumatic Stress Load

TSL

Sum of traumatic stressful events

Averaged Quantile Regression Index

aQRI

Whole brain maturation index calculated by quantile regression models

Stressor Reactivity Score

SRS

Residuals of functioning composite score regressing out traumatic stressful load, a score indicating vulnerability or resilience to poorer outcomes under stress

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Wong, T.Y., Moore, T.M., Seidlitz, J. et al. Traumatic stress load and stressor reactivity score associated with accelerated gray matter maturation in youths indexed by normative models. Mol Psychiatry 28, 1137–1145 (2023). https://doi.org/10.1038/s41380-022-01908-w

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