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

• Published in: Molecular psychiatry Vol. 28; no. 3; pp. 1137 - 1145
• Main Authors: Wong, Ting Yat, Moore, Tyler M., Seidlitz, Jakob, Yuen, Kenneth S. L., Ruparel, Kosha, Barzilay, Ran, Calkins, Monica E., Alexander-Bloch, Aaron F., Satterthwaite, Theodore D., Gur, Raquel E., Gur, Ruben C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2023; Nature Publishing Group
• Subjects: 59/57; 631/378; 631/477; Adolescent; Adult; Behavioral Sciences; Biological Psychology; Brain - pathology; Child; Cognition - physiology; Cognitive ability; Gray Matter; Humans; Magnetic Resonance Imaging - methods; Maturation; Medicine; Medicine & Public Health; Neuroimaging; Neurosciences; Pharmacotherapy; Psychiatry; Psychopathology; Substantia grisea; Young Adult
• ISSN: 1359-4184; 1476-5578
• DOI: 10.1038/s41380-022-01908-w

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.