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Am J Addict. 2018 Apr;27(3):217-224. doi: 10.1111/ajad.12710. Epub 2018 Mar 23.

Substance-use initiation moderates the effect of stress on white-matter microstructure in adolescents.

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Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut.
Child Study Center, Yale School of Medicine, New Haven, Connecticut.
Department of Neuroscience, Yale School of Medicine, New Haven, Connecticut.
Departments of Epidemiology, Pediatrics, and Psychology, Yale School of Medicine, New Haven, Connecticut.
Connecticut Mental Health Center, New Haven, Connecticut.



While childhood stress may contribute risk to substance-use initiation and differences in brain white-matter development, understanding of the potential impact of substance-use initiation on the relationship between experienced stress and white-matter microstructure remains limited.


This study examined whether substance-use initiation moderated the effect of perceived stress on white-matter differences using measures of primary white-matter fiber anisotropy.


Forty adolescents (age 14.75 ± .87 years) were assessed on the Perceived Stress Scale, and 50% were determined to have presence of substance-use initiation. White-matter microstructure was examined using primary-fiber orientations anisotropy, which may reflect white-matter integrity, modeled separately from other fiber orientations in the same voxels. Analyses were conducted on regions of interest previously associated with childhood stress and substance use.


Lower perceived stress and presence of substance-use initiation were related to greater right cingulum primary-fiber measures. Substance-use-initiation status moderated the association between perceived stress and right cingulum primary-fiber measures, such that higher perceived stress was associated with lower right cingulum primary-fiber anisotropy in adolescents without substance-use initiation, but not in those with substance-use initiation.


Findings in primary-fiber anisotropy suggest differences in right cingulum white-matter integrity is associated with substance-use initiation in higher-stress adolescents. This reflects a possible pre-existing risk factor, an impact of early substance use, or a combination thereof. Examination of potential markers associated with substance-use initiation in white-matter microstructure among stress-exposed youth warrant additional investigation as such biomarkers may inform efforts relating to tailored interventions. (Am J Addict 2018;27:217-224).

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