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

• Published in: The American journal on addictions 2018-04, Vol.27 (3), p.217-224
• Main Authors: Zhai, Zu Wei, Yip, Sarah W., Morie, Kristen P., Sinha, Rajita, Mayes, Linda C., Potenza, Marc N.
• Format: Article
• Language: English
• Subjects: Adolescent; Adverse Childhood Experiences; Age of Onset; Anisotropy; Child; Female; Humans; Male; Prognosis; Psychopathology; Risk Factors; Stress, Psychological - pathology; Stress, Psychological - psychology; Substance-Related Disorders - diagnosis; Substance-Related Disorders - epidemiology; Substance-Related Disorders - psychology; White Matter - diagnostic imaging; White Matter - ultrastructure
• ISSN: 1055-0496; 1521-0391
• DOI: 10.1111/ajad.12710

Background 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. Objectives 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. Methods 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. Results 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. Conclusions and Scientific Significance 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)