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

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).

[1]  M. Potenza,et al.  White-matter crossing-fiber microstructure in adolescents prenatally exposed to cocaine. , 2017, Drug and alcohol dependence.

[2]  R. Constable,et al.  Shared microstructural features of behavioral and substance addictions revealed in areas of crossing fibers. , 2017, Biological psychiatry. Cognitive neuroscience and neuroimaging.

[3]  Sara A. Romig-Martin,et al.  Prolonged corticosterone exposure induces dendritic spine remodeling and attrition in the rat medial prefrontal cortex , 2016, The Journal of comparative neurology.

[4]  J. Cohen-Gilbert,et al.  Neurobiological signatures associated with alcohol and drug use in the human adolescent brain , 2016, Neuroscience & Biobehavioral Reviews.

[5]  Sang-Hyuk Lee,et al.  White matter microstructural changes are associated with alcohol use in patients with panic disorder. , 2016, Journal of affective disorders.

[6]  M. Potenza,et al.  White matter development and tobacco smoking in young adults: A systematic review with recommendations for future research. , 2016, Drug and alcohol dependence.

[7]  S. Rombouts,et al.  Abnormalities of white matter integrity in the corpus callosum of adolescents with PTSD after childhood sexual abuse: a DTI study , 2015, European Child & Adolescent Psychiatry.

[8]  A. Gratton,et al.  Chronic stress alters the dendritic morphology of callosal neurons and the acute glutamate stress response in the rat medial prefrontal cortex , 2015, Stress.

[9]  M. J. Meloy,et al.  Brain development in heavy-drinking adolescents. , 2015, The American journal of psychiatry.

[10]  John M Taylor.  Psychometric analysis of the Ten-Item Perceived Stress Scale. , 2015, Psychological assessment.

[11]  Rajita Sinha,et al.  Childhood Trauma and Neural Responses to Personalized Stress, Favorite-Food and Neutral-Relaxing Cues in Adolescents , 2015, Neuropsychopharmacology.

[12]  Richard De La Garza,et al.  Characterizing white matter changes in cigarette smokers via diffusion tensor imaging. , 2014, Drug and alcohol dependence.

[13]  Rajita Sinha,et al.  Prenatal Cocaine Exposure and Adolescent Neural Responses to Appetitive and Stressful Stimuli , 2014, Neuropsychopharmacology.

[14]  E. Claus,et al.  Reduced white matter integrity in the cingulum and anterior corona radiata in posttraumatic stress disorder in male combat veterans: A diffusion tensor imaging study , 2013, Psychiatry Research: Neuroimaging.

[15]  Reza Momenan,et al.  White Matter Microstructure Alterations: A Study of Alcoholics with and without Post-Traumatic Stress Disorder , 2013, PloS one.

[16]  Derek K. Jones,et al.  Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging , 2013, Human brain mapping.

[17]  M. Potenza,et al.  Prenatal Cocaine Exposure and Gray Matter Volume in Adolescent Boys and Girls: Relationship to Substance Use Initiation , 2013, Biological Psychiatry.

[18]  M. Yücel,et al.  A systematic review of diffusion weighted MRI studies of white matter microstructure in adolescent substance users , 2013, Neuroscience & Biobehavioral Reviews.

[19]  A. Hayes.  Introduction to Mediation, Moderation, and Conditional Process Analysis: A Regression-Based Approach , 2013 .

[20]  H. Walter,et al.  WHITE MATTER INTEGRITY AND ITS RELATIONSHIP TO PTSD AND CHILDHOOD TRAUMA—A SYSTEMATIC REVIEW AND META‐ANALYSIS , 2013, Depression and anxiety.

[21]  S. Tapert,et al.  Longitudinal changes in white matter integrity among adolescent substance users. , 2012, Alcoholism, clinical and experimental research.

[22]  Sheldon Cohen,et al.  Who's Stressed? Distributions of Psychological Stress in the United States in Probability Samples from 1983, 2006, and 2009 , 2012 .

[23]  Ó. González-Pérez,et al.  Chronic exposure of juvenile rats to environmental noise impairs hippocampal cell proliferation in adulthood. , 2011, Noise & health.

[24]  V. Schmithorst,et al.  White matter development during adolescence as shown by diffusion MRI , 2010, Brain and Cognition.

[25]  Stephen M. Smith,et al.  Crossing fibres in tract-based spatial statistics , 2010, NeuroImage.

[26]  T T Yang,et al.  White matter integrity in adolescents with histories of marijuana use and binge drinking. , 2009, Neurotoxicology and teratology.

[27]  Joanna Jacobus,et al.  Altered white matter integrity in adolescent binge drinkers. , 2009, Alcoholism, clinical and experimental research.

[28]  W. K. Simmons,et al.  Circular analysis in systems neuroscience: the dangers of double dipping , 2009, Nature Neuroscience.

[29]  O. Witte,et al.  Adverse Effects of Antenatal Glucocorticoids on Cerebral Myelination in Sheep , 2009, Obstetrics and gynecology.

[30]  Rajita Sinha,et al.  Chronic Stress, Drug Use, and Vulnerability to Addiction , 2008, Annals of the New York Academy of Sciences.

[31]  Robert T. Schultz,et al.  Corpus callosum in maltreated children with posttraumatic stress disorder: A diffusion tensor imaging study , 2008, Psychiatry Research: Neuroimaging.

[32]  J. MacFall,et al.  Diffusion tensor measures of the corpus callosum in adolescents with adolescent onset alcohol use disorders. , 2008, Alcoholism, clinical and experimental research.

[33]  Mark W. Woolrich,et al.  Probabilistic diffusion tractography with multiple fibre orientations: What can we gain? , 2007, NeuroImage.

[34]  Daniel Rueckert,et al.  Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data , 2006, NeuroImage.

[35]  M. Joëls,et al.  Acute stress increases calcium current amplitude in rat hippocampus: temporal changes in physiology and gene expression , 2003, The European journal of neuroscience.

[36]  L. Kirisci,et al.  Item response theory modeling of substance use: an index based on 10 drug categories. , 2002, Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors.

[37]  Joan Kaufman,et al.  Effects of early adverse experiences on brain structure and function: clinical implications , 2000, Biological Psychiatry.

[38]  R. Hoyle.  Statistical Strategies for Small Sample Research , 1999 .

[39]  L. Kann,et al.  Reliability of the Youth Risk Behavior Survey Questionnaire. , 1995, American journal of epidemiology.

[40]  Sheldon Cohen,et al.  Who ’ s Stressed ? Distributions of Psychological Stress in the United States in Probability Samples from 1983 , 2006 , and 20091 S , 2012 .

[41]  M. Gunnar,et al.  The neurobiology of stress and development. , 2007, Annual review of psychology.

[42]  B. Grant,et al.  Age of onset of drug use and its association with DSM-IV drug abuse and dependence: results from the National Longitudinal Alcohol Epidemiologic Survey. , 1998, Journal of substance abuse.

[43]  M. Luca,et al.  Prenatally induced brain lesions, cognitive impairment and protein-kinase C-dependent phosphorylation , 1991 .

[44]  D. A. Kenny,et al.  The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. , 1986, Journal of personality and social psychology.