Female adolescents with severe substance and conduct problems have substantially less brain gray matter volume.

Manish S Dalwani,Thomas J Crowley,Kristen M Raymond,Susan K Mikulich-Gilbertson,Jody L Tanabe,Michael F Regner,Marie T Banich,Mary Agnes Mcmahon,Susan E Young,Shannon K Mcwilliams,Joseph T Sakai,Hidenori Yamasue

doi:10.1371/journal.pone.0126368

Manish S Dalwani, Thomas J Crowley + Show 10 more

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https://doi.org/10.1371/journal.pone.0126368

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Abstract

ObjectiveStructural neuroimaging studies have demonstrated lower regional gray matter volume in adolescents with severe substance and conduct problems. These research studies, including ours, have generally focused on male-only or mixed-sex samples of adolescents with conduct and/or substance problems. Here we compare gray matter volume between female adolescents with severe substance and conduct problems and female healthy controls of similar ages. Hypotheses: Female adolescents with severe substance and conduct problems will show significantly less gray matter volume in frontal regions critical to inhibition (i.e. dorsolateral prefrontal cortex and ventrolateral prefrontal cortex), conflict processing (i.e., anterior cingulate), valuation of expected outcomes (i.e., medial orbitofrontal cortex) and the dopamine reward system (i.e. striatum).MethodsWe conducted whole-brain voxel-based morphometric comparison of structural MR images of 22 patients (14-18 years) with severe substance and conduct problems and 21 controls of similar age using statistical parametric mapping (SPM) and voxel-based morphometric (VBM8) toolbox. We tested group differences in regional gray matter volume with analyses of covariance, adjusting for age and IQ at p<0.05, corrected for multiple comparisons at whole-brain cluster-level threshold.ResultsFemale adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral somatosensory cortex, left supramarginal gyrus, and bilateral angular gyrus. Considering the entire brain, patients had 9.5% less overall gray matter volume compared to controls.ConclusionsFemale adolescents with severe substance and conduct problems in comparison to similarly aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior.

Highlights

Substance use disorders (DSM-IV [1]) and conduct disorder (DSM-IV [1]), strongly comorbid in adolescents [2], are characterized, in part, by the presence of very risky behaviors [3,4,5] and are associated with severe health [6,7] and economic problems [8,9]
Female adolescents with severe substance and conduct problems compared to controls showed significantly less gray matter volume in right dorsolateral prefrontal cortex, left ventrolateral prefrontal cortex, medial orbitofrontal cortex, anterior cingulate, bilateral
Female adolescents with severe substance and conduct problems in comparison to aged female healthy controls showed substantially lower gray matter volume in brain regions involved in inhibition, conflict processing, valuation of outcomes, decision-making, reward, risk-taking, and rule-breaking antisocial behavior

Summary

Introduction

Substance use disorders (DSM-IV [1]) and conduct disorder (DSM-IV [1]), strongly comorbid in adolescents [2], are characterized, in part, by the presence of very risky behaviors [3,4,5] and are associated with severe health [6,7] and economic problems [8,9]. The presence of conduct problems in middle childhood is predictive of developing later substance problems [27], suggesting that conduct and antisocial behavior problems are not the result of substance-influenced decision making Such youths with conduct problems are likely to have early onset of substance use [28], multiple substance use disorders diagnoses [2], and persistent courses [29]. Some such youths fail to meet the technical criteria for conduct disorder, because, for example, strictly supervised probation controlled their behavior throughout the last year; we refer to such youths as having “serious substance and conduct problems” (SCP)

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