Brain Cortical Thickness Differences in Adolescent Females with Substance Use Disorders

Abstract

Some youths develop multiple substance use disorders early in adolescence and have severe, persistent courses. Such youths often exhibit impulsivity, risk-taking, and problems of inhibition. However, relatively little is known about the possible brain bases of these behavioral traits, especially among females.MethodsWe recruited right-handed female patients, 14–19 years of age, from a university-based treatment program for youths with substance use disorders and community controls similar for age, race and zip code of residence. We obtained 43 T1-weighted structural brain images (22 patients and 21 controls) to examine group differences in cortical thickness across the entire brain as well as six a priori regions-of-interest: 1) medial orbitofrontal cortex; 2) rostral anterior cingulate cortex; and 3) middle frontal cortex, in each hemisphere. Age and IQ were entered as nuisance factors for all analyses.ResultsA priori region-of-interest analyses yielded no significant differences. However, whole-brain group comparisons revealed that the left pregenual rostral anterior cingulate cortex extending into the left medial orbitofrontal region (355.84 mm2 in size), a subset of two of our a priori regions-of-interest, was significantly thinner in patients compared to controls (vertex-level threshold p = 0.005 and cluster-level family wise error corrected threshold p = 0.05). The whole-brain group differences did not survive after adjusting for depression or externalizing scores. Whole-brain within-patient analyses demonstrated a positive association between cortical thickness in the left precuneus and behavioral disinhibition scores (458.23 mm2 in size).ConclusionsAdolescent females with substance use disorders have significant differences in brain cortical thickness in regions engaged by the default mode network and that have been associated with problems of emotional dysregulation, inhibition, and behavioral control in past studies.

Mechanisms Underlying Sex Differences in Cannabis Use

“…During late adolescence and young adulthood, both female and male cannabis users had smaller grey matter volumes than non-users in decision making and executive function areas of the brain, i.e., the medial orbitofrontal and inferior parietal cortices [84]. In adolescents with substance use disorder and co-morbid conduct problems, many of whom were cannabis dependent, females had less cortical thickness in parts of the anterior cingulate cortex and medial orbitofrontal cortex compared to female controls [85], with no similar effect observed in males [86]. In a separate set of studies, comparably characterized subjects had significantly less grey matter volume than gender-matched controls in left and right dorsolateral prefrontal cortex, in males [87] and females [88], respectively.…”

Is there a relation between novelty seeking, striatal dopamine release and frontal cortical thickness?

“…It is plausible that the addition of TBV as a covariate decreased our power to detect effects, or that adjusted CT values are more sensitive in revealing a relation between striatal DA responses and cortical morphometry. Indeed, there is little consensus as to whether TBV/ICV should [66] or should not [4],[67],[68] be included as a covariate in CT analyses in the context of substance use research. More broadly, there is limited agreement as to how CT should be analyzed (i.e., absolute vs .…”

Adolescent Corticosterone and TrkB Pharmaco-Manipulations Sex-Dependently Impact Instrumental Reversal Learning Later in Life

“…For example, cocaine-dependent females and males exhibit decreased cerebral blood flow in the moPFC and loPFC, respectively (Adinoff et al, 2006 ). Adolescent females with substance dependence exhibit decreased cortical thickness and gray matter volume in regions involved in inhibitory control, decision-making, reward, and risk-taking, including the moPFC and dorsolateral PFC (DLPFC; Dalwani et al, 2015 ; Boulos et al, 2016 ), while substance-dependent adolescent males show decreased gray matter volume in DLPFC (Dalwani et al, 2011 ). Regner et al ( 2015 ) report decreased oPFC gray matter volume in abstinent stimulant-dependent women, but not men.…”

“…Substance-dependent individuals exhibit structural and functional alterations in the oPFC, including blood flow abnormalities (London et al, 2000 ; Adinoff et al, 2006 ), decreased gray matter volume (Matochik et al, 2003 ; Tanabe et al, 2009 ; Dalwani et al, 2015 ), and decreased cortical thickness (Boulos et al, 2016 ). In animal models, adolescent CORT and cocaine exposure result in long-term changes in oPFC neuron structure (Gourley et al, 2012a , 2013b ; DePoy et al, 2014 , 2016 , 2017 ) that are associated with maladaptive behaviors symptomatic of addiction (Lucantonio et al, 2012 ).…”