Most prior studies of the effects of excessive alcohol intake on the adolescent brain examined alcohol use dependent samples with comorbid psychiatric and substance use disorders. In the Cape Town region, we identified a sizeable cohort of adolescents with alcohol use disorders (AUD) without externalizing or other psychiatric disorders. We examined brain morphology in 64 such adolescents compared to age and gender matched healthy controls. Magnetic resonance imaging data were analyzed using FSL’s FIRST software for subcortical volumes, and cortical gray matter (GM) was analyzed using voxel based morphometry (VBM) and regions of interest (ROI) analysis. AUD boys had smaller thalamic and putamen volumes compared to non-drinking boys, while AUD girls had larger thalamic and putamen volumes compared to non-drinking girls. VBM revealed a large region of decreased GM density in AUDs compared to controls located in the left lateral frontal, temporal, and parietal lobes, extending medially deep into the parietal lobe. Smaller GM volume in this region was also present when examined using ROI analysis. Our lack of findings in other brain regions, particularly hippocampus, suggests that reports of smaller brain volumes in adolescent AUDs in the literature are a consequence of psychiatric and substance abuse comorbidities.
Introduction The potential neurochemical toxicity associated with methamphetamine (MA) or marijuana (MJ) use on the developing adolescent brain is unclear, particularly with regard to individuals with concomitant use of MA and MJ (MA+MJ). In this study, proton magnetic resonance spectroscopy (MRS) was utilized to measure in vivo brain N-acetylaspartate plus N-acetylaspartyl glutamate (tNAA, an indicator of intact neuronal integrity) levels. Methods Three adolescent groups from Cape Town, South Africa completed MRS scans as well as clinical measures including a drug use history. Subjects included (1) nine MA (age = 15.7 ± 1.37), (2) eight MA+MJ (age = 16.2 ± 1.16) using adolescents and (3) ten healthy controls (age = 16.8 ± 0.62). Single voxel spectra were acquired from midfrontal gray matter using a point-resolved spectroscopy sequence (PRESS). The MRS data were post-processed in the fully automated approach for quantitation of metabolite ratios to phosphocreatine plus creatine (PCr+Cr). Results A significant reduction in frontal tNAA/PCr+Cr ratios was seen in the MA+MJ group compared to the healthy controls (p = 0.01, by 7.2 %) and to the MA group (p = 0.04, by 6.9 %). Significant relationships were also observed between decreased tNAA/PCr+Cr ratios and drug use history of MA or MJ (total cumulative lifetime dose, age of onset, and duration of MA and MJ exposure) only in the MA+MJ group (all p < 0.05). Conclusions These findings suggest that in adolescents, concomitant heavy MA+MJ use may contribute to altered brain metabolites in frontal gray matter. The significant associations between the abnormal tNAA/PCr+Cr ratios and the drug use history suggest that MA+MJ abuse may induce neurotoxicity in a dose-responsive manner in adolescent brain.
It has been hypothesized that changes in striatal-mediated dopamine modulation during adolescence may increase the risk for initiating substance abuse as a result of its fundamental role in arbitrating reward sensitivity and motivation during learning and decision making. However, substance abuse during adolescence may also significantly modify striatal structure and function and concomitantly alter reward sensitivity and action control while this brain region is undergoing remodeling. In the present investigation, to assess the relationship of methamphetamine (Meth) or Meth and cannabis (CA) abuse to regional striatal morphology, we acquired structural magnetic resonance images, using a 3T Siemens Trio scanner, from three groups of adolescents composed of healthy controls (n = 10), Meth abusers (n = 9) and combined Meth and CA abusers (Meth+CA, n = 8). We also assessed novelty seeking using the novelty seeking subscale of Cloninger’s Tridimensional Character Inventory. The results indicate that adolescent Meth+CA abusers have increased regional striatal volume and show intensified novelty seeking in contrast to the controls. The degree of Meth exposure was also positively correlated with regional striatal volume and novelty seeking in both the Meth and Meth+CA users. These preliminary findings support theories that propose a role for the striatum in adolescent substance abuse and further indicate that novelty seeking may be related to the initiation of, or sustained, drug use.
ObjectiveThe objective of this study is to examine white matter microstructure using diffusion tensor imaging (DTI) in a sample of adolescents with alcohol use disorders (AUD) and no psychiatric or substance co-morbidity.MethodsFifty adolescents with AUD and fifty non-alcohol abusing controls matched on gender and age were studied with DTI, neurocognitive testing, and a clinical assessment that included measures of alcohol use and childhood trauma. Maps of fractional anisotropy (FA) and mean diffusivity (MD) were computed, registered to a common template, and voxel-wise statistical analysis used to assess group differences. Associations between regions of altered WM microstructure and clinical or neurocognitive measures were also assessed.ResultsCompared with controls, adolescent drinkers without co-morbid substance abuse or externalizing disorder, showed 1) no regions of significantly lower FA, 2) increased FA in WM tracts of the limbic system; 3) no MD differences; and 4) within the region of higher FA in AUD, there were no associations between FA and alcohol use, cognition, or trauma.DiscussionThe most important observation of this study is our failure to observe significantly smaller FA in this relatively large alcohol abuse/dependent adolescent sample. Greater FA in the limbic regions observed in this study may index a risk for adolescent AUD instead of a consequence of drinking. Drinking behavior may be reinforced in those with higher FA and perhaps greater myelination in these brain regions involved in reward and reinforcement.
ObjectivesMethamphetamine abuse affects brain structure and function. Although methamphetamine and cannabis are commonly abused together, few studies have investigated the differential neurocognitive consequences of methamphetamine abuse with or without cannabis. Furthermore, the effects of drug use on the developing adolescent brain remain poorly understood. We compared neurocognitive function between adolescents with ‘pure’ methamphetamine abuse, those with comorbid methamphetamine and cannabis abuse, and healthy controls at baseline and follow-up.MethodsIndividuals residing in the greater Cape Town region, between the ages of 13 and 18 years, were recruited into either Methamphetamine only group (Meth-only; n=10), Methamphetamine and cannabis group (Meth-cann; n=10) or healthy control (n=20) groups using a quasi-experimental design. All participants underwent a comprehensive neurocognitive assessment. Substance-use variables and psychiatric symptom counts were also recorded. A portion of the Meth-only and control participants completed 12-month follow-up assessments.ResultsWhile the Meth-cann group demonstrated widespread neurocognitive deficits at baseline, these deficits were restricted to the self-monitoring domain in the Meth-only group at baseline and at follow-up.ConclusionsMethamphetamine abuse with cannabis abuse is associated with significantly more neurocognitive impairment than methamphetamine abuse alone, and such deficits may be enduring.
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