Differentiating Prenatal Exposure to Methamphetamine and Alcohol versus Alcohol and Not Methamphetamine using Tensor-Based Brain Morphometry and Discriminant Analysis

Laboratory of Neuro Imaging, Department of Neurology, University of California, Los Angeles, Los Angeles, California 90095, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 03/2010; 30(11):3876-85. DOI: 10.1523/JNEUROSCI.4967-09.2010
Source: PubMed


Here we investigate the effects of prenatal exposure to methamphetamine (MA) on local brain volume using magnetic resonance imaging. Because many who use MA during pregnancy also use alcohol, a known teratogen, we examined whether local brain volumes differed among 61 children (ages 5-15 years), 21 with prenatal MA exposure, 18 with concomitant prenatal alcohol exposure (the MAA group), 13 with heavy prenatal alcohol but not MA exposure (ALC group), and 27 unexposed controls. Volume reductions were observed in both exposure groups relative to controls in striatal and thalamic regions bilaterally and in right prefrontal and left occipitoparietal cortices. Striatal volume reductions were more severe in the MAA group than in the ALC group, and, within the MAA group, a negative correlation between full-scale intelligence quotient (FSIQ) scores and caudate volume was observed. Limbic structures, including the anterior and posterior cingulate, the inferior frontal gyrus (IFG), and ventral and lateral temporal lobes bilaterally, were increased in volume in both exposure groups. Furthermore, cingulate and right IFG volume increases were more pronounced in the MAA than ALC group. Discriminant function analyses using local volume measurements and FSIQ were used to predict group membership, yielding factor scores that correctly classified 72% of participants in jackknife analyses. These findings suggest that striatal and limbic structures, known to be sites of neurotoxicity in adult MA abusers, may be more vulnerable to prenatal MA exposure than alcohol exposure and that more severe striatal damage is associated with more severe cognitive deficit.

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    • "structure, metabolism and function, particularly in the striatum and temporal lobe, but also in frontal and parietal regions [2] [3] [4]. "
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    ABSTRACT: There is emerging evidence on the harmful effects of prenatal methamphetamine (MA) exposure on the structure and function of the developing brain. However, few studies have assessed white matter structural integrity in the presence of prenatal MA exposure, and results are inconsistent. This investigation thus used diffusion tensor imaging (DTI) to investigate white matter microstructure and cognitive performance in a group of prenatal MA exposed (or MA) children and controls of similar age. Seventeen MA children and 15 healthy controls (aged 6-7 years) underwent DTI and assessment of motor function and general cognitive ability. Whole brain analyses of white matter structure were performed using FSL's tract-based spatial statistics comparing fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD). Mean diffusion values were extracted from white matter regions shown to differ across groups to determine whether variations in FA predicted cognitive performance. Analyses were controlled for maternal nicotine use. MA children showed significantly lower FA as well as higher MD, RD and AD in tracts that traverse striatal, limbic and frontal regions. Abnormal FA levels in MA children were significantly associated with poorer motor coordination and general cognitive ability sub-items that relate to aspects of executive function. Our findings suggest that, consistent with previous studies in older children, there are disruptions of white matter microstructural integrity in striatal, limbic and frontal regions of young MA exposed children, with prominent cognitive implications. Future longitudinal studies may clarify how prenatal MA exposure affects white matter structural connectivity at different stages of brain maturation.
    Behavioural Brain Research 11/2014; 279:62-67. DOI:10.1016/j.bbr.2014.11.005 · 3.03 Impact Factor
    • "f–h denote interaction effects in cortical thickness Metab Brain Dis (DeVane 1991; Kuhnert 1991). Our findings of (putamen) volume increases as compared to controls may seem contradictory to the reported reduction in volume in key areas of affected children to date, considering that studies mainly found reduced volumes in prenatal MA-exposed children (Chang et al. 2004; Sowell et al. 2010). However, the children were adolescent (mean age of 10 years) whereas our group was pre-adolescent. "
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    ABSTRACT: The global use of methamphetamine (MA) has increased substantially in recent years, but the effect of MA on brain structure in prenatally exposed children is understudied. Here we aimed to investigate potential changes in brain volumes and cortical thickness of children with prenatal MA-exposure compared to unexposed controls. Eighteen 6-year old children with MA-exposure during pregnancy and 18 healthy controls matched for age, gender and socio-economic background underwent structural imaging. Brain volumes and cortical thickness were assessed using Freesurfer and compared using ANOVA. Left putamen volume was significantly increased, and reduced cortical thickness was observed in the left hemisphere of the inferior parietal, parsopercularis and precuneus areas of MA-exposed children compared to controls. Compared to control males, prenatal MA-exposed males had greater volumes in striatal and associated areas, whereas MA-exposed females predominantly had greater cortical thickness compared to control females. In utero exposure to MA results in changes in the striatum of the developing child. In addition, changes within the striatal, frontal, and parietal areas are in part gender dependent.
    Metabolic Brain Disease 02/2014; 29(2). DOI:10.1007/s11011-014-9500-0 · 2.64 Impact Factor
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    • "The dose-dependent decrease in the gray matter volume observed in caudate in the present study is consistent with findings in previous studies of high-exposure cohorts. However , in those studies, in which PNAE levels were 4 times greater than the current study, exposure was also associated with locally increased gray matter volume, density, and cortical thickness bilaterally in perisylvian areas, particularly inferior parietal cortices and temporal lobes, and in frontal cortex (Sowell et al., 2001a, 2002a,b, 2008b, 2010). Interestingly , at those higher levels of exposure, these areas also exhibit considerable gross dysmorphology, parameterized as the point distance from center by Sowell and colleagues (2002a), and also are epicenters of white matter loss (Sowell et al., 2001a) and/or microstructural abnormalities (Sowell et al., 2008a). "

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