Lower diffusion in white matter of children with prenatal methamphetamine exposure.
Ontology highlight
ABSTRACT: Background
Methamphetamine use is a common problem among women of childbearing age, leading to an increasing number of children with prenatal methamphetamine exposure. Whether microstructural brain changes associated with prenatal methamphetamine exposure can be detected with diffusion tensor imaging (DTI) is unknown.Method
Twelve-direction DTI was performed in 29 methamphetamine-exposed and 37 unexposed children ages 3-4 years on a 3-T MRI scanner. Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were determined in the corpus callosum (genu and splenium) and bilaterally in the frontal and parietal white matter (WM), basal ganglia (caudate, putamen, globus pallidus), and thalamus.Results
Children with prenatal methamphetamine exposure had lower ADC in the frontal (right: -2.1%, p = 0.04; left: -2.0%, p = 0.09) and parietal WM (right: -3.9%, p = 0.002; left: -3.3%, p = 0.02) compared to unexposed children. The methamphetamine-exposed children also showed a trend for higher FA in the left frontal WM (+4.9%, p = 0.06) compared to the unexposed children.Conclusion
Since less myelination and higher dendritic or spine density have been reported in animals exposed to methamphetamine, lower diffusion in our children may reflect more compact axons or greater dendritic or spine density associated with prenatal methamphetamine exposure. These findings suggest alterations in white matter maturation in these children exposed to methamphetamine in utero.
SUBMITTER: Cloak CC
PROVIDER: S-EPMC2697962 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ImportanceMethamphetamine is a common illicit drug used worldwide. Methamphetamine and/or tobacco use by pregnant women remains prevalent. However, little is known about the effect of comorbid methamphetamine and tobacco use on human fetal brain development.ObjectiveTo investigate whether microstructural brain abnormalities reported in children with prenatal methamphetamine and/or tobacco exposure are present at birth before childhood environmental influences.Design, setting, and participantsA prospective, longitudinal study was conducted between September 17, 2008, and February 28, 2015, at an ambulatory academic medical center. A total of 752 infant-mother dyads were screened and 139 of 195 qualified neonates were evaluated (36 methamphetamine/tobacco exposed, 32 tobacco exposed, and 71 unexposed controls). They were recruited consecutively from the community.ExposuresPrenatal methamphetamine and/or tobacco exposure.Main outcomes and measuresQuantitative neurologic examination and diffusion tensor imaging performed 1 to 3 times through age 4 months; diffusivities and fractional anisotropy (FA) assessed in 7 white matter tracts and 4 subcortical brain regions using an automated atlas-based method.ResultsOf the 139 infants evaluated, 72 were female (51.8%); the mean (SE) postmenstrual age at baseline was 41.5 (0.27) weeks. Methamphetamine/tobacco-exposed infants showed delayed developmental trajectories on active muscle tone (group × age, P < .001) and total neurologic scores (group × age, P = .01) that normalized by ages 3 to 4 months. Only methamphetamine/tobacco-exposed boys had lower FA (group × age, P = .02) and higher diffusivities in superior (SCR) and posterior corona radiatae (PCR) (group × age × sex, P = .002; group × age × sex, P = .01) at baseline that normalized by age 3 months. Only methamphetamine/tobacco- and tobacco-exposed girls showed persistently lower FA in anterior corona radiata (ACR) (group, P = .04; group × age × sex, P = .01). Tobacco-exposed infants showed persistently lower axial diffusion in the thalamus and internal capsule across groups (P = .02).Conclusions and relevancePrenatal methamphetamine/tobacco exposure may lead to delays in motor development, with less coherent fibers and less myelination in SCR and PCR only in male infants, but these abnormalities may normalize by ages 3 to 4 months after cessation of stimulant exposure. In contrast, persistently less coherent ACR fibers were observed in methamphetamine/tobacco- and tobacco-exposed girls, possibly from increased dendritic branching or spine density due to epigenetic influences. Persistently lower diffusivity in the thalamus and internal capsule of all tobacco-exposed infants suggests aberrant axonal development. Collectively, prenatal methamphetamine and/or tobacco exposure may lead to delayed motor development and white matter maturation in sex- and regional-specific manners.
| S-EPMC6467201 | biostudies-literature
Project description:Children with prenatal alcohol exposure (PAE) may have cognitive, behavioral and brain abnormalities. Here, we compare rates of white matter and subcortical gray matter volume change in PAE and control children, and examine relationships between annual volume change and arithmetic ability, behavior, and executive function. Participants (n = 75 PAE/64 control; age: 7.1-15.9 years) each received two structural magnetic resonance scans, ~2 years apart. Assessments included Wechsler Intelligence Scale for Children (WISC-IV), the Child Behavior Checklist and the Behavior Rating Inventory of Executive Function. Subcortical white and gray volumes were extracted for each hemisphere. Group volume differences were tested using false discovery rate (q < 0.05). Analyses examined group-by-age interactions and group-score interactions for correlations between change in volume and raw behavioral scores. Results showed that subjects with PAE had smaller volumes than control subjects across the brain. Significant group-score interactions were found in temporal and parietal regions for WISC arithmetic scores and in frontal and parietal regions for behavioral measures. Poorer cognitive/ behavioral outcomes were associated with larger volume increases in PAE, while control subjects generally showed no significant correlations. In contrast with previous results demonstrating different trajectories of cortical volume change in PAE, our results show similar rates of subcortical volume growth in subjects with PAE and control subjects. We also demonstrate abnormal brain-behavior relationships in subjects with PAE, suggesting different use of brain resources. Our results are encouraging in that, due to the stable volume differences, there may be an extended window of opportunity for intervention in children with PAE.
| S-EPMC4631525 | biostudies-literature
Project description:BackgroundMethamphetamine (MA) use during pregnancy is a significant public health concern in the United States and affects long-term brain and behavioral development in children. We hypothesized that prenatal MA exposure would be related to greater DNA methylation of HSD11B2 and postnatal environmental stress.MethodsThe Infant Development, Environment, and Lifestyle Study (IDEAL), a longitudinal study of prenatal MA exposure enrolled mother-infant dyads in California, Hawaii, Iowa, and Oklahoma. Prenatal exposure was defined by maternal self-report and/or meconium toxicology screening. At ages 10-11 years, 100 children were assessed for drug exposure and DNA methylation of HSD11B2. Hierarchical linear models were used to determine the association between prenatal MA exposure and methylation of HSD11B2 at four CpG sites.ResultsPrenatal MA exposure (1.4% vs 0.31%, P < 0.01) and early childhood adversity (3.0 vs 2.0, P < 0.01) were associated with greater DNA methylation of HSD11B2 at the CpG2 site. The statistically significant effects of early childhood adversity (B = 0.11, P < 0.01) and prenatal MA exposure (B = 0.32, P = 0.03) on DNA methylation remained after adjusting for covariates.ConclusionsPrenatal MA exposure is related to postnatal childhood adversity and epigenetic alterations in HSD11B2, an important gene along the stress response pathway suggesting prenatal and postnatal programming effects.ImpactPrenatal methamphetamine exposure has been associated with developmental issues in newborns, yet little is known about the stress pathophysiology of methamphetamine on neurobehavior. This is the first evidence that prenatal methamphetamine exposure acts as a stressor, confirming the third pathophysiology of methamphetamine exposure.
| S-EPMC7855315 | biostudies-literature
Project description:BackgroundPrevious research reports associations between prenatal exposure to phthalates and childhood behavior problems; however, the neural mechanisms that may underlie these associations are relatively unexplored.ObjectiveThis study examined microstructural white matter as a possible mediator of the associations between prenatal phthalate exposure and behavior problems in preschool-aged children.MethodsData are from a subsample of a prospective pregnancy cohort, the Alberta Pregnancy Outcomes and Nutrition (APrON) study (n = 76). Mother-child pairs were included if mothers provided a second trimester urine sample, if the child completed a successful magnetic resonance imaging (MRI) scan at age 3-5 years, and if the Child Behavior Checklist was completed within 6 months of the MRI scan. Molar sums of high (HMWP) and low molecular weight phthalates (LMWP) were calculated from levels in urine samples. Associations between prenatal phthalate concentrations, fractional anisotropy (FA) and mean diffusivity (MD) in 10 major white matter tracts, and preschool behavior problems were investigated.ResultsMaternal prenatal phthalate concentrations were associated with MD of the right inferior fronto-occipital fasciculus (IFO), right pyramidal fibers, left and right uncinate fasciculus (UF), and FA of the left inferior longitudinal fasciculus (ILF). Mediation analyses showed that prenatal exposure to HMWP was indirectly associated with Internalizing (path ab = 0.09, CI.95 = 0.02, 0.20) and Externalizing Problems (path ab = 0.09, CI.95 = 0.01, 0.19) through MD of the right IFO, and to Internalizing Problems (path ab = 0.11, CI.95 = 0.01, 0.23) through MD of the right pyramidal fibers.DiscussionThis study provides the first evidence of childhood neural correlates of prenatal phthalate exposure. Results suggest that prenatal phthalate exposure may be related to microstructural white matter in the IFO, pyramidal fibers, UF, and ILF. Further, MD of the right IFO and pyramidal fibers may transmit childhood risk for behavioral problems.
| S-EPMC7050961 | biostudies-literature
Project description:Functional MRI studies of mental arithmetic consistently report blood oxygen level-dependent signals in the parietal and frontal regions. We tested whether white matter pathways connecting these regions are related to mental arithmetic ability by using diffusion tensor imaging (DTI) to measure these pathways in 28 children (age 10-15 years, 14 girls) and assessing their mental arithmetic skills. For each child, we identified anatomically the anterior portion of the superior longitudinal fasciculus (aSLF), a pathway connecting parietal and frontal cortex. We measured fractional anisotropy in a core region centered along the length of the aSLF. Fractional anisotropy in the left aSLF positively correlates with arithmetic approximation skill, as measured by a mental addition task with approximate answer choices. The correlation is stable in adjacent core aSLF regions but lower toward the pathway endpoints. The correlation is not explained by shared variance with other cognitive abilities and did not pass significance in the right aSLF. These measurements used DTI, a structural method, to test a specific functional model of mental arithmetic.
| S-EPMC2799736 | biostudies-literature
Project description:Despite accumulating evidence from animal models demonstrating that prenatal alcohol exposure (PAE) results in life-long neuroendocrine dysregulation, very little is known on this topic among humans with fetal alcohol spectrum disorders (FASD). We expected that alterations in gonadal hormones might interfere with the typical development of white matter (WM) myelination, and in a sex-dependent manner, in human adolescents with FASD. In order to investigate this hypothesis, we used diffusion tensor imaging (DTI) to assess: 1) whether or not sex moderates the impact of PAE on WM microstructure; and 2) how gonadal hormones relate to alterations in WM microstructure in children and adolescents affected by PAE.Methods61 youth (9 to 16 yrs.; 49% girls; 50% PAE) participated as part of the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD). DTI scans and passive drool samples were obtained to examine neurodevelopmental associations with testosterone (T) and dehydroepiandrosterone (DHEA) levels in boys and girls, and estradiol (E2) and progesterone (P) levels in girls. Tract-based spatial statistics were utilized to generate fractional anisotropy (FA) and mean diffusivity (MD) for 9 a priori WM regions of interest (ROIs).ResultsAs predicted, alterations in FA were observed in adolescents with PAE relative to controls, and these differences varied by sex. Girls with PAE exhibited lower FA (Inferior fronto-occipital and Uncinate fasciculi) while boys with PAE exhibited higher FA (Callosal body, Cingulum, Corticospinal tract, Optic radiation, Superior longitudinal fasciculus) relative to age-matched controls. When gonadal hormone levels were examined in relation to DTI measures, additional group differences in FA were revealed, demonstrating that neuroendocrine factors are associated with PAE-related brain alterations.ConclusionsThese findings provide human evidence that PAE relates to sex-specific differences in WM microstructure, and underlying alterations in gonadal hormone function may, in part, contribute to these effects. Determining PAE-effects on neuroendocrine function among humans is an essential first step towards developing novel clinical (e.g., assessment or intervention) tools that target hormone systems to improve on-going brain development among children and adolescents with FASD.
| S-EPMC5877456 | biostudies-literature
Project description:Children with prenatal exposure to cocaine are at higher risk for negative behavioral function and attention difficulties, and have demonstrated brain diffusion abnormalities in frontal white matter regions. However, brain regions beyond frontal and callosal areas have not been investigated using diffusion tensor imaging (DTI). DTI data were collected on 42 youth aged 14-16 years; subjects were divided into three groups based on detailed exposure histories: those with prenatal exposure to cocaine but not alcohol (prenatal cocaine exposure (PCE), n=12), prenatal exposure to cocaine and alcohol (cocaine and alcohol exposure (CAE), n=17), and controls (n=13). Tractography was performed and along-tract diffusion parameters were examined for group differences and correlations with executive function measures. In the right arcuate fasciculus and cingulum, the CAE group had higher fractional anisotropy (FA) and/or lower mean diffusivity (MD) than the other two groups. The PCE group demonstrated lower FA in the right arcuate and higher MD in the splenium of the corpus callosum than controls. Diffusion parameters in tracts with group differences correlated with measures of executive function. In conclusion, these diffusion differences in adolescents with prenatal cocaine exposure suggest localized, long-term structural brain alterations that may underlie attention and response-inhibition difficulties.
| S-EPMC3812806 | biostudies-literature
Project description:BackgroundPrenatal exposure to organophosphate (OP) pesticides associate with impaired neurodevelopment in humans and animal models. However, much uncertainty exists about the brain structural alterations underlying these associations. The objective of this study was to determine whether maternal OP pesticide metabolite concentrations in urine repeatedly measured during gestation are associated with brain morphology and white matter microstructure in 518 preadolescents aged 9-12 years.MethodData came from 518 mother-child pairs participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands. Maternal urine concentrations were determined for 6 dialkylphosphates (DAPs) including 3 dimethyl (DM) and 3 diethyl (DE) alkyl phosphate metabolites, collected at early, mid, and late pregnancy. At child's age 9-12 years, magnetic resonance imaging was performed to obtain T1-weighted images for brain volumes and surface-based cortical thickness and cortical surface area, and diffusion tensor imaging was used to measure white matter microstructure through fractional anisotropy (FA) and mean diffusivity (MD). Linear regression models were fit for the averaged prenatal exposure across pregnancy.ResultsDM and DE metabolite concentrations were not associated with brain volumes, cortical thickness, and cortical surface area. However, a 10-fold increase in averaged DM metabolite concentrations across pregnancy was associated with lower FA (B = -1.00, 95%CI = -1.80, -0.20) and higher MD (B = 0.13, 95%CI = 0.04, 0.21). Similar associations were observed for DE concentrations.ConclusionsThis study provides the first evidence that OP pesticides may alter normal white matter microstructure in children, which could have consequences for normal neurodevelopment. No associations were observed with structural brain morphology, including brain volumes, cortical thickness, and cortical surface area.
| S-EPMC7657967 | biostudies-literature
Project description:ObjectiveTo evaluate in-vivo neuroinflammation and white matter (WM) microstructural integrity in occupational manganese (Mn) exposure.MethodsWe assessed brain inflammation using Diffusion Basis Spectrum Imaging (DBSI) in 26 Mn-exposed welders, 17 Mn-exposed workers, and 26 non-exposed participants. Cumulative Mn exposure was estimated from work histories and the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores were completed by a movement specialist. Tract-based Spatial Statistics allowed for whole-brain voxel-wise WM analyses to compare WM DBSI-derived measures between the Mn-exposed and non-exposed groups. Exploratory grey matter region of interest (ROI) analyses examined the presence of similar alterations in the basal ganglia. We used voxelwise general linear modeling and linear regression to evaluate the association between cumulative Mn exposure, WM or basal ganglia DBSI metrics, and UPDRS3 scores, while adjusting for age.ResultsMn-exposed welders had higher DBSI-derived restricted fraction (DBSI-RF), higher DBSI-derived nonrestricted fraction (DBSI-NRF), and lower DBSI-derived fiber fraction (DBSI-FF) in multiple WM tracts (all p < 0.05) in comparison to less-exposed workers and non-exposed participants. Basal ganglia ROI analyses revealed higher average caudate DBSI-NRF and DBSI-derived radial diffusion (DBSI-RD) values in Mn-exposed welders relative to non-exposed participants (p < 0.05). Caudate DBSI-NRF was also associated with greater cumulative Mn exposure and higher UPRDS3 scores.ConclusionsMn-exposed welders demonstrate greater DBSI-derived indicators of neuroinflammation-related cellularity (DBSI-RF), greater extracellular edema (DBSI-NRF), and lower apparent axonal density (DBSI-FF) in multiple WM tracts suggesting a neuroinflammatory component in the pathophysiology of Mn neurotoxicity. Caudate DBSI-NRF was positively associated with both cumulative Mn exposure and clinical parkinsonism, indicating a possible dose-dependent effect on extracellular edema with associated motor effects.
| S-EPMC10524700 | biostudies-literature
Project description:Methamphetamine (METH) is a widespread illicit drug. If it is taken by pregnant women, it passes through the placenta and just as it affects the mother, it can impair the development of the offspring. The aim of our study was to identify candidates to investigate for changes in the gene expression in the specific regions of the brain associated with addiction to METH in rats. We examined the various areas of the central nervous system (striatum, hippocampus, prefrontal cortex) for signs of impairment in postnatal day 80 in experimental rats, whose mothers had been administered METH (5 mg/kg/day) during the entire gestation period. Changes in the gene expression at the mRNA level were determined by two techniques, microarray and real-time PCR. Results of two microarray trials were evaluated by LIMMA analysis. The first microarray trial detected either up-regulated or down-regulated expression of 2189 genes in the striatum; the second microarray trial detected either up-regulated or down-regulated expression of 1344 genes in the hippocampus of prenatally METH-exposed rats. We examined the expression of 10 genes using the real-time PCR technique. Differences in the gene expression were counted by the Mann-Whitney U-test. Significant changes were observed in the cocaine- and amphetamine-regulated transcript prepropeptide, tachykinin receptor 3, dopamine receptor D3 gene expression in the striatum regions, in the glucocorticoid nuclear receptor Nr3c1 gene expression in the prefrontal cortex and in the carboxylesterase 2 gene expression in the hippocampus of prenatally METH-exposed rats. The microarray technique also detected up-regulated expression of trace amine-associated receptor 7 h gene in the hippocampus of prenatally METH-exposed rats. We have identified susceptible genes; candidates for the study of an impairment related to methamphetamine addiction in the specific regions of the brain.
| S-EPMC6686742 | biostudies-literature