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The successful implementation of prevention programs for mother-to-child human immunodeficiency virus (HIV) transmission has dramatically reduced the prevalence of infants infected with HIV while increasing that of HIV-exposed uninfected (HEU) children. Neuropsychological assessments indicate that HEU children may exhibit differences in neurodevelopment compared to unexposed children (HUU). Pathological mechanisms leading to such neurodevelopmental delays are not clear. In this observational birth cohort study we explored the integrity of regional white matter microstructure in HEU infants, shortly after birth. Microstructural changes in white matter associated with prenatal HIV exposure were evaluated in HEU infants (n = 15) and matched controls (n = 22) using diffusion tensor imaging and tract-based spatial statistics. Additionally, diffusion values were extracted and compared for white matter tracts of interest, and associations with clinical outcomes from the Dubowitz neonatal neurobehavioral tool were investigated. Higher fractional anisotropy in the middle cerebellar peduncles of HEU compared to HUU neonates was found after correction for age and gender. Scores on the Dubowitz abnormal neurological signs subscale were positively correlated with FA (r = 0.58, P = 0.038) in the left uncinate fasciculus in HEU infants. This is the first study to present data suggesting that prenatal HIV exposure without infection is associated with altered white matter microstructural integrity in the neonatal period. Longitudinal studies of HEU infants as their brains mature are necessary to understand further the significance of prenatal HIV and antiretroviral treatment exposure on white matter integrity and neurodevelopmental outcomes., Competing Interests: The authors have no conflicts of interest to disclose.

Hair-pulling disorder (trichotillomania, HPD) is a disabling condition that is characterized by repetitive hair-pulling resulting in hair loss. Although there is evidence of structural grey matter abnormalities in HPD, there is a paucity of data on white matter integrity. The aim of this study was to explore white matter integrity using diffusion tensor imaging (DTI) in subjects with HPD and healthy controls. Sixteen adult female subjects with HPD and 13 healthy female controls underwent DTI. Hair-pulling symptom severity, anxiety and depressive symptoms were also assessed. Tract-based spatial statistics were used to analyze data on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD). There were no differences in DTI measures between HPD subjects and healthy controls. However, there were significant associations of increased MD in white matter tracts of the fronto-striatal-thalamic pathway with longer HPD duration and increased HPD severity. Our findings suggest that white matter integrity in fronto-striatal-thalamic pathways in HPD is related to symptom duration and severity. The molecular basis of measures of white matter integrity in HPD deserves further exploration., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

BackgroundNicotine and illicit stimulants are very addictive substances. Although associations between grey matter and dependence on stimulants have been frequently reported, white matter correlates have received less attention.MethodsEleven international sites ascribed to the ENIGMA-Addiction consortium contributed data from individuals with dependence on cocaine (n = 147), methamphetamine (n = 132) and nicotine (n = 189), as well as non-dependent controls (n = 333). We compared the fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD) and mean diffusivity (MD) of 20 bilateral tracts. Also, we compared the performance of various machine learning algorithms in deriving brain-based classifications on stimulant dependence.ResultsThe cocaine and methamphetamine groups had lower regional FA and higher RD in several association, commissural, and projection white matter tracts. The methamphetamine dependent group additionally showed lower regional AD. The nicotine group had lower FA and higher RD limited to the anterior limb of the internal capsule. The best performing machine learning algorithm was the support vector machine (SVM). The SVM successfully classified individuals with dependence on cocaine (AUC = 0.70, p

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

Fronto-limbic white matter (WM) abnormalities are assumed to lie at the heart of the pathophysiology of bipolar disorder (BD); however, diffusion tensor imaging (DTI) studies have reported heterogeneous results and it is not clear how the clinical heterogeneity is related to the observed differences. This study aimed to identify WM abnormalities that differentiate patients with BD from healthy controls (HC) in the largest DTI dataset of patients with BD to date, collected via the ENIGMA network. We gathered individual tensor-derived regional metrics from 26 cohorts leading to a sample size of N = 3033 (1482 BD and 1551 HC). Mean fractional anisotropy (FA) from 43 regions of interest (ROI) and average whole-brain FA were entered into univariate mega- and meta-analyses to differentiate patients with BD from HC. Mega-analysis revealed significantly lower FA in patients with BD compared with HC in 29 regions, with the highest effect sizes observed within the corpus callosum (R2 = 0.041, Pcorr

BackgroundNeuroimaging studies have indicated that prenatal alcohol exposure is associated with alterations in the structure of specific brain regions in children. However, the temporal and regional specificity of such changes and their behavioural consequences are less known. Here we explore the integrity of regional white matter microstructure in infants with in utero exposure to alcohol, shortly after birth.MethodsTwenty-eight alcohol-exposed and 28 healthy unexposed infants were imaged using diffusion tensor imaging sequences to evaluate white matter integrity using validated tract-based spatial statistics analysis methods. Second, diffusion values were extracted for group comparisons by regions of interest. Differences in fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity were compared between groups and associations with measures from the Dubowitz neonatal neurobehavioural assessment were examined.ResultsLower AD values (p

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.