Prenatal Mild Ventriculomegaly Predicts Abnormal Development of the Neonatal Brain

Schizophrenia Research Center and the Department of Psychiatry, School of Medicine, University of North Carolina, Chapel Hill, NC 27599-7160, USA.
Biological psychiatry (Impact Factor: 10.26). 10/2008; 64(12):1069-76. DOI: 10.1016/j.biopsych.2008.07.031
Source: PubMed


Many psychiatric and neurodevelopmental disorders are associated with mild enlargement of the lateral ventricles thought to have origins in prenatal brain development. Little is known about development of the lateral ventricles and the relationship of prenatal lateral ventricle enlargement with postnatal brain development.
We performed neonatal magnetic resonance imaging on 34 children with isolated mild ventriculomegaly (MVM; width of the atrium of the lateral ventricle >/= 1.0 cm) on prenatal ultrasound and 34 age- and sex-matched control subjects with normal prenatal ventricle size. Lateral ventricle and cortical gray and white matter volumes were assessed. Fractional anisotropy (FA) and mean diffusivity (MD) in corpus callosum and corticospinal white matter tracts were determined obtained using quantitative tractography.
Neonates with prenatal MVM had significantly larger lateral ventricle volumes than matched control subjects (286.4%; p < .0001). Neonates with MVM also had significantly larger intracranial volumes (ICV; 7.1%, p = .0063) and cortical gray matter volumes (10.9%, p = .0004) compared with control subjects. Diffusion tensor imaging tractography revealed a significantly greater MD in the corpus callosum and corticospinal tracts, whereas FA was significantly smaller in several white matter tract regions.
Prenatal enlargement of the lateral ventricle is associated with enlargement of the lateral ventricles after birth, as well as greater gray matter volumes and delayed or abnormal maturation of white matter. It is suggested that prenatal ventricle volume is an early structural marker of altered development of the cerebral cortex and may be a marker of risk for neuropsychiatric disorders associated with ventricle enlargement.

Download full-text


Available from: Nancy C Chescheir,
  • Source
    • "Lateral ventricle dilation is a predictor of poor neurodevelopmental outcome (Laskin et al. 2005; Tatli et al. 2012). It has been associated with multiple developmental CNS disorders, including autism and schizophrenia (Barttfeld et al. 2011; Bigler 1987; Fannon et al. 2000; Movsas et al. 2013; Sanfilipo et al. 2000; Schulz et al. 1983; Wright et al. 2000), idiopathic mental retardation, periventricular leukomalacia (Volpe 2001, 2003, 2005), fragile X syndrome, and attention deficit disorder and, in the absence of other CNS abnormalities, to developmental delays (Gilmore et al. 2001, 2008). Its consequences can include progressive hydrocephalus, gray matter migration abnormalities, loss of parenchymal brain tissue, agenesis of the corpus callosum, and delayed or abnormal maturation of white matter, that is, reduced MBP (myelin basic protein) expression, diminished total axon volume, trisomies, and microcephaly (Bigler 1987; Gilmore et al. 1998, 2001, 2008; Griffiths et al. 2010; Kuban et al. 1999; Kyriakopoulou et al. 2014, Manfredi et al. 2010). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Air pollution has been associated with adverse neurological and behavioral health effects in children and adults. Recent studies link air pollutant exposure to adverse neurodevelopmental outcomes, including increased risk for autism, cognitive decline, ischemic stroke, schizophrenia, and depression. Objectives: We sought to investigate the mechanism(s) by which exposure to ultrafine concentrated ambient particles (CAPs) adversely influences central nervous system (CNS) development. Methods: We exposed C57BL6/J mice to ultrafine (< 100 nm) CAPs using the Harvard University Concentrated Ambient Particle System or to filtered air on postnatal days (PNDs) 4–7 and 10–13, and the animals were euthanized either 24 hr or 40 days after cessation of exposure. Another group of males was exposed at PND270, and lateral ventricle area, glial activation, CNS cytokines, and monoamine and amino acid neurotransmitters were quantified. Results: We observed ventriculomegaly (i.e., lateral ventricle dilation) preferentially in male mice exposed to CAPs, and it persisted through young adulthood. In addition, CAPs-exposed males generally showed decreases in developmentally important CNS cytokines, whereas in CAPs-exposed females, we observed a neuroinflammatory response as indicated by increases in CNS cytokines. We also saw changes in CNS neurotransmitters and glial activation across multiple brain regions in a sex-dependent manner and increased hippocampal glutamate in CAPs-exposed males. Conclusions: We observed brain region– and sex-dependent alterations in cytokines and neurotransmitters in both male and female CAPs-exposed mice. Lateral ventricle dilation (i.e., ventriculomegaly) was observed only in CAPs-exposed male mice. Ventriculomegaly is a neuropathology that has been associated with poor neurodevelopmental outcome, autism, and schizophrenia. Our findings suggest alteration of developmentally important neurochemicals and lateral ventricle dilation may be mechanistically related to observations linking ambient air pollutant exposure and adverse neurological/neurodevelopmental outcomes in humans. Citation: Allen JL, Liu X, Pelkowski S, Palmer B, Conrad K, Oberdörster G, Weston D, Mayer-Pröschel M, Cory-Slechta DA. 2014. Early postnatal exposure to ultrafine particulate matter air pollution: persistent ventriculomegaly, neurochemical disruption, and glial activation preferentially in male mice. Environ Health Perspect 122:939–945;
    Environmental Health Perspectives 06/2014; 122(9). DOI:10.1289/ehp.1307984 · 7.98 Impact Factor
  • Source
    • "In the current literature, three major approaches to the group analysis of diffusion imaging data are region-of-interest (ROI) analysis, voxel based analysis, and fiber tract based analysis (Smith et al., 2006; O&apos;Donnell et al., 2009; Snook et al., 2007). The ROI analysis used in some neuroimaging studies (Bonekam et al., 2008; Gilmore et al., 2008) primarily suffers from the difficulty in identifying meaningful ROIs. Voxel based analysis is used more commonly than ROI analysis in neuroimaging studies (Chen et al., 2009; Focke et al., 2008; Camara et al., 2007; Snook et al., 2005). "

  • Source
    • "Related studies have shown that PVL in children is associated with adverse CC tractography measures in the genu (Fan et al., 2006) and splenium (Davatzikos et al., 2003; Fan et al., 2006; Nagae et al., 2007). Furthermore, higher MD values are evident in the callosal tracts of children with mild ventriculomegaly (Gilmore et al., 2008). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to relate altered corpus callosum (CC) integrity in 106 very preterm (VPT) infants (<30 weeks' gestational age or <1250 g birth weight) at term equivalent to perinatal predictors and neurodevelopmental outcomes at two years. T1 and diffusion magnetic resonance images were obtained. The CC was traced, and divided into six sub-regions for cross-sectional area and shape analyses. Fractional anisotropy, mean, axial and radial diffusivity were sampled within the CC, and probabilistic tractography was performed. Perinatal predictors were explored. The Bayley Scales of Infant Development (BSID-II) was administered at two years. Intraventricular hemorrhage was associated with a smaller genu and altered diffusion values within the anterior and posterior CC of VPT infants. White matter injury was associated with widespread alterations to callosal diffusion values, especially posteriorly, and radial diffusivity was particularly elevated, indicating altered myelination. Reduced CC tract volume related to lower gestational age, particularly posteriorly. Reduced posterior callosal skew was associated with postnatal corticosteroid exposure. This more circular CC was associated with delayed cognitive development. Higher diffusivity, particularly in splenium tracts, was associated with impaired motor development. This study elucidates perinatal predictors and adverse neurodevelopmental outcomes associated with altered callosal integrity in VPT infants.
    NeuroImage 12/2011; 59(4):3571-81. DOI:10.1016/j.neuroimage.2011.11.057 · 6.36 Impact Factor
Show more