Journal of Neurodevelopmental Disorders (J NEURODEV DISORD)

Publications in this journal

• Article: Spontaneous and cued gaze-following in autism and Williams syndrome.

  Deborah M Riby, Peter Jb Hancock, Nicola Jones, Mary Hanley
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  ABSTRACT: BACKGROUND: From a young age the typical development of social functioning relies upon the allocation of attention to socially relevant information, which in turn allows experience at processing such information and thus enhances social cognition. As such, research has attempted to identify the developmental processes that are derailed in some neuro-developmental disorders that impact upon social functioning. Williams syndrome (WS) and autism are disorders of development that are characterized by atypical yet divergent social phenotypes and atypicalities of attention to people. METHODS: We used eye tracking to explore how individuals with WS and autism attended to, and subsequently interpreted, an actor's eye gaze cue within a social scene. Images were presented for 3 seconds, initially with an instruction simply to look at the picture. The images were then shown again, with the participant asked to identify the object being looked at. Allocation of eye gaze in each condition was analyzed by analysis of variance and accuracy of identification was compared with t tests. RESULTS: Participants with WS allocated more gaze time to face and eyes than their matched controls, both with and without being asked to identify the item being looked at; while participants with autism spent less time on face and eyes in both conditions. When cued to follow gaze, participants with WS increased gaze to the correct targets; those with autism looked more at the face and eyes but did not increase gaze to the correct targets, while continuing to look much more than their controls at implausible targets. Both groups identified fewer objects than their controls. CONCLUSIONS: The atypicalities found are likely to be entwined with the deficits shown in interpreting social cognitive cues from the images. WS and autism are characterized by atypicalities of social attention that impact upon socio-cognitive expertise, but, importantly, the type of atypicality is syndrome specific.
  Journal of Neurodevelopmental Disorders 05/2013; 5(1):13.
• Article: Repetitive and self-injurious behaviors: associations with caudate volume in autism and fragile X syndrome.

  Jason J Wolff, Heather C Hazlett, Amy A Lightbody, Allan L Reiss, Joseph Piven
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  ABSTRACT: BACKGROUND: Following from previous work suggesting that neurobehavioral features distinguish fragile X and idiopathic variants of autism, we investigated the relationships between four forms of repetitive behavior (stereotypy, self-injury, compulsivity, ritual behavior) and caudate nuclei volume in two groups: boys with fragile X syndrome, a subset of whom met criteria for autism, and a comparison group of boys with idiopathic autism. METHODS: Bilateral caudate nuclei volumes were measured in boys aged 3 to 6 years with fragile X syndrome (n = 41), the subset of boys with fragile X syndrome and autism (n = 16), and boys with idiopathic autism (n = 30). Repetitive behaviors were measured using the Repetitive Behavior Scales-Revised. RESULTS: For boys with idiopathic autism, left caudate volume was modestly associated with self-injury, while both compulsive and ritual behaviors showed significant positive correlations with bilateral caudate nuclei volumes, replicating previous results. For boys with fragile X syndrome, there was no such association between caudate volume and compulsive behaviors. However, we did identify significant positive correlations between self-injury total scores and number of self-injury topographies with bilateral caudate nuclei volumes. CONCLUSIONS: These findings suggest a specific role for the caudate nucleus in the early pathogenesis of self-injurious behavior associated with both idiopathic autism and fragile X syndrome. Results further indicate that the caudate may be differentially associated with compulsive behavior, highlighting the utility of isolating discrete brain-behavior associations within and between subtypes of autism spectrum disorder.
  Journal of Neurodevelopmental Disorders 05/2013; 5(1):12.
• Article: Developmental patterns of DR6 in normal human hippocampus and in Down syndrome.

  Anand Iyer, Jackelien van Scheppingen, Jasper Anink, Ivan Milenkovic, Gabor G Kovács, Eleonora Aronica
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  ABSTRACT: BACKGROUND: Death receptor 6 (DR6) is highly expressed in the human brain: it has been shown to induce axon pruning and neuron death via distinct caspases and to mediate axonal degeneration through binding to N-terminal beta amyloid precursor protein (N-APP). METHODS: We investigated the expression of DR6 during prenatal and postnatal development in human hippocampus and temporal cortex by immunocytochemistry and Western blot analysis (118 normal human brain specimens; 9 to 41 gestational weeks; 1 day to 7 months postnatally; 3 to 91 years). To investigate the role of N-APP/DR6/caspase 6 pathway in the development of hippocampal Alzheimer's disease (AD)-associated pathology, we examined DR6 immunoreactivity (IR) in the developing hippocampus from patients with Down syndrome (DS; 48 brain specimens; 14 to 41 gestational weeks; 7 days to 8 months postnatally; 15 to 64 years) and in adults with DS and AD. RESULTS: DR6 was highly expressed in human adult hippocampus and temporal cortex: we observed consistent similar temporal and spatial expression in both control and DS brain. Western blot analysis of total homogenates of temporal cortex and hippocampus showed developmental regulation of DR6. In the hippocampus, DR6 IR was first apparent in the stratum lacunosum-moleculare at 16 weeks of gestation, followed by stratum oriens, radiatum, pyramidale (CA1 to CA4) and molecular layer of the dentate gyrus between 21 and 23 gestational weeks, reaching a pattern similar to adult hippocampus around birth. Increased DR6 expression in dystrophic neurites was detected focally in a 15-year-old DS patient. Abnormal DR6 expression pattern, with increased expression within dystrophic neurites in and around amyloid plaques was observed in adult DS patients with widespread AD-associated neurodegeneration and was similar to the pattern observed in AD hippocampus. Double-labeling experiments demonstrated the colocalization, in dystrophic neurites, of DR6 with APP. We also observed colocalization with hyper-phosphorylated Tau and with caspase 6 (increased in hippocampus with AD pathology) in plaque-associated dystrophic neurites and within the white matter. CONCLUSIONS: These findings demonstrate a developmental regulation of DR6 in human hippocampus and suggest an abnormal activation of the N-APP/DR6/caspase 6 pathway, which can contribute to initiation or progression of hippocampal AD-associated pathology.
  Journal of Neurodevelopmental Disorders 04/2013; 5(1):10.
• Article: A pilot open-label trial of minocycline in patients with autism and regressive features.

  Carlos A Pardo, Ashura Buckley, Audrey Thurm, Li-Ching Lee, Arun Azhagiri, David M Neville, Susan E Swedo
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  ABSTRACT: BACKGROUND: Minocycline is a tetracycline derivative that readily crosses the blood brain barrier and appears to have beneficial effects on neuroinflammation, microglial activation and neuroprotection in a variety of neurological disorders. Both microglial activation and neuroinflammation have been reported to be associated with autism. The study was designed to evaluate the effects of minocycline treatment on markers of neuroinflammation and autism symptomatology in children with autism and a history of developmental regression. METHODS: Eleven children were enrolled in an open-label trial of six months of minocycline (1.4 mg/kg). Ten children completed the trial. Behavioral measures were collected and cerebrospinal fluid (CSF), serum and plasma were obtained before and at the end of minocycline treatment and were analyzed for markers of neuroinflammation. RESULTS: Clinical improvements were negligible. The laboratory assays demonstrated significant changes in the expression profile of the truncated form of brain derived neurotrophic factor (BDNF) (P = 0.042) and hepatic growth factor (HGF) (P = 0.028) in CSF. In serum, the ratio of the truncated BDNF form and alpha-2 macroglobulin (alpha-2 M), was also significantly lower (P = 0.028) while the mature BDNF/alpha-2 M ratio revealed no difference following treatment. Only the chemokine CXCL8 (IL-8) was significantly different (P = 0.047) in serum while no significant changes were observed in CSF or serum in chemokines such as CCL2 (MCP-1) or cytokines such as TNF-alpha, CD40L, IL-6, IFN-gamma and IL-1beta when pre- and post-treatment levels of these proteins were compared. No significant pre- and post-treatment changes were seen in the profiles of plasma metalloproteinases, putative targets of the effects of minocycline. CONCLUSIONS: Changes in the pre- and post-treatment profiles of BDNF in CSF and blood, HGF in CSF and CXCL8 (IL-8) in serum, suggest that minocycline may have effects in the CNS by modulating the production of neurotrophic growth factors. However, in this small group of children, no clinical improvements were observed during or after the six months of minocycline administration. .Trail registration: NCT00409747.
  Journal of Neurodevelopmental Disorders 04/2013; 5(1):9.
• Article: A quantitative homogeneous assay for fragile X mental retardation 1 protein.

  Gabi Schutzius, Dorothee Bleckmann, Sandra Kapps-Fouthier, Francesco di Giorgio, Bernd Gerhartz, Andreas Weiss
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  ABSTRACT: BACKGROUND: Hypermethylation of the fragile X mental retardation 1 gene FMR1 results in decreased expression of FMR1 protein FMRP, which is the underlying cause of Fragile X syndrome -- an incurable neurological disorder characterized by mental retardation, anxiety, epileptic episodes and autism. Disease-modifying therapies for Fragile X syndrome are thus aimed at treatments that increase the FMRP expression levels in the brain. We describe the development and characterization of two assays for simple and quantitative detection of FMRP protein. METHOD: Antibodies coupled to fluorophores that can be employed for time-resolved Forster's resonance energy transfer were used for the development of homogeneous, one-step immunodetection. Purified recombinant human FMRP and patient cells were used as control samples for assay development. RESULTS: The assays require small sample amounts, display high stability and reproducibility and can be used to quantify endogenous FMRP in human fibroblasts and peripheral blood mononuclear cells. Application of the assays to FXS patient cells showed that the methods can be used both for the characterization of clinical FXS patient samples as well as primary readouts in drug-discovery screens aimed at increasing endogenous FMRP levels in human cells. CONCLUSION: This study provides novel quantitative detection methods for FMRP in FXS patient cells. Importantly, due to the simplicity of the assay protocol, the method is suited to be used in screening applications to identify compounds or genetic interventions that result in increased FMRP levels in human cells.
  Journal of Neurodevelopmental Disorders 04/2013; 5(1):8.
• Article: Social and emotional processing in Prader-Willi syndrome: genetic subtype differences.

  Alexandra P Key, Dorita Jones, Elisabeth M Dykens
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  ABSTRACT: BACKGROUND: People with Prader-Willi syndrome (PWS) demonstrate social dysfunction and increased risk of autism spectrum disorder, especially those with the maternal uniparental disomy (mUPD) versus paternal deletion genetic subtype. This study compared the neural processing of social (faces) and nonsocial stimuli, varying in emotional valence, across genetic subtypes in 24 adolescents and adults with PWS. METHODS: Upright and inverted faces, and nonsocial objects with positive and negative emotional valence were presented to participants with PWS in an oddball paradigm with smiling faces serving as targets. Behavioral and event-related potential (ERP) data were recorded. RESULTS: There were no genetic subtype group differences in accuracy, and all participants performed above chance level. ERP responses revealed genetic subtype differences in face versus object processing. In those with deletions, the face-specific posterior N170 response varied in size for face stimuli versus inverted faces versus nonsocial objects. Persons with mUPD generated N170 of smaller amplitude and showed no stimulus differentiation. Brain responses to emotional content did not vary by subtype. All participants elicited larger posterior and anterior late positive potential responses to positive objects than to negative objects. Emotion-related differences in response to faces were limited to inverted faces only in the form of larger anterior late positive potential amplitudes to negative emotions over the right hemisphere. Detection of the target smiling faces was evident in the increased amplitude of the frontal and central P3 responses but only for inverted smiling faces. CONCLUSION: Persons with the mUPD subtype of PWS may show atypical face versus object processes, yet both subtypes demonstrated potentially altered processing, attention to and/or recognition of faces and their expressions.
  Journal of Neurodevelopmental Disorders 03/2013; 5(1):7.
• Article: Neurodevelopmental alcohol exposure elicits long-term changes to gene expression that alter distinct molecular pathways dependent on timing of exposure.

  Morgan L Kleiber, Katarzyna Mantha, Randa L Stringer, Shiva M Singh
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  ABSTRACT: BACKGROUND: Maternal alcohol consumption is known to adversely affect fetal neurodevelopment. While it is known that alcohol dose and timing play a role in the cognitive and behavioral changes associated with prenatal alcohol exposure, it is unclear what developmental processes are disrupted that may lead to these phenotypes. METHODS: Mice (n=6 per treatment per developmental time) were exposed to two acute doses of alcohol (5 g/kg) at neurodevelopmental times representing the human first, second, or third trimester equivalent. Mice were reared to adulthood and changes to their adult brain transcriptome were assessed using expression arrays. These were then categorized based on Gene Ontology annotations, canonical pathway associations, and relationships to interacting molecules. RESULTS: The results suggest that ethanol disrupts biological processes that are actively occurring at the time of exposure. These include cell proliferation during trimester one, cell migration and differentiation during trimester two, and cellular communication and neurotransmission during trimester three. Further, although ethanol altered a distinct set of genes depending on developmental timing, many of these show interrelatedness and can be associated with one another via 'hub' molecules and pathways such as those related to huntingtin and brain-derived neurotrophic factor. CONCLUSIONS: These changes to brain gene expression represent a 'molecular footprint' of neurodevelopmental alcohol exposure that is long-lasting and correlates with active processes disrupted at the time of exposure. This study provides further support that there is no neurodevelopmental time when alcohol cannot adversely affect the developing brain.
  Journal of Neurodevelopmental Disorders 03/2013; 5(1):6.
• Article: Using infrared eye-tracking to explore ordinal numerical processing in toddlers with Fragile X Syndrome.

  Emily R Owen, Heidi A Baumgartner, Susan M Rivera
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  ABSTRACT: BACKGROUND: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and non-idiopathic autism. Individuals with FXS present with a behavioral phenotype of specific and selective deficits in an array of cognitive skills. Disruption of number processing and arithmetic abilities in higher-functioning adults and female adolescents with FXS has been well established. Still, both numerical skills and developmentally antecedent cognitive processes have just begun to be investigated in toddlers with FXS. The goal of the current study was to assess how very young children with FXS respond to ordinal relationships among numerical magnitudes. METHODS: Infrared eye-tracking was used to explore infants' novelty recognition during passive viewing of ordinal numerical sequences; t-tests were used to analyze group differences in looking time. RESULTS: Ordinal recognition of numerical magnitudes is significantly impaired in young toddlers with FXS. CONCLUSIONS: This study is the first to experimentally evaluate early number sense and ordinal recognition in toddlers with FXS, and our findings reveal that ordinal recognition of numerical magnitudes is significantly impaired in young toddlers with FXS, suggesting that later arithmetic impairments associated with FXS may have their origins in a developmental impairment of this more basic aspect of numerical cognition.
  Journal of Neurodevelopmental Disorders 02/2013; 5(1):1.
• Article: Journal of Neurodevelopmental Disorders reviewer acknowledgement 2012.

  Joseph Piven
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  ABSTRACT: CONTRIBUTING REVIEWERS: The editors of Journal of Neurodevelopmental Disorders would like to thank all of our reviewers who have contributed to the journal in volume 4 (2012). High quality and timely reviews are critical to the overall quality of the journal. We are committed to providing a unique and important outlet for scholarship regarding neurodevelopmental disorders and are indebted to the outstanding reviewers who have contributed their time over the last year in helping us to reach this goal.
  Journal of Neurodevelopmental Disorders 01/2013; 5(1):5.
• Article: The regulatory function of social referencing in preschoolers with Down syndrome or Williams syndrome.

  Angela John Thurman, Carolyn B Mervis
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  ABSTRACT: An important developmental task is to learn to recognize another person as a source of information and to utilize this information as a method of learning about the surrounding world. This socially guided form of learning, referred to as social referencing, is critical for the development of children's understanding of other people, themselves and their surrounding world. In the present project, the regulatory function of social referencing was examined in two genetic disorders that are characterized by differing patterns of socio-cognitive development: Down syndrome (DS) and Williams syndrome (WS). Participants were 20 children with DS and 20 children with WS aged 42 to 71 months, matched on chronological age and gender. Each child participated in four studies: one study in which we examined performance in a social referencing paradigm and three studies in which we considered performance on tasks designed to tap each of three component abilities (initiating eye contact, gaze following and emotional responsivity) important for success in social referencing. The majority of children in both groups demonstrated positive behavioral responses regarding the stimulus in the Social Referencing task when the adult communicated a joyful message but did not regulate their own behavior in accordance with the adult's expression of fear. Between-group differences were observed in both conditions, with most differences indicating more advanced socio-communicative competence for children with DS than for children with WS even though the overall intellectual abilities and receptive language abilities of the children with WS were significantly higher than were those of the children with DS. The results of follow-up studies indicated that children with DS were more likely to initiate eye contact (unsolicited) and to follow another person's gaze in triadic situations than were children with WS. Neither group regulated their behavior in response to expressions of fear. These findings provide new insight into the development of the social cognitive phenotypes associated with DS and WS. These social cognitive differences found during the preschool years likely contribute to the differing phenotypes observed later in life between individuals with DS and individuals with WS.
  Journal of Neurodevelopmental Disorders 01/2013; 5(1):2.
• Article: Development of neurodevelopmental disorders: a regulatory mechanism involving bromodomain-containing proteins.

  Junlin Li, Guifang Zhao, Xiaocai Gao
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  ABSTRACT: Neurodevelopmental disorders are classified as diseases that cause abnormal functions of the brain or central nervous system. Children with neurodevelopmental disorders show impaired language and speech abilities, learning and memory damage, and poor motor skills. However, we still know very little about the molecular etiology of these disorders. Recent evidence implicates the bromodomain-containing proteins (BCPs) in the initiation and development of neurodevelopmental disorders. BCPs have a particular domain, the bromodomain (Brd), which was originally identified as specifically binding acetyl-lysine residues at the N-terminus of histone proteins in vitro and in vivo. Other domains of BCPs are responsible for binding partner proteins to form regulatory complexes. Once these complexes are assembled, BCPs alter chromosomal states and regulate gene expression. Some BCP complexes bind nucleosomes, are involved in basal transcription regulation, and influence the transcription of many genes. However, most BCPs are involved in targeting. For example, some BCPs function as a recruitment platform or scaffold through their Brds-binding targeting sites. Others are recruited to form a complex to bind the targeting sites of their partners. The regulation mediated by these proteins is especially critical during normal and abnormal development. Mutant BCPs or dysfunctional BCP-containing complexes are implicated in the initiation and development of neurodevelopmental disorders. However, the pathogenic molecular mechanisms are not fully understood. In this review, we focus on the roles of regulatory BCPs associated with neurodevelopmental disorders, including mental retardation, Fragile X syndrome (FRX), Williams syndrome (WS), Rett syndrome and Rubinstein-Taybi syndrome (RTS). A better understanding of the molecular pathogenesis, based upon the roles of BCPs, will lead to screening of targets for the treatment of neurodevelopmental disorders.
  Journal of Neurodevelopmental Disorders 01/2013; 5(1):4.
• Article: Enhanced prefrontal serotonin 5-HT1A currents in a mouse model of Williams-Beuren syndrome with low innate anxiety

  Éliane Proulx, Edwin J. Young, Lucy R. Osborne, Evelyn K. Lambe
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  ABSTRACT: Williams-Beuren syndrome (WBS) is a neurodevelopmental disorder caused by the hemizygous deletion of 28 genes on chromosome 7, including the general transcription factor GTF2IRD1. Mice either hemizygously (Gtf2ird1 +/− ) or homozygously (Gtf2ird1 −/− ) deleted for this transcription factor exhibit low innate anxiety, low aggression and increased social interaction, a phenotype that shares similarities to the high sociability and disinhibition seen in individuals with WBS. Here, we investigated the inhibitory effects of serotonin (5-HT) on the major output neurons of the prefrontal cortex in Gtf2ird1 −/− mice and their wildtype (WT) siblings. Prefrontal 5-HT receptors are known to modulate anxiety-like behaviors, and the Gtf2ird1 −/− mice have altered 5-HT metabolism in prefrontal cortex. Using whole cell recording from layer V neurons in acute brain slices of prefrontal cortex, we found that 5-HT elicited significantly larger inhibitory, outward currents in Gtf2ird1 −/− mice than in WT controls. In both genotypes, these currents were resistant to action potential blockade with TTX and were suppressed by the selective 5-HT1A receptor antagonist WAY-100635, suggesting that they are mediated directly by 5-HT1A receptors on the recorded neurons. Control experiments suggest a degree of layer and receptor specificity in this enhancement since 5-HT1A receptor-mediated responses in layer II/III pyramidal neurons were unchanged as were responses mediated by two other inhibitory receptors in layer V pyramidal neurons. Furthermore, we demonstrate GTF2IRD1 protein expression by neurons in layer V of the prefrontal cortex. Our finding that 5-HT1A-mediated responses are selectively enhanced in layer V pyramidal neurons of Gtf2ird1 −/− mice gives insight into the cellular mechanisms that underlie reduced innate anxiety and increased sociability in these mice, and may be relevant to the low social anxiety and disinhibition in patients with WBS and their sensitivity to serotonergic medicines. Keywords5-HT1A receptors- Gtf2ird1 transcription factor-Williams syndrome-Prefrontal cortex-Social anxiety-Electrophysiology-Mice-Serotonin-GABA-B-Metabotropic glutamate receptors 2/3 (mGluR2/3)
  Journal of Neurodevelopmental Disorders 04/2012; 2(2):99-108.
• Article: Role for TGF-β superfamily signaling in telencephalic GABAergic neuron development

  Mario Maira, Jason E. Long, Amie Y. Lee, John L. R. Rubenstein, Stefano Stifani
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  ABSTRACT: Signaling mechanisms mediated by the Transforming Growth Factor-β (TGF-β) superfamily regulate a variety of developmental processes. Here we show that components of both bone morphogenetic protein/growth differentiation factor and TGF-β/activin/Nodal branches of TGF-β superfamily signaling are expressed in the developing subpallium. Furthermore, Smad proteins, transcriptional effectors of TGF-β signaling, are co-expressed and physically interact in the basal ganglia with Dlx homeodomain transcription factors, which are critical regulators of the differentiation, migration and survival of telencephalic GABAergic neurons. We also show that Dlx and Smad proteins localize to promoters/enhancers of a number of common telencephalic genes in vivo and that Smad proteins co-activate transcription with Dlx family members, except with certain mutated human DLX proteins identified in autistic individuals. In agreement with these observations, expression of dominant-negative Smads in the developing basal ganglia phenocopies the cell migration defects observed in Dlx1/2-deficient mice. Together, these results suggest that TGF-β superfamily signaling plays a role in telencephalic GABAergic neuron development through functional interactions with Dlx transcription factors. KeywordsBasal ganglia-Dlx-GABA-Interneurons-Smad-TGF-β
  Journal of Neurodevelopmental Disorders 04/2012; 2(1):48-60.
• Article: Cover essay.

  Mark Antliff
  Journal of Neurodevelopmental Disorders 03/2009; 1(1):1.
• Article: Foreword for inaugural issue of Journal of Neurodevelopmental Disorders.

  Thomas R Insel
  Journal of Neurodevelopmental Disorders 03/2009; 1(1):2-3.
• Article: Deficient maternal care resulting from immunological stress during pregnancy is associated with a sex-dependent enhancement of conditioned fear in the offspring.

  Severin Schwendener, Urs Meyer, Joram Feldon
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  ABSTRACT: Activation of maternal stress response systems during pregnancy has been associated with altered postpartum maternal care and subsequent abnormalities in the offspring's brain and behavioral development. It remains unknown, however, whether similar effects may be induced by exposure to immunological stress during pregnancy. The present study was designed to address this issue in a mouse model of prenatal immune activation by the viral mimic polyriboinosinic-polyribocytidilic acid (PolyI:C). Pregnant mice were exposed to PolyI:C-induced immune challenge or sham treatment, and offspring born to PolyI:C- and sham-treated dams were simultaneously cross-fostered to surrogate rearing mothers, which had either experienced inflammatory or vehicle treatment during pregnancy. We evaluated the effects of the maternal immunological manipulation on postpartum maternal behavior, and we assessed the prenatal and postnatal maternal influences on anxiety- and fear-related behavior in the offspring at the peri-adolescent and adult stage of development. We found that PolyI:C treatment during pregnancy led to changes in postpartum maternal behavior in the form of reduced pup licking/grooming and increased nest building activity. Furthermore, the adoption of neonates by surrogate rearing mothers, which had experienced PolyI:C-induced immunological stress during pregnancy, led to enhanced conditioned fear in the peri-adolescent and adult offspring, an effect that was exclusively seen in female but not male subjects. Unconditioned (innate) anxiety-related behavior as assessed in the elevated plus maze and open field explorations tests were not affected by the prenatal and postnatal manipulations. Our results thus highlight that being raised by gestationally immune-challenged surrogate mothers increases the vulnerability for specific forms of fear-related behavioral pathology in later life, and that this association may be mediated by deficits in postpartum maternal care. This may have important implications for the identification and characterization of early-life risk factors involved in the developmental etiology of fear-related neuropsychiatric disorders.
  Journal of Neurodevelopmental Disorders 03/2009; 1(1):15-32.
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  Article: Functional magnetic resonance imaging outcomes from a comprehensive magnetic resonance study of children with fetal alcohol spectrum disorders.

  Susan J Astley, Elizabeth H Aylward, Heather Carmichael Olson, Kimberly Kerns, Allison Brooks, Truman E Coggins, Julian Davies, Susan Dorn, Beth Gendler, Tracy Jirikowic, Paul Kraegel, Kenneth Maravilla, Todd Richards
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  ABSTRACT: A comprehensive neuropsychological/psychiatric, MR imaging, (MRI), MR spectroscopy (MRS), and functional MRI (fMRI) assessment was administered to children with fetal alcohol spectrum disorders (FASD) to determine if global and/or focal abnormalities could be identified, and distinguish diagnostic subclassifications across the spectrum. The four study groups included: 1. FAS/Partial FAS; 2. Static Encephalopathy/Alcohol Exposed (SE/AE); 3. Neurobehavioral Disorder/Alcohol Exposed (ND/AE); and 4. healthy peers with no prenatal alcohol exposure. fMRI outcomes are reported here. The neuropsychological/psychiatric, MRI, and MRS outcomes are reported separately. fMRI was used to assess activation in seven brain regions during performance of N-back working memory tasks. Children across the full spectrum of FASD exhibited significant working memory deficits and altered activation patterns in brain regions that are known to be involved in working memory. These results demonstrate the potential research and diagnostic value of this non-invasive MR tool in the field of FASD.
  Journal of Neurodevelopmental Disorders 03/2009; 1(1):61-80.