Prenatal exposure to valproic acid induces a dose dependent impairment in sensorimotor gating in a mouse model of autism

Poster Sessionspublished_or_final_versionThe 27th World Congress of the International College of Neuro-Psychopahrmacology (CINP), Hong Kong, 6–10 June 2010. In International Journal of Neuropsychopharmacology, 2010, v. 13, suppl. S1, p. 68, abstract no. P-02.03

Magnetic resonance spectroscopy reveals N-acetylaspartate reduction in hippocampus and cingulate cortex after fear conditioning

The fear conditioning in rodents provides a valuable translational tool to investigate the neural basis of learning and memory and potentially the neurobiology of post-traumatic stress disorder (PTSD). Neurobiological changes induced by fear conditioning have largely been examined ex vivo while progressive 'real-time' changes in vivo remain under-explored. Single voxel proton magnetic resonance spectroscopy (1H MRS) of the hippocampus, cingulate cortex and thalamus of adult male C57BL/6N mice (N=12) was performed at 1 day before, 1 day and 1 week after, fear conditioning training using a 7T scanner. N-acetylaspartate (NAA), a marker for neuronal integrity and viability, significantly decreased in the hippocampus at 1 day and 1 week post-conditioning. Significant NAA reduction was also observed in the cingulate cortex at 1 day post-conditioning. These findings of hippocampal NAA decrease indicate reduced neuronal dysfunction and/or neuronal integrity, contributing to the trauma-related PTSD-like symptoms. The neurochemical changes characterized by 1H MRS can shed light on the biochemical mechanisms of learning and memory. Moreover, such information can potentially facilitate prompt intervention for patients with psychiatric disorders. © 2012 Elsevier Ireland Ltd.postprin

Intra-orbital distance as a record of social brain dysmorphology in autism

Minor Physical Anomalies (MPAs) arise during the first trimester of prenatal life and occur more frequently in autism and related neurodevelopmental disorders. We measured intra-orbital distances from T1 weighted images of children with autism aged 6 – 16 years and typically developing peers. We report a significant increase in intra-orbital distance in autism. Using voxel-wise linear regression analysis intra-orbital distances were found to positively correlate with the volume of inferio-temporal regions including the amygdala in the autism group only. We suggest that intra-orbital MPA may provide a ‘fossil’ record of much earlier childhood brain expansion in autism.published_or_final_versionThe 19th Annual Meeting of the International Society for Magnetic Resonance in Medicine (ISMRM), Montreal, Canada, 7-13 May 2011. In Proceedings of the 19th ISMRM, 2011, p. 252

White matter volume and anisotropy in very low birth weight preterm born children: association with cognitive outcome

INTRODUCTION: Low birth weight premature infants are at risk of brain injury, especially to the white matter. These complications result from either the inability to repair the lesions acquired around birth, or disruption of the normal maturation process. It has been shown in normal and disease populations that white matter parameters are associated with cognitive function (1-3). We hypothesize that mean white matter volume and anisotropy are reduced in children who were born very low birth weight (2500grams) and that these parameters of white matter damage correlate with cognitive outcome …published_or_final_versio

MRI brain scan study of minor physical anomalies to aid the early diagnosis of autism

Poster Sessionspublished_or_final_versionThe 27th International College of Neuropsychopharmacology Congress (CINP 2010), Hong Kong, China, 6-10 June 2010. In International Journal of Neuropsychopharmacology, 2010, v. 13, suppl. S1, p. 182, abstract no. P-14.03

The Nucleosome Assembly Protein TSPYL2 Regulates the Expression of NMDA Receptor Subunits GluN2A and GluN2B

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MRI Study of Minor Physical Anomaly in Childhood Autism Implicates Aberrant Neurodevelopment in Infancy

Background: MPAs (minor physical anomalies) frequently occur in neurodevelopmental disorders because both face and brain are derived from neuroectoderm in the first trimester. Conventionally, MPAs are measured by evaluation of external appearance. Using MRI can help overcome inherent observer bias, facilitate multi-centre data acquisition, and explore how MPAs relate to brain dysmorphology in the same individual. Optical MPAs exhibit a tightly synchronized trajectory through fetal, postnatal and adult life. As head size enlarges with age, inter-orbital distance increases, and is mostly completed before age 3 years. We hypothesized that optical MPAs might afford a retrospective 'window' to early neurodevelopment; specifically, inter-orbital distance increase may represent a biomarker for early brain dysmaturation in autism. Methods: We recruited 91 children aged 7-16; 36 with an autism spectrum disorder and 55 age- and gender-matched typically developing controls. All children had normal IQ. Inter-orbital distance was measured on T1-weighted MRI scans. This value was entered into a voxel-by-voxel linear regression analysis with grey matter segmented from a bimodal MRI data-set. Age and total brain tissue volume were entered as covariates. Results: Intra-class coefficient for measurement of the inter-orbital distance was 0.95. Inter-orbital distance was significantly increased in the autism group (p = 0.03, 2-tailed). The autism group showed a significant relationship between inter-orbital distance grey matter volume of bilateral amygdalae extending to the unci and inferior temporal poles. Conclusions: Greater inter-orbital distance in the autism group compared with healthy controls is consistent with infant head size expansion in autism. Inter-orbital distance positively correlated with volume of medial temporal lobe structures, suggesting a link to "social brain" dysmorphology in the autism group. We suggest these data support the role of optical MPAs as a "fossil record" of early aberrant neurodevelopment, and potential biomarker for brain dysmaturation in autism. © 2011 Cheung et al.published_or_final_versio

Volume increases in putamen associated with positive symptom reduction in previously drug-naive schizophrenia after 6 weeks antipsychotic treatment

Background Brain structure appears to alter after antipsychotic administration, but it is unknown whether these alterations are associated with improvement of psychopathology in patients with schizophrenia. In this study, the authors explore this relationship.Method Altogether, 66 first-episode, drug-naive patients with schizophrenia and 23 well-matched healthy controls underwent brain magnetic resonance imaging scans at baseline. All 23 healthy controls and 42 of the patients were rescanned after 6 weeks follow-up. The patients received regular antipsychotic treatment during the 6-week period and their psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and 6 weeks. The difference in PANSS scores between baseline and 6 weeks was expressed as a ratio of the scores at baseline a- a PANSS reduction ratio. A modified tensor-based morphometry procedure was applied to analyse longitudinal images. Correlations between regional volume changes, PANSS reduction ratio and antipsychotic drug dosages were explored.Results Compared with healthy controls, there was a significant increase in grey-matter volume of the right putamen in patients after 6 weeks treatment. This volume change was positively correlated with a positive PANSS reduction score but not related to drug dosages.Conclusions Putaminal volume increased after 6 weeks antipsychotic treatment in first-episode schizophrenia. The increased volume was closely correlated with improved psychopathology, suggesting the putamen might be a biomarker to predict the treatment response in schizophrenia. © 2011 Cambridge University Press.published_or_final_versio

ANS: Aberrant Neurodevelopment of the Social Cognition Network in Adolescents with Autism Spectrum Disorders

Background: Autism spectrum disorders (ASD) are characterized by aberrant neurodevelopment. Although the ASD brain undergoes precocious growth followed by decelerated maturation during early postnatal period of childhood, the neuroimaging approach has not been empirically applied to investigate how the ASD brain develops during adolescence. Methodology/Principal Findings: We enrolled 25 male adolescents with high functioning ASD and 25 typically developing controls for voxel-based morphometric analysis of structural magnetic resonance image. Results indicate that there is an imbalance of regional gray matter volumes and concentrations along with no global brain enlargement in adolescents with high functioning ASD relative to controls. Notably, the right inferior parietal lobule, a role in social cognition, have a significant interaction of age by groups as indicated by absence of an age-related gain of regional gray matter volume and concentration for neurodevelopmental maturation during adolescence. Conclusions/Significance: The findings indicate the neural correlates of social cognition exhibits aberrant neurodevelopment during adolescence in ASD, which may cast some light on the brain growth dysregulation hypothesis. The period of abnormal brain growth during adolescence may be characteristic of ASD. Age effects must be taken into account while measures of structural neuroimaging have been clinically put forward as potential phenotypes for ASD