Shaping the future for primary care education and training project. Finding the evidence for education & training to deliver integrated health and social care: the primary care workforce perspective

This report is one of a series of outputs from the Shaping the Future in Primary Care Education and Training project (www.pcet.org.uk) funded by the North West Development Agency (NWDA). It is the result of a collaborative initiative between the NWDA, the North West Universities Association and seven Higher Education Institutions in the North West of England. The report presents an evidence base drawn from the analysis of the experiences and aspirations of integrated health and social care, as reported by members of the current primary health and social care workforce working in or with Primary Care Trusts (PCTs) in the North West region

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

Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain

Epigenetic processes such as DNA methylation have been implicated in the pathophysiology of neurodevelopmental disorders including schizophrenia and autism. Epigenetic changes can be induced by environmental exposures such as inflammation. Here we tested the hypothesis that prenatal inflammation, a recognized risk factor for schizophrenia and related neurodevelopmental conditions, alters DNA methylation in key brain regions linked to schizophrenia, namely the dopamine rich striatum and endocrine regulatory centre, the hypothalamus. DNA methylation across highly repetitive elements (long interspersed element 1 (LINE1) and intracisternal A-particles (IAPs)) were used to proxy global DNA methylation. We also investigated the Mecp2 gene because it regulates transcription of LINE1 and has a known association with neurodevelopmental disorders. Brain tissue was harvested from 6 week old offspring of mice exposed to the viral analog PolyI:C or saline on gestation day 9. We used Sequenom EpiTYPER assay to quantitatively analyze differences in DNA methylation at IAPs, LINE1 elements and the promoter region of Mecp2. In the hypothalamus, prenatal exposure to PolyI:C caused significant global DNA hypomethylation (t=2.44, P=0.019, PolyI:C mean 69.67%, saline mean 70.19%), especially in females, and significant hypomethylation of the promoter region of Mecp2, (t=3.32, P=0.002; PolyI:C mean 26.57%, saline mean 34.63%). IAP methylation was unaltered. DNA methylation in the striatum was not significantly altered. This study provides the first experimental evidence that exposure to inflammation during prenatal life is associated with epigenetic changes, including Mecp2 promoter hypomethylation. This suggests that environmental and genetic risk factors associated with neurodevelopmental disorders may act upon similar pathways. This is important because epigenetic changes are potentially modifiable and their investigation may open new avenues for treatment

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

Evaluation of a Screening Instrument for Autism Spectrum Disorders in Prisoners

There have been concerns that individuals with autism spectrum disorders (ASDs) are over-represented but not recognised in prison populations. A screening tool for ASDs in prisons has therefore been developed

Impaired Communication Between the Motor and Somatosensory Homunculus Is Associated With Poor Manual Dexterity in Autism Spectrum Disorder

ABSTRACTBackgroundFine motor skill impairments are common in autism spectrum disorder (ASD), significantly affecting quality of life. Sensory inputs reaching the primary motor cortex (M1) from the somatosensory cortex (S1) are likely involved in fine motor skill and specifically motor learning. However, the role of these connections has not been directly investigated in humans. This study aimed to investigate, for the first time, the role of the S1-M1 connections in healthy subjects in vivo and whether microstructural alterations are associated with motor impairment in ASD.MethodsSixty right-handed neurotypical adult men aged 18 to 45 years, and 60 right-handed age- and sex-matched subjects diagnosed with ASD underwent fine motor skill assessment and scanning with diffusion tensor imaging (DTI). The streamlines of the hand region connecting S1-M1 of the motor-sensory homunculus were virtually dissected using TrackVis, and diffusion properties were extracted. The face/tongue region connections were used as control tracts.ResultsThe ASD group displayed lower motor performances and altered DTI measurements of the hand-region connection. Behavioral performance correlated with hand-region DTI measures in both groups, but not with the face/tongue connections, indicating anatomical specificity. There was a left-hemisphere association of motor ability in the control group and an atypical rightward shift in the ASD group.ConclusionsThese findings suggest that direct interaction between S1 and M1 may contribute to the human ability to precisely interact with and manipulate the environment. Because electrophysiological evidence indicates that these connections may underpin long-term potentiation in M1, our findings may lead to novel therapeutic treatments for motor skill disorders

Age-related grey matter volume correlates of response inhibition and shifting in Attention Deficit Hyperactivity Disorder

Background Children with attention-deficit hyperactivity disorder (ADHD) have difficulties with executive function and impulse control which may improve with age. Aims To map the brain correlates of executive function in ADHD and determine age-related changes in reaction times and brain volumes. Method Attention-deficit hyperactivity disorder and control groups were compared on the change task measures of response inhibition (stop signal reaction time, SSRT) and shifting (change response reaction time, CRRT). voxel-wise magnetic resonance imaging (MRI) correlations of reaction times and grey matter volume were determined, along with bivariate correlations of reaction times, brain volumes and age.Results Individuals in the ADHD group had longer SSRTs and CRRTs. Anterior cingulate, striatal and medial temporal volumes highly correlated with SSRT. Striatal and cerebellar volumes strongly correlated with CRRT. Older children had faster reaction times and larger regional brain volumes. In controls, orbitofrontal, medial temporal and cerebellar volumes correlated with CRRT but not SSRT. Neither reaction times nor regional brain volumes were strongly age- dependent. Conclusions Our evidence supports delayed brain maturation in ADHD and implies that some features of ADHD improve with age.link_to_subscribed_fulltex

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

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