Social attention: a possible early indicator of efficacy in autism clinical trials

For decades, researchers have sought to clarify the nature of the social communication impairments in autism, highlighting impaired or atypical 'social attention' as a key measurable construct that helps to define the core impairment of social communication. In this paper, we provide an overview of research on social attention impairments in autism and their relation to deficiencies in neural circuitry related to social reward. We offer a framework for considering social attention as a potential moderator or mediator of response to early behavioral intervention, and as an early indicator of efficacy of behavioral and/or pharmacological treatments aimed at addressing the social impairments in autism

Histopathologic characterization of the BTBR mouse model of autistic-like behavior reveals selective changes in neurodevelopmental proteins and adult hippocampal neurogenesis

<p>Abstract</p> <p>Background</p> <p>The inbred mouse strain BTBR T+ tf/J (BTBR) exhibits behavioral deficits that mimic the core deficits of autism. Neuroanatomically, the BTBR strain is also characterized by a complete absence of the corpus callosum. The goal of this study was to identify novel molecular and cellular changes in the BTBR mouse, focusing on neuronal, synaptic, glial and plasticity markers in the limbic system as a model for identifying putative molecular and cellular substrates associated with autistic behaviors.</p> <p>Methods</p> <p>Forebrains of 8 to 10-week-old male BTBR and age-matched C57Bl/6J control mice were evaluated by immunohistochemistry using free-floating and paraffin embedded sections. Twenty antibodies directed against antigens specific to neurons, synapses and glia were used. Nissl, Timm and acetylcholinesterase (AchE) stains were performed to assess cytoarchitecture, mossy fibers and cholinergic fiber density, respectively. In the hippocampus, quantitative stereological estimates for the mitotic marker bromodeoxyuridine (BrdU) were performed to determine hippocampal progenitor proliferation, survival and differentiation, and brain-derived neurotrophic factor (BDNF) mRNA was quantified by <it>in situ </it>hybridization. Quantitative image analysis was performed for NG2, doublecortin (DCX), NeuroD, GAD67 and Poly-Sialic Acid Neural Cell Adhesion Molecule (PSA-NCAM).</p> <p>Results</p> <p>In midline structures including the region of the absent corpus callosum of BTBR mice, the myelin markers 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase) and myelin basic protein (MBP) were reduced, and the oligodendrocyte precursor NG2 was increased. MBP and CNPase were expressed in small ectopic white matter bundles within the cingulate cortex. Microglia and astrocytes showed no evidence of gliosis, yet orientations of glial fibers were altered in specific white-matter areas. In the hippocampus, evidence of reduced neurogenesis included significant reductions in the number of doublecortin, PSA-NCAM and NeuroD immunoreactive cells in the subgranular zone of the dentate gyrus, and a marked reduction in the number of 5-bromo-2'-deoxyuridine (BrdU) positive progenitors. Furthermore, a significant and profound reduction in BDNF mRNA was seen in the BTBR dentate gyrus. No significant differences were seen in the expression of AchE, mossy fiber synapses or immunoreactivities of microtubule-associated protein MAP2, parvalbumin and glutamate decarboxylase GAD65 or GAD67 isoforms.</p> <p>Conclusions</p> <p>We documented modest and selective alterations in glia, neurons and synapses in BTBR forebrain, along with reduced neurogenesis in the adult hippocampus. Of all markers examined, the most distinctive changes were seen in the neurodevelopmental proteins NG2, PSA-NCAM, NeuroD and DCX. Our results are consistent with aberrant development of the nervous system in BTBR mice, and may reveal novel substrates to link callosal abnormalities and autistic behaviors. The changes that we observed in the BTBR mice suggest potential novel therapeutic strategies for intervention in autism spectrum disorders.</p

Predicting Energy Expenditure from Accelerometry Counts in Adolescent Girls

Calibration of accelerometer counts against oxygen consumption to predict energy expenditure has not been conducted in middle school girls. We concurrently assessed energy expenditure and accelerometer counts during physical activities on adolescent girls to develop an equation to predict energy expenditure

Comparison of Two Approaches to Structured Physical Activity Surveys of Adolescents

Purpose - To compare the test-retest reliability, convergent validity, and overall feasibility/usability of activity-based (AB) and time-based (TB) approaches for obtaining self-reported moderate-to-vigorous physical activity (MVPA) from adolescents. Methods - Adolescents (206 females and 114 males) completed two 3-d physical activity recalls using the AB and TB surveys, which contained identical lists of physical activities. The participants wore an MTI Actigraph® accelerometer for the same period. Results - The TB instrument took about 3 min longer to complete (P=0.022). Overall 2-d test-retest correlations for MVPA were similar for the two surveys (r=0.676 and 0.667), but the girls had higher reliability on the AB survey than the boys (girls: r=0.713; boys: r=0.568). The overall 3-d correlations for MVPA surveys and Actigraph counts varied by gender (girls: AB=0.265 vs TB=0.314; boys: AB=0.340 vs TB=0.277). Correlations for vigorous physical activity and Actigraph counts were higher for the AB than for the TB (r=0.281 vs 0.162). As the interval between completing the surveys and the days being recalled increased, reliability and validity were lower, especially for the AB survey. Conclusion - For both genders, either approach is acceptable for obtaining MVPA information on a single day, but the TB approach appears to be slightly favored over the AB approach for obtaining multiple days of MVPA. A 3-d recall period appears to be too long for accurate recall of MVPA information from either instrument. For both genders, the surveys overestimate activity levels; thus, self-reports should be supplemented with objective data

A Randomized Trial Examining the Effectiveness of Switching From Olanzapine, Quetiapine, or Risperidone to Aripiprazole to Reduce Metabolic Risk: Comparison of Antipsychotics for Metabolic Problems (CAMP)

We conducted a multi-site, randomized controlled trial examining the strategy of switching from olanzapine, quetiapine, or risperidone to aripiprazole to ameliorate metabolic risk factors for cardiovascular disease

Orthotopic liver transplantation for acute and subacute hepatic failure in adults

The role of liver transplantation in 29 patients with fulminant and subacute hepatic failure due to a variety of different causes was examined by comparing the outcome and a variety of “hospitalization” variables. Transplanted patients (n = 13) were more likely to survive (p < 0.05), were younger (p < 0.05) and spent more time in the hospital (p < 0.025) than did those who were not transplanted (n = 16). Despite spending a much longer time in the hospital, transplanted patients spent less time in the intensive care unit (p < 0.05) in coma (p < 0.01) and on a respirator (p < 0.01) than did those not transplanted. Most importantly, the survival rate for transplanted patients was significantly improved (p < 0.05) as compared to those not transplanted. We conclude that liver transplantation can be applied successfully to the difficult clinical problem of fulminant and subacute hepatic failure. Copyright © 1987 American Association for the Study of Liver Disease

Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort

Antibodies against pathogens provide information on exposure to infectious agents and are meaningful measures of past and present infection. Antibodies were measured in the plasma of children that are the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Plasma was collected during clinics at age 5, 7, 11 and 15 years. The antigens examined include: fungal (Saccharomyces cerevisiae); protozoan (Toxoplasma gondii and surface antigen 1 of T. gondii); herpes viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1); common colds (influenza virus subtypes H1N1 and H3N2); other antigens (measles); animal (feline herpes virus, Theiler’s virus); bacteria (Helicobacter pylori); dietary antigens (bovine casein alpha protein, bovine casein beta protein). Alongside the depth of data available within the ALSPAC cohort, this longitudinal resource will enable the investigation of the association between infections and a wide variety of outcomes.</ns4:p

Longitudinal serological measures of common infection in the Avon Longitudinal Study of Parents and Children cohort [version 2; referees: 2 approved]

Antibodies against pathogens provide information on exposure to infectious agents and are meaningful measures of past and present infection. Antibodies were measured in the plasma of children that are the offspring in a population-based birth cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Plasma was collected during clinics at age 5, 7, 11 and 15 years. The antigens examined include: fungal (Saccharomyces cerevisiae); protozoan (Toxoplasma gondii and surface antigen 1 of T. gondii); herpes viruses (cytomegalovirus, Epstein-Barr virus, herpes simplex virus type 1); common colds (influenza virus subtypes H1N1 and H3N2); other antigens (measles); animal (feline herpes virus, Theiler’s virus); bacteria (Helicobacter pylori); dietary antigens (bovine casein alpha protein, bovine casein beta protein). Alongside the depth of data available within the ALSPAC cohort, this longitudinal resource will enable the investigation of the association between infections and a wide variety of outcomes

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition