1. Koh HC, Milne E, Dobkins K. {{Contrast Sensitivity for Motion Detection and Direction Discrimination in Adolescents with Autism Spectrum Disorders and their Siblings}}. {Neuropsychologia} (Oct 8)
The magnocellular (M) pathway hypothesis proposes that impaired visual motion perception observed in individuals with Autism Spectrum Disorders (ASD) might be mediated by atypical functioning of the subcortical M pathway, as this pathway provides the bulk of visual input to cortical motion detectors. To test this hypothesis, we measured luminance and chromatic contrast sensitivity, thought to tap M and Parvocellular (P) pathway processing respectively. We also tested the hypothesis that motion processing is impaired in ASD using a novel paradigm that measures motion processing while controlling for detectabilty. Specifically, this paradigm compares contrast sensitivity for detection of a moving grating with contrast sensitivity for direction-of-motion discrimination of that same moving grating. Contrast sensitivities from adolescents with ASD were compared to typically-developing adolescents, and also unaffected siblings of individuals with ASD (SIBS). The results revealed significant group differences on P, but not M, pathway processing, with SIBS showing higher chromatic contrast sensitivity than both participants with ASD and TD participants. This atypicality, unique to SIBS, suggests the possible existence of a protective factor in these individuals against developing ASD. The results also revealed impairments in motion perception in both participants with ASD and SIBS, which may be an endophenotype of ASD. This impairment may be driven by impairments in motion detectors and/or by reduced input from neural areas that project to motion detectors, the latter possibility being consistent with the notion of reduced connectivity between neural areas in ASD.
2. Macfabe DF, Cain NE, Boon F, Ossenkopp KP, Cain DP. {{Effects of the enteric bacterial metabolic product propionic acid on object-directed behavior; social behavior; cognition; and neuroinflammation in adolescent rats: Relevance to autism spectrum disorder}}. {Behav Brain Res} (Oct 8)
Recent evidence suggests that a variety of environmental factors, including dietary and gastrointestinal agents, may contribute to autism spectrum disorders (ASD). Here we administered propionic acid (PPA), a short chain fatty acid that is used as a food preservative and also is a metabolic end-product of enteric bacteria in the gut, to adolescent (41 +/-4 d) male rats in a study of restricted/repetitive behavior, social behavior, and cognition. The goal was to further evaluate the effects of PPA in young rodents. PPA (4mul of 0.26M solution) was administered intracerebroventricularly prior to each behavioral test. Rats treated with PPA displayed restricted behavioral interest to a specific object among a group of objects, impaired social behavior, and impaired reversal in a T-maze task compared to controls given phosphate buffered saline. Immunohistochemical analysis of brain tissue from PPA rats revealed reactive astrogliosis and activated microglia, indicating an innate neuroinflammatory response. These findings are consistent with our earlier findings of ASD-relevant behavioral and brain events in adult rats given PPA, and support further study of effects of PPA in young rodents by establishing similar effects in adolescent animals.
3. Maimburg RD, Bech BH, Vaeth M, Moller-Madsen B, Olsen J. {{Neonatal Jaundice, Autism, and Other Disorders of Psychological Development}}. {Pediatrics} (Oct 11)
Objectives: The goals were to study the association between neonatal jaundice and disorders of psychological development in a national, population-based cohort and to study whether gestational age, parity, and season of birth influenced that association. Methods: A population-based, follow-up study of all children born alive in Denmark between 1994 and 2004 (N = 733 826) was performed, with data collected from 4 national registers. Survival analysis was used to calculate hazard ratios (HRs). Results: Exposure to jaundice in neonates was associated with increased risk of disorders of psychological development for children born at term. The excess risk of developing a disorder in the spectrum of psychological development disorders after exposure to jaundice as a neonate was between 56% (HR: 1.56 [95% confidence interval [CI]: 1.05-2.30]) and 88% (HR: 1.88 [95% CI: 1.17-3.02]). The excess risk of infantile autism was 67% (HR: 1.67 [95% CI: 1.03-2.71]). This risk for infantile autism was higher if the child was conceived by a parous woman (HR: 2.71 [95% CI: 1.57-4.66]) or was born between October and March (HR: 2.21 [95% CI: 1.24-3.94]). The risk for infantile autism disappeared if the child was conceived by a primiparous woman (HR: 0.58 [95% CI: 0.18-1.83]) or was born between April and September (HR: 1.02 [95% CI: 0.41-2.50]). Similar risk patterns were found for the whole spectrum of autistic disorders. Conclusions: Neonatal jaundice in children born at term is associated with disorders of psychological development. Parity and season of birth seem to play important roles.
4. Nickl-Jockschat T, Michel TM. {{The role of neurotrophic factors in autism}}. {Mol Psychiatry} (Oct 12)
Autism spectrum disorders (ASDs) are pervasive developmental disorders that frequently involve a triad of deficits in social skills, communication and language. For the underlying neurobiology of these symptoms, disturbances in neuronal development and synaptic plasticity have been discussed. The physiological development, regulation and survival of specific neuronal populations shaping neuronal plasticity require the so-called ‘neurotrophic factors’ (NTFs). These regulate cellular proliferation, migration, differentiation and integrity, which are also affected in ASD. Therefore, NTFs have gained increasing attention in ASD research. This review provides an overview and explores the key role of NTFs in the aetiology of ASD. We have also included evidence derived from neurochemical investigations, gene association studies and animal models. By focussing on the role of NTFs in ASD, we intend to further elucidate the puzzling aetiology of these conditions.Molecular Psychiatry advance online publication, 12 October 2010; doi:10.1038/mp.2010.103.
5. Russell G, Steer C, Golding J. {{Social and demographic factors that influence the diagnosis of autistic spectrum disorders}}. {Soc Psychiatry Psychiatr Epidemiol} (Oct 12)
PURPOSE: Recent studies in epidemiology have highlighted the existence of children with autistic difficulties who remain undiagnosed. Other studies have identified ‘access barriers’ to clinics which include factors mediated by parents as well as health and education services. The purpose of this study was to examine whether social and demographic factors play a role in receiving a diagnosis of autistic spectrum disorder (ASD) independently of symptom severity. METHODS: Retrospective secondary analysis of a longitudinal UK cohort study, namely, the Avon Longitudinal Study of Parents and Children (ALSPAC). RESULTS: With the severity of autistic traits held constant, boys were more likely to receive an ASD diagnosis than girls. Younger mothers and mothers of first-born children were significantly less likely to have children diagnosed with ASD. Maternal depression before and around the time of their children’s autistic difficulties was associated with lack of diagnosis. CONCLUSIONS: The study provides evidence that social as well as biological factors can influence whether children are brought to the clinic.
6. Santos M, Summavielle T, Teixeira-Castro A, Silva-Fernandes A, Duarte-Silva S, Marques F, Martins L, Dierssen M, Oliveira P, Sousa N, Maciel P. {{Monoamine deficits in the brain of methyl-CpG binding protein 2 null mice suggest the involvement of the cerebral cortex in early stages of Rett syndrome}}. {Neuroscience} (Oct 13);170(2):453-467.
Rett syndrome is a neurodevelopmental disorder caused by mutations in the methyl-CpG binding protein 2 gene (MECP2). Several neural systems are affected in Rett, resulting in an autonomic dysfunction, a movement disorder with characteristic loss of locomotor abilities and profound cognitive impairments. A deregulation of monoamines has been detected in the brain and cerebrospinal fluid of both Rett patients and a Rett syndrome murine model, the Mecp2 knock-out mouse. Our goal was to characterize the onset and progression of motor dysfunction in Mecp2(tm1.1Bird) knock-out mice and the possible neurochemical alterations in different brain regions potentially playing a role in Rett-like pathophysiology, at two different time-points, at weaning (3 weeks old) and in young adults when overt symptoms are observed (8 weeks old). Our results revealed significant age- and region-dependent impairments in these modulatory neurotransmitter systems that correspond well with the motor phenotype observed in these mice. At 3 weeks of age, male Mecp2 knock-out mice exhibited ataxia and delayed motor initiation. At this stage, noradrenergic and serotonergic transmission was mainly altered in the prefrontal and motor cortices, whereas during disease progression the neurochemical changes were also observed in hippocampus and cerebellum. Our data suggest that the deregulation of norepinephrine and serotonin systems in brain regions that participate in motor control are involved in the pathophysiology of Rett syndrome motor phenotypes. Moreover, we highlight the contribution of cortical regions along with the brainstem to be in the origin of the pathology and the role of hippocampus and cerebellum in the progression of the disease rather than in its establishment.
