1. Kinney DK, Barch DH, Chayka B, Napoleon S, Munir KM. {{Environmental risk factors for autism: Do they help cause de novo genetic mutations that contribute to the disorder?}} {Med Hypotheses};2009 (Aug 20)
Recent research has discovered that a number of genetic risk factors for autism are de novo mutations. Advanced parental age at the time of conception is associated with increased risk for both autism and de novo mutations. We investigated the hypothesis that other environmental factors associated with increased risk for autism might also be mutagenic and contribute to autism by causing de novo mutations. A survey of the research literature identified 9 environmental factors for which increased pre-conceptual exposure appears to be associated with increased risk for autism. Five of these factors – mercury, cadmium, nickel, trichloroethylene, and vinyl chloride – are established mutagens. Another four – including residence in regions that are urbanized, located at higher latitudes, or experience high levels of precipitation – are associated with decreased sun exposure and increased risk for vitamin D deficiency. Vitamin D plays important roles in repairing DNA damage and protecting against oxidative stress – a key cause of DNA damage. Factors associated with vitamin D deficiency will thus contribute to higher mutation rates and impaired repair of DNA. We note how de novo mutations may also help explain why the concordance rate for autism is so markedly higher in monozygotic than dizygotic twins. De novo mutations may also explain in part why the prevalence of autism is so remarkably high, given the evidence for a strong role of genetic factors and the low fertility of individuals with autism – and resultant selection pressure against autism susceptibility genes. These several lines of evidence provide support for the hypothesis, and warrant new research approaches – which we suggest – to address limitations in existing studies. The hypothesis has implications for understanding possible etiologic roles of de novo mutations in autism, and it suggests possible approaches to primary prevention of the disorder, such as addressing widespread vitamin D deficiency and exposure to known mutagens.
2. Sahyoun CP, Belliveau JW, Soulieres I, Schwartz S, Mody M. {{Neuroimaging of the Functional and Structural Networks Underlying Visuospatial versus Linguistic Reasoning in High-Functioning Autism}}. {Neuropsychologia};2009 (Aug 18)
High-functioning individuals with autism have been found to favor visuospatial processing in the face of typically poor language abilities. We aimed to examine the neurobiological basis of this difference using functional magnetic resonance imaging and diffusion tensor imaging. We compared 12 children with high functioning autism (HFA) to 12 age- and IQ-matched typically developing controls (CTRL) on a pictorial reasoning paradigm under three conditions: V, requiring visuospatial processing, S, requiring language (i.e. semantic) processing, and V+S, a hybrid condition in which language use could facilitate visuospatial transformations. Activated areas in the brain were chosen as endpoints for probabilistic diffusion tractography to examine tract integrity (FA) within the structural network underlying the activation patterns. The two groups showed similar networks, with linguistic processing activating inferior frontal, superior and middle temporal, ventral visual, and temporo-parietal areas, whereas visuospatial processing activated occipital and inferior parietal cortices. However, HFA appeared to activate occipito-parietal and ventral temporal areas, whereas CTRL relied more on frontal and temporal language regions. The increased reliance on visuospatial abilities in HFA was supported by intact connections between the inferior parietal and the ventral temporal ROIs. In contrast, the inferior frontal region showed reduced connectivity to ventral temporal and middle temporal areas in this group, reflecting impaired activation of frontal language areas in autism. The HFA group’s engagement of posterior brain regions along with its weak connections to frontal language areas suggest support for a reliance on visual mediation in autism, even in tasks of higher cognition.
3. Saresella M, Marventano I, Guerini FR, Mancuso R, Ceresa L, Zanzottera M, Rusconi B, Maggioni E, Tinelli C, Clerici M. {{An Autistic Endophenotype Results in Complex Immune Dysfunction in Healthy Siblings of Autistic Children}}. {Biol Psychiatry};2009 (Aug 21)
BACKGROUND: Endophenotypes are simple biological aspects of a disease that can be observed in unaffected relatives at a higher rate than in the general population; an « autism endophenotype » justifies the observation that a mild reduction in ideational fluency and nonverbal generativity might be observed in healthy, unaffected relatives of children with autism. Because it is becoming apparent that autism is associated with given alleles encoding within the human leukocyte antigens region, a region of pivotal importance in immunity, we examined whether the « autism endophenotype » would extend its effects on the immune system. METHODS: Multiple immune parameters were analyzed in autistic children (AC) (n = 20), their siblings (HSAC) (n = 15), and age- and gender-comparable healthy control subjects (HC) (n = 20) without any familiarity for autism. RESULTS: The immune profiles of HSAC were significantly more similar to those of their autistic siblings than to what was observed in HC. Thus, in AC and HSAC compared with HC: 1) proinflammatory and interleukin-10-producing immune cells were augmented (p < .01 in both comparisons); 2) CD8(+) naive (CD45RA(+)/CCR7+) T lymphocytes were increased (p < .0001 and p = .001); and 3) CD8(+) effector memory (CD45RA(-)/CCR7-) (p < .0001 and p = .03) as well as CD4(+) terminally differentiated (CD45RA(-)/CCR7+) (p < .05 in both comparisons) lymphocytes were diminished. Serum autoantibodies (GM1) could be detected in 10% of AC children alone. CONCLUSIONS: Results of this pilot study indicate that a complex immune dysfunction is present both in autistic children and in their non-autistic siblings and show the presence of an « autism endophenotype » that expands its effects on immunologic functions.
4. Tuchman R. {{CSWS-related autistic regression versus autistic regression without CSWS}}. {Epilepsia};2009 (Aug);50 Suppl 7:18-20.
Continuous spike-waves during slow-wave sleep (CSWS) and Landau-Kleffner syndrome (LKS) are two clinical epileptic syndromes that are associated with the electroencephalography (EEG) pattern of electrical status epilepticus during slow wave sleep (ESES). Autistic regression occurs in approximately 30% of children with autism and is associated with an epileptiform EEG in approximately 20%. The behavioral phenotypes of CSWS, LKS, and autistic regression overlap. However, the differences in age of regression, degree and type of regression, and frequency of epilepsy and EEG abnormalities suggest that these are distinct phenotypes. CSWS with autistic regression is rare, as is autistic regression associated with ESES. The pathophysiology and as such the treatment implications for children with CSWS and autistic regression are distinct from those with autistic regression without CSWS.
5. Van Dyke EM, CSAC, The Clinical and Scientific Affairs Council of the AAPA. {{Autistic disorder: early interventions can improve outcomes}}. {Jaapa};2009 (Jul);22(7):18-19.
6. Wang L, Angley MT, Gerber JP, Young RL, Abarno DV, McKinnon RA, Sorich MJ. {{Is urinary indolyl-3-acryloylglycine a biomarker for autism with gastrointestinal symptoms?}} {Biomarkers};2009 (Aug 21)
An autism spectrum disorder (ASD) diagnosis is based on clinical behaviours as there are no validated biological diagnostic tools. Indolyl-3-acryloylglycine (IAG) is a chemical produced by gut microflora and there are conflicting reports as to whether urinary levels are elevated in children with ASD compared with controls. Urinary IAG levels in morning urine samples were statistically significantly higher in children with ASD whose caregivers reported the presence of chronic gastrointestinal (GI) disturbance than children with ASD without chronic GI disturbance. Urinary IAG, however, was not statistically significantly higher in children with ASD, compared with siblings or unrelated controls without ASD.
