Olfaction in the Autism Spectrum

Galle, Sara A; Courchesne, Valérie; Mottron, Laurent; Frasnelli, Johannes

doi:10.1068/p7337

Cited by 55 publications

(75 citation statements)

References 71 publications

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“…This gene appears to be especially labile in ASD in terms of DNA methylation and expression – mixed leukocytes from the monozygotic twins study shows increased DNA methylation at this locus, whereas there is decreased DNA methylation in the ectodermal cells we studied, and expression of this gene is significantly upregulated in the Brodmann Area (BA) 44/45 and downregulated in the BA9/41 regions of the brain [32]. Whether this olfactory receptor gene is a contributor to the distinctive olfaction in subjects with ASD [47], [48] remains to be determined, although it should also be noted that the Human Brain Transcriptome (HBT) studies categorized this gene, alone among all olfactory receptor genes, into a post-natal synaptic transmission co-expression module [31], indicating unique transcriptional properties for this gene among those encoding olfactory receptors. This gene merits further studies as being unusually prone to dysregulation in ASD.…”

Section: Discussionmentioning

confidence: 87%

Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder

et al. 2014

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DNA mutational events are increasingly being identified in autism spectrum disorder (ASD), but the potential additional role of dysregulation of the epigenome in the pathogenesis of the condition remains unclear. The epigenome is of interest as a possible mediator of environmental effects during development, encoding a cellular memory reflected by altered function of progeny cells. Advanced maternal age (AMA) is associated with an increased risk of having a child with ASD for reasons that are not understood. To explore whether AMA involves covert aneuploidy or epigenetic dysregulation leading to ASD in the offspring, we tested a homogeneous ectodermal cell type from 47 individuals with ASD compared with 48 typically developing (TD) controls born to mothers of ≥35 years, using a quantitative genome-wide DNA methylation assay. We show that DNA methylation patterns are dysregulated in ectodermal cells in these individuals, having accounted for confounding effects due to subject age, sex and ancestral haplotype. We did not find mosaic aneuploidy or copy number variability to occur at differentially-methylated regions in these subjects. Of note, the loci with distinctive DNA methylation were found at genes expressed in the brain and encoding protein products significantly enriched for interactions with those produced by known ASD-causing genes, representing a perturbation by epigenomic dysregulation of the same networks compromised by DNA mutational mechanisms. The results indicate the presence of a mosaic subpopulation of epigenetically-dysregulated, ectodermally-derived cells in subjects with ASD. The epigenetic dysregulation observed in these ASD subjects born to older mothers may be associated with aging parental gametes, environmental influences during embryogenesis or could be the consequence of mutations of the chromatin regulatory genes increasingly implicated in ASD. The results indicate that epigenetic dysregulatory mechanisms may complement and interact with DNA mutations in the pathogenesis of the disorder.

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Section: Discussionmentioning

confidence: 87%

Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder

et al. 2014

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“…These genes were reported to be essential in neuronal activity, normal brain development, memory and cognition [43–45]. Genetic variants in these genes have been linked to neuropsychiatric or neurodegenerative diseases that are often associated with olfactory dysfunction, for example, deletions of PCDH10 with autism-spectrum disorders, TCF4 with schizophrenia, CD2-associated protein with late-onset AD [43,46,45,47]. Of interest, KLF4 has been confirmed to directly interact with TCF4 in vitro [48], suggesting our findings may have some biological connections that yet to be found.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults: Identification of Novel Risk Loci in African-Americans and European-Americans

et al. 2016

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The human sense of smell decreases with age, and a poor sense of smell are among the most important prodromal symptoms of several neurodegenerative diseases. Recent evidence further suggests a racial difference in the sense of smell among U.S. older adults. However, no genome-wide association study (GWAS) on the sense of smell has been conducted in African-Americans (AAs). We performed the first genome-wide meta-analysis of the sense of smell among 1,979 AAs and 6,582 European-Americans (EAs) from three U.S. aging cohorts. In the AA population, we identified nine novel regions (KLF4-ACTL7B, RAPGEF2-FSTL5, TCF4-LOC100505474, PCDH10, KIAA1751, MYO5B, MIR320B1-CD2, NR5A2-LINC00862, SALL1-C16orf97) that were associated with the sense of smell (P < 5 × 10−8). Many of these regions have been previously linked to neuropsychiatric (schizophrenia or epilepsy) or neurodegenerative (Parkinson’s or Alzheimer’s disease) diseases associated with a decreased sense of smell. In the EA population, we identified two novel loci in or near RASGRP1 and ANXA2P3 associated with sense of smell. In conclusion, this study identified several ancestry-specific loci that are associated with the sense of smell in older adults. While these findings need independent confirmation, they may lead to novel insights into the biology of the sense of smell in older adults and its relationships to neuropsychological and neurodegenerative diseases.

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“…Defined as unusual reactions to stimuli, atypical reactivity can be observed as hypersensitivity and/or hyposensitivity, sensory distortions (e.g., inconsistent spatial localization of percepts), and/or sensory blackouts where sound and vision vanish and return. Abnormal reactivity in ASD has been reported for taste [Bennetto, Kuschner, & Hyman, 2007;Tavassoli & Baron-Cohen, 2012], smell [Bennetto et al, 2007;Galle, Courchesne, Mottron, & Frasnelli, 2013], touch [Blakemore et al, 2006;Puts, Wodka, Tommerdahl, Mostofsky, & Edden, 2014], vision [Bryson et al, 1990;Grandin, 2009;Mottron et al, 2007;Simmons et al, 2009;Trachtman, 2008;Wainwright & Bryson, 1996;Wainwright-Sharp & Bryson, 1993], and hearing [Crane et al, 2009;O'Neill & Jones, 1997;Wiggins, Robins, Bakeman, & Adamson, 2009]. General, unspecified sensory hyperactivity and over-selectivity across all sensory modalities has also been acutely described in people with ASD [Tavassoli, Miller, Schoen, Nielsen, & BaronCohen, 2014].…”

Section: Introductionmentioning

confidence: 91%

Atypical sensory reactivity influences auditory attentional control in adults with autism spectrum disorders

Karhson

Golob

2016

Autism Research

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Frequent observations of atypical sensory reactivity in people with autism spectrum disorders (ASD) suggest that the perceptual experience of those on the Spectrum is dissimilar to neurotypicals. Moreover, variable attention abilities in people with ASD, ranging from good control to periods of high distractibility, may be related to atypical sensory reactivity. This study used auditory event-related potential (ERP) measures to evaluate top-down and bottom-up attentional processes as a function of perceptual load, and examined these factors with respect to sensory reactivity. Twenty-five age and IQ-matched participants (ASD: 22.5 year, SD = 4.1 year; Controls: 22.8 year, SD = 5.1 year) completed the Adolescent/Adult Sensory Profile prior to performing a modified 3-stimulus (target, non-target, and distractor) auditory oddball target detection task EEG was recorded during task completion. ERP analysis assessed early sensory processing (P50, ∼50 ms latency; N100, ∼100 ms latency), cognitive control (N200, ∼200 ms latency), and attentional processing (P3a and P3b, ∼300 ms latency). Behavioral data demonstrates participants with ASD and neurotypical performed similarly on auditory target detection, but diverged on sensory profiles. Target ERP measures associated with top-down control (P3b latency) significantly increased under greater load in controls, but not in participants with ASD. Early ERP responses associated with bottom-up attention (P50 amplitude) were positively correlated to increased sensory sensitivity. Findings suggest specific neural mechanisms for increased perceptual capacity and enhanced bottom-up processing of sensory stimuli in people with autism. Results from participants with ASD are consistent with load theory and enhanced perceptual functioning. Autism Res 2016, 9: 1079-1092. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

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Olfaction in the Autism Spectrum

Cited by 55 publications

References 71 publications

Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder

Mosaic Epigenetic Dysregulation of Ectodermal Cells in Autism Spectrum Disorder

Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults: Identification of Novel Risk Loci in African-Americans and European-Americans

Atypical sensory reactivity influences auditory attentional control in adults with autism spectrum disorders

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