Social timing, clock genes and autism: a new hypothesis

Wimpory, Dawn; Nicholas, Bradley; Nash, Susan M.

doi:10.1046/j.1365-2788.2002.00423.x

Cited by 100 publications

(106 citation statements)

References 48 publications

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“…21 In this candidate gene study, we found significant associations in two of the genes studied: per1 and npas2, with two SNPs in each gene reaching conventional levels of statistical significance. In addition, a high proportion of all possible haplotypes in npas2 was also significant.…”

Section: Discussionmentioning

confidence: 59%

“…6 The role of per1 in modulating high-frequency oscillators concerned with communicative timing, [69][70][71] together with our findings of association of per1 with autistic disorder, strengthens the notion that temporal deficits are quintessential to autistic disorder. [21][22][23][24][25][26]28,29,39 Purkinje neurons are important for learning appropriate timing 120,121 and their abnormally low number in the cerebella of autistic subjects 115,122 is considered a keystone biological observation implicating cerebellar dysfunction. 123,124 In this context, reports of a per1 interacting protein (PIPS) in rat that co-translocates with per1 into the nucleus 125 and which is further shown to be required for neuronal growth factor-mediated neuronal survival in P12 cells, 126 tentatively suggests a role for per1 in the lack of Purkinje neurons of the cerebellum in autism.…”

Section: Discussionmentioning

confidence: 99%

“…Newson 22 ), with hypotheses encompassing circadian, communicative and/or neurological aspects of timing. 21,[23][24][25][26][27][28][29] For example, Boucher 25 suggests a core timing deficit presenting different manifestations by its effect on the elements of an integrated system of neural and physiological oscillators. Wimpory et al 21 hypothesize a causative, concurrent and developmental role 30 for timing deficit in autistic disorder and that this deficit is derived from pathological variations in the structure/ function of clock/clock-related genes.…”

Section: Timing Difficulties and Autismmentioning

confidence: 99%

“…21,[23][24][25][26][27][28][29] For example, Boucher 25 suggests a core timing deficit presenting different manifestations by its effect on the elements of an integrated system of neural and physiological oscillators. Wimpory et al 21 hypothesize a causative, concurrent and developmental role 30 for timing deficit in autistic disorder and that this deficit is derived from pathological variations in the structure/ function of clock/clock-related genes. Drawing on the above hypotheses, we conceive that timing deficit may manifest in autism as both temporally measured anomalies and apparently disparate symptoms (such as anomalous performance in tasks involving perceptual and cognitive coherence (see review, Happe and Frith 31 ), relational memory (episodic [32][33][34][35] ) and diachronic thinking 36 ); each with some temporal and/or clock gene dependency.…”

Section: Timing Difficulties and Autismmentioning

confidence: 99%

“…[17][18][19][20] The scope of candidate gene studies in autism is generally limited by the lack of credible supporting hypotheses. Our candidate gene study was prompted by Wimpory et al's 21 hypothesis that autism reflects a disturbance of clock gene function, from a molecular level to the manifestation of autistic disorder as a psychological phenomenon.…”

Section: Introductionmentioning

confidence: 99%

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Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis

et al. 2007

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4Specialist Children's Services, North West Wales NHS Trust, Bangor, UK Clock gene anomalies have been suggested as causative factors in autism. We screened eleven clock/clock-related genes in a predominantly high-functioning Autism Genetic Resource Exchange sample of strictly diagnosed autistic disorder progeny and their parents (110 trios) for association of clock gene variants with autistic disorder. We found significant association (P < 0.05) for two single-nucleotide polymorphisms in per1 and two in npas2. Analysis of all possible combinations of two-marker haplotypes for each gene showed that in npas2 40 out of the 136 possible two-marker combinations were significant at the P < 0.05 level, with the best result between markers rs1811399 and rs2117714, P = 0.001. Haplotype analysis within per1 gave a single significant result: a global P = 0.027 for the markers rs2253820-rs885747. No two-marker haplotype was significant in any of the other genes, despite the large number of tests performed. Our findings support the hypothesis that these epistatic clock genes may be involved in the etiology of autistic disorder. Problems in sleep, memory and timing are all characteristics of autistic disorder and aspects of sleep, memory and timing are each clock-gene-regulated in other species. We identify how our findings may be relevant to theories of autism that focus on the amygdala, cerebellum, memory and temporal deficits. We outline possible implications of these findings for developmental models of autism involving temporal synchrony/social timing.

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Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Timing Difficulties and Autismmentioning

confidence: 99%

Section: Timing Difficulties and Autismmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis

et al. 2007

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Role of microRNAs in Autism Spectrum Disorder

Sarachana

2013

microRNAs in Toxicology and Medicine

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Time Reproduction Performance Is Associated With Age and Working Memory in High‐Functioning Youth With Autism Spectrum Disorder

et al. 2014

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Lay Abstract Temporal processing refers to our ability to “sense” or register the passage of time and to use that information to guide behavior. There is evidence that children with autism spectrum disorders (ASD) differ from children without ASD in their ability to process temporal information. Prior research has shown that age and working memory (the ability to hold and manipulate information in short-term memory storage) impact performance on temporal processing tasks in typically developing children, but it is not known whether there are similar associations in youth with ASD. It is also known that children with high levels of inattention and hyperactivity/impulsivity, who do not have ASD, tend to perform more poorly on measures of temporal processing. Our study examined the effects of working memory, age, and inattention/hyperactivity on the accuracy and consistency of temporal processing in 27 high-functioning youth with ASD and 25 youth without ASD. Our results show that youth with ASD are less accurate and less consistent in their ability to estimate time intervals, relative to typically developing youth. The difference in accuracy between the groups is more pronounced at younger ages, while working memory has a differential effect on consistency. Within the ASD group, inattention/hyperactivity was not associated with either accuracy or consistency. This study shows for the first time that both age and working memory affect how youth with and without ASD perceive and represent the passage of time. Scientific Abstract Impaired temporal processing has historically been viewed as a hallmark feature of attention-deficit/hyperactivity disorder (ADHD). Recent evidence suggests temporal processing deficits may also be characteristic of autism spectrum disorder (ASD). However, little is known about the factors that impact temporal processing in children with ASD. The purpose of this study was to assess the effects of co-morbid attention problems, working memory (WM), age, and their interactions, on time reproduction in youth with and without ASD. Twenty-seven high functioning individuals with ASD and 25 demographically comparable typically developing individuals (ages 9–17; 85% male) were assessed on measures of time reproduction, auditory WM, and inattention/hyperactivity. The time reproduction task required depression of a computer key to mimic interval durations of 4, 8, 12, 16, or 20 seconds. Mixed effects regression analyses were used to model accuracy and variability of time reproduction as functions of diagnostic group, interval duration, age, WM, and inattention/hyperactivity. A significant group by age interaction was detected for accuracy, with the deficit in the ASD group being greater in younger children. There was a significant group by WM interaction for consistency, with the effects of poor WM on performance consistency being more pronounced in youth with ASD. All participants tended to underestimate longer interval durations and to be less consistent for shorter interval durations; these effec...

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Social timing, clock genes and autism: a new hypothesis

Abstract: We suggest that anomalies in clock genes operating as timing genes in high frequency oscillator systems may underlie the timing deficits of autism. We outline how anomalies in methylation-related genes may also be implicated.

Cited by 100 publications

References 48 publications

Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis

Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis

Role of microRNAs in Autism Spectrum Disorder

Time Reproduction Performance Is Associated With Age and Working Memory in High‐Functioning Youth With Autism Spectrum Disorder

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