Genes Controlling Affiliative Behavior as Candidate Genes for Autism

Yrigollen, Carolyn M.; Han, Summer S.; Kochetkova, Anna; Babitz, Tammy; Chang, Joseph T.; Volkmar, Fred R.; Leckman, James F.; Grigorenko, Elena L.

doi:10.1016/j.biopsych.2007.11.015

Cited by 162 publications

(136 citation statements)

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“…These were reported to be associated with ASD in the previous studies. [20][21][22][23] Thus, a total of 12 SNPs were selected. All SNPs were genotyped by using TaqMan genotyping platform.…”

Section: Genotyping and Selection Of The Snpsmentioning

confidence: 99%

“…Lerer et al 22 found an association of a haplotype comprising rs22254298 and four other SNPs (rs237897-rs13316193-rs237889-rs2254298-rs2268494) with ASD, but as a single SNP, rs2254298 was not associated with ASD (Lerer et al 22 ). Yrigollen et al 23 found that rs2268490, which was in the same haploblock of rs2254298, was associated with ASD.…”

Section: Introductionmentioning

confidence: 99%

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Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population

et al. 2010

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The oxytocin receptor (OXTR) gene, which is located on chromosome 3p25.3, has been implicated as a candidate gene for susceptibility of autism spectrum disorder (ASD). Positive associations between OXTR and ASD have been reported in earlier studies. However, the results were inconsistent and demand further studies. In this study, we investigated the associations between OXTR and ASD in a Japanese population by analyzing 11 single-nucleotide polymorphisms (SNPs) using both familybased association test (FBAT) and population-based case-control test. No significant signal was detected in the FBAT test. However, significant differences were observed in allelic frequencies of four SNPs, including rs2254298 between patients and controls. The risk allele of rs2254298 was 'A', which was consistent with the previous study in Chinese, and not with the observations in Caucasian. The difference in the risk allele of this SNP in previous studies might be attributable to an ethnic difference in the linkage disequilibrium structure between the Asians and Caucasians. In addition, haplotype analysis exhibits a significant association between a five-SNP haplotype and ASD, including rs22542898. In conclusion, our study might support that OXTR has a significant role in conferring the risk of ASD in the Japanese population.

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Section: Genotyping and Selection Of The Snpsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population

et al. 2010

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“…Firstly, significant association between OXTR SNPs [21][22][23][24][25][26] and risk for autism has been provisionally shown (but also see [27,28]) and, notably, was mediated by socialization skills in our study [23]. Additionally, SNPs associated with ASD are also associated with amygdala volume [29], depression/anxiety [29], negative emotionality [30], attention deficit [31], adult attachment styles [32,33] (but see [34]), affectivity, emotional loneliness and IQ [35], empathy and stress reactivity [36], observed parenting [37], with sexual phenotypes [38] and in our own studies with prosocial behavior [39].…”

Section: Oxytocin and Autism Spectrum Disorders (Asd)mentioning

confidence: 99%

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

et al. 2011

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Edited by Sergio Papa, Gianfranco Gilardi and Wilhelm JustKeywords: Autism spectrum disorder (ASD) All-trans retinoic acid (ATRA) CD38 Oxytocin Polymorphism a b s t r a c t Increasing evidence suggests that the nonapeptide, oxytocin (OT), helps shape social and affiliative behaviors not only in lower mammals but also in humans. Recently, an essential mediator of brain OT release has been discovered, ADP-ribosyl cyclase and/or CD38. We have subsequently shown that polymorphisms across the CD38 gene are associated with autism spectrum disorders (ASD). Notably, CD38 expression in lymphoblastoid cells (LBC) is reduced in cell lines derived from ASD subjects compared to parental cell lines. Intriguingly, a correlation was observed between CD38 expression and measures of social function in ASD. Finally, we have shown that all-trans retinoic acid (ATRA), a known inducer of CD38 transcription, can rescue low CD38 expressing LBC lines derived from ASD subjects and restore normal levels of transcription of this ectoenzyme providing 'proof of principle' in a peripheral model that retinoids are potential therapeutic agents in ASD. Ó 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. OxytocinClassically, the nonapeptide oxytocin (OT) has been viewed as a hypothalamic neuropeptide that is released into the general circulation from the neural lobe of the pituitary, inducing uterine contractions during parturition and milk ejection during lactation. OT is derived from a pre-prohormone precursor that is synthesized in the hypothalamus and stored in vesicles at the posterior pituitary for storage and subsequent release into the bloodstream (see [1] for comprehensive review of the oxytocin receptor system). OT and social behaviorBeyond the long-known peripheral effects of OT, a wealth of animal studies have elaborated the role of OT, or their analogues such as isotocin and vasotocin [2], in molding social behavior from fish to mammals [3]. In the past few years the role of OT has also been examined in our own species, and similar to what has been learned from animal studies, it appears that this nonapeptides also influence social behaviors in humans [4,5]. Indeed, OT has been suggested as the 'great facilitator of life' in a recent review [6].In humans, intranasal administration of OT has been shown to increase trust [7], facilitate mind-reading [8], enhance human memory for social identity [9], increase positive communication between couples [10], increase gaze to the eye region [11] and increase generosity [12]. Intriguingly, OT plasma levels have been linked to individual patterns of maternal-fetal attachment [13] and salivary OT levels were associated with bonding to own parents and inversely related to psychological distress, particularly depressive symptoms [14]. Social anxiety symptom severity, adjusted for age and gender in a healthy group of subjects, was associated with higher plasma oxytocin levels [15]. Imaging studies reinforce the role of OT in influencing human social ...

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“…As regards this latter pathway, decreased circulating oxytocin levels in individuals with ASD has been observed (Modahl et al, 1998), and administration of oxytocin to individuals with ASD has been reported to reduce repetitive behaviors (Hollander et al, 2003), enhance retention of social cognition (Hollander et al, 2007) and improve emotional recognition (Guastella et al, 2010). Furthermore, OXTR, which is located at chromosome 3p25 and encodes a G-protein coupled receptor, has been associated with ASD in numerous studies (Wu et al, 2005;Ylisaukko-oja et al, 2006;Jacob et al, 2007;Lerer et al, 2008;Yrigollen et al, 2008;Gregory et al, 2009;Liu et al, 2010;Wermter et al, 2010).…”

Section: The Oxytocin System In Asd and Its Interactions With Other Pmentioning

confidence: 99%

A Candidate Circuit Approach to Investigating Autism

Page

2011

The Anatomical Record

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A major problem in understanding mechanisms of pathogenesis in autism spectrum disorder (ASD) is deciphering how risk factors act via the brain to influence the behavioral symptoms of this disorder. We may start to bridge this gap in our understanding by systematically examining the structure and function of cell types that make up circuits underlying behavioral endophenotypes in animal models for ASD. A confluence of advances in basic behavioral neurobiology, in ASD mechanisms and animal models, and in genetic tools for imaging and manipulating brain circuits will make this possible. Through a process of elimination of candidates and comparison across models, we may hope to understand how ASD risk factors influence the development and function of neural circuitry at the level of genetically defined cell types. As an example of how this candidate circuit approach may be applied to investigating ASD, here I focus on social behavior as an endophenotype, and I discuss recent findings regarding the development and function of the oxytocin system, which is implicated in both normal social behavior and ASD pathogenesis. I stress the importance of a collaborative, multidisciplinary approach to probing candidate cell types and circuits across mouse models of ASD.

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Genes Controlling Affiliative Behavior as Candidate Genes for Autism

Abstract: Background-Autism Spectrum Disorders (ASD) are neurodevelopmental disorders of complex etiology, with a recognized substantial contribution of heterogeneous genetic factors; one of the core features of ASD is a lack of affiliative behaviors.

Cited by 162 publications

References 57 publications

Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population

Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population

Are retinoids potential therapeutic agents in disorders of social cognition including autism?

A Candidate Circuit Approach to Investigating Autism

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