Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene,
            <i>RORA</i>
            , whose protein product is reduced in autistic brain

Nguyen, AnhThu; Rauch, Tibor A.; Pfeifer, Gerd P.; Hu, Valerie W.

doi:10.1096/fj.10-154484

Cited by 319 publications

(287 citation statements)

References 67 publications

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“…Most of the studies to date have focused on human lymphocytes gene expression profiling, comparison between illness groups and normal controls, and cross-matching with human postmortem brain gene expression data. A number of studies have specifically examined gene expression patterns in ASD [90][91][92][114][115][116][117][118][119][120][121][122][123]. It should be noted that predating this gush of expression studies in ASD, hyperserotonemia was observed in one third of patients and platelet serotonin was suggested as a marker for this disorder [124][125][126][127].…”

Section: Biomarkers For Autism Spectrum Disordersmentioning

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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Section: Biomarkers For Autism Spectrum Disordersmentioning

confidence: 99%

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

et al. 2011

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“…RORA was first identified as a PTSD risk gene in a cohort of combat veterans [52], and subsequently replicated in a cohort of hurricane survivors experiencing psychological distress [53]. However, RORA may demonstrate the broad-reaching influence of the clock across psychiatric disorders, having also been implicated in anti-depressant response [54], BD [55], dimensional depression [56], autism [57], ADHD and SCZ [58].…”

mentioning

confidence: 99%

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Landgraf

McCarthy

Welsh

2014

Curr Psychiatry Rep

140

100

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Many psychiatric disorders are characterized by circadian rhythm abnormalities including disturbed sleep/wake cycles, changes in locomotor activity, and abnormal endocrine function. Animal models with mutations in circadian "clock genes" commonly show disturbances in reward processing, locomotor activity and novelty seeking behaviors, further supporting the idea of a connection between the circadian clock and psychiatric disorders. However, if circadian clock dysfunction is a common risk factor for multiple psychiatric disorders, it is unknown if and how these putative clock abnormalities could be expressed differently, and contribute to multiple, distinct phenotypes. One possible explanation is that the circadian clock modulates the biological responses to stressful environmental factors that vary with an individual's experience. It is known that the circadian clock and the stress response systems are closely related: Circadian clock genes regulate the physiological sensitivity to, and rhythmic release of glucocorticoids (GC). In turn, GCs have reciprocal effects on the clock. Since stressful life events or increased vulnerability to stress are risk factors for multiple psychiatric disorders including posttraumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), bipolar disorder (BD), major depressive disorder (MDD), alcohol use disorder (AUD) and schizophrenia (SCZ), we propose that modulation of the stress response is a common mechanism by which circadian clock genes affect these illnesses. Presently, we review how molecular components of the circadian clock may contribute to these six psychiatric disorders, and present the hypothesis that modulation of the stress response may constitute a common mechanism by which the circadian clock affects multiple psychiatric disorders.

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“…They identified over 200 differentially methylated CpG islands, with an enrichment of "nervous system development and function" in gene ontology analysis (GO) [46]. In 2014, two important studies further addressed role of DNA methylation in ASD.…”

Section: Altered Dna Methylation In Asdmentioning

confidence: 99%

Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism

2015

Sci. China Life Sci.

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Autism spectrum disorder (ASD) is a spectral neurodevelopment disorder affecting approximately 1% of the population. ASD is characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Multiple factors, including genetic/genomic, epigenetic/epigenomic and environmental, are thought to be necessary for autism development. Recent reviews have provided further insight into the genetic/genomic basis of ASD. It has long been suspected that epigenetic mechanisms, including DNA methylation, chromatin structures and long non-coding RNAs may play important roles in the pathology of ASD. In addition to genetic/genomic alterations and epigenetic/epigenomic influences, environmental exposures have been widely accepted as an important role in autism etiology, among which immune dysregulation and gastrointestinal microbiota are two prominent ones. autism spectrum disorder, genetic architecture, genomic disorder, gene mutation, copy number variants, single nucleotide variants, genetic pathways, epigenetic influence, DNA methylation, chromatin remodeling, long non-coding RNAs, environment exposure, immune dysregulation, gastrointestinal microbiota Citation:Yu L, Wu YM, Wu BL. Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism. Sci China Life Sci, 2015, 58: 958-967,

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Global methylation profiling of lymphoblastoid cell lines reveals epigenetic contributions to autism spectrum disorders and a novel autism candidate gene, RORA , whose protein product is reduced in autistic brain

Cited by 319 publications

References 67 publications

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

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

Circadian Clock and Stress Interactions in the Molecular Biology of Psychiatric Disorders

Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism

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