1. Bai Y, Qiu S, Li Y, Li Y, Zhong W, Shi M, Zhu X, Jiang H, Yu Y, Cheng Y, Liu Y. {{Genetic association between SHANK2 polymorphisms and susceptibility to autism spectrum disorder}}. {IUBMB life}. 2018.
Autism spectrum disorder (ASD), as one of early-onset neurodevelopmental disorders, is characterized by the following symptoms, including repetitive and stereotyped behaviors, impairments in social interaction, and dysfunctions in communication. ASD afflicts approximately 1.5% of children aged 8 years in America and approximately 4.5 per thousand of children aged 0-6 years in China. Existing studies suggest that SH3 and multiple ankyrin repeat domains protein 2 (SHANK2) is implicated in ASD. However, associations between SNPs in SHANK2 introns and ASD risk have been less investigated. In this study, on the basis of case-control study (226 cases and 239 controls), we selected nine SNPs (rs76717360, rs11236697, rs74336682, rs77950809, rs17428526, rs35459123, rs75357229, rs61887413, and rs77716438) in SHANK2 introns to investigate genetic associations between SHANK2 polymorphisms and susceptibility to ASD using improved multiple ligase detection reaction (iMLDR). We identified that the polymorphism of rs76717360 was associated with risk of ASD in Chinese population; the haplotype of rs11236697 C (T) or rs74336682 G (A) increased ASD risk; and haplotypes with >/= five SNPs containing rs11236697 and rs74336682 were associated with risk of ASD. Our results indicate SHANK2 is a susceptibility gene for ASD in Chinese children. (c) 2018 IUBMB Life, 2018.
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2. Courchesne E, Pramparo T, Gazestani VH, Lombardo MV, Pierce K, Lewis NE. {{The ASD Living Biology: from cell proliferation to clinical phenotype}}. {Mol Psychiatry}. 2018.
Autism spectrum disorder (ASD) has captured the attention of scientists, clinicians and the lay public because of its uncertain origins and striking and unexplained clinical heterogeneity. Here we review genetic, genomic, cellular, postmortem, animal model, and cell model evidence that shows ASD begins in the womb. This evidence leads to a new theory that ASD is a multistage, progressive disorder of brain development, spanning nearly all of prenatal life. ASD can begin as early as the 1st and 2nd trimester with disruption of cell proliferation and differentiation. It continues with disruption of neural migration, laminar disorganization, altered neuron maturation and neurite outgrowth, disruption of synaptogenesis and reduced neural network functioning. Among the most commonly reported high-confidence ASD (hcASD) genes, 94% express during prenatal life and affect these fetal processes in neocortex, amygdala, hippocampus, striatum and cerebellum. A majority of hcASD genes are pleiotropic, and affect proliferation/differentiation and/or synapse development. Proliferation and subsequent fetal stages can also be disrupted by maternal immune activation in the 1st trimester. Commonly implicated pathways, PI3K/AKT and RAS/ERK, are also pleiotropic and affect multiple fetal processes from proliferation through synapse and neural functional development. In different ASD individuals, variation in how and when these pleiotropic pathways are dysregulated, will lead to different, even opposing effects, producing prenatal as well as later neural and clinical heterogeneity. Thus, the pathogenesis of ASD is not set at one point in time and does not reside in one process, but rather is a cascade of prenatal pathogenic processes in the vast majority of ASD toddlers. Despite this new knowledge and theory that ASD biology begins in the womb, current research methods have not provided individualized information: What are the fetal processes and early-age molecular and cellular differences that underlie ASD in each individual child? Without such individualized knowledge, rapid advances in biological-based diagnostic, prognostic, and precision medicine treatments cannot occur. Missing, therefore, is what we call ASD Living Biology. This is a conceptual and paradigm shift towards a focus on the abnormal prenatal processes underlying ASD within each living individual. The concept emphasizes the specific need for foundational knowledge of a living child’s development from abnormal prenatal beginnings to early clinical stages. The ASD Living Biology paradigm seeks this knowledge by linking genetic and in vitro prenatal molecular, cellular and neural measurements with in vivo post-natal molecular, neural and clinical presentation and progression in each ASD child. We review the first such study, which confirms the multistage fetal nature of ASD and provides the first in vitro fetal-stage explanation for in vivo early brain overgrowth. Within-child ASD Living Biology is a novel research concept we coin here that advocates the integration of in vitro prenatal and in vivo early post-natal information to generate individualized and group-level explanations, clinically useful prognoses, and precision medicine approaches that are truly beneficial for the individual infant and toddler with ASD.
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3. Daghsni M, Rima M, Fajloun Z, Ronjat M, Bruses JL, M’Rad R, De Waard M. {{Autism throughout genetics: Perusal of the implication of ion channels}}. {Brain and behavior}. 2018: e00978.
BACKGROUND: Autism spectrum disorder (ASD) comprises a group of neurodevelopmental psychiatric disorders characterized by deficits in social interactions, interpersonal communication, repetitive and stereotyped behaviors and may be associated with intellectual disabilities. The description of ASD as a synaptopathology highlights the importance of the synapse and the implication of ion channels in the etiology of these disorders. METHODS: A narrative and critical review of the relevant papers from 1982 to 2017 known by the authors was conducted. RESULTS: Genome-wide linkages, association studies, and genetic analyses of patients with ASD have led to the identification of several candidate genes and mutations linked to ASD. Many of the candidate genes encode for proteins involved in neuronal development and regulation of synaptic function including ion channels and actors implicated in synapse formation. The involvement of ion channels in ASD is of great interest as they represent attractive therapeutic targets. In agreement with this view, recent findings have shown that drugs modulating ion channel function are effective for the treatment of certain types of patients with ASD. CONCLUSION: This review describes the genetic aspects of ASD with a focus on genes encoding ion channels and highlights the therapeutic implications of ion channels in the treatment of ASD.
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4. Hamm J, Yun J. {{The motivational process for physical activity in young adults with autism spectrum disorder}}. {Disability and health journal}. 2018.
BACKGROUND: Many young adults, specifically those with a diagnosis of autism spectrum disorder (ASD), do not meet the national physical activity (PA) guidelines. One way to address this problem may be to examine the factors that motivate individuals to engage in PA. However, the majority of current literature does not consider the unique characteristics of individuals with ASD, which may influence their motivation. OBJECTIVE: The purpose of this research was to examine Self-Determination Theory predictors for PA for young adults with ASD. METHODS: Respondents included 143 young adults with ASD who completed a survey pertaining to their motivational process to engage in physical activity, based on self-determination theory variables. RESULTS: Goodness of fit indices reported from a path analysis suggests the current data closely align with the self-determination theory (chi(2) (3, N=143)=11.99, p>.01, GFI=0.97, NFI=0.95, CFI=. 96, RMSEA=0.15). The three basic psychological needs explained 39% of the variance within respondents’ self-determined motivation, and self-determined motivation explained 8% of the variance in PA levels. CONCLUSIONS: These findings support utilizing the self-determination theory within health promotion efforts for young adults with ASD. Practitioners should focus on enhancing the perceived basic psychological needs of young adults within physical activity settings.
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5. Jones KL, Van de Water J. {{Maternal autoantibody related autism: mechanisms and pathways}}. {Mol Psychiatry}. 2018.
It has been estimated that autism spectrum disorder (ASD) now affects 1 in 59 children in the United States. Although the cause(s) of ASD remain largely unknown, it is becoming increasingly apparent that ASD can no longer be defined simply as a behavioral disorder, but is in effect a rather complex and highly heterogeneous biological disorder. Up until recently the brain was thought to be « immune privileged. » However, it is now known that the immune system plays critical roles in the development and functioning of the brain throughout life. Recent evidence from multiple investigators has illustrated the deleterious role that dysregulation of the maternal immune system during gestation can play in the manifestation of changes in neurodevelopment, resulting in the development of neurobehavioral disorders such as ASD. One potential etiologic pathway through which the maternal immune system can interfere with neurodevelopment is through maternal autoantibodies that recognize proteins in the developing fetal brain. This mechanism of pathogenesis is now thought to lead to a subphenotype of ASD that has been termed maternal autoantibody related (MAR) ASD. This review provides an overview of the current research implicating the presence of brain-reactive maternal autoantibodies as a risk factor for MAR ASD.
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6. Tanigawa J, Kagitani-Shimono K, Matsuzaki J, Ogawa R, Hanaie R, Yamamoto T, Tominaga K, Nabatame S, Mohri I, Taniike M, Ozono K. {{Atypical auditory language processing in adolescents with autism spectrum disorder}}. {Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology}. 2018.
OBJECTIVE: Individuals with autism spectrum disorder (ASD) often show characteristic differences in auditory processing. To clarify the mechanisms underlying communication impairment in ASD, we examined auditory language processing with both anatomical and functional methods. METHODS: We assessed the language abilities of adolescents with ASD and typically developing (TD) adolescents, and analyzed the surface-based morphometric structure between the groups using magnetic resonance imaging. Furthermore, we measured cortical responses to an auditory word comprehension task with magnetoencephalography and performed network-based statistics using the phase locking values. RESULTS: We observed no structural differences between the groups. However, the volume of the left ventral central sulcus (vCS) showed a significant correlation with linguistic scores in ASD. Moreover, adolescents with ASD showed weaker cortical activation in the left vCS and superior temporal sulcus. Furthermore, these regions showed differential correlations with linguistic scores between the groups. Moreover, the ASD group had an atypical gamma band (25-40Hz) network centered on the left vCS. CONCLUSIONS: Adolescents with ASD showed atypical responses on the auditory word comprehension task and functional brain differences. SIGNIFICANCE: Our results suggest that phonological processing and gamma band cortical activity play a critical role in auditory language processing-related pathophysiology in adolescents with ASD.
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7. Yap VMZ, McLachlan NM, Scheffer IE, Wilson SJ. {{Enhanced Sensitivity to Angry Voices in People with Features of the Broader Autism Phenotype}}. {J Autism Dev Disord}. 2018.
The present study examined whether the ability to recognize vocal emotional expressions is negatively related to features of the Broader Autism Phenotype (BAP) in the general population. We assessed 61 typically developing adults on a BAP self-report measure (Broader Autism Phenotype Questionnaire) and a purpose-developed online emotion recognition task for efficient delivery of non-linguistic vocal stimuli corresponding to the six basic emotions. Contrary to expectations, we found that higher self-ratings of rigid BAP traits correlated with better recognition accuracy and higher intensity ratings for angry voices. We interpret this anger-specific association as an advantage for enhanced threat detection in the BAP and discuss this finding in the broader context of personality research and interpersonal theory.
