1. {{Autism DNA hub opens}}. {Nat Biotechnol}. 2016; 34(4): 364.
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2. Barnhill K, Tami A, Schutte C, Hewitson L, Olive ML. {{Targeted Nutritional and Behavioral Feeding Intervention for a Child with Autism Spectrum Disorder}}. {Case Rep Psychiatry}. 2016; 2016: 1420549.
A variety of feeding issues and concerns, including food aversion, food selectivity, and complete food refusal, are not uncommon among children with autism spectrum disorder (ASD). Other underlying issues are often comorbid with the concerns for feeding and ASD. These may include food allergies, gastrointestinal issues, oral motor issues, and swallowing disorders. The refusal to consume particular foods coupled with the inability to tolerate, digest, and absorb these foods can compromise an individual’s overall nutrition status. Therefore, a child’s behavior toward food and feeding activities has great impact on dietary intake, nutritional status, and growth. This case report is the first to document combined medical, behavioral, and nutritional intervention for a toddler with ASD and comorbid feeding disorder.
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3. Brandler WM, Antaki D, Gujral M, Noor A, Rosanio G, Chapman TR, Barrera DJ, Lin GN, Malhotra D, Watts AC, Wong LC, Estabillo JA, Gadomski TE, Hong O, Fajardo KV, Bhandari A, Owen R, Baughn M, Yuan J, Solomon T, Moyzis AG, Maile MS, Sanders SJ, Reiner GE, Vaux KK, Strom CM, Zhang K, Muotri AR, Akshoomoff N, Leal SM, Pierce K, Courchesne E, Iakoucheva LM, Corsello C, Sebat J. {{Frequency and Complexity of De Novo Structural Mutation in Autism}}. {Am J Hum Genet}. 2016; 98(4): 667-79.
Genetic studies of autism spectrum disorder (ASD) have established that de novo duplications and deletions contribute to risk. However, ascertainment of structural variants (SVs) has been restricted by the coarse resolution of current approaches. By applying a custom pipeline for SV discovery, genotyping, and de novo assembly to genome sequencing of 235 subjects (71 affected individuals, 26 healthy siblings, and their parents), we compiled an atlas of 29,719 SV loci (5,213/genome), comprising 11 different classes. We found a high diversity of de novo mutations, the majority of which were undetectable by previous methods. In addition, we observed complex mutation clusters where combinations of de novo SVs, nucleotide substitutions, and indels occurred as a single event. We estimate a high rate of structural mutation in humans (20%) and propose that genetic risk for ASD is attributable to an elevated frequency of gene-disrupting de novo SVs, but not an elevated rate of genome rearrangement.
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4. Brooks J, Kellett J, Seeanner J, Jenkins C, Buchanan C, Kinsman A, Kelly D, Pierce S. {{Training the Motor Aspects of Pre-driving Skills of Young Adults With and Without Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2016.
The purpose of this study was to investigate the utility of using a driving simulator to address the motor aspects of pre-driving skills with young adults with Autism Spectrum Disorder (ASD). A group of neurotypical control participants and ten participants with ASD completed 18 interactive steering and pedal exercises with the goal to achieve error-free performance. Most participants were able to achieve this goal within five trials for all exercises except for the two most difficult ones. Minimal performance differences were observed between the two groups. Participants with ASD needed more time to complete the tasks. Overall, the interactive exercises and the process used worked well to address motor related aspects of pre-driving skills in young adults with ASD.
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5. Chung US, Han DH, Shin YJ, Renshaw PF. {{A prosocial online game for social cognition training in adolescents with high-functioning autism: an fMRI study}}. {Neuropsychiatr Dis Treat}. 2016; 12: 651-60.
To help patients with autism spectrum disorder (ASD) improve their social skills, effective interventions and new treatment modalities are necessary. We hypothesized that a prosocial online game would improve social cognition in ASD adolescents, as assessed using metrics of social communication, facial recognition, and emotional words. Ten ASD adolescents underwent cognitive behavior therapy (CBT) using a prosocial online game (game-CBT), and ten ASD adolescents participated in an offline-CBT. At baseline and 6 weeks later, social communication quality, correct identification of emotional words and facial emoticons, and brain activity were assessed in both groups. Social communication quality and correct response rate of emotional words and facial emoticons improved in both groups over the course of the intervention, and there were no significant differences between groups. In response to the emotional words, the brain activity within the temporal and parietal cortices increased in the game-CBT group, while the brain activity within cingulate and parietal cortices increased in the offline-CBT group. In addition, ASD adolescents in the game-CBT group showed increased brain activity within the right cingulate gyrus, left medial frontal gyrus, left cerebellum, left fusiform gyrus, left insular cortex, and sublobar area in response to facial emoticons. A prosocial online game designed for CBT was as effective as offline-CBT in ASD adolescents. Participation in the game especially increased social arousal and aided ASD adolescents in recognizing emotion. The therapy also helped participants more accurately consider associated environments in response to facial emotional stimulation. However, the online CBT was less effective than the offline-CBT at evoking emotions in response to emotional words.
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6. de la Torre-Ubieta L, Won H, Stein JL, Geschwind DH. {{Advancing the understanding of autism disease mechanisms through genetics}}. {Nat Med}. 2016; 22(4): 345-61.
Progress in understanding the genetic etiology of autism spectrum disorders (ASD) has fueled remarkable advances in our understanding of its potential neurobiological mechanisms. Yet, at the same time, these findings highlight extraordinary causal diversity and complexity at many levels ranging from molecules to circuits and emphasize the gaps in our current knowledge. Here we review current understanding of the genetic architecture of ASD and integrate genetic evidence, neuropathology and studies in model systems with how they inform mechanistic models of ASD pathophysiology. Despite the challenges, these advances provide a solid foundation for the development of rational, targeted molecular therapies.
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7. Edmunds SR, Ibanez LV, Warren Z, Messinger DS, Stone WL. {{Longitudinal prediction of language emergence in infants at high and low risk for autism spectrum disorder}}. {Dev Psychopathol}. 2016: 1-11.
This study used a prospective longitudinal design to examine the early developmental pathways that underlie language growth in infants at high risk (n = 50) and low risk (n = 34) for autism spectrum disorder in the first 18 months of life. While motor imitation and responding to joint attention (RJA) have both been found to predict expressive language in children with autism spectrum disorder and those with typical development, the longitudinal relation between these capacities has not yet been identified. As hypothesized, results revealed that 15-month RJA mediated the association between 12-month motor imitation and 18-month expressive vocabulary, even after controlling for earlier levels of RJA and vocabulary. These results provide new information about the developmental sequencing of skills relevant to language growth that may inform future intervention efforts for children at risk for language delay or other developmental challenges.
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8. Egilson ST, Olafsdottir LB, Leosdottir T, Saemundsen E. {{Quality of life of high-functioning children and youth with autism spectrum disorder and typically developing peers: Self- and proxy-reports}}. {Autism}. 2016.
Studies have shown parents to report lower quality of life for their children with autism spectrum disorder than children’s self-report scores and the same applies for data on typically developing children. Our objectives were to: (1) explore how high-functioning children with autism spectrum disorder rate their quality of life compared with paired controls without autism spectrum disorder; (2) explore how parents of high-functioning children with autism spectrum disorder rate their children’s quality of life compared with parents of paired controls; and (3) compare child self-reports of quality of life with their parent’s proxy-reports for both groups of children. Data were collected with the Icelandic self- and proxy-reported versions of the KIDSCREEN-27. Reports of 96 children with autism spectrum disorder, 211 controls and their parents were included in the analyses. Compared with controls, children with autism spectrum disorder had lower means on all quality of life dimensions. Parents of children with autism spectrum disorder evaluated their children’s quality of life lower on all dimensions than did parents of controls. On four out of five dimensions, children with autism spectrum disorder reported better quality of life than did their parents. Despite differences in ratings children with autism spectrum disorder and their parents agreed on the most problematic dimensions, namely,social support and peersandphysical well-being Our results highlight the importance of seeking the viewpoints of both children and their parents.
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9. Homberg JR, Kyzar EJ, Nguyen M, Norton WH, Pittman J, Poudel MK, Gaikwad S, Nakamura S, Koshiba M, Yamanouchi H, Scattoni ML, Ullman JF, Diamond DM, Kaluyeva AA, Parker MO, Klimenko VM, Apryatin SA, Brown RE, Song C, Gainetdinov RR, Gottesman, II, Kalueff AV. {{Understanding autism and other neurodevelopmental disorders through experimental translational neurobehavioral models}}. {Neurosci Biobehav Rev}. 2016.
Neurodevelopmental disorders (NDDs) are highly prevalent and severely debilitating brain illnesses caused by aberrant brain growth and development. Resulting in cognitive, social, motor, language and affective disabilities, common NDDs include autism spectrum disorder (ASD), intellectual disability, communication/speech disorders, motor/tic disorders and attention deficit hyperactivity disorder. Affecting neurogenesis, glia/neuronal proliferation and migration, synapse formation and myelination, aberrant neural development occurs over a substantial period of time. Genetic, epigenetic, and environmental factors play a key role in NDD pathogenesis. Animal models are an indispensable tool to study NDDs. Paralleling clinical findings, we comprehensively evaluate various preclinical tests and models which target key (social, cognitive, motor) neurobehavioral domains of ASD and other common NDDs. Covering both traditional (rodent) and alternative NDD models, we outline the emerging areas of research and emphasize how preclinical models play a key role in gaining translational and mechanistic insights into NDDs and their therapy.
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10. Huang CT, Chiang CH, Hung CY. {{Young children with autism spectrum disorders imitate in the context of others’ prior intention}}. {Autism}. 2016.
Many studies have shown that children with autism spectrum disorder have some understanding of intentions behind others’ goal-directed actions on objects. It is not clear whether they understand intentions at a high level of abstraction reliant on the context in which the actions occur. This study tested their understanding of others’ prior intentions with typically developing and developmentally delayed children. We replicated Carpenter et al.’s test of the ability to understand prior intentions embedded in the social situation with an additional context of no prior intention. Results showed that when the experimenter’s intention was made known before the demonstration, children without autism spectrum disorder performed not only better than the autism spectrum disorder children but also better than themselves when there was no information about prior intention. No between-condition difference was found in the autism spectrum disorder group. It thus appears that children with autism spectrum disorder have difficulty decoupling intentions from the context of the situation. The present findings, together with previous evidence for the intactness of the ability to understand and to imitate goal-directed actions, suggest that asymmetrical imitation performance occurs at different levels of understanding of intention by children with autism spectrum disorder.
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11. Humphreys P, Barrowman N. {{The Incidence and Evolution of Parkinsonian Rigidity in Rett Syndrome: A Pilot Study}}. {Can J Neurol Sci}. 2016: 1-7.
BACKGROUND: Patients with Rett syndrome (RTT) may demonstrate parkinsonian features. Here, we report a preliminary cross-sectional and prospective evaluation of the evolution, regional distribution, and eventual incidence of rigid tone in a cohort of MECP2 mutation-positive patients. METHODS: In 51 participants, muscle tone rigidity in extremity regions and neck plus hypomimia were quantified using an RTT rigidity distribution (RTTRD) score with a range of 0 to 15. RTTRD scores were correlated with age, ability to walk and speak, mutation type, and, in a small subgroup (n=9), cerebrospinal fluid (CSF) homovanillic acid (HVA) and 5-hydroxyindole-acetic acid levels. RESULTS: Participant ages ranged from 2 years and 5 months, to 54 years. Rigidity was found in 43/51 (84.3%); it appeared as early as age 3, increased in extent with age, and was present in all participants aged >/=13. Ankle region rigidity appeared first, followed by proximal legs, arms, neck, and face. Ambulatory participants (n=21) had lower RTTRD scores than nonambulatory (n=30; p=0.003). We found a trend to lower scores in participants with retained speech (n=13) versus those with none (n=38; p=0.074), and no difference in scores for those with truncating (n=25) versus missense mutations (n=22; p=0.387). RTTRD scores correlated negatively with CSF HVA levels (R=-0.83; p=0.005), but not with 5-hydroxyindole-acetic acid levels (R=-0.45; p=0.22). CONCLUSIONS: Although assessment of muscle tone is somewhat subjective and the RTTRD has not been validated, this study nevertheless suggests that parkinsonian rigidity in RTT is common and frequently increases in extent with age; its severity correlates directly with impaired ambulation and inversely with CSF HVA levels.
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12. Lopata C, Lipinski AM, Thomeer ML, Rodgers JD, Donnelly JP, McDonald CA, Volker MA. {{Open-trial pilot study of a comprehensive outpatient psychosocial treatment for children with high-functioning autism spectrum disorder}}. {Autism}. 2016.
This study examined the feasibility and initial outcomes of a comprehensive outpatient psychosocial treatment (MAXout) for children aged 7-12 years with high-functioning autism spectrum disorder. The 18-week treatment, two 90-minute sessions per week, included instruction and therapeutic activities targeting social/social communication skills, facial emotion recognition, non-literal language skills, and interest expansion. A behavioral system was implemented to reduce autism spectrum disorder symptoms and problem behaviors and increase skills acquisition and maintenance. Feasibility was supported via high levels of treatment fidelity and parent, child, and staff satisfaction. Significant post-treatment improvements were found for the children’s non-literal language skills and facial emotion recognition skills, and parent and staff clinician ratings of targeted social/social communication skills, broad social skills, autism spectrum disorder symptoms, and problem behaviors. Results suggested that MAXout was feasible and may yield positive outcomes for children with high-functioning autism spectrum disorder.
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13. Mintz M. {{Evolution in the Understanding of Autism Spectrum Disorder: Historical Perspective}}. {Indian J Pediatr}. 2016.
The study of the evolution in the diagnosis and treatment of autism is a lesson in the dangers of medical beliefs or doctrines that are not grounded in medical science. The early descriptions of autism suggested that it was the result of childhood psychoses or psychodynamic disturbances of parent-child relationships. This flawed conceptualization of autism spectrum disorders (ASD) gave way to advances in medical science, which have established ASD as a neurobiological disorder of early brain development. There are many genetic, epigenetic, metabolic, hormonal, immunological, neuroanatomical and neurophysiological etiologies of ASD, as well as an array of gastrointestinal and other systemic co-morbid disorders. Thus, ASD are a biologically heterogeneous population with extensive neurodiversity. Early identification and understanding of ASD is crucial; interventions at younger ages are associated with improved outcomes. The advent of understanding the biological sub-phenotypes of ASD, along with targeted medical therapies, coupled with a multimodal therapeutic approach that encompasses behavioral, educational, social, speech, occupational, creative arts, and other forms of therapies has created a new and exciting era for individuals with ASD and their families: « personalized » and « precision » medical care based upon underlying biological sub-phenotypes and clinical profiles. For many individuals and their families dealing with the scourge of autism, their long and frustrating diagnostic journey is beginning to come to an end, with a hope for improved outcomes and quality of life.
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14. Neuhaus E, Jones EJ, Barnes K, Sterling L, Estes A, Munson J, Dawson G, Webb SJ. {{The Relationship Between Early Neural Responses to Emotional Faces at Age 3 and Later Autism and Anxiety Symptoms in Adolescents with Autism}}. {J Autism Dev Disord}. 2016.
Both autism spectrum (ASD) and anxiety disorders are associated with atypical neural and attentional responses to emotional faces, differing in affective face processing from typically developing peers. Within a longitudinal study of children with ASD (23 male, 3 female), we hypothesized that early ERPs to emotional faces would predict concurrent and later ASD and anxiety symptoms. Greater response amplitude to fearful faces corresponded to greater social communication difficulties at age 3, and less improvement by age 14. Faster ERPs to neutral faces predicted greater ASD symptom improvement over time, lower ASD severity in adolescence, and lower anxiety in adolescence. Early individual differences in processing of emotional stimuli likely reflect a unique predictive contribution from social brain circuitry early in life.
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15. Osuagwu FC, Amalraj B, Noveloso BD, Aikoye SA, Bradley R. {{Autism Spectrum Disorder and Chiari 1 Malformation Co-occurring in a Child}}. {Tokai J Exp Clin Med}. 2016; 41(1): 54-6.
Very few studies have shown associations between autism spectrum disorder, attention deficit hyperactivity disorder and Chiari 1 malformation. Here, we report an 10-year-old male that presented after having seizures with a history of Chiari 1 malformation, autism spectrum disorder and ADHD with moderate mental retardation and speech delay. This case highlights the fact that autism spectrum disorder as biologically based neurodevelopmental disorder with altered brain growth may be associated with Chiari 1 malformation and ADHD.
16. Pan CY, Chu CH, Tsai CL, Sung MC, Huang CY, Ma WY. {{The impacts of physical activity intervention on physical and cognitive outcomes in children with autism spectrum disorder}}. {Autism}. 2016.
This study examined the effects of a 12-week physical activity intervention on the motor skill proficiency and executive function of 22 boys (aged 9.08 +/- 1.75 years) with autism spectrum disorder. In Phase I of the 12 weeks, 11 boys with autism spectrum disorder (Group A) received the intervention, whereas the other 11 boys with autism spectrum disorder (Group B) did not (true control, no intervention). The arrangement was reversed in Phase II, which lasted an additional 12 weeks. The Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, and the Wisconsin Card Sorting Test were conducted three times for each participant (Group A, primary grouping: baseline (T1), post-assessment (T2), and follow-up assessment (T3); Group B, control grouping: T1-T2; intervention condition, T2-T3). The main findings were that both groups of children with autism spectrum disorder significantly exhibited improvements in motor skill proficiency (the total motor composite and two motor-area composites) and executive function (three indices of the Wisconsin Card Sorting Test) after 12 weeks of physical activity intervention. In addition, the effectiveness appeared to have been sustained for at least 12 weeks in Group A. The findings provide supporting evidence that physical activity interventions involving table tennis training may be a viable therapeutic option for treating children with autism spectrum disorder.
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17. Patak J, Zhang-James Y, Faraone SV. {{Endosomal System Genetics and Autism Spectrum Disorders: A Literature Review}}. {Neurosci Biobehav Rev}. 2016.
Autism spectrum disorders (ASDs) are a group of debilitating neurodevelopmental disorders thought to have genetic etiology, due to their high heritability. The endosomal system has become increasingly implicated in ASD pathophysiology. In an attempt to summarize the association between endosomal system genes and ASDs we performed a systematic review of the literature. We searched PubMed for relevant articles. Simons Foundation Autism Research Initiative (SFARI) gene database was used to exclude articles regarding genes with less than minimal evidence for association with ASDs. Our search retained 55 articles reviewed in two categories: genes that regulate and genes that are regulated by the endosomal system. Our review shows that the endosomal system is a novel pathway implicated in ASDs as well as other neuropsychiatric disorders. It plays a central role in aspects of cellular physiology on which neurons and glial cells are particularly reliant, due to their unique metabolic and functional demands. The system shows potential for biomarkers and pharmacological intervention and thus more research into this pathway is warranted.
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18. Samadi SA, Mohammad MP, Ghanimi F, McConkey R. {{The challenges of screening pre-school children for autism spectrum disorders in Iran}}. {Disabil Rehabil}. 2016: 1-9.
PURPOSE: Early identification and diagnosis of children with autism spectrum disorder is recommended, but this is difficult to achieve in less developed countries due to a lack of suitable tools and personnel. This two-phase study, undertaken in Iran, aimed to develop culturally appropriate and feasible means for screening pre-school children for autism spectrum disorder (ASD). METHOD: The first phase involved information and training events held in four cities to alert parents and to recruit and train professionals to undertake screenings and diagnostic assessments. In phase 2, a screening tool developed in Iran was administered to over 20 000 preschool children with the Iranian version of the GARS2 scale used to assess the probability of the child having ASD. RESULTS: Over 250 professionals were trained and assessed as competent screeners of whom a further 67 were trained and accredited to use GARS2. They included postgraduate students and practitioners from a range of disciplines. In all, 1579 children screened positive; however, only 130 parents brought their child for the diagnostic assessment of whom 22% had a high probability of having ASD. CONCLUSION: The feasibility of undertaking a screening programme for ASD with Iranian preschoolers has been demonstrated although further research is needed to refine the screening and diagnostic tools, monitor assessors and promote greater engagement of families. Implications for Rehabilitation Sizeable numbers of postgraduate students and practitioners were recruited to assist with the screening and assessments of preschoolers. The uptake of screening was highest among parents of four and five years olds but much less so for younger children and in bringing children for further assessments. Further research is needed into the development of more suitable screening and diagnostic tools for ASD with Iranian preschoolers and the training of assessors in their use.
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19. Stasolla F, Perilli V, Damiani R, Albano V. {{Assistive technology to promote occupation and reduce mouthing by three boys with fragile X syndrome}}. {Dev Neurorehabil}. 2016: 1-9.
OBJECTIVES: To extend the use of assistive technology (AT) for promoting a new adaptive response and to reduce hand mouthing, by three boys with fragile X syndrome. To monitor the effects of the intervention program on the positive mood. To carry out a three month follow-up phases. To conduct a social validation assessment involving 30 parents of children who presented multiple disabilities as raters. METHODS: The study was implemented according to an ABAB experimental design, where A represented baseline phases (technology available but inactive) and B represented intervention phases (the technology ensured 7 s of positive stimulation). RESULTS: All participants improved and consolidated their performance. Parents involved in the social validation assessment rated positively the use of such technology. CONCLUSION: AT-based program was useful, affordable, and effective for enhancing constructive engagement, self-determination, and for improving quality of life by children with fragile X syndrome and severe to profound developmental disabilities.
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20. Van Dijck A, Helsmoortel C, Vandeweyer G, Kooy F. {{ADNP-Related Intellectual Disability and Autism Spectrum Disorder}}. 1993.
ADNP-related intellectual disability and autism spectrum disorders (ADNP-related ID/ASD) are characterized by mild to severe intellectual disability and autism spectrum disorder (ASD). Of the 24 individuals reported to date, 23 were ascertained in cohorts with autism spectrum disorder (ASD) / intellectual disability (ID); one was identified in a clinical setting. The clinical information available on 12 of the 24 revealed: delayed developmental milestones (walking independently between 19 months and 4.5 years) and speech ranging from no words to sentences. ASD was characterized by stereotypic behavior and impaired social interaction. Other common findings include behavioral problems, sleep disturbance, hypotonia, seizures, feeding difficulties, visual problems (hypermetropia, strabismus, cortical visual impairment), and cardiac defects. The diagnosis of ADNP-related ID/ASD is established by identification of a heterozygous ADNP pathogenic variant on molecular genetic testing. Treatment of manifestations: Treatment is symptomatic and can include: speech, occupational, and physical therapy; specialized learning programs depending on individual needs; treatment of neuropsychiatric features (e.g., sleep disorders, behavioral problems, and/or seizures); nutritional support as needed; routine treatment of ophthalmologic and cardiac findings. ADNP-related ID/ASD is expressed in an autosomal dominant manner. Given that all affected individuals with ADNP-related syndromic autism reported to date have the disorder as a result of a de novo ADNP pathogenic variant, the risk to other family members is presumed to be low. Prenatal testing and preimplantation genetic diagnosis are possible options.
21. Wen Y, Alshikho MJ, Herbert MR. {{Pathway Network Analyses for Autism Reveal Multisystem Involvement, Major Overlaps with Other Diseases and Convergence upon MAPK and Calcium Signaling}}. {PLoS One}. 2016; 11(4): e0153329.
We used established databases in standard ways to systematically characterize gene ontologies, pathways and functional linkages in the large set of genes now associated with autism spectrum disorders (ASDs). These conditions are particularly challenging-they lack clear pathognomonic biological markers, they involve great heterogeneity across multiple levels (genes, systemic biological and brain characteristics, and nuances of behavioral manifestations)-and yet everyone with this diagnosis meets the same defining behavioral criteria. Using the human gene list from Simons Foundation Autism Research Initiative (SFARI) we performed gene set enrichment analysis with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database, and then derived a pathway network from pathway-pathway functional interactions again in reference to KEGG. Through identifying the GO (Gene Ontology) groups in which SFARI genes were enriched, mapping the coherence between pathways and GO groups, and ranking the relative strengths of representation of pathway network components, we 1) identified 10 disease-associated and 30 function-associated pathways 2) revealed calcium signaling pathway and neuroactive ligand-receptor interaction as the most enriched, statistically significant pathways from the enrichment analysis, 3) showed calcium signaling pathways and MAPK signaling pathway to be interactive hubs with other pathways and also to be involved with pervasively present biological processes, 4) found convergent indications that the process « calcium-PRC (protein kinase C)-Ras-Raf-MAPK/ERK » is likely a major contributor to ASD pathophysiology, and 5) noted that perturbations associated with KEGG’s category of environmental information processing were common. These findings support the idea that ASD-associated genes may contribute not only to core features of ASD themselves but also to vulnerability to other chronic and systemic problems potentially including cancer, metabolic conditions and heart diseases. ASDs may thus arise, or emerge, from underlying vulnerabilities related to pleiotropic genes associated with pervasively important molecular mechanisms, vulnerability to environmental input and multiple systemic co-morbidities.
