Autism Diagnosis Brisbane: Understanding ASD and Pathways to Assessment

Autism spectrum disorder (ASD) encompasses a range of neurodevelopmental conditions that affect how individuals perceive the world and interact with others. Once considered separate conditions like Asperger’s syndrome and pervasive developmental disorder, these are now unified under the single diagnostic umbrella of ASD, reflecting the spectrum’s diverse nature. Diagnosing ASD is a crucial first step for accessing support and understanding, particularly in communities like Brisbane, where families seek clear pathways for assessment and intervention.

Understanding Autism Spectrum Disorder (ASD)

What is ASD?

Autism spectrum disorder is characterized by differences in social communication and interaction, alongside restricted or repetitive behaviors or interests. The term “spectrum” highlights the wide variation in the type and severity of challenges individuals may experience. These differences are thought to arise from a combination of genetic predispositions and environmental influences affecting brain development. Unlike conditions with biological markers, ASD diagnosis relies on observing and assessing behavioral characteristics.

Clinical Features of ASD

Historically, ASD was identified by a ‘triad of impairments’: challenges in speech, social interaction, and the presence of repetitive behaviors. However, our understanding has expanded to recognize a broader range of features and co-occurring conditions.

Early Signs and Symptoms: ASD typically manifests in early childhood, often diagnosed by the age of three. Early indicators can include a lack of response to their name or limited eye contact in infants and toddlers. As children develop, other signs may become apparent, such as delays in speech and language, difficulties in understanding social cues, and engaging in repetitive movements or play patterns.

Core Features: The diagnostic criteria for ASD emphasize two main areas:

Social Communication and Interaction: Individuals with ASD may find it challenging to initiate or maintain conversations, understand nonverbal communication, share interests, or form social relationships. This can range from subtle difficulties to significant impairments impacting daily life.
Restricted and Repetitive Behaviors, Interests, or Activities: This can include stereotyped movements like hand-flapping or rocking, a need for sameness and routines, intense interests in specific topics, or sensory sensitivities. These behaviors can sometimes be coping mechanisms or sources of comfort for individuals with ASD.

Co-occurring Conditions: ASD is often accompanied by other conditions, both psychological and physiological.

Psychological Comorbidities: Attention-deficit hyperactivity disorder (ADHD) is frequently seen in individuals with ASD, sharing features like hyperactivity and social difficulties. Anxiety, depression, and obsessive-compulsive disorder (OCD) are also more common, potentially stemming from the challenges of navigating a world not always designed for neurodiversity. Intellectual disability can also co-occur, though many individuals with ASD have average to above-average intelligence.
Physiological Comorbidities: Epilepsy is more prevalent in the ASD population, particularly in those with intellectual disability. Sleep disorders and gastrointestinal (GI) issues are also commonly reported. Emerging research is exploring links between immune system dysfunction and ASD, including increased inflammation and associations with autoimmune disorders.

Variability of Symptoms: It’s essential to remember the heterogeneity of ASD. Symptoms and their severity vary greatly. Some individuals may have significant communication challenges and require substantial support, while others may be highly articulate and independent, experiencing more subtle social communication differences. This spectrum is why personalized approaches to diagnosis and support are so critical.

Clinical features of ASD. The three core features of ASD are deficits in social communication, restricted and fixated interests together with speech deficits, and language delays. The first two features are used to diagnose ASD according to the Diagnostic (more…)

Etiology of ASD: Genetic and Environmental Factors

The exact causes of ASD are complex and not fully understood, but research points to a combination of genetic and environmental factors.

Genetic Factors: ASD has a strong genetic component. Twin studies show significantly higher concordance rates in identical twins compared to fraternal twins. Researchers have identified numerous genes associated with ASD, some of which are involved in brain development, synaptic function, and neuronal communication. These genetic factors can range from rare, high-impact mutations to common genetic variations that, in combination, increase ASD risk. Databases like SFARI Gene categorize genes based on the strength of their association with ASD, aiding ongoing research.

Environmental Factors: Non-genetic factors also play a role, potentially interacting with genetic predispositions. These include:

Parental Age: Advanced paternal age has been linked to an increased risk of ASD in offspring, possibly due to the accumulation of genetic mutations.
Maternal Health During Pregnancy: Factors like maternal nutritional status (e.g., folic acid levels), metabolic conditions, infections during pregnancy, prenatal stress, and exposure to certain toxins or medications have been investigated as potential risk factors. Maternal immune activation, where the mother’s immune system is activated during pregnancy due to infection, is a significant area of research.
Immune System and Inflammation: Research suggests that immune system dysregulation and inflammation, both during prenatal development and postnatally, may contribute to ASD. Maternal antibodies and cytokine levels are being studied for their potential impact on fetal brain development.

It’s crucial to understand that ASD etiology is multifactorial. It’s not typically caused by a single gene or environmental factor but rather a complex interplay of multiple influences.

Model for the etiology of ASD. A. ASD are caused by genetic or environmental factors or a combination of these. For some individuals, ASD is solely caused by the presence of the genetic mutation(s) (red line). Exposure to a certain environment may cause (more…)

The Process of Autism Diagnosis in Brisbane (and Generally)

Seeking an autism diagnosis in Brisbane, or anywhere, involves a multi-step process aimed at thoroughly assessing an individual’s developmental history, current behaviors, and communication patterns. It’s important to note that there is no single medical test for ASD; diagnosis is based on clinical observation and standardized assessment tools.

Who Diagnoses Autism?

An autism diagnosis is typically made by a team of professionals, often including:

Developmental Pediatricians: These specialists are experts in child development and can assess for a range of developmental conditions, including ASD. In Brisbane, developmental pediatricians are key figures in the diagnostic pathway for children.
Child Psychiatrists: Psychiatrists specializing in children and adolescents can diagnose ASD and address any co-occurring mental health conditions.
Psychologists: Clinical psychologists and neuropsychologists trained in ASD assessment use standardized tests and observations to evaluate cognitive and behavioral characteristics.
Speech Pathologists: Speech and language skills are central to ASD diagnosis. Speech pathologists assess communication abilities and identify any speech or language delays or differences.
Occupational Therapists: Occupational therapists evaluate sensory processing and motor skills, which can be affected in ASD.

In Brisbane, families often begin the diagnostic journey by consulting their general practitioner (GP) or pediatrician, who can then refer them to specialists for comprehensive assessment.

Steps in the Diagnostic Process

The diagnostic process generally involves several key steps:

Initial Screening: This may be initiated by parents, educators, or healthcare providers who notice potential signs of ASD. Screening tools like the Autism Spectrum Quotient (AQ) or the Social Communication Questionnaire (SCQ) may be used to identify individuals who would benefit from a more comprehensive evaluation.
Comprehensive Assessment: This is the core of the diagnostic process and typically includes:
- Autism Diagnostic Observation Schedule-Second Edition (ADOS-2): This is a semi-structured, standardized assessment that involves direct observation of social communication and interaction behaviors.
- Autism Diagnostic Interview-Revised (ADI-R): This is a structured interview conducted with parents or caregivers to gather detailed information about the individual’s developmental history and ASD-related behaviors.
- Developmental History Review: Professionals will collect information about the individual’s developmental milestones, medical history, and family history.
- Cognitive and Language Assessments: These tests evaluate intellectual abilities, language comprehension, and expressive language skills.
- Adaptive Behavior Assessments: Tools like the Vineland Adaptive Behavior Scales assess daily living skills, social skills, and communication skills.
- Observation in Different Settings: Observing the individual in various settings, such as at home, school, or in social situations, can provide valuable insights.
Multidisciplinary Team Meeting: After the assessments are completed, the team of professionals meets to review all the information, discuss their findings, and determine if the diagnostic criteria for ASD are met.
Diagnosis and Feedback: If a diagnosis of ASD is made, the team will provide feedback to the individual and their family, explaining the diagnosis, discussing strengths and challenges, and recommending appropriate support and intervention services.

Navigating the Diagnostic Journey in Brisbane

For families in Brisbane seeking an autism diagnosis, several resources and pathways are available:

General Practitioners (GPs) and Pediatricians: Your GP or pediatrician is usually the first point of contact. They can provide initial advice, conduct preliminary screenings, and make referrals to specialist diagnostic services.
Specialist Clinics and Centers: Brisbane has specialist clinics and centers dedicated to ASD diagnosis and assessment. These centers often have multidisciplinary teams and offer comprehensive diagnostic services for children and adults. Researching “Autism Diagnosis Brisbane clinics” online can provide local options.
Queensland Health Services: Public health services in Queensland may offer diagnostic pathways for ASD, particularly for children. Contacting Queensland Health or local community health centers can provide information on available public services.
Private Practitioners: Many private psychologists, psychiatrists, and developmental pediatricians in Brisbane specialize in ASD diagnosis. Private assessments may offer shorter wait times but typically involve out-of-pocket costs or require private health insurance.
Support Organizations: Organizations like Autism Queensland can provide information and support throughout the diagnostic process, including directories of professionals and services in Brisbane.

Wait Times: It’s important to be aware that wait times for autism assessments can vary, particularly within the public system. Private assessments may be available sooner but at a cost. Planning ahead and starting the process as early as possible is advisable if you have concerns.

Adult Autism Diagnosis Brisbane

While ASD is often diagnosed in childhood, adults can also seek a diagnosis. Adult autism diagnosis in Brisbane follows a similar process to child diagnosis, but may be adapted to suit adult experiences and presentations. Adults seeking diagnosis may be doing so for various reasons, including gaining self-understanding, accessing workplace accommodations, or seeking appropriate mental health support. Finding professionals experienced in adult ASD assessment is key.

Pathology and Research

Research into the pathology of ASD is ongoing and aims to understand the underlying biological mechanisms contributing to the condition.

Neuropathology: Studies have identified differences in brain structure and function in individuals with ASD. Early brain overgrowth followed by altered growth patterns, differences in brain connectivity, and abnormalities in brain cell cytoarchitecture have been reported. Synaptic dysfunction is a key area of focus. Many genes linked to ASD play crucial roles in synapse formation and function, leading to the classification of ASD as a “synaptopathy.” Signaling pathways at synapses, such as the mTOR/PI3K and NRXN-NLGN-SHANK pathways, are implicated in ASD pathology.

Extracerebral Pathology: Research has expanded beyond the brain to explore other body systems in ASD. Gastrointestinal (GI) issues are common, with many individuals experiencing GI symptoms. Gut microbiome dysbiosis and altered intestinal permeability (“leaky gut”) are being investigated for their potential role in ASD and their connection to brain function through the gut-brain axis. Immune system abnormalities and inflammation are also areas of active research.

Understanding the complex pathology of ASD is crucial for developing potential biomarkers, targeted treatments, and prevention strategies in the future. Accurate and timely diagnosis is fundamental for research progress and for ensuring individuals with ASD receive appropriate and personalized support.

Conclusion

Autism spectrum disorder is a complex and heterogeneous neurodevelopmental condition. Seeking an autism diagnosis is a significant step towards understanding oneself or a loved one, accessing appropriate support, and connecting with the autism community. In Brisbane, as in other regions, navigating the diagnostic pathway requires awareness of available services, professionals, and assessment processes. Continued research into the etiology and pathology of ASD is essential to improve diagnostic accuracy, develop effective interventions, and ultimately enhance the quality of life for individuals on the autism spectrum. For those in Brisbane with concerns about ASD, seeking professional assessment is a vital step towards understanding and support.

References

1.Kanner L. Autistic disturbances of affective contact. Nerv Child. 1943;2:217–50.

2.Asperger H. Die “Autistischen Psychopathen” im Kindesalter. Arch Psychiatr Nervenkr. 1944;117(1):76–136. https://doi.org/10.1007/BF01837709 .

3.American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders [Internet]. Diagnostic and Statistical Manual of Mental Disorders. 5th Edition. American Psychiatric Association; 2013. https://doi.org/10.1176/appi.books.9780890425596 .

4.Masi A, DeMayo MM, Glozier N, Guastella AJ. An Overview of Autism Spectrum Disorder, Heterogeneity and Treatment Options. Neurosci Bull. 2017;33(2):183–93. https://doi.org/10.1007/s12264-017-0100-y . [PMC free article: PMC5360849] [PubMed: 28213805]

5.Volkmar FR, Wolf JM. When children with autism become adults. World Psychiatry. 2013;12(1):79–80. https://doi.org/10.1002/wps.20020 . [PMC free article: PMC3619174] [PubMed: 23471806]

6.Kim SH, Lord C. Restricted and repetitive behaviors in toddlers and preschoolers with autism spectrum disorders based on the Autism Diagnostic Observation Schedule (ADOS). Autism Res. 2010;3(4):162–73. https://doi.org/10.1002/aur.142 . [PMC free article: PMC3005305] [PubMed: 20589716]

7.Leitner Y. The co-occurrence of autism and attention deficit hyperactivity disorder in children – What do we know? Front Hum Neurosci. 2014;8:268. https://doi.org/10.3389/fnhum.2014.00268 . [PMC free article: PMC4010758] [PubMed: 24808851]

8.Besag FMC. Epilepsy in patients with autism: Links, risks and treatment challenges. Neuropsychiatr Dis Treat. 2018;14:1–10. https://doi.org/10.2147/NDT.S120509 . [PMC free article: PMC5739118] [PubMed: 29296085]

9.Careaga M, Van de Water J, Ashwood P. Immune dysfunction in autism: A pathway to treatment. Neurotherapeutics. 2010;7(3):283–92. https://doi.org/10.1016/j.nurt.2010.05.003 . [PMC free article: PMC5084232] [PubMed: 20643381]

10.Boulanger-Bertolus J, Pancaro C, Mashour GA. Increasing role of maternal immune activation in neurodevelopmental disorders. Front Behav Neurosci. 2018;12:1–6. https://doi.org/10.3389/fnbeh.2018.00230 . [PMC free article: PMC6182081] [PubMed: 30344483]

11.Mandell DS, Novak MM, Zubritsky CD. Factors associated with age of diagnosis among children with autism spectrum disorders. Pediatrics. 2005;116(6):1480–6. https://doi.org/10.1542/peds.2005-0185 . [PMC free article: PMC2861294] [PubMed: 16322174]

12.Woodbury-Smith MR, Volkmar FR. Asperger syndrome. Eur Child Adolesc Psychiatry. 2009;18(1):2–11. https://doi.org/10.1007/s00787-008-0701-0 . [PubMed: 18563474]

13.Sztainberg Y, Zoghbi HY. Lessons learned from studying syndromic autism spectrum disorders. Nat Neurosci. 2016;19(11):1408–18. https://doi.org/10.1038/nn.4420 . [PubMed: 27786181]

14.Maenner MJ, Shaw KA, Baio J, Washington A, Patrick M, DiRienzo M, et al. Prevalence of autism spectrum disorder among children aged 8 Years-Autism and developmental disabilities monitoring network, 11 Sites, United States, 2016. MMWR Surveill Summ. 2020;69(4) https://doi.org/10.15585/mmwr.ss6903a1 . [PMC free article: PMC7119644] [PubMed: 32214087]

15.Chiarotti F, Venerosi A. Epidemiology of autism spectrum disorders: A review of worldwide prevalence estimates since 2014. Brain Sci. 2020;10(5) https://doi.org/10.3390/brainsci10050274 . [PMC free article: PMC7288022] [PubMed: 32370097]

16.Qiu S, Lu Y, Li Y, Shi J, Cui H, Gu Y, et al. Prevalence of autism spectrum disorder in Asia: A systematic review and meta-analysis. Psychiatry Res. 2020;284:112679. https://doi.org/10.1016/j.psychres.2019.112679 . [PubMed: 31735373]

17.Autism spectrum disorders [Internet]. [cited 2021 May 14]. Available from: https://www.who.int/news-room/fact-sheets/detail/autism-spectrum-disorders.

18.Rivet TT, Matson JL. Review of gender differences in core symptomatology in autism spectrum disorders. Research in Autism Spectrum Disorders. 2011;5(3):957–76. https://doi.org/10.1016/j.rasd.2010.12.003 .

19.Ferri SL, Abel T, Brodkin ES. Sex Differences in Autism Spectrum Disorder: a Review. Curr Psychiatry Rep. 2018;20(2):9. https://doi.org/10.1007/s11920-018-0874-2 . [PMC free article: PMC6477922] [PubMed: 29504047]

20.Abrahams BS, Geschwind DH. Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet. 2008;9(5):341–55. https://doi.org/10.1038/nrg2346 . [PMC free article: PMC2756414] [PubMed: 18414403]

21.Genovese A, Butler MG. Clinical assessment, genetics, and treatment approaches in autism spectrum disorder (ASD). Int J Mol Sci. 2020;21(13):1–18. https://doi.org/10.3390/ijms21134726 . [PMC free article: PMC7369758] [PubMed: 32630718]

22.Ozonoff S, Young GS, Carter A, Messinger D, Yirmiya N, Zwaigenbaum L, et al. Recurrence risk for autism spectrum disorders: A baby siblings research consortium study. Pediatrics. 2011;128(3):e488–95. https://doi.org/10.1542/peds.2010-2825 . [PMC free article: PMC3164092] [PubMed: 21844053]

23.Geschwind DH. Genetics of autism spectrum disorders. Trends Cogn Sci. 2011;15(9):409–16. https://doi.org/10.1016/j.tics.2011.07.003 . [PMC free article: PMC3691066] [PubMed: 21855394]

24.Miles JH. Autism spectrum disorders–a genetics review. Genet Med. 2011;13(4):278–94. https://doi.org/10.1097/GIM.0b013e3181ff67ba . [PubMed: 21358411]

25.About the Gene Scoring Module – SFARI Gene [Internet]. [cited 2021 May 14]. Available from: https://gene.sfari.org/about-gene-scoring/

26.Gene Scoring Module – SFARI Gene [Internet]. [cited 2021 May 14]. Available from: https://gene.sfari.org/database/gene-scoring/

27.Satterstrom FK, Kosmicki JA, Wang J, Breen MS, De Rubeis S, An J-Y, et al. Large-Scale Exome Sequencing Study Implicates Both Developmental and Functional Changes in the Neurobiology of Autism. Cell. 2020;180(3):568–584.e23. [PMC free article: PMC7250485] [PubMed: 31981491]

28.Wu S, Wu F, Ding Y, Hou J, Bi J, Zhang Z. Advanced parental age and autism risk in children: a systematic review and meta-analysis. Acta Psychiatr Scand. 2017;135(1):29–41. https://doi.org/10.1111/acps.12666 . [PubMed: 27858958]

29.Karimi P, Kamali E, Mousavi SM, Karahmadi M. Environmental factors influencing the risk of autism. J Res Med Sci. 2017;22:27. https://doi.org/10.4103/1735-1995.200272 . [PMC free article: PMC5377970] [PubMed: 28413424]

30.Emberti Gialloreti L, Mazzone L, Benvenuto A, Fasano A, Alcon AG, Kraneveld A, et al. Risk and Protective Environmental Factors Associated with Autism Spectrum Disorder: Evidence-Based Principles and Recommendations. J Clin Med. 2019;8(2):217. https://doi.org/10.3390/jcm8020217 . [PMC free article: PMC6406684] [PubMed: 30744008]

31.Hagmeyer S, Mangus K, Boeckers TM, Grabrucker AM. Effects of trace metal profiles characteristic for autism on synapses in cultured neurons. Neural Plast. 2015;2015:985083. https://doi.org/10.1155/2015/985083 . [PMC free article: PMC4352758] [PubMed: 25802764]

32.Careaga M, Murai T, Bauman MD. Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates. Biol Psychiatry. 2017;81(5):391–401. https://doi.org/10.1016/j.biopsych.2016.10.020 . [PMC free article: PMC5513502] [PubMed: 28137374]

33.Bölte S, Girdler S, Marschik PB. The contribution of environmental exposure to the etiology of autism spectrum disorder. Cell Mol Life Sci. 2019;76(7):1275–97. https://doi.org/10.1007/s00018-018-2988-4 . [PMC free article: PMC6420889] [PubMed: 30570672]

34.Jyonouchi H, Sun S, Le H. Proinflammatory and regulatory cytokine production associated with innate and adaptive immune responses in children with autism spectrum disorders and developmental regression. J Neuroimmunol. 2001;120(1–2):170–9. https://doi.org/10.1016/S0165-5728(01)00421-0 . [PubMed: 11694332]

35.Malik M, Sheikh AM, Wen G, Spivack W, Brown WT, Li X. Expression of inflammatory cytokines, Bcl2 and cathepsin D are altered in lymphoblasts of autistic subjects. Immunobiology. 2011;216(1–2):80–5. https://doi.org/10.1016/j.imbio.2010.03.001 . [PubMed: 20399529]

36.Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA. Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol. 2005;57(1):67–81. https://doi.org/10.1002/ana.20315 . [PubMed: 15546155]

37.Modabbernia A, Velthorst E, Reichenberg A. Environmental risk factors for autism: an evidence-based review of systematic reviews and meta-analyses. Mol Autism. 2017;8(1):1–16. https://doi.org/10.1186/s13229-017-0121-4 . [PMC free article: PMC5356236] [PubMed: 28331572]

38.Matelski L, Van de Water J. Risk factors in autism: Thinking outside the brain. J Autoimmun. 2016;67:1–7. https://doi.org/10.1016/j.jaut.2015.11.003 . [PMC free article: PMC5467975] [PubMed: 26725748]

39.Haar S, Berman S, Behrmann M, Dinstein I. Anatomical Abnormalities in Autism? Cereb Cortex. 2016;26(4):1440–52. https://doi.org/10.1093/cercor/bhu242 . [PubMed: 25316335]

40.Nickl-Jockschat T, Habel U, Maria Michel T, Manning J, Laird AR, Fox PT, et al. Brain structure anomalies in autism spectrum disorder-a meta-analysis of VBM studies using anatomic likelihood estimation. Hum Brain Mapp. 2012;33(6):1470–89. https://doi.org/10.1002/hbm.21299 . [PMC free article: PMC4801488] [PubMed: 21692142]

41.Courchesne E, Campbell K, Solso S. Brain growth across the life span in autism: Age-specific changes in anatomical pathology. Brain Res. 2011;1380:138–45. https://doi.org/10.1016/j.brainres.2010.09.101 . [PMC free article: PMC4500507] [PubMed: 20920490]

42.Mohammad-Rezazadeh I, Frohlich J, Loo SK, Jeste SS. Brain connectivity in autism spectrum disorder. Casanova MF, El-Baz A, Suri JS, editors. Curr Opin Neurol. 2016;29(2):137–47. https://doi.org/10.1097/WCO.0000000000000301 . [PMC free article: PMC4843767] [PubMed: 26910484]

43.Fatemi SH, Aldinger KA, Ashwood P, Bauman ML, Blaha CD, Blatt GJ, et al. Consensus paper: Pathological role of the cerebellum in Autism. Cerebellum. 2012;11(3):777–807. https://doi.org/10.1007/s12311-012-0355-9 . [PMC free article: PMC3677555] [PubMed: 22370873]

44.Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, et al. Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2007;39(1):25–7. https://doi.org/10.1038/ng1933 . [PMC free article: PMC2082049] [PubMed: 17173049]

45.Leblond CS, Nava C, Polge A, Gauthier J, Huguet G, Lumbroso S, et al. Meta-analysis of SHANK Mutations in Autism Spectrum Disorders: A Gradient of Severity in Cognitive Impairments. PLoS Genet. 2014;10(9):e1004580. https://doi.org/10.1371/journal.pgen.1004580 . [PMC free article: PMC4154644] [PubMed: 25188300]

46.Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, et al. Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet. 2007;81(6):1289–97. https://doi.org/10.1086/522590 . [PMC free article: PMC2276348] [PubMed: 17999366]

47.Autism Genome Project Consortium. Szatmari P, Paterson AD, Zwaigenbaum L, Roberts W, Brian J, et al. Mapping autism risk loci using genetic linkage and chromosomal rearrangements. Nat Genet. 2007;39(3):319–28. https://doi.org/10.1038/ng1985 . [PMC free article: PMC4867008] [PubMed: 17322880]

48.Kim H-G, Kishikawa S, Higgins AW, Seong I-S, Donovan DJ, Shen Y, et al. Disruption of Neurexin 1 Associated with Autism Spectrum Disorder. Am J Hum Genet [Internet] 2008;82(1):199–207. https://doi.org/10.1016/j.ajhg.2007.09.011 . [PMC free article: PMC2253961] [PubMed: 18179900]

49.Yan J, Noltner K, Feng J, Li W, Schroer R, Skinner C, et al. Neurexin 1α structural variants associated with autism. Neurosci Lett. 2008;438(3):368–70. https://doi.org/10.1016/j.neulet.2008.04.074 . [PubMed: 18490107]

50.De Rubeis S, He X, Goldberg AP, Poultney CS, Samocha K, Ercument Cicek A, et al. Synaptic, transcriptional and chromatin genes disrupted in autism. Nature. 2014;515(7526):209–15. https://doi.org/10.1038/nature13772 . [PMC free article: PMC4402723] [PubMed: 25363760]

51.Parente DJ, Garriga C, Baskin B, Douglas G, Cho MT, Araujo GC, et al. Neuroligin 2 nonsense variant associated with anxiety, autism, intellectual disability, hyperphagia, and obesity. Am J Med Genet Part A. 2017;173(1):213–6. https://doi.org/10.1002/ajmg.a.37977 . [PubMed: 27865048]

52.Xu X, Xiong Z, Zhang L, Liu Y, Lu L, Peng Y, et al. Variations analysis of NLGN3 and NLGN4X gene in Chinese autism patients. Mol Biol Rep. 2014;41(6):4133–40. https://doi.org/10.1007/s11033-014-3284-5 . [PubMed: 24570023]

53.Jamain S, Quach H, Betancur C, Råstam M, Colineaux C, Gillberg C, et al. Mutations of the X-linked genes encoding neuroligins NLGN3 and NLGN4 are associated with autism. Nat Genet. 2003;34(1):27–9. https://doi.org/10.1038/ng1136 . [PMC free article: PMC1925054] [PubMed: 12669065]

54.Bourgeron T. Les connaissances actuelles sur la génétique de l’autisme et propositions pour la recherche future. Comptes Rendus – Biol. 2016;339(7–8):300–7. https://doi.org/10.1016/j.crvi.2016.05.004 . [PubMed: 27289453]

55.Huguet G, Ey E, Bourgeron T. The Genetic Landscapes of Autism Spectrum Disorders. Annu Rev Genomics Hum Genet. 2013;14:191–213. https://doi.org/10.1146/annurev-genom-091212-153431 . [PubMed: 23875794]

56.Bagni C, Zukin RS. A Synaptic Perspective of Fragile X Syndrome and Autism Spectrum Disorders. Neuron. 2019;101(6):1070–1088. https://doi.org/10.1016/j.neuron.2019.02.041 . [PMC free article: PMC9628679] [PubMed: 30897358]

57.Guang S, Pang N, Deng X, Yang L, He F, Wu L, et al. Synaptopathology involved in autism spectrum disorder. Front Cell Neurosci. 2018;12:1–16. https://doi.org/10.3389/fncel.2018.00470 . [PMC free article: PMC6309163] [PubMed: 30627085]

58.Bourgeron T. A synaptic trek to autism. Curr Opin Neurobiol. 2009;19(2):231–4. https://doi.org/10.1016/j.conb.2009.06.003 . [PubMed: 19545994]

59.Grabrucker AM, Schmeisser MJ, Schoen M, Boeckers TM. Postsynaptic ProSAP/Shank scaffolds in the cross-hair of synaptopathies. Trends Cell Biol. 2011;21(10):594–603. https://doi.org/10.1016/j.tcb.2011.07.003 . [PubMed: 21840719]

60.Grabrucker AM. Environmental factors in autism. Front Psychiatry. 2013;3:1–13. https://doi.org/10.3389/fpsyt.2012.00118 . [PMC free article: PMC3548163] [PubMed: 23346059]

61.Buie T, Campbell DB, Fuchs GJ, Furuta GT, Levy J, VandeWater J, et al. Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: a consensus report. Pediatrics. 2010;125 Suppl 1:1–18. https://doi.org/10.1542/peds.2009-1878C . [PubMed: 20048083]

62.Adams JB, Johansen LJ, Powell LD, Quig D, Rubin RA. Gastrointestinal flora and gastrointestinal status in children with autism – comparisons to typical children and correlation with autism severity. BMC Gastroenterol. 2011;11(1):22. https://doi.org/10.1186/1471-230X-11-22 . [PMC free article: PMC3072352] [PubMed: 21410934]

63.Bjørklund G, Pivina L, Dadar M, Meguid NA, Semenova Y, Anwar M, et al. Neuroscience and Biobehavioral Reviews Gastrointestinal alterations in autism spectrum disorder : What do we know? Neurosci Biobehav Rev. 2020;118:111–20. https://doi.org/10.1016/j.neubiorev.2020.06.033 . [PubMed: 32621940]

64.Wasilewska J, Klukowski M. Gastrointestinal symptoms and autism spectrum disorder: links and risks – a possible new overlap syndrome. Pediatr Heal Med Ther. 2015;6:153–166. https://doi.org/10.2147/PHMT.S85717 . [PMC free article: PMC5683266] [PubMed: 29388597]

65.Wang LW, Tancredi DJ, Thomas DW. The prevalence of gastrointestinal problems in children across the United States with autism spectrum disorders from families with multiple affected members. J Dev Behav Pediatr. 2011;32(5):351–60. https://doi.org/10.1097/DBP.0b013e31821bd06a . [PubMed: 21555957]

66.de Magistris L, Familiari V, Pascotto A, Sapone A, Frolli A, Iardino P, et al. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr. 2010;51(4):418–24. https://doi.org/10.1097/MPG.0b013e3181dcc4a5 . [PubMed: 20683204]

67.D’Eufemia P, Celli M, Finocchiaro R, Pacifico L, Viozzi L, Zaccagiiini M, et al. Abnormal intestinal permeability in children with autism. Acta Paediatr. 1996;85(9):1076–9. https://doi.org/10.1111/j.1651-2227.1996.tb14220.x . [PubMed: 8888921]

68.Hsiao EY, McBride SW, Chow J, Mazmanian SK, Patterson PH. Modeling an autism risk factor in mice leads to permanent immune dysregulation. Proc Natl Acad Sci USA. 2012;109(31):12776–81. https://doi.org/10.1073/pnas.1202556109 . [PMC free article: PMC3411999] [PubMed: 22802640]

69.Fröhlich H, Kollmeyer ML, Linz VC, Stuhlinger M, Groneberg D, Reigl A, et al. Gastrointestinal dysfunction in autism displayed by altered motility and achalasia in Foxp1 +/− mice. Proc Natl Acad Sci USA. 2019;116(44):22237–45. https://doi.org/10.1073/pnas.1911429116 . [PMC free article: PMC6825283] [PubMed: 31611379]

70.James DM, Kozol RA, Kajiwara Y, Wahl AL, Storrs EC, Buxbaum JD, et al. Intestinal dysmotility in a zebrafish (Danio rerio) shank3a;shank3bmutant model of autism. Mol Autism. 2019;10:3. https://doi.org/10.1186/s13229-018-0250-4 . [PMC free article: PMC6357389] [PubMed: 30733854]

71.Mayer E a, Knight R, Mazmanian SK, Cryan JF, Tillisch K. Gut microbes and the brain: paradigm shift in neuroscience. J Neurosci. 2014;34(46):15490–6. https://doi.org/10.1523/JNEUROSCI.3299-14.2014 . [PMC free article: PMC4228144] [PubMed: 25392516]

72.De Angelis M, Piccolo M, Vannini L, Siragusa S, De Giacomo A, Serrazzanetti DI, et al. Fecal Microbiota and Metabolome of Children with Autism and Pervasive Developmental Disorder Not Otherwise Specified. PLoS One. 2013;8(10):1–18. https://doi.org/10.1371/journal.pone.0076993 . [PMC free article: PMC3793965] [PubMed: 24130822]

73.Finegold SM, Dowd SE, Gontcharova V, Liu C, Henley KE, Wolcott RD, et al. Pyrosequencing study of fecal microflora of autistic and control children. Anaerobe. 2010;16(4):444–53. https://doi.org/10.1016/j.anaerobe.2010.06.008 . [PubMed: 20603222]

74.Kang DW, Park JG, Ilhan ZE, Wallstrom G, LaBaer J, Adams JB, et al. Reduced Incidence of Prevotella and Other Fermenters in Intestinal Microflora of Autistic Children. PLoS One. 2013;8(7):e68322. https://doi.org/10.1371/journal.pone.0068322 . [PMC free article: PMC3700858] [PubMed: 23844187]

75.Kang DW, Adams JB, Gregory AC, Borody T, Chittick L, Fasano A, et al. Microbiota Transfer Therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: An open-label study. Microbiome. 2017;5(1):1–16. https://doi.org/10.1186/s40168-016-0225-7 . [PMC free article: PMC5264285] [PubMed: 28122648]

76.Kang DW, Ilhan ZE, Isern NG, Hoyt DW, Howsmon DP, Shaffer M, et al. Differences in fecal microbial metabolites and microbiota of children with autism spectrum disorders. Anaerobe. 2018;49(2018):121–31. https://doi.org/10.1016/j.anaerobe.2017.12.007 . [PubMed: 29274915]

77.Vela G, Stark P, Socha M, Sauer AK, Hagmeyer S, Grabrucker AM. Zinc in Gut-Brain Interaction in Autism and Neurological Disorders. Neural Plast. 2015;2015:972791. https://doi.org/10.1155/2015/972791 . [PMC free article: PMC4386645] [PubMed: 25878905]

78.Coretti L, Paparo L, Riccio MP, Amato F, Cuomo M, Natale A, et al. Gut microbiota features in young children with autism spectrum disorders. Front Microbiol. 2018;9:1–12. https://doi.org/10.3389/fmicb.2018.03146 . [PMC free article: PMC6305749] [PubMed: 30619212]

79.de Angelis M, Francavilla R, Piccolo M, De Giacomo A, Gobbetti M. Autism spectrum disorders and intestinal microbiota. Gut Microbes. 2015;6(3):207–13. https://doi.org/10.1080/19490976.2015.1035855 . [PMC free article: PMC4616908] [PubMed: 25835343]

80.Kong X, Liu J, Cetinbas M, Sadreyev R, Koh M, Huang H, et al. New and preliminary evidence on altered oral and gut microbiota in individuals with autism spectrum disorder (ASD): Implications for ASD diagnosis and subtyping based on microbial biomarkers. Nutrients. 2019;11(9) https://doi.org/10.3390/nu11092128 . [PMC free article: PMC6770733] [PubMed: 31489949]

81.Strati F, Cavalieri D, Albanese D, De Felice C, Donati C, Hayek J, et al. New evidences on the altered gut microbiota in autism spectrum disorders. Microbiome. 2017;5(1):24. https://doi.org/10.1186/s40168-017-0242-1 . [PMC free article: PMC5320696] [PubMed: 28222761]

82.Williams BL, Hornig M, Buie T, Bauman ML, Cho Paik M, Wick I, et al. Impaired carbohydrate digestion and transport and mucosal dysbiosis in the intestines of children with autism and gastrointestinal disturbances. PLoS One. 2011;6(9):e24585. https://doi.org/10.1371/journal.pone.0024585 . [PMC free article: PMC3174969] [PubMed: 21949732]

83.Liu F, Li J, Wu F, Zheng H, Peng Q, Zhou H. Altered composition and function of intestinal microbiota in autism spectrum disorders: a systematic review. Transl Psychiatry. 2019;9(1):43. https://doi.org/10.1038/s41398-019-0389-6 . [PMC free article: PMC6351640] [PubMed: 30696816]

84.Cryan JF, O’Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, et al. The Microbiota-Gut-Brain Axis. Physiol Rev. 2019;99(4):1877–2013. https://doi.org/10.1152/physrev.00018.2018 . [PubMed: 31460832]

85.Rogers GB, Keating DJ, Young RL, Wong M-L, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016;21(6):738–48. https://doi.org/10.1038/mp.2016.50 . [PMC free article: PMC4879184] [PubMed: 27090305]

86.Leigh JP, Du J. Brief Report: Forecasting the Economic Burden of Autism in 2015 and 2025 in the United States. J Autism Dev Disord. 2015;45(12):4135–9. https://doi.org/10.1007/s10803-015-2521-7 . [PubMed: 26183723]

Doi: https://doi.org/10.36255/exonpublications.autismspectrumdisorders.2021.etiology