Autism is demanding increased attention by professional and lay audiences; prevalence seems to be increasing. There are differing opinions about whether the increase is due to greater recognition and reporting, diagnostic expansion and substitution, or increasing acceptability. On the other hand, the increase may be a consequence of environmental toxins or infectious and immune vulnerability and epigenetics or perhaps a combination of social and environmental factors.
Clearly, autism has a large genetic component and multiple genes are involved in various combinations. Nevertheless, the prevalence of autism in the United States and in other countries has increased exponentially; this trend would not happen with a purely genetic disorder. Most autism researchers accept a theory of etiology that starts with a genetic neurodevelopmental vulnerability combined with an environmental stressor through such epigenetic processes as immune function.1
Increasingly, researchers and clinicians refer to autism to describe a wide variety of phenotypes that start with genes and gene expression and range through a variety of metabolic functions to symptoms that cluster diagnostically but have a great deal of individuality. Symptoms can range from mild to severe and may be associated with mental retardation; GI and neurological involvement; and behavioral, emotional, cognitive, and whole body pathology.2
Here we discuss diagnostic assessment and classification, co-occurring or comorbid psychiatric disorders and their differential diagnosis, the medical workup, and possible medical comorbidities. We also review a model for psychosocial treatment as well as psychopharmacological and alternative treatments. We conclude with a brief look at the future of research and treatment.
Diagnostic assessment and classification
The term “autism (or autistic) spectrum disorder” (ASD) is likely to be replaced with “pervasive developmental disorder” in DSM-5. ASD is a collection of neurodevelopmentally based conditions of social and communicative impairments, each with varying severity and broadness of expression.
Autism was originally described by Leo Kanner in the early 1940s and termed “early infantile autism” of unknown etiology. By the 1960s, work on high concordance of autism in monozygotic twins and lower concordance in dizygotic twins and siblings led to the present-day understanding of ASD as a developmental and neurobiological condition with heterogeneous genetic and possible epigenetic triggers.
Diagnosis of ASD remains an empirical and behavioral procedure with no clear or single biological marker or assay. This has made reliable and valid diagnosis problematic: signs of ASD selected for inclusion in DSM have had fairly high diagnostic sensitivity but often poor specificity.3-5 Symptoms of ASD overlap with those of other neurodevelopmental disorders. Accurate differential diagnosis and diagnosis of comorbid conditions in ASD are therefore difficult.
The best practice for clinical assessment of ASD involves multiple methods of measuring multiple traits (Figure). Both parents and child contribute to data collection via interview and record review. The child is also observed directly or on video in the home, at school, and in the clinic under structured and unstructured conditions.6-8 The Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) are considered to be the gold standard in ASD diagnosis and are widely used in research.
Psychiatric workup and comorbidity
Because a behavior can reflect different etiologies and symptoms can overlap, other disorders need to be carefully considered. Within the differential for ASD are anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), and even prodromal schizophrenia or schizoid personality disorder.
When children are anxious, particularly when they have symptoms consistent with obsessive-compulsive disorder, they can manifest an inflexibility about routines (serving to bind their anxiety) and exhibit tics or behavioral compulsions that can be mistaken for stereotypies. Likewise, it can be difficult to delineate anxiety from the overwhelming biological basis for ASD in which learning deficits lead to anxious behavior.
Children with ADHD can seem socially impaired. But rather than having a deficit in theory of mind, the ability to understand another’s perspective through one’s own similar reasoning and experience, these children miss social cues (because they do not attend to them) or behave impulsively around peers, which can result in their being ostracised. The social withdrawal associated with thought disorders can be mistaken for the impairments in social interaction characteristic of ASD.
? Signs of autism spectrum disorder (ASD) selected for inclusion in DSM have had fairly high sensitivity to the clinical diagnosis of autism, but they often show poor specificity.
? A diagnosis of autism can be made only if the child’s social interactions are not commensurate with his or her developmental level.
? Psychiatric comorbidities, such as anxiety and attention-deficit/hyperactivity disorder, and medical comorbidities, such as epilepsy, sleep disorders, and Tourette syndrome, are frequent in ASD.
? ASD is heterogeneous in expression, and treatment plans must target ASD and comorbid disorders that may require integrated yet separate treatment..
? Psychopharmacological agents can help with symptoms of ASD, such as irritability, impulsivity, and anxiety; however, they do not seem to help directly with core symptoms of social reciprocity or communication, although they may do so indirectly through improved availability for treatment.
ASD can also be misdiagnosed in children who have a language disorder.9 Communication deficits can lead to social impairment, but these are secondary to limitations in reciprocal exchanges (and resultant frustration). In addition, the classification of receptive and expressive language disorders in DSM is nosologically different from American Speech-Language-Hearing Association standards.
1. Pardo CA, Eberhart CG. The neurobiology of autism. Brain Pathol. 2007;17:434-447.
2. Herbert MR. Contributions of the environment and environmentally vulnerable physiology to autism spectrum disorders. Curr Opin Neurol. 2010;23:103-110.
3. Andrews G, Pine DS, Hobbs MJ, et al. Neurodevelopmental disorders: cluster 2 of the proposed meta-structure for DSM-V and ICD-11. Psychol Med. 2009;39:2013-2023.
4. Siegel B. Helping Children With Autism Learn: A Guide to Treatment Approaches for Parents and Professionals. New York: Oxford University Press; 2003.
5. Siegel B, Ficcaglia M, Hayer C, et al. Treatment of pervasive developmental disorders. In: Weller E, McDermott J, Gabbard GO, eds. Gabbard’s Treatment of Psychiatric Disorders. 4th ed. Washington, DC: American Psychiatric Association Press; 2007:79-92.
6. Lord C, McGee JP, eds. Educating Children With Autism. Washington, DC: National Academy Press; 2001.
7.National Association for the Education of Young Children. Developmentally Appropriate Practice in Early Childhood Program Serving Children Birth Through Age 8. 2009. http://www.naeyc.org/files/naeyc/file/positions/position%20statement%20Web.pdf. Accessed August 31, 2010.
8. Sandall S, Smith BJ, McLean M, et al. DEC Recommended Practices: A Comprehensive Guide. Dallas: Cambium Learning Group Inc; 2005.
9. Bishop DV, Whitehouse AJ, Watt HJ, Line EA. Autism and diagnostic substitution: evidence from a study of adults with a history of developmental language disorder. Dev Med Child Neurol. 2008;50:341-345.
10. Matson JL, Shoemaker M. Intellectual disability and its relationship to autism spectrum disorders. Res Dev Disabil. 2009;30:1107-1114.
11.Mattila ML, Hurtig T, Haapsamo H, et al. Comorbid psychiatric disorders associated with Asperger syndrome/high-functioning autism: a community- and clinic-based study. J Autism Dev Disord. 2010;40:1080-1093.
12. Simonoff E, Pickles A, Charman T, et al. Psychiatric disorders in children with autism spectrum disorders: prevalence, comorbidity, and associated factors in a population-derived sample. J Am Acad Child Adolesc Psychiatry. 2008;47:921-929.
13. Spence SJ, Schneider MT. The role of epilepsy and epileptiform EEGs in Autism spectrum disorders. Pediatr Res. 2009;65:599-606.
14. Amiet C, Gourfinkel-An I, Bouzamondo A, et al. Epilepsy in autism is associated with intellectual disability and gender: evidence from a meta-analysis. Biol Psychiatry. 2008;64:577-582.
15. Hara H. Autism and epilepsy: a retrospective follow-up study. Brain Dev. 2007;29:486-490.
16. Elia M, Musumeci SA, Ferri R, Bergonzi P. Clinical and neurophysiological aspects of epilepsy in subjects with autism and mental retardation. Am J Ment Retard. 1995;100:6-16.
17. Wong V. Study of the relationship between tuberous sclerosis complex and autistic disorder. J Child Neurol. 2006;21:199-204.
18. Wisniewski KE, Segan SM, Miezejeski CM, et al. The Fra(X) syndrome: neurological, electrophysiological, and neuropathological abnormalities. Am J Med Genet. 1991;38:476-480.
19. Battaglia A. The inv dup(15) or idic(15) syndrome: a clinically recognisable neurogenetic disorder. Brain Dev. 2005;27:365-369.
20. Sherr EH. The ARX story (epilepsy, mental retardation, autism, and cerebral malformations): one gene leads to many phenotypes. Curr Opin Pediatr. 2003;15:567-571.
21. Richdale AL, Schreck KA. Sleep problems in autism spectrum disorders: prevalence, nature, and possible biospsychosocial aetiologies. Sleep Med Rev. 2009;13:403-411.
22. Krakowiak P, Goodlin-Jones B, Hertz-Picciotto I, et al. Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study. J Sleep Res. 2008;17:197-206.
23.Liu X, Hubbard JA, Fabes RA, Adam JB. Sleep disturbances and correlates of children with autism spectrum disorders. Child Psychiatry Hum Dev. 2006;37:179-191.
24. Nicholas B, Rudrasingham V, Nash S, et al. Association of Per1 and Npas2 with autistic disorder: support for the clock genes/social timing hypothesis. Mol Psychiatry. 2007;12:581-592.
25. Allik H, Larsson JO, Smedje H. Insomnia in school-age children with Asperger syndrome or high-functioning autism. BMC Psychiatry. 2006;6:18.
26. DeVincent CJ, Gadow KD, Delosh D, Geller L. Sleep disturbance and its relation to DSM-IV psychiatric symptoms in preschool-age children with pervasive developmental disorder and community controls. J Child Neurol. 2007;22:161-169.
27. Fernandez-Mendoza J, Calhoun S, Bixler EO, et al. Insomnia with objective short sleep duration is associated with deficits in neuropsychological performance: a general population study. Sleep. 2010;33:459-465.
28. Sancisi E, Cevoli S, Vignatellli L, et al. Increased prevalence of sleep disorders in chronic headache: a case-control study. Headache. 2010 Jun 21; [Epub ahead of print].
29. Koh S, Ward SL, Lin M, Chen LS. Sleep apnea treatment improves seizure control in children with neurodevelopmental disorders. Pediatr Neurol. 2000;22:36-39.
30. Wright B, Sims D, Smart S, et al. Melatonin versus placebo in children with autism spectrum conditions and severe sleep problems not amenable to behavioral management strategies: a randomized controlled crossover trial. J Autism Dev Disord. 2010 Jun 10; [Epub ahead of print].
31. Baron-Cohen S, Scahill VL, Izaguirre J, et al. The prevalence of Gilles de la Tourette syndrome in children and adolescents with autism: a large scale study. Psychol Med. 1999;29:1151-1159.
32. McConnell SR. Interventions to facilitate social interaction for young children with autism: review of available research and reccomendations for educational interventions and future research. J Autism Dev Disord. 2002;32:351-372.
33. Swiezy N, Stuart M, Korzekwa P. Bridging for success in autism: training and collaboration across medical, educational, and community settings. Child Adolesc Psychiatr Clin N Am. 2008;17:907-922, xi.
34. Siegel B. Getting the Best for Your Child With Autism: An Expert’s Guide to Treatment. New York: Guilford Press; 2008.
35. McCracken JT, McGough J, Shah B, et al; Research Units on Pediatric Psychopharmacology Autism Network. Risperidone in children with autism and serious behavioral problems. N Engl J Med. 2002;347:314-321.
36. Owen R, Sikich L, Marcus RN, et al. Aripiprazole in the treatment of irritability in children and adolescents with autistic disorder. Pediatrics. 2009;124:1533-1540.
37. Marcus RN, Owen R, Kamen L, et al. A placebo-controlled, fixed-dose study of aripiprazole in children and adolescents with irritability associated with autistic disorder. J Am Acad Child Adolesc Psychiatry. 2009;48:1110-1119.
38. King BH, Hollander E, Sikich L, et al STAART Psychopharmacology Network. Lack of efficacy of citalopram in children with autism spectrum disorders and high levels of repetitive behavior: citalopram ineffective in children with autism. Arch Gen Psychiatry. 2009;66:583-590.
39. Research Units on Pediatric Psychopharmacology Autism Network. Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity. Arch Gen Psychiatry. 2005;62:1266-1274.
40. Handen BL, Sahl R, Hardan AY. Guanfacine in children with autism and/or intellectual disabilities. J Dev Behav Pediatr. 2008;29:303-308.
41.Hollander E, Soorya L, Wasserman S, et al. Divalproex sodium vs. placebo in the treatment of repetitive behaviours in autism spectrum disorder. Int J Neuropsychopharmacol. 2006;9:209-213.
42. Chez MG, Burton Q, Dowling T, et al. Memantine as adjunctive therapy in children diagnosed with autistic spectrum disorders: an observation of initial clinical response and maintenance tolerability. J Child Neurol. 2007;22:574-579.
43. Dawson G, Rogers S, Munson J, et al. Randomized, controlled trial of an intervention for toddlers with autism: the Early Start Denver Model. Pediatrics. 2010;125:e17-e23.
44.Bent S, Hendren RL. Improving the prediction of response to therapy in autism. Neurotherapeutics. 2010;7:232-240.