While misdiagnosis can be a dilemma, overlooking a diagnosis can also be challenging. It is unclear why the diagnosis of intellectual disability is often missed, given that 50% to 70% of children with ASD have some level of intellectual disability.10 Clinicians may be reluctant to make this diagnosis in children who are difficult to assess, or to discuss this diagnosis with parents. Alternatively, assessment of cognitive functioning may not be part of the clinical evaluation. Ideally, patients should undergo a battery of clinical assessments that includes a test of cognitive functioning. A diagnosis of autism can be made only if the child’s social interactions are not commensurate with his or her developmental level.
It is worth noting that disorders that can be mistaken for ASD can co-occur with ASD. The diagnosis of ASD does not exclude the possibility of a comorbid brain disorder. ADHD and anxiety disorders are frequently associated with ASD, with mood disorders occurring less frequently.11,12
ASD is a heterogeneous set of disorders that is occasionally associated with (and secondary to) a particular neurological disease. In this situation, syndromic autism, there can be autistic features (ie, behaviors that appear to have their basis in a deficit in theory of mind) associated with, for example, tuberous sclerosis, fragile X syndrome, and agenesis of the corpus callosum.
Common medical comorbid conditions
Medical comorbidities, such as epilepsy, sleep disorders, and Tourette syndrome, are frequent in ASD. Their recognition and treatment form a core component of symptom management in affected individuals and highlight the importance of a multidisciplinary health care team.
Epilepsy occurs in up to one-third of individuals with ASD and suggests an imbalance of neural excitation and inhibition. Seizure onset has been noted to present during 2 peak periods: early childhood and adolescence.13-15 In addition, there is some suggestion of an increased risk of epilepsy in females and individuals with intellectual disability.14,16 Although there are no primary seizure types specifically associated with idiopathic ASD, specific neurogenetic disorders (eg, tuberous sclerosis complex, fragile X syndrome, chromosome 15q duplication syndrome, ARX-related conditions) confer increased risk of ASD and epilepsy.17-20 There are also reports of higher rates of epileptiform electroencephalograms in children who do not have clinical seizures.
Sleep disorders affect up to two-thirds of children with ASD.21 Insomnias are predominant; however, parasomnias, breathing disorders, and movement disorders have also been reported.22,23 Recent work in ASD genetics suggests a relationship between polymorphisms in the biological clock genes, per1 and npas2, and autism.24 Although the effects of sleep disorders are difficult to separate from the effects of neurodevelopmental disability in general, insomnia is important to treat because it may exacerbate challenging behaviors, hyperactivity, cognitive deficits, headaches, and seizure frequency.25-29 For sleep difficulties related to disrupted circadian cycles, it may be helpful to limit daytime sleeping and caffeine(Drug information on caffeine) intake and to ensure regular exercise. Exogenous treatment with melatonin(Drug information on melatonin) may decrease time to sleep onset.30
In patients with ASD, the prevalence of Tourette syndrome is increased (6.5%).31 Unifying theories posit a common genetic liability factor for ASD and tics; however, these theories have not been substantiated. Complex motor tics can be distinguished from common ASD stereotypies in that complex motor tics are involuntary, are quick and random, and tend to subside when an individual is engrossed in an activity. Behavioral and pharmacological interventions are only indicated when tics limit function and comfort.
Evidence-based ASD treatment must be intensive and individualized, with learning opportunities that are an integral part of educational and social interactions.32,33 Treatments for ASD begin with an understanding that the syndrome is heterogeneous in expression and that treatment plans must target ASD rather than comorbid disorders that may require integrated yet separate treatment. From the psychoeducational or behavioral treatment perspective, one heuristic for conceptualizing this clinical variability is to functionally translate DSM symptoms into autism-specific learning disabilities and autism-specific learning styles. This allows the clinician to think in terms of an autism treatment “toolbox” that can be used to assess a patient’s learning disabilities and learning styles and to choose specific intervention strategies to target them (Table).34 Research standards support ASD treatments that are behavioral in meth-odology and developmental with respect to curriculum content.3-5
Psychopharmacological agents can help with symptoms associated with ASD, such as irritability, impulsivity, anxiety, cognitive disorganization, aggression, difficulty in shifting attention from one area of interest to another, and distractible inattention. However, these medications do not seem to help directly with core symptoms of social reciprocity or communication, although improvement in the above-mentioned symptoms can help indirectly.
In 2006, the FDA approved risperidone(Drug information on risperidone) to treat irritability in autism.35 On the basis of 2 studies, aripiprazole(Drug information on aripiprazole) was approved for the same indication in November 2009.36,37 Other atypical antipsychotics have also been found to be effective in open-label trials. Except for ziprasidone(Drug information on ziprasidone), all are associated with weight gain, at least initially.
SSRIs have long been used to treat impulsivity, difficulty in shifting attention, anxiety, and repetitive behaviors on the basis of the finding of low serotonin levels in patients with ASD. However, a large, multisite, placebo-controlled trial of citalopram(Drug information on citalopram) in ASD did not find significant differences on the Clinical Global Impression Improvement (CGI-I) scale or the Children’s Yale-Brown OC [obsessive-compulsive] Scale (CY-BOCS).38 Factors that may account for this could have been the 30% placebo response rate.
Other medications that might be judiciously considered in the treatment of ASD include stimulants, a2-adrenergic agonists, divalproex, and memantine(Drug information on memantine).39-42 Alternative treatments under investigation include melatonin, ω-3 fatty acids, methyl B12, the casein-/gluten-free diet, digestive enzymes, hyperbaric oxygen therapy, and chelation. Most alternative treatments do not have published studies to guide treatment selection and for some, there is a question of safety.
The study of autism is progressing rapidly. Early identification and intervention is increasingly possible and effective.43 Further delineation of the gene-environment interaction theories of etiology are coming from large, collaborative studies. The number of treatment studies lags far behind that of studies of genetics and other etiologies, but the number is growing because of more sophisticated ideas about etiology and treatment targets.44
Community organizations, school personnel, and treatment providers are gaining increasing skill at personalizing treatments for patients with autism, with significant improvements in outcome. The rising number of adults with ASD presents a considerable challenge for suitable housing, employment, and effective interventions. It is likely that facing these challenges and the new understandings that are being developed will benefit not only people with ASD but all people with neurodevelopmental disorders.