Chapter 1
Autism Heterogeneity
Contents
Autism Heterogeneity is Extensive and Unexplained
Autism Heterogeneity has Blocked Medical Treatment Discovery
Diagnostic Criteria have not Constrained Autism Heterogeneity
Variation in Autism Diagnostic Features
Variation in Autism Brain Deficits, Medical Conditions, and Non-Diagnostic Symptoms
Variation in Genetic Risk Factors for Autism
Variation in Environmental Risk Factors for Autism
Summary: Variation Exists in all Autism Domains
Autism Subgroups and Unifying Theories for Autism have Addressed Heterogeneity
Competing Proposals for Autism Subgroups
Competing Brain Deficit Theories of Autism
Autism is Unified by a Shared Brain Disruption in Social Information Processing
Autism is Unified by a Failure to Sparsify Information to Prototypes
Autism is Unified by the Failure to Have a Theory Of Mind
Autism is Unified by Brain Underconnectivity
Autism is Unified by Impaired Attention to Biological Motion
Competing Genetic Risk Factor Theories of Autism
Competing Speculative Environmental Cause Theories of Autism
The Wakefield Vaccine Theory Fraud
Two Harmful Theories of Environmental Causes for Autism
Four Foolishly Speculative Theories of Environmental Causes for Autism
Competing GeneâEnvironment Interaction Theories of Autism
Subgroups and Unifying Theories have not Explained the Variation in Autism
Has Autism been Reified?
Saving the Phenomena of Autism Variation
How Should We View the Variation in Autism?
Serious Concerns for Maintaining the Autism Diagnosis
Eight Claims Concerning Autism Variation and the Autism Diagnosis
Chapter 1 Claim 1: Autism Heterogeneity is Meaningful
Chapter 2 Claim 2: Autism Symptom Heterogeneity Exists in Family Members
Chapter 3 Claim 3: The Social Brain is a Complex Super-Network
Chapter 4 Claim 4: Genetic Risk Factors Link Autism to Many Other Disorders
Chapter 5 Claim 5: Environmental Risk Factors Link Autism to Many Other Outcomes
Chapter 6 Claim 6: Savant Skills, Special Skills, and Intelligence Vary Widely in Autism
Chapter 7 Claim 7: Increasing Prevalence and the Problem Of Diagnosis
Chapter 8 Claim 8: Autism Symptoms Exist but the Disorder Remains Elusive
Summary of the Eight Claims Regarding Autism Variation
Belief in autism exists worldwide. Teachers, psychologists, doctors, and social workers are trained to recognize or diagnose autism. Parents whose children were diagnosed with autism learn about the disorder and search for treatments. Celebrity parents of children with autism, such as golfer Ernie Els, quarterback Doug Flutie, and comedian Jenny McCarthy, have made public statements about their children and publicly advocated for autism research and treatment. Numerous groups such as Autism Speaks and the Global Autism Project have advocated for autism. Individuals with autism Donna Williams (1998) and Temple Grandin (1996) have written memoirs. The movie Rain Man (Levinson, 1988) and the novel The Curious Incident of the Dog in the Night-time (Haddon, 2003) each told dramatic stories of autistic savantsâindividuals with autism who have remarkable memories or remarkable skills.
In most countries, magazines, newspapers, television broadcasts, and social media have reported news of autism, and many reports have raised alarm about the increased prevalence of autism. In the United States, the National Institutes of Health, as well as other government agencies, and private funding sources provide grant money to study autism, and the Centers for Disease Control and Prevention has monitored the startling increase in the diagnosis of autism.
In 1975 when I began studying autism I believed it was a distinct behavioral syndrome, and believed a unitary brain basis for it would soon be discovered. But by the middle of the 1990s many brain deficits had already been found in association with autism. Evidence suggested that subsets of individuals diagnosed with autism had deficits in one or more brain regions and brain neurochemicals, including the amygdala, the hippocampus, temporal and parietal regions of the cortex, and the neurohormone oxytocin (Waterhouse, Fein, & Modahl, 1996). Our research group did find evidence for abnormal oxytocin in autism (Green et al., 2001; Modahl et al., 1998). However, despite substantial financial support from the National Institutes of Mental Health, National Institutes of Child Health and Development, and support from several private funding agencies, and despite the intellectual effort of all on our research teams, we failed to find meaningful brain-based behavioral subgroups of autism (Stevens et al., 2000; Waterhouse et al., 1996). Our problems reflected the fieldâs problems.
No researcher or research group has found valid, empirically based behavioral subgroups within autism spectrum disorder (ASD) (Rutter, 2011; Witwer & Lecavalier, 2008). More significantly, no one has yet proven any specific brain deficit predicts a specific autism diagnostic behavior (Rutter, 2011; Waterhouse, 2008, 2011). Boucher (2011) suggested âthe concept of autism as a unitary disorder resulting from a single common cause ⊠may be at the point of being abandonedâ (p. 473).
Autism Heterogeneity is Extensive and Unexplained
The central challenge to understanding autism has been its heterogeneity. While any psychiatric disorder can be expected to include heterogeneity, the amount of heterogeneity in autism exceeds that found in other psychiatric disorders. Schaaf and Zoghbi (2011) stated, âIt is well established that the ASDs represent a heterogeneous group of disordersâ (p. 806). Jones and Klin (2009) stated, âIndividuals with autism show a vast clinical variability in the expression and severity of their symptoms. This heterogeneity spans the entire range of IQ and language function and a wide array of communicative, social, and behavioral disabilitiesâ (p. 471). Amaral (2011) asserted, âA hallmark of virtually every biological parameter assayed in individuals with autism is the enormous heterogeneityâfar greater than in the general populationâ (p. 6). HappĂ©, Ronald, and Plomin (2006) declared, âHeterogeneity within the autism spectrum is perhaps the biggest single obstacle to research at all levelsâ (p. 1220). Heterogeneity exists in autism diagnostic behaviors and in a wide range of additional behavioral impairments, medical conditions, brain deficits, as well as in genetic and environmental risk factors.
Autism researcher Robert Schultz said, âIf youâve seen one child with autism, youâve seen one child with autism. Autismâs like a snowflakeâ (Scott, 2011). Lord (2011) noted that anyone who has met more than one person with autism is struck by the differences between diagnosed individuals. For example, researchers Sullivan, Laverick, and Lewis (1995) described a young girl, Vanessa, who experienced repeated seizures as a child, did not talk, had little eye contact, and had such poor muscle tone her body had to be strapped into an orthopedic chair. She was diagnosed with autism and diagnosed with Rett syndrome caused by a gene mutation (Sullivan et al., 1995). Daniel Corney, like Vanessa, experienced repeated seizures as a child, was socially aloof, and he was diagnosed with autism. Unlike Vanessa, Daniel had intact motor skills, could speak, and had a remarkable memory. As a young adult he set the European record for reciting pi to 22,514 decimal places in just over 5 hours. He changed his name to Daniel Tammet, and wrote two books about his experience of being an autistic savant with synesthesia: Born on a Blue Day (2007), and Embracing the Wide Sky, A Tour Across the Horizons of the Mind (2009).
Autism Heterogeneity has Blocked Medical Treatment Discovery
The most serious problem caused by the failure to understand autism heterogeneity is the failure to discover any autism-specific effective drug. Unlike other psychiatric disorders, the core diagnostic symptom of autismâimpaired social interactionâis not improved by any psychotropic medication (Rutter, 2011). Levy, Mandel, and Schultz (2009) pointed out that âexisting pharmacotherapeutic agents are not effective for treatment of core symptoms of autism spectrum disordersâ (p. 1633), and they noted that drug treatments are rarely effective for addressing non-diagnostic symptoms in autism. Rogers and Vismara (2008) reported that no one knows which treatments or combinations of types of treatments will be most effective for which symptoms of autism, and no one knows if there are subgroups of individuals with autism who would benefit from a particular medical treatment. McPheeters et al. (2011) concluded, âAlthough many children with ASDs are currently treated with medical interventions, strikingly little evidence exists to support benefit for most treatmentsâ (p. e1312).
Effective medication for autism cannot be developed until the heterogeneity in autism is understood, and the heterogeneity in autism is extensive. Many different efforts have been made to resolve the heterogeneity. One line of attack has been to refine the diagnosis of autism. Unfortunately, reformulations of diagnostic criteria for autism have not decreased heterogeneity.
Diagnostic Criteria have not Constrained Autism Heterogeneity
Although diagnostic criteria are designed to narrowly define a disorder, the diagnostic criteria for autism have allowed for wide heterogeneity. The fifth Diagnostic and Statistical Manual of the American Psychiatric Association (www.dsm5.org) recognized the heterogeneity within autism by expanding Autism Disorder to become Autism Spectrum Disorder (ASD). Throughout this book, I have used the term autism rather than the DSM-5 diagnostic label Autism Spectrum Disorder. As used here the term autism is intended to include or represent diagnoses used in research and theory, including the proposed DSM-5 (APA, 2011) and the previous DSM-IV (APA, 1994) and DSM-IV-TR (APA, 2000).
DSM-5 mandated two diagnostic criteria for autism spectrum disorders. The first was social communication and interaction deficits as shown in impaired social approach, impaired social reciprocity, impaired non-verbal communication, and impaired social relationships. The second was restricted repetitive behavior patterns, including interests or activities such as repetitive phrases, resistance to change, over- or under-reactivity to sensory experience, and unusually intense and/or limited interests.
Kuenssberg, McKenzie, and Jones (2011) reviewed research on the DSM-IV and DSM-IV-TR diagnostic criteria for autism: (1) qualitative impairment in social interaction; (2) qualitative impairments in communication; and (3) restricted repetitive and stereotyped patterns of behavior, interests, and activities. They concluded that only the two criteria now mandated for DSM-5 autism spectrum disorderâsocial interaction and repetitive and restricted interestsâbest characterized individuals with autism. Conversely, Szatmari (2011) argued against the change from three to two criteria for the DSM-5. He stated, âThe two dimensions of social communication and repetitive behaviours may not be the most useful for categorising children with autistic spectrum disorder in terms of the causes, outcomes, and response to treatment because variation in these dimensions seems to be only weakly associated with variation in outcome and response to treatment, which are more closely related to cognitive and language abilitiesâ (2011, p. 6).
Because Kanner first identified autism, his 1943 observations about autism have been identified as âclassicâ autism. Kanner (1943) proposed that a profound lack of understanding of social interaction and a need for sameness were the core diagnostic characteristics of autism. The increase in autism prevalence and heterogeneity led some researchers to call for a return to Kannerâs autism in hopes of limiting prevalence and reducing heterogeneity. For example, autism researcher Folstein (2006) asserted that Kannerâs autism was a true unitary disorder because Kanner âdid not diagnose autism in every child who had social impairment or repetitive behaviors. The children Kanner diagnosed needed to âlookâ intelligent, to be alert and to show interest in things (although not people). He excluded children who had dysmorphic features or very low IQ, below perhaps 35 or 40â (p. 116). Folstein argued that autism heterogeneity resulted from the autism diagnosis being applied to too many non-Kannerâs autism cases including âthose who have profound mental handicap, dysmorphic features, and specific etiologiesâ ...