642 Alison Tepper Singer’s comments were made in an interview in 2007.
643 The quotations from Micki Bresnahan are from our interview in 2008; the unnamed mother expressed her view about learning Sign in a personal communication in 2008.
644 The quotations from Carly Fleischmann and her father come from two reports: John McKenzie, “Autism breakthrough: Girl’s writings explain her behavior and feelings,” ABC News, February 19, 2008; and Carly Fleischmann, “You asked, she answered: Carly Fleischmann, 13, talks to our viewers about autism,” ABC News, February 20, 2008.
645 The passage about Harry and Laura Slatkin is based on my interview with them in 2008 and subsequent communications.
646 New York Center for Autism organizational website: http://www.nyc4a.org/.
647 The scene described here appears in Autism Every Day.
648 The term the autisms was first proposed by Daniel H. Geschwind and Pat Levitt in “Autism spectrum disorders: Developmental disconnection syndromes,” Current Opinion in Neurobiology 17, no. 1 (February 2007). From the abstract: “Autism is a common and heterogeneous childhood neurodevelopmental disorder. Analogous to broad syndromes such as mental retardation, autism has many etiologies and should be considered not as a single disorder but, rather, as ‘the autisms.’”
649 The “mindblindness” hypothesis was proposed by Simon Baron-Cohen in Mindblindness: An Essay on Autism and Theory of Mind (1995).
650 Mirror neuron dysfunction in autism is discussed in Lindsay M. Oberman et al., “EEG evidence for mirror neuron dysfunction in autism spectrum disorders,” Cognitive Brain Research 24, no. 2 (July 2005); and Lucina Q. Uddin et al., “Neural basis of self and other representation in autism: An fMRI study of self-face recognition,” PLoS ONE 3, no. 10 (2008).
651 The “weak central coherence” hypothesis is proposed in Uta Frith, Autism: Explaining the Enigma (2003).
652 Arousal hypotheses are discussed in Corinne Hutt et al., “Arousal and childhood autism,” Nature 204 (1964); and Elisabeth A. Tinbergen and Nikolaas Tinbergen, “Early childhood autism: An ethological approach,” Advances in Ethology, Journal of Comparative Ethology, suppl . no. 10 (1972). Numerous respected autism researchers subsequently challenged Tinbergen regarding his speculations; see, e.g., Bernard Rimland et al., “Autism, stress, and ethology,” Science, n.s., 188, no. 4187 (May 2, 1975).
653 The quotations by Kamran Nazeer occur on pages 68 and 69 of Send in the Idiots: Stories from the Other Side of Autism (2006).
654 John Elder Robison speaks of his fondness for machines on page 12 of Look Me in the Eye: My Life with Asperger’s (2007).
655 For the report of the Yale face-processing study, see Robert T. Schultz et al., “Abnormal ventral temporal cortical activity during face discrimination among individuals with autism and Asperger syndrome,” Archives of General Psychiatry 57, no. 4 (April 2000). Additionally, Vicki Bruce and Andy Young’s In the Eye of the Beholder: The Science of Face Perception (1998) is a useful basic reference on the subject.
656 The Digimon aficionado features in David J. Grelotti et al., “fMRI activation of the fusiform gyrus and amygdala to cartoon characters but not to faces in a boy with autism,” Neuropsychologia 43, no. 3 (2005).
657 This passage is based on my interview with Bob, Sue, and Ben Lehr in 2008 and subsequent communications.
658 The seminal book on FC is Douglas Biklen’s Communication Unbound: How Facilitated Communication Is Challenging Traditional Views of Autism and Ability/Disability (1993). For an account by a college professor and personal acquaintance whose son communicates via FC, see Ralph James Savarese, Reasonable People: A Memoir of Autism and Adoption: On the Meaning of Family and the Politics of Neurological Difference (2007); see also the made-for-television feature, Autism Is a World (2006). The Autism National Committee supports the continued development of the technique; see its 2008 statement, “AutCom policy and principles regarding facilitated communication,” at http://www.autcom.org/articles/PPFC.pdf. Literature reviews that largely dismiss FC as ineffective include Mark P. Mostert, “Facilitated communication since 1995: A review of published studies,” Journal of Autism & Developmental Disabilities 31, no. 3 (June 2001), and “Facilitated communication and its legitimacy: Twenty-first century developments.” Exceptionality 18, no. 1 (January 2010). The American Academy of Pediatrics does not recommend FC outside of the research context; see American Academy of Pediatrics Policy Committee on Children with Disabilities, “Auditory integration training and facilitated communication for autism,” AAP Policy Committee on Children with Disabilities 102, no. 2 (1998).
659 For more information on brain development in autism, see Stephen R. Dager et al., “Imaging evidence for pathological brain development in autism spectrum disorders,” in Autism: Current Theories and Evidence (2008); Martha R. Herbert et al., “Localization of white matter volume increase in autism and developmental language disorder,” Annals of Neurology 55, no. 4 (April 2004); Eric Courchesne et al., “Evidence of brain overgrowth in the first year of life in autism,” Journal of the American Medical Association 290, no. 3 (July 2003); Nancy J. Minshew and Timothy A. Keller, “The nature of brain dysfunction in autism: Functional brain imaging studies,” Current Opinion in Neurology 23, no. 2 (April 2010); and Eric Courchesne et al., “Brain growth across the life span in autism: Age-specific changes in anatomical pathology,” Brain Research 1380 (March 2011).
660 Useful recent reviews of the state of the science in autism genetics include Judith Miles, “Autism spectrum disorders: A genetics review,” Genetics in Medicine 13, no. 4 (April 2011); and Daniel H. Geschwind, “Genetics of autism spectrum disorders,” Trends in Cognitive Sciences 15, no. 9 (September 2011).
661 Prenatal contributors to autism are discussed in Tara L. Arndt, Christopher J. Stodgell, and Patricia M. Rodier, “The teratology of autism,” International Journal of Developmental Neuroscience 23, nos. 2–3 (April–May 2005).
662 For more information on the association between paternal age and autism, see Abraham Reichenberg et al., “Advancing paternal age and autism,” Archives of General Psychiatry 63, no. 9 (September 2006); Rita M. Cantor et al., “Paternal age and autism are associated in a family-based sample,” Molecular Psychiatry 12 (2007); and Maureen S. Durkin et al., “Advanced parental age and the risk of autism spectrum disorder,” American Journal of Epidemiology 168, no. 11 (December 2008).
663 The possible contribution of genetic incompatibility to the development of autism is discussed in William G. Johnson et al., “Maternally acting alleles in autism and other neurodevelopmental disorders: The role of HLA-DR4 within the major histocompatibility complex,” in Maternal Influences on Fetal Neurodevelopment, edited by Andrew W. Zimmerman and Susan L. Connors (2010).
664 For more on assortative mating hypotheses, see Simon Baron-Cohen, “The hyper-systemizing, assortative mating theory of autism,” Progress in Neuropsychopharmacology & Biological Psychiatry 30, no. 5 (July 2006); and Steve Silberman, “The geek syndrome,” Wired, December 2001.
665 A new multicenter sibling study has identified mutations in 279 genes occurring only in the autistic subjects; see Stephen Sanders et al., “De novo mutations revealed by whole-exome sequencing are strongly associated with autism,” Nature 485, no. 7397 (May 10, 2012).
666 Influences on genetic expression are discussed in Isaac N. Pessah and Pamela J. Lein, “Evidence for environmental susceptibility in autism: What we need to know about gene x environment interactions,” in Autism: Current Theories and Evidence, edited by Andrew Zimmerman (2008).
667 Variable penetrance is the subject of Dan Levy, Michael Wigler et al., “Rare de novo and transmitted copy-number variation in autistic spectrum disorders,” Neuron 70, no. 5 (June 2011).
668 Figures on autism and genetic concordance in identical twins come from Anthony Bailey et al., “Autism as a strongly genetic disorder: Evidence from a British twin study,” Psychological Medicine 25 (1995).
669 Studies on the
broad autism phenotype, i.e., the manifestation of autistic traits in immediate and extended family members of people with autism, include Nadia Micali et al., “The broad autism phenotype: Findings from an epidemiological survey,” Autism 8, no. 1 (March 2004); Joseph Piven et al., “Broader autism phenotype: Evidence from a family history study of multiple-incidence autism families,” American Journal of Psychiatry 154 (February 1997); and Molly Losh et al., “Neuropsychological profile of autism and the broad autism phenotype,” Archives of General Psychiatry 66, no. 5 (May 2009).
670 For scholarly discussion of the genome-wide incidence of autism-related genes, see Joseph T. Glessner et al., “Autism genome-wide copy number variation reveals ubiquitin and neuronal genes,” Nature 459 (May 28, 2009).
671 This 20 to 30 percent statistic reflects risk to the sibling over general population risk as established by the CDC. Accepting an autism prevalence that is constantly being recalculated but that is hovering at about one in a hundred, and a risk for siblings is about one in five, we come up with this comparative statistic; see Brett S. Abrahams and Daniel H. Geschwind, “Advances in autism genetics: On the threshold of a new neurobiology,” Nature Review Genetics 9, no. 5 (May 2008).
672 Interview with Matthew State, 2009.
673 Interview with Thomas Insel, 2010.
674 Interview with Michael Wigler and Jonathan Sebat, 2008.
675 More background on pleiotropism and autism can be found in Annemarie Ploeger et al., “The association between autism and errors in early embryogenesis: What is the causal mechanism?,” Biological Psychiatry 67, no. 7 (April 2010).
676 For a study linking genes associated with autism and co-morbid conditions, see Daniel B. Campbell et al., “Distinct genetic risk based on association of MET in families with co-occurring autism and gastrointestinal conditions,” Pediatrics 123, no. 3 (March 2009).
677 Sebat and Wigler’s report on their autism genetics research is Jonathan Sebat et al., “Strong association of de novo copy number mutations with autism,” Science 316, no. 5823 (April 20, 2007).
678 Jonathan Sebat’s study of the association between microdeletions and increased head circumference is described in the Simons Foundation press release “Relating copy-number variants to head and brain size in neuropsychiatric disorders,” at http://sfari.org/funding/grants/abstracts/relating-copy-number-variants-to-head-and-brain-size-in-neuropsychiatric-disorders.
679 The quotation from Daniel Geschwind comes from a personal interview in 2012. Geschwind’s recent papers on the genetics of autism include “Autism: Many genes, common pathways?,” Cell 135, no. 3 (October 31, 2008); and “The genetics of autistic spectrum disorders,” Trends in Cognitive Sciences 15, no. 9 (September 2011).
680 For studies of rapamycin’s effect on learning, memory deficits, and seizures in mice, see Dan Ehninger et al., “Reversal of learning deficits in a Tsc2+/- mouse model of tuberous sclerosis,” Nature Medicine 14, no. 8 (August 2008); and L.-H. Zeng et al., “Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex,” Annals of Neurology 63, no. 4 (April 2008).
681 The quotation from Alcino Silva comes from a 2008 UCLA press release, “Drug reverses mental retardation in mice,” at http://www.newswise.com/articles/drug-reverses-mental-retardation-in-mice.
682 The role of mGluR receptors in autism is discussed in Mark F. Bear et al., “The mGluR theory of fragile X mental retardation,” Trends in Neurosciences 27, no. 7 (July 2004); and Randi Hagerman et al., “Fragile X and autism: Intertwined at the molecular level leading to targeted treatments,” Molecular Autism 1, no. 12 (September 2010). For a study finding amelioration of behavioral abnormalities in genetically engineered mice administered mGluR antagonists, see Zhengyu Cao et al., “Clustered burst firing in FMR1 premutation hippocampal neurons: Amelioration with allopregnanolone,” Human Molecular Genetics (published online ahead of print, April 6, 2012).
683 For a preliminary report of findings in a clinical trial of drug treatment for Rett syndrome, see Eugenia Ho et al., “Initial study of rh-IGF1 (Mecasermin [DNA] injection) for treatment of Rett syndrome and development of Rett-specific novel biomarkers of cortical and autonomic function (S28.005),” Neurology 78, meeting abstracts 1 (April 25, 2012).
684 For discussion of potential drug therapies for fragile X syndrome, see the recent review article by Randi Hagerman et al., “Fragile X syndrome and targeted treatment trials,” Results and Problems in Cell Differentiation 54 (2012), pages 297–335. Recruitment efforts are under way for a new fragile X study; see the press release “Clinical trials of three experimental new treatments for Fragile X are accepting participants,” FRAXA Research Foundation, March 22, 2012.
685 The quote by Geraldine Dawson comes from her presentation at the Alexandria Summit, “Translating Innovation into New Approaches for Neuroscience,” in 2012. Dawson is chief scientific officer for Autism Speaks.
686 For the study finding similar genetic mutations in fragile X and in autism, see Ivan Iossifov et al., “De novo gene disruptions in children on the autistic spectrum,” Neuron 74, no. 2 (April 2012); and Cold Spring Harbor Laboratory’s press release about the study, “A striking link is found between the Fragile-X gene and mutations that cause autism,” at http://www.cshl.edu/Article-Wigler/a-striking-link-is-found-between-the-fragile-x-gene-and-mutations-that-cause-autism.
687 Simon Baron-Cohen discusses his “empathizing/systemizing” hypothesis in “The extreme male brain theory of autism,” Trends in Cognitive Science 6, no. 6 (June 2002); “Autism: The empathizing-systemizing (E-S) theory,” Annals of the New York Academy of Sciences 1156 (March 2009); and “Empathizing, systemizing, and the extreme male brain theory of autism,” Progress in Brain Research 186 (2010).
688 The association of high levels of fetal testosterone and autistic traits is discussed in Bonnie Auyeung and Simon Baron-Cohen, “A role for fetal testosterone in human sex differences: Implications for understanding autism,” in Autism: Current Theories and Evidence, edited by Andrew Zimmerman (2008); and Bonnie Auyeung et al., “Foetal testosterone and autistic traits in 18 to 24-month-old children,” Molecular Autism 1, no. 11 (July 2010).
689 The study of savants is the lifework of Darold Treffert; for just two of his reports on the subject, see “The savant syndrome in autism,” in Autism: Clinical and Research Issues, edited by Pasquale J. Accardo et al. (2000); and “The savant syndrome: An extraordinary condition. A synopsis: Past, present, future,” Philosophical Transactions of the Royal Society, Part B 364, no. 1522 (May 2009). The perfect map of Rome was created by Stephen Wiltshire and is displayed on his website, http://www.stephenwiltshire.co.uk/Rome_Panorama_by_Stephen_Wiltshire.aspx.
690 Michael Rutter reported on the impact of institutionalization on Romanian orphans in Michael Rutter et al., “Are there biological programming effects for psychological development?: Findings from a study of Romanian adoptees,” Developmental Psychology 40, no. 1 (2004).
691 Bettelheim’s comparison of autistic children to concentration camp inmates occurs on pages 66–78 of The Empty Fortress (1972).
692 Margaret Bauman’s clinical experiences are discussed in Rachel Zimmerman, “Treating the body vs. the mind,” Wall Street Journal, February 15, 2005.
693 Statistics on the percentage of autistic individuals with comorbid diagnoses of depression and anxiety were provided by Lonnie Zwaigenbaum at a 2009 presentation at Cold Spring Harbor Laboratory.
Studies establishing a high frequency of comorbid psychiatric problems include Luke Tsai, “Comorbid psychiatric disorders of autistic disorder,” Journal of Autism & Developmental Disorders 26, no. 2 (April 1996); Christopher Gillberg and E. Billstedt, “Autism and Asperger syndrome: coexistence with other clinical disorders,” Acta Psychiatrica Scandinavica 102, no. 5 (November 2000); and Gagan Joshi et al., “The heavy burden of psychiatric comorbidity in youth with autism spectrum disorders: A large comparative study of a psychiatrically referred population,” Journal of Autism & Developmental Dis
orders 40, no. 11 (November 2010).
694 The quotation from Kamran Nazeer comes from pages 161–62 of Send in the Idiots: Stories from the Other Side of Autism (2006).
695 This passage is based on my interview with John Shestack and Portia Iversen in 2008. Iversen is author of Strange Son: Two Mothers, Two Sons, and the Quest to Unlock the Hidden World of Autism (2006). The Autism Genetic Resource Exchange website: http://www.familyagre.org.
696 The quotation from Daniel Geschwind comes from personal communication in 2011.
697 The quotation from Isabelle Rapin comes from a 2009 presentation at Cold Spring Harbor Laboratory.
698 Laura Schreibman discusses autism diagnostic instruments on page 68 of The Science and Fiction of Autism (2005).
699 I have taken the August Bier quotation from Victoria Costello, “Reaching children who live in a world of their own,” Psychology Today, December 9, 2009.
The original German is Eine gute Mutter diagnostiziert oft viel besser wie ein schlechter Arzt and may be found at http://dgrh.de/75jahredgrh0.html.
700 Interview with Kathleen Seidel in 2008. I note in the interest of full disclosure that I employed Kathleen Seidel to help me with research, citations, and the bibliography for this book starting in 2009.
701 This passage is based on my interview with Icilda Brown in 2005. All names in this passage are pseudonyms.
702 The Autism Society of America’s estimates of the incidence of autism come from their organizational website, http://www.autism-society.org/.
Far From the Tree Page 117
