News Article | February 23, 2017
Dinosaurs, Star Wars, train schedules, Disney princesses, maps, LEGO—subjects such as these can become all-consuming passions for children on the autism spectrum. What therapists and educators often call “circumscribed” or “restricted” interests (or, more generously, “special” interests) make up a characteristic symptom of autism spectrum disorder (ASD). The current edition of psychiatry’s Diagnostic and Statistical Manual of Mental Disorders describes them as “highly restricted, fixated interests that are abnormal in intensity or focus.” Roughly 90 percent of high-functioning kids with ASD display at least one such interest during their elementary school years, according to a 2007 survey conducted at the Yale University Child Study Center, one of the few studies to have examined the topic. For a family with an affected child, this kind of narrow preoccupation can be tedious and exhausting. Imagine a kid who will talk about nothing but the exits on the New Jersey Turnpike or the Captain Underpants book series. (Both actual examples.) Therapists and educators have traditionally tried to suppress or modulate a child’s special interest, or use it as a tool for behavior modification: Keep your hands still and stop flapping, and you will get to watch a Star Wars clip; complete your homework or no Harry Potter. But what if these obsessions themselves can be turned into pathways to growth? What if these intellectual cul-de-sacs can open up worlds? That is the idea explored in the film Life, Animated, a contender for the Academy Award for Best Documentary this Sunday night. The film is based on the 2014 book of the same title by the Pulitzer Prize–winning journalist and author Ron Suskind. It tells the remarkable story of how the author and his wife, Cornelia, were able to reach their silent and withdrawn autistic son, Owen, by actively embracing and nurturing in his passionate interest in animated Disney films. The Suskinds happened upon this method after noticing that a line of apparent gibberish that Owen kept repeating at around age four was actually a key bit of dialogue from The Little Mermaid. Although Owen’s pediatrician initially dismissed the phenomenon as echolalia—the seemingly random repetition of familiar phrases that is a common feature of autism—the Suskinds became convinced that Owen was using Disney characters and scripts, which he memorized, to understand the world around him. As the film and book recount, a breakthrough moment arrived when six-year-old Owen—having noticed his older brother looked sad after a birthday celebration—walked up to his parents and observed that “Walter doesn’t want to grow up, like Mowgli [the hero of The Jungle Book] or Peter Pan.” It was his first burst of spontaneous and complex speech. From that point on, Disney therapy—watching the films together, talking about the characters and their feelings, relating them to Owen’s life, relishing them—became a way of life in the Suskind home, ultimately helping Owen find his voice and place in the world. Why did it work? Ron Suskind believes it is because kids with autism “have the full complement of emotions and they want to share them and grow in all the ways the rest of us grow,” as he explained in an interview. “What we began to realize is that just by loving what he loved, we were signaling to him a whole basket of things that parents are traditionally able to signal to their children. And the more we did that, the more he opened up.” Another crucial element, Suskind says, is sharing joy. “Owen was noticing our desire 24/7 to ‘fix’ him, but you can’t spend your life trying to fix someone. It’s not an appropriate relationship between a parent and a child. We realized we were not finding joy together, and that’s a big part of this equation.” Suskind’s book and the Oscar-nominated film quickly caught the attention of the autism community, and have triggered a growing reappraisal of restricted interests, which the Suskinds call “affinities.” The result has been new technology and, soon, a spurt of new research. In response to the many families who contacted him after reading about Owen, Suskind began to work with one of the inventors of Apple’s Siri and other technologists to create a specialized personal assistant designed to nurture a child’s affinity. The result is an app called Sidekicks—so named because of Owen’s fascination with Disney sidekick characters. Running on mobile devices, it uses a cartoonlike avatar (the child picks one of several options) as an intermediary for a parent or therapist to explore the child’s special interest. Suskind says about a hundred families have been testing the app, which is marketed by The Affinities Project, a privately held company that he formed. Response has been enthusiastic, he says. “There are studies that indicate that children on the spectrum often feel more comfortable talking to an animated character or an entity that is not overstimulating them with confusing gestures and, in many cases, sounds that they have trouble processing.” Suskind firmly believes any affinity—even something as dry as maps or train schedules—can become “a pathway, not a prison” if tapped with imagination and perhaps the help of something like Sidekicks. “Think about maps,” he says. “Maps are the two-dimensional renderings of all humanity and have been for thousands of years. A map is not only geography and topography—it is also identity, it’s where you sit in the world.” Families with a map kid can tap this affinity, if they “learn to speak map.” Suskind is eager to see if the Sidekicks app will prove to be clinically useful as well as fun and engaging. To that end, the first formal study of the technology will kick off sometime this year. Kirstin Birtwell, a clinical psychologist at Massachusetts General Hospital’s Lurie Center for Autism, will be overseeing a pilot study involving 30 children with ASD. Half of them will get 12 weekly therapy sessions involving the Sidekicks app. Birtwell’s research team will then look for effects on emotional regulation, expressive speech, social communication and problem-solving. Birtwell, whose study is not funded by Suskind’s company, has patients who are using the app on their own. “My colleagues and I at the Lurie Center are very excited about this technology, but it’s difficult to put too much stock in it quite yet without the scientific evidence to do so,” she says. “We want to validate patients’ and families’ experiences.” If the pilot experiment shows promise, she adds, “we would want to conduct a much, much larger study.” Others in the research community are also taking a closer look at affinities. At Massachusetts Institute of Technology, neuroscientist John Gabrieli is about to shine an fMRI scanner on the subject. His team will be recruiting 40 children with ASD for a study that will examine what happens in their brains when they are shown videos known to be deeply tied to their affinities, contrasting that with their reactions to related materials that the children or their families have indicated are somewhat less compelling. “We are individually tailoring the stimulus to each child’s selected interest,” he explains. Gabrieli is also unaffiliated with Suskind’s company. A preliminary trial with one subject showed selective activation in the orbital frontal cortex, which is a major component of the brain’s reward circuitry. This finding would need to be confirmed by the full study—but the idea makes sense, because for many kids with ASD there is nothing more rewarding than engaging in their special interest. Ultimately, Gabrieli hopes a better understanding of the neural underpinnings of affinity could help identify which kids would benefit from an affinity-related intervention—whether Sidekicks or something else. In general, he notes, it has been “spectacularly difficult” to understand what’s going on in the autistic brain. And the area of affinities has been particularly understudied. In an additional effort to fill that gap, Autism Speaks—the largest autism-related advocacy organization in the U.S.—has collaborated with the Sidekicks group to conduct an online survey that will attempt to measure the prevalence of affinities among kids with autism. The survey, which launched today, will examine the various types of affinities, whether they are a help or a hindrance and how individuals use their affinities, along with a great deal of related information. Given the organization’s reach of 1.7 million followers of its Facebook page, this promises to be the largest and most comprehensive survey ever done on the subject. Suskind has high hopes that the survey will ultimately help individuals who share the same or related affinities to connect with one another in virtual communities. “With Autism Speaks and with other autism organizations we will build out community forums and sites for people to gather around the campfire of their shared passions,” he explains. It is part of what he sees as a movement that “will not only change how we see people on the spectrum, but how we judge what they have to offer.” An Oscar, of course, would add little glitz to that movement. On Sunday night, Owen, his parents and older brother will step onto the red carpet at the Dolby Theater in Los Angeles. The two young men will be wearing tuxedos by designer Tommy Hilfiger, himself an “autism dad.” For a journey that began with Disney films, it’s a fitting milestone.
Doyle C.A.,Indiana University |
Doyle C.A.,Riley Hospital for Children |
McDougle C.J.,Harvard University |
McDougle C.J.,Lurie Center for Autism
Expert Opinion on Pharmacotherapy | Year: 2012
Introduction: Autistic disorder, Asperger's disorder, and pervasive developmental disorder not otherwise specified (PDD-NOS) are pervasive developmental disorders (PDDs) frequently associated with behavioral symptoms that may require pharmacotherapy to manage. Areas covered: Behavioral symptoms in children with autism include interfering repetitive behaviors, irritability, and hyperactivity and inattention, among others. The psychotropic medications examined in this review include: serotonin reuptake inhibitors, typical and atypical antipsychotics, medications used to treat attention-deficit/ hyperactivity disorder, naltrexone, buspirone, divalproex sodium, lamotrigine, levetiracetam, memantine, mirtazapine, riluzole, pioglitazone, and topiramate. Expert opinion: For the treatment of interfering repetitive behaviors, serotonin reuptake inhibitors demonstrate less efficacy and are more poorly tolerated in children with autism compared to adults. Antipsychotics are the most efficacious drugs for the treatment of irritability in children with autism and other PDDs. For the treatment of hyperactivity and inattention, psychostimulants demonstrate some benefit. However, they are overall less efficacious and cause more side effects in children with PDDs compared to typically developing children with attention-deficit/hyperactivity disorder. Results from double-blind, placebo-controlled trials of these agents and others for the treatment of the behavioral symptom domains described above will be discussed in this review. © 2012 Informa UK, Ltd.
Adler B.A.,Seattle Childrens Hospital |
Wink L.K.,Cincinnati Childrens Hospital Medical Center |
Early M.,Riley Childrens Hospital |
Early M.,Indiana University |
And 6 more authors.
Autism | Year: 2015
Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define drugrefractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole. We reviewed the medical records of individuals of all ages referred to our clinic for autism spectrum disorder diagnostic evaluation, as well as pharmacotherapy follow-up notes for all people meeting autism spectrum disorder criteria, for drug-refractory symptoms. Among 250 consecutively referred individuals, 135 met autism spectrum disorder and enrollment criteria, and 53 of these individuals met drug-refractory symptom criteria. Factors associated with drug-refractory symptoms included age 12 years or older (p < 0.0001), diagnosis of autistic disorder (p = 0.0139), and presence of intellectual disability (p = 0.0273). This pilot report underscores the significance of drug-refractory aggression, self-injurious behavior, and severe tantrums; suggests the need for future study clarifying factors related to symptom development; and identifies the need for focused treatment study of this impairing symptom domain. © The Author(s) 2014.
Politte L.C.,Massachusetts General Hospital |
McDougle C.J.,Lurie Center for Autism
Expert Opinion on Orphan Drugs | Year: 2013
Introduction: Fragile X syndrome (FXS), the most common inherited form of intellectual disability and autism, is caused by expansion of CGG trinucleotide repeats in FMR1 and marked reduction or absence of the gene product, FMRP. FMRP suppresses synaptic protein synthesis resulting from group 1 metabotropic glutamate receptor (mGluR) activation, a process critical to normal synaptic plasticity. FXS can be characterized as a disorder of synaptic plasticity with physical, cognitive and behavioral manifestations attributable to, at least in part, excessive mGluR activity and downstream effects. Areas covered: This paper reviews the 'mGluR theory' of FXS and the targeted drugs investigated in Phase II and III trials based on this theory of pathogenesis. A literature review was conducted using the PubMed database with search terms 'fragile X syndrome', 'mGluRs', 'pharmacotherapy' and specific drug-related terms. Other resources were identified by review of relevant reference lists and consultation with experts in the field. Expert opinion: While preclinical trials of targeted drugs in animal models of FXS have been encouraging, more studies are needed to determine clinical efficacy in humans. Challenges to clinical trial design and direction for future drug studies, including consideration of NMDA receptor partial agonists and mGluR2/3 agonists, are discussed. © Informa UK, Ltd.
Dominick K.,Cincinnati Childrens Hospital Medical Center |
Wink L.K.,Cincinnati Childrens Hospital Medical Center |
McDougle C.J.,Harvard University |
McDougle C.J.,Lurie Center for Autism |
Erickson C.A.,Cincinnati Childrens Hospital Medical Center
Journal of Child and Adolescent Psychopharmacology | Year: 2015
Objective: The purpose of this study was to assess the impact of ziprasidone monoantipsychotic treatment targeting irritability in a naturalistic outpatient autism spectrum disorder (ASD) clinical setting. Methods: We examined the use of ziprasidone, predominantly in combination with other psychotropic agents, targeting irritability in 42 youth with ASD in a large ASD-specific treatment database. Mean age at start of treatment, treatment duration, final dose, body mass index (BMI), BMI Z score, and Clinical Global Impressions-Improvement Scale (CGI-I) score at final visit were determined, and changes with treatment were analyzed using paired t tests. Cardiac corrected QT (QTc) interval data were extracted from electrocardiograms when available. Results: Mean age at start of treatment was 11.8 years. And final mean dose of ziprasidone was 98.7 mg/day or 1.7 mg/kg/day. Seventeen (40%) participants were considered treatment responders based on the CGI-I. No changes in QTc (although only examined in nine participants), weight, BMI, or other vital signs were noted, with ziprasidone use. The rate of treatment response was less than what has been reported for the two atypical antipsychotics, risperidone and aripiprazole, approved by the Food and Drug Administration (FDA) for the treatment of irritability in autistic disorder. The response rate with ziprasidone may be more consistent with response rates for other atypical antipsychotics, although none of these agents has been studied in larger-scale double-blind, placebo-controlled trials. The lower rate of response to ziprasidone in this open-label trial is likely influenced by the treatment-refractory nature of the population studied. Conclusions: The weight neutrality of ziprasidone appears favorable compared with other second generation antipsychotics in this population. The response rate to ziprasidone targeting irritability may be lower than response rates associated with FDA-approved agents for this indication. Overall, ziprasidone use appeared well tolerated in youth with ASD. © Copyright 2015, Mary Ann Liebert, Inc.
McDougle C.J.,Lurie Center for Autism |
McDougle C.J.,Massachusetts General Hospital |
McDougle C.J.,Harvard University |
Landino S.M.,Behavioral Genetics Laboratory |
And 26 more authors.
Brain Research | Year: 2015
Abstract A role for immunological involvement in autism spectrum disorder (ASD) has long been hypothesized. This review includes four sections describing (1) evidence for a relationship between familial autoimmune disorders and ASD; (2) results from post-mortem and neuroimaging studies that investigated aspects of neuroinflammation in ASD; (3) findings from animal model work in ASD involving inflammatory processes; and (4) outcomes from trials of anti-inflammatory/immune-modulating drugs in ASD that have appeared in the literature. Following each section, ideas are provided for future research, suggesting paths forward in the continuing effort to define the role of immune factors and inflammation in the pathophysiology of a subtype of ASD. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. © 2014 Elsevier B.V.
Vahabzadeh A.,Massachusetts General Hospital |
Vahabzadeh A.,McLean Hospital |
Vahabzadeh A.,Harvard University |
Landino S.M.,McLean Hospital |
And 7 more authors.
Handbook of Experimental Pharmacology | Year: 2015
The purpose of this chapter is to present results from recent research on social cognition in autism spectrum disorder (ASD). The clinical phenomenology and neuroanatomical circuitry of ASD are first briefly described. The neuropharmacology of social cognition in animal models of ASD and humans is then addressed. Next, preclinical and clinical research on the neurohormone oxytocin is reviewed. This is followed by a presentation of results from preclinical and clinical studies on the excitatory amino acid glutamate. Finally, the role of neuroinflammation in ASD is addressed from the perspectives of preclinical neuroscience and research involving humans with ASD. © 2015 Springer International Publishing Switzerland.
Friedman N.D.B.,Harvard University |
Friedman N.D.B.,Lurie Center for Autism |
Warfield M.E.,Brandeis University |
Parish S.L.,Brandeis University
Neuropsychiatry | Year: 2013
Rising autism prevalence rates have lent urgency to efforts to improve outcomes for individuals with autism spectrum disorder (ASD). Stakeholders have focused, in particular, on the transition to adulthood that can occur over a range of ages, typically between 18 and 22 years, and often corresponding to when the youth finishes secondary school. This represents a particularly vulnerable time, as the entitlements of the childrens service system end and young adults with ASD and their families encounter fragmented and underfunded systems of care. Research across multiple domains - education, vocational training and employment, social support and community involvement, housing and healthcare - reveals poor outcomes for this population during the transition to adulthood, suggesting that the current models of school-based transition planning are not meeting the needs of youth with ASD. This article highlights findings from some of this literature, examines financial aspects of the transition process, and offers our perspectives on current practices and recommendations for future study. An organized program of research coupled with aggressive policy and service system changes are needed to achieve more favorable transition outcomes for the ASD population. © 2013 Future Medicine Ltd.
PubMed | Seattle Childrens Hospital, Cincinnati Childrens Hospital Medical Center, Indiana University and Lurie Center for Autism
Type: Journal Article | Journal: Autism : the international journal of research and practice | Year: 2014
Aggression, self-injurious behavior, and severe tantrums are impairing symptoms frequently experienced by individuals with autism spectrum disorders. Despite US Food and Drug Administration approval of two atypical antipsychotics targeting these symptoms in youth with autistic disorder, they remain frequently drug refractory. We define drug-refractory aggression, self-injurious behavior, and severe tantrums in people with autism spectrum disorders as behavioral symptoms requiring medication adjustment despite previous trials of risperidone and aripiprazole or previous trials of three psychotropic drugs targeting the symptom cluster, one of which was risperidone or aripiprazole. We reviewed the medical records of individuals of all ages referred to our clinic for autism spectrum disorder diagnostic evaluation, as well as pharmacotherapy follow-up notes for all people meeting autism spectrum disorder criteria, for drug-refractory symptoms. Among 250 consecutively referred individuals, 135 met autism spectrum disorder and enrollment criteria, and 53 of these individuals met drug-refractory symptom criteria. Factors associated with drug-refractory symptoms included age 12 years or older (p < 0.0001), diagnosis of autistic disorder (p = 0.0139), and presence of intellectual disability (p = 0.0273). This pilot report underscores the significance of drug-refractory aggression, self-injurious behavior, and severe tantrums; suggests the need for future study clarifying factors related to symptom development; and identifies the need for focused treatment study of this impairing symptom domain.