Global scientists to discuss latest findings on diagnosis, causes and treatments of ASD

The International Society for Autism Research (INSAR), a scientific and professional organization devoted to advancing knowledge about autism spectrum disorders, convened more than 1700 researchers, delegates, autism specialists and students from 40 countries for the 13th Annual International Meeting for Autism Research (IMFAR), the world's largest scientific gathering on autism research, from May 15 through May 17 at the Atlanta Marriott Marquis in Atlanta, GA.

Researchers and clinicians exchanged and disseminated the latest scientific findings and stimulated progress in autism research into the nature, causes and treatments for ASD during a series of scientific and educational panels, oral sessions and poster presentations. The meeting also featured demonstrations of innovative technologies and events designed for stakeholders and special interest groups`.

"As the scientific investigation of ASD continues to advance at a remarkable pace, IMFAR has become an essential and exciting forum for researchers and clinicians to share findings with each other and the broader autism community," said Francesca Happ-, PhD, president of INSAR. "It is impossible to attend IMFAR and not be inspired and energized by what we are learning from our colleagues, as well as our stakeholders."

"The research presented at this year's IMFAR is incredibly promising as we are translating scientific discoveries into clinical programs that make a difference in our ability to diagnose and treat autism from infancy to adulthood," said Laura Klinger, PhD, co-chair of the IMFAR Scientific Program Committee. "For example, we will be discussing ways to detect symptoms of autism as early as two months of age and the importance of treating anxiety and depression among adults with ASD. The global reach of this conference, with researchers from Atlanta to Addis Ababa presenting and sharing ideas to better serve individuals with ASD and their families worldwide, is particularly inspiring."

"I can't think of a more dynamic area of scientific endeavor than the field of autism research, which, as this meeting demonstrates, has attracted many of the most impressive scientific minds to the cause of helping people with autism, including some impressive, young researchers," said Joseph Piven, MD, co-chair of the IMFAR Scientific Program Committee. "IMFAR provides a critical opportunity for dialogue and fosters a spirit of collaboration among the full array of scientists focused on ASD research."

A press conference was held on May 14 focusing on notable research at IMFAR. The following studies were featured:

A first glimpse of the developmental profile of sibling resilience: 2-24 months eye tracking-based developmental trajectories of eye fixation -- W. Jones and A. Klin, Marcus Autism Center, Children's Healthcare of Atlanta and Emory University School of Medicine.

Among the younger siblings of children with autism spectrum disorders (ASD), 1 in 5 also develops ASD and another 1 in 5 displays some vulnerabilities associated with ASD without presenting with the whole condition (this is often called the "Broader Autism Phenotype", or BAP). In a recent study published in Nature, we showed that ongoing decline in eye fixation - looking at another person's eyes - in the first 6 months of life predicted the diagnosis of ASD at the age of 24 and 36 months. Also, decline in eye fixation in the first 12 months of life predicted the child's level of disability at the age of 24 and 36 months. In this study, we show that the trajectory of eye fixation in the first 24 months of life in unaffected siblings is virtually identical to that of typically developing babies. However, the trajectory of eye fixation for the children characterized as "BAP" begins very similarly as in children with ASD - declining from about the age of 2 months - but there is a "course correction" - i.e., increase in eye fixation - occurring at 18 months. When we mathematically transformed these "growth curves" to identify when this process began in development - i.e., when there was a change in the dynamic of the trajectory - we could pinpoint a shift in rate of change in eye fixation to the 9th month of life in these children. These results suggest a period of malleability in this phenomenon, with some children naturally undergoing course correction. If so, this early period of plasticity might be capitalized upon for early treatment and intervention with the goal of fostering such "course correction" in a larger number of children at greater genetic risk for ASD.

Insulin-like growth factor-1 rescues synaptic and motor deficits in a mouse model of autism and developmental delay -- J. D. Buxbaum, Seaver Autism Center for Research and Treatment, Department of Psychiatry, Icahn School of Medicine at Mount Sinai.

SHANK3 gene deletions and mutations result in Phelan McDermid Syndrome (PMS) and cause ASD with a frequency of 0.5% of ASD cases. Loss of SHANK3 is sufficient to cause the syndrome and is known to produce significant disruption in nerve cell function and plasticity in animal models. Our recent evidence from preclinical studies with mouse models of SHANK3 deficiency indicates that Insulin-Like Growth Factor-1 (IGF-1) can reverse synaptic plasticity and motor learning deficits at clinically approved doses. More recently another group has shown beneficial effects of IGF-1 in human nerve cells carrying SHANK3 mutations. IGF-1 is a commercially available therapeutic compound that enters the brain and has beneficial effects on nerve development by promoting nerve cell survival, synaptic maturation, and synaptic plasticity. We have now carried out a pilot study of IGF-1 treatment in nine patients with PMS (ages 5-15) in order to evaluate safety, tolerability, and efficacy for core deficits of ASD, including social impairment and restricted and repetitive behaviors. We approached this aim by employing a placebo-controlled, double-blind, crossover design with three months of treatment with IGF-1 and three months of placebo in random order, separated by a four week wash-out period. Results provide evidence that IGF-1 is safe, well tolerated, and associated with significant improvement in social impairment as measured by the Aberrant Behavior Checklist Social Withdrawal subscale and in repetitive behaviors as measured by the Repetitive Behavior Scale. This study establishes the feasibility of IGF-1 treatment in PMS and contributes pilot data from the first controlled treatment trial in the syndrome. It also provides proof of concept to advance knowledge about developing targeted treatments for additional causes of ASD associated with impaired synaptic development and function.

Neural responsivity to tactile and auditory sensory stimuli in youth with and without ASD -- S. Green; D. Beck-Pancer ;L. M. Hernandez; J. J. Wood; J. D. Rudie; M. Dapretto and S. Y. Bookheimer, UCLA.

The extreme sensitivity to sensory stimuli often exhibited by children with autism may be caused by heightened responses in areas of the brain that process sensory stimuli and regulate emotion, according to a recent study at UCLA. Children with autism often avoid or become extremely upset in response to sensory stimuli, such as noisy environments or scratchy clothing. This condition is known as sensory over-responsivity (SOR) but until now, very little was known about why SOR occurs. In this study, first author Shulamite Green, M.A., along with senior authors Mirella Dapretto , Ph.D. and Susan Bookheimer, Ph.D., of UCLA, examined how children and adolescents with and without autism spectrum disorders responded to sensory stimuli - in this case, noisy environmental sounds and being rubbed with a scratchy fabric - while in a brain scanner. They found that the brains of youth with autism activate much more strongly in response to the slightly unpleasant touch and sound. In particular, the brain areas that were hyperactive included areas responsible for processing sound and touch (the primary auditory and somatosensory cortices), areas responsible for recognizing saliency and novel and/or unpleasant events (striatum), and areas responsible for emotion processing (amygdala, hippocampus, and orbital frontal cortex). Even more striking than the group differences was the finding that youth with autism whose parents reported higher SOR symptoms had higher activation in these brain areas. As such, youth with SOR may constitute a subgroup of individuals with autism who both initially respond too strongly to sensory stimuli but also fail to regulate their subsequent emotional response to the stimuli.

Emerging patterns of repetitive behavior linked to clinical and behavioral outcomes in high-risk infant siblings -- Jason J. Wolff1, Jed T. Elison2, Heather C. Hazlett1, Juhi Pandey3, Sarah J. Paterson3, Kelly N. Botteron, Annette M. Estes, Lonnie Zwaigenbaum4, Joseph Piven1, & the IBIS Network, 1University of North Carolina at Chapel Hill, 2University of Minnesota, 3Children's Hospital of Philadelphia, 4University of Alberta.

Restricted and repetitive behaviors are a core symptom of autism. These behaviors can range from arm and hand flapping to insistence on a set routine or limited set of interests and activities. Our longitudinal study focused on how these behaviors unfold very early in the lives of children at-risk for autism. We tracked profiles of restricted and repetitive behaviors in 243 toddlers at low- and high-risk for autism from ages 12 to 24 months using a parent-report measure. We found that all forms of restricted and repetitive behavior were significantly increased in children who developed autism. These differences were evident starting at age 12 months, years before the average age of diagnosis. Children with elevated repetitive behavior at age 12 months were 4 times more likely to show signs of autism by age 2 than children with little or no repetitive behavior. Though some degree of repetitive behavior is expected in healthy early development, significantly elevated repetitive behavior at 12 months age may be a 'red flag' for autism. It is notable that we found differences using a simple, 5-10 minute parent report. This suggests that parents are able to detect these behaviors early on, making restricted and repetitive behavior a good potential target for early screening and intervention programs.

The use of high density EEG to investigate circuit miswiring in infants at risk for autism -- C. A. Nelson; A. R. Levin; M. F. Shi and H. Tager-Flusberg, Boston Children's Hospital; Harvard; Boston University.

Autism spectrum disorder (ASD) is a complex, highly heritable disorder that involves primary impairments in language and communication. The disorder is heterogeneous and long-term outcomes vary considerably. In large scale studies of infants with an older sibling with the disorder, it has been estimated that approximately 1:5 such infants will eventually be diagnosed with an ASD. Despite this elevated risk, distinguishing which infants will go on to develop an ASD from those who will not remain challenging.

In our longitudinal study of "infant sibs," we operate from the premise that autism reflects altered neural connectivity. Examining neural circuitry in living children is challenging. In our work we have made use of the recording of the electroencephalogram (EEG) as a way to infer the development of neural circuitry. We report that at different ages, using different analytic routines and different elements of the EEG, we are able to consistently distinguish high risk from low risk infants and in some cases, distinguish infants who subsequently develop an ASD from those who do not. For example, we have reported that gamma activity from 6 to18 months distinguishes high from low risk infants, and the mu rhythm appears to distinguish high risk infants who do vs. do not develop autism. These and related findings will be discussed in our presentation.

Psychiatric and Medical Conditions Among Adults with ASD -- L. A. Croen; O. Zerbo; Y. Qian and M. L. Massolo, Division of Research, Kaiser Permanente Northern California.

Children with autism spectrum disorders (ASD) have more medical and psychiatric diagnoses compared to their non-autistic peers. Given that increasing numbers of children with ASD are entering adulthood each year, understanding the general health status of adults with ASD is critical for resource planning and the development of effective strategies for health care delivery to this growing population. This study describes the frequency of psychiatric and medical conditions among a large, diverse, insured population of adults with ASD in the US. Based on information recorded by doctors in the medical records of adult members (≥ 18 years) of Kaiser Permanente Northern California (KPNC) from 2008-2012, we found that adults with ASD had significantly increased rates of depression, anxiety, bipolar disorder, and suicide attempts, compared to adults without autism. Nearly all medical conditions were significantly more common in adults with ASD than controls, including diabetes, gastrointestinal disorders, epilepsy, sleep disorders, dyslipidemia, hypertension, and obesity. Rarer conditions, such as eating disorders, mechanical falls, vision and hearing impairments, osteoporosis, and chronic heart failure were also significantly more common among adults with ASD than controls. Of note, adults with ASD were significantly less likely to use alcohol or smoke. Finally, the rate of cancer was similar between ASD cases and controls. This study is among the first to highlight the significant excess burden of major psychiatric and medical conditions among adults with ASD. Their underlying impairments in social communication and increased sensory sensitivities likely impede the delivery of preventive health care. Improved strategies for delivering the most appropriate and effective health care are needed for this growing population.

Keynote speakers at IMFAR were: John Colombo, PhD, Director, Schiefelbusch Institute for Life Span Studies and professor of psychology, University of Kansas on The Development of Attention: Implications for Early Identification; Marsha R. Mailick, PhD, director of the Waisman Center at the University of Wisconsin-Madison (UW-Madison) on Adolescents and Adults with ASD and their Families: Life Course Development and Bi-Directional Effects; and Declan Murphy, the Mortimer D Sackler Professor of Translational Neurodevelopment, and Director of the Sackler Institute of Translational Neurodevelopment, Institute of Psychiatry (IOP), King's College London on Why Are There So Few Effective Treatments for Autism - and Can Translational Neuroscience Help?

The INSAR Lifetime Achievement Award, which acknowledges an individual who has made significant fundamental contributions to research on ASD that have had a lasting impact on the field, was presented to Fred Volkmar, MD, director of the Yale University Child Study Center. The INSAR Advocate Award, which honors community members/advocates who have influenced the ability to carry out autism research, was presented to Peter Bell, president and CEO of Eden Autism Services. The winners of two Slifka / Ritvo Innovation in Autism Research Awards, funded by the Alan B. Slifka Foundation to promote innovative research on autism spectrum disorders conducted by junior investigators, were also announced at the awards ceremony.

Source: Rubenstein Associates, Inc.