In addition to our regular CRI Activities Update, this month’s Research Focus highlights collaborative work from the team led by Joseph Piven, MD; Professor of Psychiatry; Director of the Carolina Institute for Developmental Disabilities (CIDD); and Thomas E. Castelloe Distinguished Professor of Psychiatry, Pediatrics, and Psychology.

Activities Update: In the spirit of increasing collaborations and broadening attendance, we are excited to begin co-hosting certain CRI seminars, which have a child environmental health focus, with the UNC Center for Environmental Health and Susceptibility (CEHS).  The CEHS promotes research collaborations by funding institutional infrastructure to support scientific equipment, facilities, and other resources that can be shared among environmental health researchers. By pursuing shared research questions, CEHS can identify emerging issues that advance understanding about how pollutants and other environmental factors affect human biology and may lead to disease. Please email Micheal_Sanderson@unc.edu if you would like to get more involved with CEHS. Upcoming seminars cohosted by the CRI and CEHS are:

  • Ilona Jaspers (May 8)
  • Mark Zylka (Oct 9)
  • Mike O’Shea & Rebecca Fry (Dec 11)

Our full CRI Seminar Series schedule for 2018 can be found here.

Our website continues to evolve, with ongoing funding announcements added as received (https://childrensresearch.unc.edu/research/funding-opportunities/).  Also, we have created the beginnings of a clinical trials page that will be fleshed out and have begun listing research by disease topic/area of interest.  If you have content you would like to see added, please send your text for consideration to: childrensresearch@med.unc.edu.

Finally, we continue to be active with grant submissions. The latest 2 of which are focused on developing and retaining junior physician scientists. We collaborated with Janet Rubin, MD, Sarah Graham Kenan Distinguished Professor of Medicine, Division of Endocrinology and Metabolism, Joint Professor, Pediatrics and Pharmacology, Adjunct Professor, Bioengineering, Vice Chair for Research, Department of Medicine; along with NC TraCS; the Department of Psychiatry; and the Department of Surgery to submit a Burroughs Wellcome grant promoting the transition from K to R awards by expanding Dr. Rubin’s current writing group program. Also, we are working hard to gather data for our Unified Program for Therapeutics in Children (UPTiC) resubmission, led by Ian Davis, MD, PhD.  UPTiC is focused on supporting and mentoring pediatric physician-scientists who research the development, implementation, and evaluation of novel prophylactics and therapeutics for pediatric populations.

ReminderJoseph Piven, MD is presenting on “Imaging Infant Brain Development in Autism” at our next CRI monthly luncheon seminar series, on Tuesday, April 10 at 12:15 pm-1:30 pm in the Bioinformatics Auditorium (room 1131). Please mark your calendars. We look forward to seeing you there.

Research Focus of the Month: This month, we are excited to feature the research of Joseph Piven, MD; Professor of Psychiatry; Director of the Carolina Institute for Developmental Disabilities (CIDD); and Thomas E. Castelloe Distinguished Professor of Psychiatry, Pediatrics, and Psychology.

Joseph Piven, MD

Autism spectrum disorder (ASD) is a developmental disability characterized by significant social and behavioral challenges, and includes a number of conditions previously diagnosed separately, such as autistic disorder, pervasive developmental disorder not otherwise specified, and Asperger syndrome. The exact causes of ASD are unknown, but are thought to relate to genetic and environmental factors. To improve the ability to predict who will develop ASD and potentially benefit from early interventions, Dr. Piven and his collaborators are conducting cutting edge research to identify the neurodevelopmental pathology of ASD.

The CDC reports ASD prevalence at about 1 in 68 children (1.5%). This rate increases to about 1 in 5 for infants who have an older sibling with ASD. The diagnosis for ASD can be made in children as young as 18 months, when behavioral symptoms first start to appear, with evidence indicating that early intervention provides a better chance of changing brain development (neuroplasticity) than delaying intervention. However, these interventions are not started until the emergence of autistic behaviors because current testing for ASD is behavior-based. To address this, Dr. Piven and his collaborators are using structural Magnetic Resonance Imaging (MRI) diffusion tensor imaging in the developing brain of infants to predict autism diagnosis. They reported that structural MRI scans done at 6 and 12 months of age could predict 8 out of 10 infants meeting autism criteria at 24 months of age (81% positive predictive value and 88% sensitivity). [Hazlett, H et al. Nature. 2017 Feb 15;542:348, Hampton, T. JAMA. 2017 Oct 3;318(13)1211].

In a separate study investigating brain function using functional connectivity MRI to identify brain region synchronization, they were able to predict 9 out of 11 infants meeting an autism diagnosis at 24 months of age from a scan done at 6 months of age (100% positive predictive value, 81.8% sensitivity) [Emerson RW. Science Translational Medicine 2017 Jun 7;9, Hampton, T. JAMA. 2017 Oct 3;318(13)1211]. More research (eg, replication studies) is needed before these results can be translated into the clinic setting for presymptomatic treatments.

The research conducted at the CIDD is part of the Infant Brain Imaging Study (IBIS) funded by the National Institutes of Health to investigate presymptomatic detection of autism as a step towards presymptomatic intervention. Dr. Piven’s colleagues include a team of psychologists, computer scientists, magnetic resonance physicists, radiologists, speech language pathologists, geneticists, epidemiologists, and biostatisticians. Along with the UNC CIDD, study sites include: Children’s Hospital of Philadelphia, Washington University in St. Louis, and the University of Washington in Seattle.

Dr. Piven’s work towards an establishment of an accurate, predictive model of ASD development has potential to translate into other neurodevelopmental disorders, including Fragile X syndrome, which Dr. Piven also has long standing research interests in.

Links to more information about Dr. Piven, his work and a selection of publications are listed below.

Carolina Institute for Developmental Disabilities

Infant Brain Imaging Study (IBIS)

UNC Autism Research Center

Piven J, Elison JT, Zylka MJ. Toward a conceptual framework for early brain and behavior development in autism. Mol Psychiatry. 2017 Oct;22(10):1385-1394.  PMID: 28937691

Emerson RW, Adams C, Nishino T, Sc M, Hazlett HC, Wolff JJ, Zwaigenbaum, L, Constantino JN, Shen MD, Swanson MR, Elison JT, Kandala S, Estes AM, Botteron KN, Collins L, Dager SR, Evans AC, Gerig G, Gu H, McKinstry RC, Paterson SR, Schultz RT, Styner M, Schlaggar BL, Pruett, JR Jr., *Piven J, * for the IBIS Network. Functional neuroimaging in 6-month-old high-risk infants predicts later autism (*co-senior authors.) Science Translational Medicine 2017 Jun 7;9(393). PMID: 28592562

Hazlett, H., Gu, H., Munsell, B., Kim, S., Styner, M., Wolff, J., Elison, K., Meghan Swanson, M., Botteron, K., Collins, L., Constantino, J., Dager, S., Estes, A., Evans, A., Fonov, V., Gerig, G., Kostopoulos, P., McKinstry, R., J., Pruett, Jr., J., Schultz, R., Shaw, D., Zwaigenbaum, L., Piven, J., for the IBIS Network. Early brain development in infants at high risk for autism spectrum disorder. Nature. 2017 Feb 15;542(7641):348-351. PMID: 28202961

Hampton, T. Early brain imaging in infants may help predict autism. JAMA. 2017 Oct 3;318(13)1211-1212.