During the previous funding cycle of this project (R01 MH073402) we identified distinct subtypes of repetitive behavior validated by the presence of subtype-specific clinical correlates. The potential impact of this finding is that these distinct repetitive behavior subtypes could be leveraged to help parse the biological, behavioral, and treatment-response heterogeneity that heretofore has constrained research on the etiology and treatment of autism. This idea is the focus of our next round of studies in this systematic program of research on repetitive behaviors: By focusing on specific subtypes of repetitive behaviors, can we identify unique pathophysiologic factors that could be used to guide the development of novel treatment strategies? Our focus in this application is on one of these distinct subtypes of repetitive behavior - unusual and intense interests, preoccupations, and attachments - that has received virtually no attention in autism. In recent studies we have found that these so-called Circumscribed Interests (CI) appear to impart significant added impairment in autism over and above other core deficits. Clinically, CI seem to be associated with strong positive affect and anticipatory motivation in contrast to repetitive behaviors in other disorders such as obsessive compulsive disorder (OCD) that seem to be associated with negative affect and anxiety-reduction (e.g. rituals, compulsions, insistence on sameness). The heightened interest and restricted focus that are characteristic of CI suggest that the functioning of neural circuitry that mediate reward processing may be altered in persons with autism. Consistent with this, we hypothesize that the development of CI in autism is mediated by an underlying cognitive-affective reward system that is biased away from social information and towards nonsocial information and thus that a unique cognitive-attentional phenotype may characterize CI. The goals of the proposed continuation of this project are to elucidate the clinical significance of CI in autism and to identify cognitive and neurobiological markers of this subtype. We propose to compare children (ages 12 - 18 years) with low-functioning (n = 40) and high-functioning autism (n = 40) to individuals with obsessive-compulsive disorder (n = 40), developmental delay (n=40) and typically developing controls (n = 40) on (a) a standardized assessment battery for measuring CI and the other varieties of repetitive behavior (Aim 1); (b) a passive visual exploration, eye-tracking task that measures differential attention to CI and non-CI images (Aim 2); and (c) to compare the HFA and TYP samples on two fMRI tasks comparing brain activation to CI versus non-CI images under conditions of reward anticipation and target detection (Aim 3).

Public Health Relevance

Autism is a devastating neurodevelopmental disorder that is characterized by restricted repetitive behaviors. We propose to examine which types of repetitive behaviors are clinically significant for persons with autism. Answering this question would refine diagnostic practice, would focus the search for specific genetic, neurobiologic, and cognitive mechanisms of autism, and would ultimately direct the development of novel forms of treatment for autism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH073402-09
Application #
8885893
Study Section
Special Emphasis Panel (ZRG1-BBBP-R (05))
Program Officer
Gilotty, Lisa
Project Start
2004-07-13
Project End
2016-03-31
Budget Start
2015-04-01
Budget End
2016-03-31
Support Year
9
Fiscal Year
2015
Total Cost
$398,185
Indirect Cost
$108,901
Name
University of North Carolina Chapel Hill
Department
Psychiatry
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Shafer, Robin L; Newell, Karl M; Lewis, Mark H et al. (2017) A Cohesive Framework for Motor Stereotypy in Typical and Atypical Development: The Role of Sensorimotor Integration. Front Integr Neurosci 11:19
Mosner, Maya G; Kinard, Jessica L; McWeeny, Sean et al. (2017) Vicarious Effort-Based Decision-Making in Autism Spectrum Disorders. J Autism Dev Disord 47:2992-3006
Benning, Stephen D; Kovac, Megan; Campbell, Alana et al. (2016) Late Positive Potential ERP Responses to Social and Nonsocial Stimuli in Youth with Autism Spectrum Disorder. J Autism Dev Disord 46:3068-77
DiCriscio, Antoinette Sabatino; Miller, Stephanie J; Hanna, Eleanor K et al. (2016) Brief Report: Cognitive Control of Social and Nonsocial Visual Attention in Autism. J Autism Dev Disord 46:2797-805
Kovac, Megan; Mosner, Maya; Miller, Stephanie et al. (2016) Experience Sampling of Positive Affect in Adolescents with Autism: Feasibility and Preliminary Findings. Res Autism Spectr Disord 29-30:57-65
Watson, Karli K; Miller, Stephanie; Hannah, Eleanor et al. (2015) Increased reward value of non-social stimuli in children and adolescents with autism. Front Psychol 6:1026
Richey, J Anthony; Damiano, Cara R; Sabatino, Antoinette et al. (2015) Neural Mechanisms of Emotion Regulation in Autism Spectrum Disorder. J Autism Dev Disord 45:3409-23
Richey, John A; Rittenberg, Alison; Hughes, Lauren et al. (2014) Common and distinct neural features of social and non-social reward processing in autism and social anxiety disorder. Soc Cogn Affect Neurosci 9:367-77
Moy, Sheryl S; Riddick, Natallia V; Nikolova, Viktoriya D et al. (2014) Repetitive behavior profile and supersensitivity to amphetamine in the C58/J mouse model of autism. Behav Brain Res 259:200-14
Damiano, Cara R; Aloi, Joseph; Dunlap, Kaitlyn et al. (2014) Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards. Mol Autism 5:7

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