24662
Striatal and Thalamic Metabolite Levels and Restricted and Repetitive Behaviors in Twins with Autism Spectrum Disorder

Friday, May 12, 2017: 5:00 PM-6:30 PM
Golden Gate Ballroom (Marriott Marquis Hotel)
J. P. Hegarty1, M. Gu2, D. Spielman2, S. Cleveland1, J. Hallmayer1, L. Lazzeroni1, M. Raman1, T. W. Frazier3, J. M. Phillips1, A. L. Reiss1 and A. Y. Hardan1, (1)Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, (2)Radiology, Stanford University, Stanford, CA, (3)Cleveland Clinic Center for Autism, Cleveland, OH
Background:

Cortico-striatal-thalamo-cortical (CSTC) circuits are involved with carrying out goal-directed behaviors and disruption of these pathways is associated with aberrant behaviors, such as atypical repetition. Although limited, investigations of individuals with ASD support a relationship between CSTC circuit abnormalities and restricted and repetitive behaviors (RRB). For example, volumetric abnormalities in the striatum and thalamus in individuals with ASD are significantly associated with the severity of RRB symptoms.

Objectives:

The goal of this investigation was to examine neurochemical profiles of CSTC regions to determine whether children with ASD exhibit abnormalities that are related to RRB symptom severity.

Methods:

Data were acquired as part of a neuroimaging study of same-sex twin pairs that included monozygotic (MZ) and dizygotic (DZ) twins with ASD and typically-developing (TD) control twins. Clinical diagnosis of ASD was confirmed with the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS). Cognitive and behavioral assessment included measures of intelligence, the Stanford Binet Intelligence Scales-Fifth Edition (SB-5), and autism-related symptom severity, the Social Responsiveness Scale (SRS) and Repetitive Behaviors Scale-Revised (RBS-R). Magnetic resonance imaging was carried out on a 3T GE scanner and an axial MR spectroscopy chemical shift imaging slab was acquired. The corresponding grid was shifted during post-processing to center voxels on the left and right thalamic nuclei and striatum. Metabolites were assessed in relation to internal creatine levels and adjusted for tissue composition. A subset of participants (only a single twin from each pair) with valid spectra from the thalamus and striatum (CRLB < 20%) were included.

Results:

For this preliminary analysis, thalamic voxels were available from 47 individuals with ASD (21 MZ and 26 DZ) and 33 TD (19 MZ and 14 DZ) and striatal voxels were available from 15 individuals with ASD (6 MZ and 9 DZ) and 20 TD (11 MZ and 9 DZ). The ASD and TD samples included children and adolescents (age range: 6-15 years) and were adequately matched as there were no group differences in age or gender, p>0.05. However, individuals with ASD exhibited lower IQ compared to controls (MASD=74.49,SD=26.76; MCTRL=112.00,SD=11.86), p<0.001. Examining metabolite levels, N-acetyl aspartate (NAA) was significantly lower in ASD in the left thalamus (MASD=1.39,SD=0.17; MCTRL=1.47,SD=0.12; F(1,77)=7.89, p=0.021) and left striatum (MASD=1.32,SD=0.21; MCTRL=1.47,SD=0.26; F(1,32)=7.36, p=0.011). Furthermore, NAA levels in the thalamus (rRBS-R=-0.34,p=0.004) and striatum (rRBS-R=-0.43,p=0.021) were significantly associated with RRB symptoms, such as the compulsive behavior subscale of the RBS-R.

Conclusions:

Preliminary data from this investigation indicate that children and adolescents with ASD may be more likely to exhibit lower NAA levels in regions comprising CSTC circuits. NAA is a marker of neuronal integrity and is decreased in numerous neurological conditions; thus decreased NAA is considered a marker of underlying neuropathology. Our findings suggest that perturbation of CSTC circuits is associated with the presentation of RRB. Larger samples, more regions, and additional analyses, such as the assessment of heritability, will be examined as additional data is processed and will allow further elucidation of the neurobiological basis of restricted and repetitive behaviors in individuals with ASD.