Brain Metabolites and Behavior in Autism: A Twins Study

Background:  Using proton magnetic resonance spectroscopy (1H MRS) to examine a variety of brain metabolites in twins provides an opportunity to assess the contributions of genetic inheritance, disease state, as well as confounding factors while controlling for metabolite variability in the population. The present ongoing study looks to elucidate relationships between 1H MRS metabolite levels and clinical features across a cohort of same-sex twin pairs with autism and high variability in disease severity. 

Objectives:  1) To explore differences and similarities among different brain metabolites in MZ and DZ twins, where at least one sibling serves as a proband with autism, and 2) To evaluate the relationship between clinical features and reliably calculated metabolite levels. 

Methods:  The study aims to recruit 120 same-sex twin pairs, 80 with at least one pair with autism, 40 monozygotic (MZ) and 40 dizygotic (DZ), and 40 typically developing twin pair controls, 20 MZ and 20 DZ. High- resolution MRI and 1H MRS imaging scans are being obtained from all participants. Behavior and cognition are also being assessed to provide specific covariates for neuroimaging variables. 

Results:  In this preliminary examination, data from 45 twin pairs were analyzed (age range: 6-15 yrs; Mean 11.04 years ± SD 3.23). Correlations between clinical measures of social abilities and repetitive/restricted behaviors and differences in N Acetyl Aspartate/Creatine levels between twin pairs were examined and several associations were observed including relationships in caudate and putamen with measures of rigidity/restricted behaviors and social cognition, respectively. Among the present findings, our investigation has found lower levels of NAA correlated with symptoms such as repetitive behaviors (Left Putamen NAA/Cre vs total RBS-R score, 95% CI -0.001 : -0.03), sensory abnormalities (Left Caudate NAA/Cre vs SPQ total, 95% CI -0.001 : -0.03), affect recognition (Right Putamen NAA/Cre vs NEPSY AR raw score, 95% CI 0.02 : 0.41), and social responsiveness (Right Thalamus GCP+PCh/Cre vs SRS raw score, 95% CI 0.01 : 0.98). 

Conclusions:  Findings from this preliminary analysis indicate a relationship in autism between brain metabolites and behavior. These observations appear to be consistent with previous reports. Further analyses including more twin pairs will help further current knowledge metabolite abnormalities and neuroanatomic pathways implicated in autism.