Phenotypic Plasticity in the Cingulate Cortex in Autism Spectrum Disorders: Target on Etiology?

Background:  Phenotypic plasticity is the ability of the human brain to change its morphological patterns, interactions in its sensory modalities and patterns of release of neurotransmitters. In previous studies, we observed changes in the levels of the neurotransmitters in the cingulate cortex in adult autism spectrum disorders (ASD) using ¹H-MRS techniques and this led us to further investigate these changes.

Objectives:  The purpose of this study was the detection of a possible secretion pattern of specific neurotransmitters in the cingulate cortex in adults with Autism Spectrum Disorder.

Methods:  In this case-control study, in vivo single-voxel proton magnetic resonance spectroscopy signals (¹H-MRS) were recorded in 12 right-handed young adults with ASD (median age, 22 years ± 2.2), and 19 typically developing (TD) controls (mean age, 22.80 ± 3.25) who were well matched for age, IQ and different AQ score groups: (AQ1=0-10; AQ2=11-22; AQ3=23-31) and AQ4=32-50. The diagnosis of autism was established by a neurologist, psychiatrist and psychologist in every case. The Autism Spectrum Quotient (AQ) designed by Baron-Cohen et al., 2001 to assess Autistic Spectrum traits in intellectually competent adults in both the general population and the Autism Spectrum community. Imaging was performed on a 3.0-T scanner using a single-voxel point-resolved spectroscopy technique. The volume of interest (VOI) was located in the anterior and posterior bilateral cingulate cortex. The absolute concentrations of creatine + phosphocreatine (Cr+Pcr), N-acetyl-aspartate (NAA), N-acetyl-aspartate+N-acetyl-aspartyl-glutamate (NAA+ NAAG), N-acetyl-aspartyl-glutamate (NAAG), glycerophosphocholine + phosphatidylcholine (GCP+PCh), myo-inositol (mI), glutamate (Glu) and glutamate+glutamine (Glu+Gln) were processed by the LC Model 6.2-3A.

Results:  A significant increase glutamate + glutamine (Glu+Gln) was observed, F=20.77; t= 4.73, in the subject group with AQ3 = 23-31 between the bilateral anterior cingulate cortex (ACC) and the posterior bilateral cingulate cortex (PCC).   While, this group (AQ3 = 23-31) showed a significant increase in the level of glutamate (Glu) in the anterior cingulate cortex (ACC), F=23.43; t=4.06, compared with the control group (AQ1=0-10). One-way ANOVA and Bonferroni's Multiple Comparison Test. P < 0.05 were applied to perform the statistical analysis.  

Conclusions:  The presence of an imbalance in the glutamate (Glu) system between the anterior and posterior cingulate cortex was apparent in the ASD group with AQ3 = 23-31. The elucidation of the etiology of this difference in this brain region studied in autism spectrum disorders is and will be a research goal for our team.