Background: The sensory impairment is a core diagnostic feature of autism spectrum disorder. However, the underlying mechanisms of symptoms across spectrum remain unknown. Deficits in eye contact are a hallmark of autism diagnostic [1], and figure most prominently determined by in clinical instruments knower [2]. The original triad of autism impairments in the late 1970s [3] described the behavioral manifestation (impaired communication, impaired social skills, and a restricted and repetitive way to existing), while the actual triad of impairment in autism is visual as opposed to linguistic processing, impaired abstraction, and lack of theory of mind, and it is central to all diagnoses that together makes up the autism spectrum disorders (ASD) [4]. In this sense, deficits of in "attention switching/tolerance to change" are one of autism impairments that is linked to the limbic system, according to early neuropathology studies [5]. More recently, ASD has been associated with metabolic and functional abnormalities of the posterior cingulated cortex (PCC), specifically, abnormal functional responses and reductions in functional connectivity [6, 7].

Aim: To study of neuropeptide NAAG metabolism in the cingulated cortices correlated with the AQ domain ‘attention switching /tolerance of change’ associated with the actual triad of impairment in ASD.

Methods: To examine the NAAG metabolism imbalance correlates of attentional impairment symptoms that are associated with autism spectrum disorder, we analyzed spectroscopy MRI data obtained from 65 people with either autism spectrum disorder (n = 21 autism spectrum disorder, mean age = 21.0) and 44 neurotypical controls (mean age = 23.3, range: 18–35 years) using a cases-control study design. Autism quotients (AQ) scores were assessed. Statistic one-way ANOVA and Pearson correlation coefficient was applied.

Results: The results shown there is a significant positive correlation between NAA/Cr ratio and ‘attention switching /tolerance of change’ in the node PCC (r = 0.5396; p = 0.0116), and opposite direction to negative (This means that when one variable increases, the other variable decreases) correlation in TD (see Figure 1). Despite, although positive correlation is moderate (0.40 < r < 0.60) in magnitude, its direction show there is significant, i.e., the changes in the variable influence the changes in the other variable in ASD. Besides, there is a higher significant negative correlation with NAAG/Cr (r = - 0.7924, p = 0.0109), and higher significant positive correlation with NAA/NAAG (r = 0.7775, p = 0.0137) in ASD, compared to TD. In contrast in ACC, a moderate positive correlation with NAAG/Cr (r = 0.4395, p = 0.2759) highlight in ASD. According to, other authors that reported that attention is closely related to the reward value of stimuli, activating the ACC to mediate attention [8], which supports our results.

Conclusion: The neuropeptide N-Acetyl aspartyl glutamate (NAAG) is non correlated to the 'Socio-communicative' skills ASD impairment [9], however was correlated to 'Attention switching / tolerance of change' in ASD suggesting the neuropeptide imbalance as biomarker of diagnostic to the real triad of autism.

References

1. Jones, W., Carr, K., & Klin, A. (2008). Absence of preferential looking to the eyes of approaching adults predicts level of social disability in 2-year-old toddlers with autism spectrum disorder. Archives of general psychiatry, 65(8), 946-954.
2. Lord, C., Risi, S., Lambrecht, L., Cook, E. H., Leventhal, B. L., DiLavore, P. C., ... & Rutter, M. (2000). The Autism Diagnostic Observation Schedule—Generic: A standard measure of social and communication deficits associated with the spectrum of autism. Journal of autism and developmental disorders, 30(3), 205-223.
3. Wing, Lorna. "The diagnosis of autism." Diagnosis and treatment of autism. Springer, Boston, MA, 1989. 5-22.
4. Cashin, Andrew, and Philip Barker. "The triad of impairment in autism revisited." Journal of Child and Adolescent Psychiatric Nursing 22.4 (2009): 189-193.
5. Pugliese, L., Catani, M., Ameis, S., Dell'Acqua, F., de Schotten, M. T., Murphy, C., ... & Murphy, D. G. (2009). The anatomy of extended limbic pathways in Asperger syndrome: a preliminary diffusion tensor imaging tractography study. Neuroimage, 47(2), 427-434.
6. Rudie, J.D.; Dapretto, M. (2013). Convergent Evidence of Brain Overconnectivity in Children with Autism? Cell Rep. 5, 565–566.
7. Jiménez-Espinoza, C., Francisco Marcano, and J. Gonzalez-Mora. "Heterogeneity neurochemistry in cingulate cortex in adults with autism spectrum disorders: A proton MR spectroscopy study." Med. Health Sci. J 18 (2017): 2-13.
8. Dawson, Geraldine, et al. "Early social attention impairments in autism: social orienting, joint attention, and attention to distress." Developmental psychology 40.2 (2004): 271.
9. Jiménez- Espinoza, C.D. NAA-NAAG metabolism imbalance associated neuronal damage and socio-communicative impairment correlation in ASD., in Proceedings of the MOL2NET'20, Conference on Molecular, Biomedical & Computational Sciences and Engineering, 6th ed., 30 January 2020–30 January 2021, MDPI: Basel, Switzerland, doi:10.3390/mol2net-06-08816