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Educação/Ensino
Publicado: 2024-04-30

GABA and Executive functions in ASD

National and Kapodistrian University of Athens, Department of Secondary Education
N.C.S.R. Demokritos
GABA, executive functions, ASD, self – control, behavioral – control, attention – control

Resumo

Gamma-aminobutyric acid (GABA) is a neurotransmitter critically involved in various psychological and behavioral processes. This review highlights the impact of GABAergic dysfunction within specific brain regions on a range of mental disorders, executive processes, self-control, and behavioral regulation.Reductions in GABAergic neurotransmission within distinct brain regions have been consistently associated with several mental health conditions. Within the context of anxiety disorders, depression, and post-traumatic stress disorder (PTSD), alterations in GABAergic function contribute to symptomatology. GABA plays a pivotal role in anxiety and mood regulation, with its impairment linked to symptoms of depression and mood disorders. Dysfunctional GABAergic transmission also contributes to fear dysregulation and features of PTSD. In terms of executive functions, GABAergic neurotransmission affects working memory, attentional control, and inhibitory regulation. Changes in GABA levels have been linked to decision-making abilities, impulsivity, and attention deficits, especially in conditions like attention deficit hyperactivity disorder (ADHD). GABA further plays a crucial role in self-control mechanisms by regulating impulsivity and prefrontal cortex functionality. Substance use disorders, often accompanied by impaired self-control, are significantly influenced by GABAergic system changes. Additionally, GABA's involvement in anxiety and emotional management affects the control of emotional responses. Behavioral control is modulated by GABAergic action in motor circuitry, where GABA provides inhibitory control for motor actions. Spontaneity, aggression, and stress are influenced by GABAergic dysfunction, impacting behavioral control. In the realm of attentional control, GABAergic neurotransmission influences selective attention and sensory salience, maintaining a balance between neural stimulation and inhibition. The study also explores executive function deficits in individuals with Autism Spectrum Disorder (ASD) in relation to GABA levels within specific brain regions. Moreover, GABA and its network connectivity contribute to individual variations in sensory responsiveness, emphasizing the dynamic role of GABA in the phenotypic heterogeneity of ASD. In summary, this research underscores the critical role of GABAergic neurotransmission within specific brain regions in various psychological disorders, executive functions, self-control, behavioral regulation, and attentional processes. Understanding the directional influence of GABAergic changes on behavior and mental health conditions can pave the way for more targeted interventions in neuropsychiatric disorders.

Referências

  1. Etkin, A., Prater, K. E., Schatzberg, A. F., Menon, V., & Greicius, M. D. (2009). Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Archives of General Psychiatry, 66(12), 1361-1372.
  2. Hasler, G., van der Veen, J. W., Tumonis, T., Meyers, N., Shen, J., & Drevets, W. C. (2007). Reduced prefrontal glutamate/glutamine and γ-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy. Archives of General Psychiatry, 64(2), 193-200.
  3. Liberzon, I., & Abelson, J. L. (2016). Context processing and the neurobiology of post-traumatic stress disorder. Neuron, 92(1), 14-30.
  4. Gabbay, V., Mao, X., Klein, R. G., et al. (2012). Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: relationship to anhedonia. Archives of General Psychiatry, 69(2), 139-149.
  5. Fatemi, S. H., & Folsom, T. D. (2009). The neurodevelopmental hypothesis of schizophrenia, revisited. Schizophrenia Bulletin, 35(3), 528-548.
  6. Olsen, R. W., & Sieghart, W. (2009). GABA A receptors: Subtypes provide diversity of function and pharmacology. Neuropharmacology, 56(1), 141-148.
  7. Schousboe, A. (2003). Role of astrocytes in the maintenance and modulation of glutamatergic and GABAergic neurotransmission. Neurochemical Research, 28(3-4), 347-352.
  8. Petroff, O. A. (2002). GABA and glutamate in the human brain. Neuroscientist, 8(6), 562-573. Clark, L., Robbins, T. W., Ersche, K. D., & Sahakian, B. J. (2006). Reflection impulsivity in current and former substance users. Biological Psychiatry, 60(5), 515-522.
  9. Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005). Cortical inhibitory neurons and schizophrenia. Nature Reviews Neuroscience, 6(4), 312-324.
  10. Volkow, N. D., Wang, G. J., Kollins, S. H., et al. (2009). Evaluating dopamine reward pathway in ADHD: clinical implications. JAMA, 302(10), 1084-1091.
  11. Whittington, M. A., Traub, R. D., Faulkner, H. J., et al. (1997). Neuronal fast oscillations in cortical networks. Trends in Neurosciences, 20(10), 443-444.
  12. Feja, M., & Koch, M. (2014). Ventral medial prefrontal cortex inactivation impairs impulse control but does not affect delay-discounting in rats. Behavioural Brain Research, 264, 230-239.
  13. Jupp, B., Caprioli, D., Saigal, N., Reverte, I., Shrestha, S., Cumming, P., Everitt, B. J., Robbins, T. W., & Dalley, J. W. (2013). Dopaminergic and GABA-ergic markers of impulsivity in rats: evidence for anatomical localisation in ventral striatum and prefrontal cortex. Neuropsychopharmacology, 37(9).
  14. Ribeiro, M. J., Violante, I. R., Bernardino, I. R., Edden, R. A. E., & Castelo-Branco, M. (2015). Abnormal relationship between GABA, neurophysiology and impulsive behavior in neurofibromatosis type 1. Cortex, 64, 194-208.
  15. Ende, G., Cackowski, S., Van Eijk, J., Sack, M., Demirakca, T., Kleindienst, N., Bohus, M., Sobanski, E., Krause-Utz, A., & Schmahl, C. (2016). Impulsivity and Aggression in Female BPD and ADHD Patients: Association with ACC Glutamate and GABA Concentrations. Neuropsychopharmacology, 41, 410–418.
  16. Hatoum, A. S., Morrison, C. L., Mitchell, E. C., Lam, M., Benca-Bachman, C. E., Reineberg, A. E., Palmer, R. H. C., Evans, L. M., Keller, M. C., & Friedman, N. P. (2022). Genome-Wide Association Study of Over 427,000 Individuals Establishes Executive Functioning as a Neurocognitive Basis of Psychiatric Disorders Influenced by GABAergic Processes. bioRxiv. Advance online publication.
  17. Tangney, J. P., Baumeister, R. F., & Boone, A. L. (2004). High self-control predicts good adjustment, less pathology, better grades, and interpersonal success. Journal of Personality, 72(2), 271-324.
  18. Huber, R. S., Kondo, D. G., Shi, X.-F., Prescot, A. P., Clark, E., Renshaw, P. F., & Yurgelun-Todd, D. A. (2018). Relationship of executive functioning deficits to N-acetyl aspartate (NAA) and gamma-aminobutyric acid (GABA) in youth with bipolar disorder. Journal of Affective Disorders, 225, 71-78.
  19. Heatherton, T. F., & Wagner, D. D. (2011). Cognitive neuroscience of self-regulation failure. Trends in Cognitive Sciences, 15(3), 132-139.
  20. Ersche, K. D., Turton, A. J., Pradhan, S., et al. (2010). Drug addiction endophenotypes: impulsive versus sensation-seeking personality traits. Biological Psychiatry, 68(8), 770-773. doi:10.1016/j.biopsych.2010.06.015
  21. Smith, J. L., Johnstone, S. J., & Barry, R. J. (2008). Movement-related potentials in the Go/NoGo task: the P3 reflects both cognitive and motor inhibition. Clinical Neurophysiology, 119(3), 704-714.
  22. Winstanley, C. A., Olausson, P., Taylor, J. R., & Jentsch, J. D. (2010). Insight into the relationship between impulsivity and substance abuse from studies using animal models. Alcoholism: Clinical and Experimental Research, 34(8), 1306-1318.
  23. Benarroch, E. E. (2013). GABAergic systems: Anatomy and clinical correlations. Neurology, 80(10), 970-977.
  24. Manto, M., Laute, M. A., & Pandolfo, M. (2012). Cerebellar control of motion: Functional localization and clinical relevance. Cerebellum, 11(2), 437-441.
  25. Gabbay, V., Bradley, K. A., Mao, X., et al. (2012). Anterior cingulate cortex γ-aminobutyric acid in depressed adolescents: Relationship to anhedonia. Archives of General Psychiatry, 69(2), 139-149.
  26. Petrovic, P., & Castellanos, F. X. (2016). Top-down dysregulation-from ADHD to emotional instability. Frontiers in Behavioral Neuroscience, 10, 70.
  27. Clarke, A. R., Barry, R. J., Dupuy, F. E., et al. (2013). Excess beta activity in the EEG of children with attention-deficit/hyperactivity disorder: A disorder of arousal? International Journal of Psychophysiology, 89(3), 314-319.
  28. Schneider, S., Peters, J., Brosch, M., et al. (2020). GABA concentration in superior temporal sulcus predicts gamma power and perception in the sound-induced flash illusion. NeuroImage, 204, 116261.
  29. Gao, X., Xu, S., Yin, D., et al. (2009). Inhibitory deficits in patients with anterior cingulate cortex lesions in a voluntary action task. Journal of Cognitive Neuroscience, 21(4), 777-790.
  30. Demetriou, E. A., DeMayo, M. M., & Guastella, A. J. (2019). Executive Function in Autism Spectrum Disorder: History, Theoretical Models, Empirical Findings, and Potential as an Endophenotype. Frontiers in Psychiatry, 10, 753.
  31. Wood, E. T., Cummings, K. K., Jung, J., Patterson, G., Okada, N., Guo, J., O’Neill, J., Dapretto, M., Bookheimer, S. Y., & Green, S. A. (2021). Sensory over-responsivity is related to GABAergic inhibition in thalamocortical circuits. Translational Psychiatry.
  32. Naaijen, J., Bralten, J., Poelmans, G., The IMAGE consortium, Glennon, J. C., Franke, B., & Buitelaar, J. K. (2017). Glutamatergic and GABAergic gene sets in attention-deficit/hyperactivity disorder: association to overlapping traits in ADHD and autism. Translational Psychiatry, 7, e999.
  33. Piccardi, E. S., Ali, J. B., Jones, E. J. H., Mason, L., Charman, T., Johnson, M. H., Gliga, T., (2021). Behavioural and neural markers of tactile sensory processing in infants at elevated likelihood of autism spectrum disorder and/or attention deficit hyperactivity disorder. Journal of Neurodevelopmental Disorders.
  34. Lou, H. C., Thomsen, K. R., & Changeux, J.-P. (2020). The Molecular Organization of Self-awareness: Paralimbic Dopamine-GABA Interaction. Frontiers in Systems Neuroscience, 14.
  35. Hampshire, A., Highfield, R. R., Parkin, B. L., & Owen, A. M. (2012). Fractionating human intelligence. Neuron, 76(6), 1225-1237.
  36. Jaeggi, S. M., Buschkuehl, M., Jonides, J., & Perrig, W. J. (2011). Improving fluid intelligence with training on working memory. Proceedings of the National Academy of Sciences, 108(25), 10456-10461.
  37. Smith, S. M., Nichols, T. E., Vidaurre, D., Winkler, A. M., Behrens, & Uğurbil, K. (2019). A positive-negative mode of population covariation links brain connectivity, demographics and behavior. Nature Neuroscience, 22(10), 1747-1755.
  38. Toril, P., Reales, J. M., & Mayas, J. (2016). Does an active training program always improve working memory? Experimental Psychology, 63(6), 402-411.
  39. Kühn, S., Gleich, T., Lorenz, R. C., Lindenberger, U., Gallinat, J., & Moritz, S. (2013). Playing Super Mario induces structural brain plasticity: gray matter changes resulting from training with a commercial video game. Molecular Psychiatry, 19(2), 265-271.
  40. Zhou, Z., Fan, Y., Du, H., Li, Y., Jin, J., & Wang, L. (2017). Alzheimer’s disease neuroimaging initiative. Effects of computerized cognitive training on neuroimaging outcomes in mild cognitive impairment. Journal of Alzheimer's Disease, 58(3), 769-778.

Como Citar

Sideraki, A. ., & Drigas, A. (2024). GABA and Executive functions in ASD. Scientific Electronic Archives, 17(3). https://doi.org/10.36560/17320241940