Chapter 3. Meaning making in Vygotsky’s theory
3.1. Child’s development from a cognitive perspective
3.1.4. Thinking and language
Aproximadamente 7% das crianças apresentam dificuldade matemática (DM), enquanto 5 a 12% sofrem de dificuldade de leitura (DL) (De Weerdt et al., 2013). Apesar de adequadas oportunidades de aprendizagem, normalmente, ambas as dificuldades costumam persistir ou aumentar ao longo da vida escolar, o que pode resultar em consequências negativas, tais como ansiedade, baixa motivação e alta frustração acadêmica, bem como isolamento social (Schuchardt et al., 2008; Willcutt et al., 2013).
Déficits na memória de trabalho (MT) são características comuns tanto da DL quanto da DM. Diversas pesquisas demonstraram que crianças com DL exibem danos nos componentes fonológico e executivo central da MT. Para a DM, déficits em todos os três componentes da MT já foram descritos (De Weerdt et al., 2013).
Apesar da grande importância da MT, especialmente para o processo de aprendizagem, pouco se conhece sobre suas bases genético-moleculares e, consequentemente, como estas bases influenciam no fenótipo final em diferentes grupos étnicos e diferentes idades. Há uma carência em pesquisas buscando investigar polimorfismos genéticos entre indivíduos brasileiros de desenvolvimento típico, principalmente crianças, que possam estar associados ao grau de performance da MT. Estudos voltados para a população brasileira se fazem necessários, pois a alta taxa de miscigenação da mesma pode acarretar em padrões de associação diferentes dos encontrados nas pesquisas com populações caucasianas. Diferenças estas já comprovadas para as populações asiáticas.
Sendo assim, este presente trabalho objetiva identificar as contribuições de polimorfismos da COMT (SNPs rs4680 e rs2075507) para o desempenho da MT, em crianças provenientes de escolas públicas e privadas de Belo Horizonte. Além de dar continuidade a linha de pesquisa desenvolvida pelo Laboratório de Genética Humana e Médica em parceria com o Laboratório de Neuropsicologia do Desenvolvimento, ambos da UFMG, busca-se aprofundar os resultados encontrados por Júlio-Costa et al. (2013).
Analisando o contexto atual, este trabalho é inovador, pois procura compreender a influência de alterações genéticas comuns e, portanto, de seus mecanismos moleculares subjacentes, na performance de MT, em crianças da população brasileira. Uma vez que a MT é uma medida relativamente pura da capacidade de aprendizagem, os resultados deste trabalho poderão auxiliar no desenvolvimento de estratégias educacionais compensatórias eficazes para o combate das dificuldades de leitura e Matemática nas escolas.
Referências Bibliográficas
ALLOWAY, T. P. Working memory, but not IQ, predicts subsequent learning in children with learning difficulties. European J of Psychological
Assessment, v. 25, p. 92–98, 2009.
ALLOWAY, T. P.; GATHERCOLE, S. E.; KIRKWOOD, H.; ELLIOTT, J. The cognitive and behavioral characteristics of children with low working memory. Child Dev, v. 80, n. 2, p. 606-21, 2009 Mar-Apr 2009.
ALLOWAY, T. P.; GATHERCOLE, S. E.; WILLIS, C.; ADAMS, A. M. Working memory and special educational needs. Edu and Child
Psychol, v. 22, p. 56–67, 2005.
ANDO, J.; ONO, Y.; WRIGHT, M. J. Genetic structure of spatial and verbal working memory. Behav Genet, v. 31, n. 6, p. 615-24, Nov 2001. BADDELEY, A. The episodic buffer: a new component of working memory?
Trends Cogn Sci, v. 4, n. 11, p. 417-423, Nov 1 2000.
BADDELEY, A. Working memory and language: an overview. J Commun
Disord, v. 36, n. 3, p. 189-208, 2003 May-Jun 2003a.
BADDELEY, A. Working memory: looking back and looking forward. Nat Rev
Neurosci, v. 4, n. 10, p. 829-39, Oct 2003b.
BADDELEY, A. D.; HITCH, G. J. Working memory. Recent advances in learning and motivation, v. 8, n. New York: Academic Press, p. 44 - 90, 1974.
BAILEY, D. B.; HATTON, D. D.; SKINNER, M. Early developmental trajectories of males with fragile X syndrome. Am J Ment Retard, v. 103, n. 1, p. 29-39, Jul 1998.
BERTOCCI, B.; MIGGIANO, V.; DA PRADA, M.; DEMBIC, Z.; LAHM, H. W.; MALHERBE, P. Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form. Proc Natl Acad Sci U
S A, v. 88, n. 4, p. 1416-20, Feb 1991.
BRAY, S.; DUNKIN, B.; HONG, D. S.; REISS, A. L. Reduced functional connectivity during working memory in Turner syndrome. Cereb
Cortex, v. 21, n. 11, p. 2471-81, Nov 2011.
CASE, R.; KURLAND, D. M.; GOLDBERG, J. Operational efficiency and the growth of short-term memory span. J Experimental Child Psychol, v. 33, p. 386-404, 1982.
CHEN, J.; LIPSKA, B. K.; HALIM, N.; MA, Q. D.; MATSUMOTO, M.; MELHEM, S.; KOLACHANA, B. S.; HYDE, T. M.; HERMAN, M. M.; APUD, J.; EGAN, M. F.; KLEINMAN, J. E.; WEINBERGER, D. R. Functional analysis of genetic variation in catechol-O- methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet, v. 75, n. 5, p. 807-21, Nov 2004.
CHEN, L. S.; RICE, T. K.; THOMPSON, P. A.; BARCH, D. M.; CSERNANSKY, J. G. Familial aggregation of clinical and neurocognitive features in sibling pairs with and without schizophrenia.
Schizophr Res, v. 111, n. 1-3, p. 159-66, Jun 2009.
CONKLIN, H. M.; LUCIANA, M.; HOOPER, C. J.; YARGER, R. S. Working memory performance in typically developing children and adolescents: behavioral evidence of protracted frontal lobe development. Dev
Neuropsychol, v. 31, n. 1, p. 103-28, 2007.
CONWAY, A. R.; KANE, M. J.; BUNTING, M. F.; HAMBRICK, D. Z.; WILHELM, O.; ENGLE, R. W. Working memory span tasks: A methodological review and user's guide. Psychon Bull Rev, v. 12, n. 5, p. 769-86, Oct 2005.
CORSO, L. V.; DORNELES, B. V. What Role does the Working Memory Play in Mathematics Learning? Bolema: Boletim de Educação Matemática, v. 26, p. 627- 47, 2012.
DAUVILLIERS, Y.; TAFTI, M.; LANDOLT, H. P. Catechol-O- methyltransferase, dopamine, and sleep-wake regulation. Sleep Med
Rev, Oct 2014.
DE LUCA, C. R.; WOOD, S. J.; ANDERSON, V.; BUCHANAN, J. A.; PROFFITT, T. M.; MAHONY, K.; PANTELIS, C. Normative data from the CANTAB. I: development of executive function over the lifespan. J Clin Exp Neuropsychol, v. 25, n. 2, p. 242-54, Apr 2003. DE SMEDT, B.; DEVRIENDT, K.; FRYNS, J. P.; VOGELS, A.; GEWILLIG,
M.; SWILLEN, A. Intellectual abilities in a large sample of children with Velo-Cardio-Facial Syndrome: an update. J Intellect Disabil Res, v. 51, n. Pt 9, p. 666-70, Sep 2007.
DE SMEDT, B.; SWILLEN, A.; VERSCHAFFEL, L.; GHESQUIÈRE, P. Mathematical learning disabilities in children with 22q11.2 deletion syndrome: a review. Dev Disabil Res Rev, v. 15, n. 1, p. 4-10, 2009. DE WEERDT, F.; DESOETE, A.; ROEYERS, H. Working memory in children
with reading disabilities and/or mathematical disabilities. J Learn
Disabil, v. 46, n. 5, p. 461-72, 2013 Sep-Oct 2013.
DIAMOND, A.; BRIAND, L.; FOSSELLA, J.; GEHLBACH, L. Genetic and neurochemical modulation of prefrontal cognitive functions in children.
Am J Psychiatry, v. 161, n. 1, p. 125-32, Jan 2004.
DUMONTHEIL, I.; ROGGEMAN, C.; ZIERMANS, T.; PEYRARD-JANVID, M.; MATSSON, H.; KERE, J.; KLINGBERG, T. Influence of the COMT genotype on working memory and brain activity changes during development. Biol Psychiatry, v. 70, n. 3, p. 222-9, Aug 2011.
EGAN, M. F.; GOLDBERG, T. E.; KOLACHANA, B. S.; CALLICOTT, J. H.;
MAZZANTI, C. M.; STRAUB, R. E.; GOLDMAN, D.;
WEINBERGER, D. R. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S
A, v. 98, n. 12, p. 6917-22, Jun 2001.
FIGUEIREDO, V. L. M. WISC-III: Escala de Inteligência Wechsler para Crianças. Manual, Adaptação e Padronização Brasileira. São Paulo:
FLODERUS, Y.; ROSS, S. B.; WETTERBERG, L. Erythrocyte catechol-O- methyltransferase activity in a Swedish population. Clin Genet, v. 19, n. 5, p. 389-92, May 1981.
GOLDBERG, T. E.; EGAN, M. F.; GSCHEIDLE, T.; COPPOLA, R.;
WEICKERT, T.; KOLACHANA, B. S.; GOLDMAN, D.;
WEINBERGER, D. R. Executive subprocesses in working memory: relationship to catechol-O-methyltransferase Val158Met genotype and schizophrenia. Arch Gen Psychiatry, v. 60, n. 9, p. 889-96, Sep 2003. HART, S. J.; DAVENPORT, M. L.; HOOPER, S. R.; BELGER, A. Visuospatial
executive function in Turner syndrome: functional MRI and neurocognitive findings. Brain, v. 129, n. Pt 5, p. 1125-36, May 2006. HONG, J.; SHU-LEONG, H.; TAO, X.; LAP-PING, Y. Distribution of catechol-
O-methyltransferase expression in human central nervous system.
Neuroreport, v. 9, n. 12, p. 2861-4, Aug 1998.
JÚLIO-COSTA, A.; ANTUNES, A. M.; LOPES-SILVA, J. B.; MOREIRA, B. C.; VIANNA, G. S.; WOOD, G.; CARVALHO, M. R.; HAASE, V. G. Count on dopamine: influences of COMT polymorphisms on numerical cognition. Front Psychol, v. 4, p. 531, 2013.
KARLSGODT, K. H.; BACHMAN, P.; WINKLER, A. M.; BEARDEN, C. E.; GLAHN, D. C. Genetic influence on the working memory circuitry: behavior, structure, function and extensions to illness. Behav Brain Res, v. 225, n. 2, p. 610-22, Dec 2011.
KARLSGODT, K. H.; KOCHUNOV, P.; WINKLER, A. M.; LAIRD, A. R.; ALMASY, L.; DUGGIRALA, R.; OLVERA, R. L.; FOX, P. T.; BLANGERO, J.; GLAHN, D. C. A multimodal assessment of the genetic control over working memory. J Neurosci, v. 30, n. 24, p. 8197- 202, Jun 2010.
KAROUM, F.; CHRAPUSTA, S. J.; EGAN, M. F. 3-Methoxytryramine is the major metabolite of released dopamine in the rat frontal cortex:reassessment of the effects of antipsychotics on the dynamics of dopamine release and metabolism in the frontal cortex, nucleus accumbens, and striatum bya simple two pool model. J. Neurochem, v. 63, p. 972–79, 1994.
KEBABIAN, J. W.; CALNE, D. B. Multiple receptors for dopamine. Nature, v. 277, n. 5692, p. 93-6, Jan 1979.
KESSELS, R. P.; VAN ZANDVOORT, M. J.; POSTMA, A.; KAPPELLE, L. J.; DE HAAN, E. H. The Corsi Block-Tapping Task: standardization and normative data. Appl Neuropsychol, v. 7, n. 4, p. 252-8, 2000. KUKSHAL, P.; KODAVALI, V. C.; SRIVASTAVA, V.; WOOD, J.;
MCCLAIN, L.; BHATIA, T.; BHAGWAT, A. M.; DESHPANDE, S. N.; NIMGAONKAR, V. L.; THELMA, B. K. Dopaminergic gene polymorphisms and cognitive function in a north Indian schizophrenia cohort. J Psychiatr Res, v. 47, n. 11, p. 1615-22, Nov 2013.
LACHMAN, H. M.; PAPOLOS, D. F.; SAITO, T.; YU, Y. M.; SZUMLANSKI, C. L.; WEINSHILBOUM, R. M. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics, v. 6, n. 3, p. 243-50, 1996.
LEE, T.; MOSING, M. A.; HENRY, J. D.; TROLLOR, J. N.; AMES, D.; MARTIN, N. G.; WRIGHT, M. J.; SACHDEV, P. S.; TEAM, O. R. Genetic influences on four measures of executive functions and their covariation with general cognitive ability: the Older Australian Twins Study. Behav Genet, v. 42, n. 4, p. 528-38, Jul 2012.
LINDSAY, E. A. Chromosomal microdeletions: dissecting del22q11 syndrome.
Nat Rev Genet, v. 2, n. 11, p. 858-68, Nov 2001.
LUCIANA, M.; CONKLIN, H. M.; HOOPER, C. J.; YARGER, R. S. The development of nonverbal working memory and executive control processes in adolescents. Child Dev, v. 76, n. 3, p. 697-712, 2005 May- Jun 2005.
LUNA, B.; GARVER, K. E.; URBAN, T. A.; LAZAR, N. A.; SWEENEY, J. A. Maturation of cognitive processes from late childhood to adulthood.
Child Dev, v. 75, n. 5, p. 1357-72, 2004 Sep-Oct 2004.
LUNDSTRÖM, K.; SALMINEN, M.; JALANKO, A.; SAVOLAINEN, R.; ULMANEN, I. Cloning and characterization of human placental catechol-O-methyltransferase cDNA. DNA Cell Biol, v. 10, n. 3, p. 181- 9, Apr 1991.
MÄNNISTÖ, P. T.; KAAKKOLA, S. Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacol Rev, v. 51, n. 4, p. 593-628, Dec 1999.
MATSUMOTO, M.; WEICKERT, C. S.; AKIL, M.; LIPSKA, B. K.; HYDE, T. M.; HERMAN, M. M.; KLEINMAN, J. E.; WEINBERGER, D. R. Catechol O-methyltransferase mRNA expression in human and rat brain: evidence for a role in cortical neuronal function. Neuroscience, v. 116, n. 1, p. 127-37, 2003.
MAYNARD, T. M.; HASKELL, G. T.; PETERS, A. Z.; SIKICH, L.; LIEBERMAN, J. A.; LAMANTIA, A. S. A comprehensive analysis of 22q11 gene expression in the developing and adult brain. Proc Natl
Acad Sci U S A, v. 100, n. 24, p. 14433-8, Nov 2003.
MAZZOCCO, M. M. Math learning disability and math LD subtypes: evidence from studies of Turner syndrome, fragile X syndrome, and neurofibromatosis type 1. J Learn Disabil, v. 34, n. 6, p. 520-33, 2001 Nov-Dec 2001.
MAZZOCCO, M. M. Mathematical learning disability in girls with Turner syndrome: a challenge to defining MLD and its subtypes. Dev Disabil
Res Rev, v. 15, n. 1, p. 35-44, 2009.
MEYER-LINDENBERG, A.; NICHOLS, T.; CALLICOTT, J. H.; DING, J.; KOLACHANA, B.; BUCKHOLTZ, J.; MATTAY, V. S.; EGAN, M.; WEINBERGER, D. R. Impact of complex genetic variation in COMT on human brain function. Mol Psychiatry, v. 11, n. 9, p. 867-77, 797, Sep 2006.
MONTOJO, C. A.; IBRAHIM, A.; KARLSGODT, K. H.; CHOW, C.; HILTON, A. E.; JONAS, R. K.; VESAGAS, T. K.; BEARDEN, C. E. Disrupted working memory circuitry and psychotic symptoms in 22q11.2 deletion syndrome. Neuroimage Clin, v. 4, p. 392-402, 2014. MURPHY, M. M. A review of mathematical learning disabilities in children
with fragile X syndrome. Dev Disabil Res Rev, v. 15, n. 1, p. 21-7, 2009.
MURPHY, M. M.; MAZZOCCO, M. M.; GERNER, G.; HENRY, A. E. Mathematics learning disability in girls with Turner syndrome or fragile X syndrome. Brain Cogn, v. 61, n. 2, p. 195-210, Jul 2006.
PENG, P.; FUCHS, D. A Meta-Analysis of Working Memory Deficits in Children With Learning Difficulties: Is There a Difference Between Verbal Domain and Numerical Domain? J Learn Disabil, Feb 2014. PRESCOTT, K.; SCAMBLER, P. Molecular genetics of velo-cardio-facial
syndrome. In: KC, M. e PJ, S. (Ed.). Velo-cardio-facial syndrome: a model for understanding microdeletion disorders. Cambridge:
Cambridge University Press, 2005. p.19–46.
ROSS, J.; ZINN, A. Turner syndrome: Potential hormonal and genetic influences on the neurocognitive profile. In: (Ed.). Neurodevelopmental
Disorders. Cambridge, MA, The MIT Press, cap. 251–268, 1999.
ROUSSEAU, F.; HEITZ, D.; TARLETON, J.; MACPHERSON, J.; MALMGREN, H.; DAHL, N.; BARNICOAT, A.; MATHEW, C.; MORNET, E.; TEJADA, I.; ET AL. A multicenter study on genotype- phenotype correlations in the fragile X syndrome, using direct diagnosis with probe StB12.3: the first 2,253 cases. Am J Hum Genet, v. 55, n. 2, p. 225-37, Aug 1994.
ROVET, J. F. The psychoeducational characteristics of children with Turner syndrome. J Learn Disabil, v. 26, n. 5, p. 333-41, May 1993.
SCAMBLER, P. J.; KELLY, D.; LINDSAY, E.; WILLIAMSON, R.; GOLDBERG, R.; SHPRINTZEN, R.; WILSON, D. I.; GOODSHIP, J. A.; CROSS, I. E.; BURN, J. Velo-cardio-facial syndrome associated with chromosome 22 deletions encompassing the DiGeorge locus.
Lancet, v. 339, n. 8802, p. 1138-9, May 1992.
SCHUCHARDT, K.; MAEHLER, C.; HASSELHORN, M. Working memory deficits in children with specific learning disorders. J Learn Disabil, v. 41, n. 6, p. 514-23, 2008 Nov-Dec 2008.
SWIFT-SCANLAN, T.; SMITH, C. T.; BARDOWELL, S. A.; BOETTIGER, C. A. Comprehensive interrogation of CpG island methylation in the gene encoding COMT, a key estrogen and catecholamine regulator. BMC
SWILLEN, A.; DEVRIENDT, K.; LEGIUS, E.; EYSKENS, B.; DUMOULIN, M.; GEWILLIG, M.; FRYNS, J. P. Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS. J Med Genet, v. 34, n. 6, p. 453-8, Jun 1997. TENHUNEN, J.; SALMINEN, M.; LUNDSTRÖM, K.; KIVILUOTO, T.;
SAVOLAINEN, R.; ULMANEN, I. Genomic organization of the human catechol O-methyltransferase gene and its expression from two distinct promoters. Eur J Biochem, v. 223, n. 3, p. 1049-59, Aug 1994. TUNBRIDGE, E. M.; BANNERMAN, D. M.; SHARP, T.; HARRISON, P. J.
Catechol-o-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex. J Neurosci, v. 24, n. 23, p. 5331-5, Jun 2004.
TUNBRIDGE, E. M.; HARRISON, P. J.; WEINBERGER, D. R. Catechol-o- methyltransferase, cognition, and psychosis: Val158Met and beyond.
Biol Psychiatry, v. 60, n. 2, p. 141-51, Jul 2006.
VERKERK, A. J.; PIERETTI, M.; SUTCLIFFE, J. S.; FU, Y. H.; KUHL, D. P.; PIZZUTI, A.; REINER, O.; RICHARDS, S.; VICTORIA, M. F.; ZHANG, F. P. Identification of a gene (FMR-1) containing a CGG repeat coincident with a breakpoint cluster region exhibiting length variation in fragile X syndrome. Cell, v. 65, n. 5, p. 905-14, May 1991. VINKHUYZEN, A. A.; VAN DER SLUIS, S.; BOOMSMA, D. I.; DE GEUS,
E. J.; POSTHUMA, D. Individual differences in processing speed and working memory speed as assessed with the Sternberg memory scanning task. Behav Genet, v. 40, n. 3, p. 315-26, May 2010.
VOGLER, C.; GSCHWIND, L.; COYNEL, D.; FREYTAG, V.; MILNIK, A.;
EGLI, T.; HECK, A.; DE QUERVAIN, D. J.;
PAPASSOTIROPOULOS, A. Substantial SNP-based heritability estimates for working memory performance. Transl Psychiatry, v. 4, p. e438, 2014.
WAHLSTROM, D.; WHITE, T.; HOOPER, C. J.; VRSHEK-SCHALLHORN, S.; OETTING, W. S.; BROTT, M. J.; LUCIANA, M. Variations in the catechol O-methyltransferase polymorphism and prefrontally guided behaviors in adolescents. Biol Psychiatry, v. 61, n. 5, p. 626-32, Mar 2007.
WAHLSTROM, D.; WHITE, T.; LUCIANA, M. Neurobehavioral evidence for changes in dopamine system activity during adolescence. Neurosci
Biobehav Rev, v. 34, n. 5, p. 631-48, Apr 2010.
WANG, Y.; LI, J.; CHEN, C.; CHEN, C.; ZHU, B.; MOYSIS, R. K.; LEI, X.; LI, H.; LIU, Q.; XIU, D.; LIU, B.; CHEN, W.; XUE, G.; DONG, Q. COMT rs4680 Met is not always the ‘smart allele’: Val allele is associated with better working memory and larger hippocampal volume in healthy Chinese. Genes, Brain and Behavior, v. 12, p. 323–29, 2013. WILLCUTT, E. G.; PETRILL, S. A.; WU, S.; BOADA, R.; DEFRIES, J. C.;
OLSON, R. K.; PENNINGTON, B. F. Comorbidity between reading disability and math disability: concurrent psychopathology, functional impairment, and neuropsychological functioning. J Learn Disabil, v. 46, n. 6, p. 500-16, 2013 Nov-Dec 2013.
WILSON, R. S.; BARRAL, S.; LEE, J. H.; LEURGANS, S. E.; FOROUD, T. M.; SWEET, R. A.; GRAFF-RADFORD, N.; BIRD, T. D.; MAYEUX, R.; BENNETT, D. A. Heritability of different forms of memory in the Late Onset Alzheimer's Disease Family Study. J Alzheimers Dis, v. 23, n. 2, p. 249-55, 2011.
WINTERER, G.; WEINBERGER, D. R. Genes, dopamine and cortical signal- to-noise ratio in schizophrenia. Trends Neurosci, v. 27, n. 11, p. 683-90, Nov 2004.
WOODIN, M.; WANG, P. P.; ALEMAN, D.; MCDONALD-MCGINN, D.; ZACKAI, E.; MOSS, E. Neuropsychological profile of children and adolescents with the 22q11.2 microdeletion. Genet Med, v. 3, n. 1, p. 34-9, 2001 Jan-Feb 2001.
YU, S.; PRITCHARD, M.; KREMER, E.; LYNCH, M.; NANCARROW, J.; BAKER, E.; HOLMAN, K.; MULLEY, J. C.; WARREN, S. T.; SCHLESSINGER, D. Fragile X genotype characterized by an unstable region of DNA. Science, v. 252, n. 5009, p. 1179-81, May 1991.
ZHU, B. T. Catechol-O-Methyltransferase (COMT)-mediated methylation metabolism of endogenous bioactive catechols and modulation by endobiotics and xenobiotics: importance in pathophysiology and pathogenesis. Curr Drug Metab, v. 3, n. 3, p. 321-49, Jun 2002.
3. Objetivos
3.1. Objetivo Geral
Investigar os efeitos de polimorfismos da COMT sobre o desempenho da memória de trabalho de crianças saudáveis.
3.2. Objetivos específicos
· Investigar os efeitos do polimorfismo Val158Met (SNP rs4680) do gene
COMT na memória de trabalho, em uma amostra de crianças, entre 6 e
14 anos de idade, provenientes de escolas públicas e privadas de Belo Horizonte;
· Averiguar os efeitos do polimorfismo A287G (SNP rs2075507), também localizado no gene COMT, sobre a memória de trabalho, dentro da mesma amostra de crianças;
· Buscar evidência de interação entre estes polimorfismos;
· Investigar influência do sexo sobre os efeitos exercidos pelos polimorfismos;
· Averiguar influência da idade sobre os efeitos exercidos pelos polimorfismos.
4. Artigo: Influence of Catechol-O-methyltransferase Polymorphisms on