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Heritability of Response Inhibition in Children

Published online by Cambridge University Press:  21 December 2010

Russell J. Schachar ,
Nadine Forget-Dubois ,
Ginette Dionne ,
Michel Boivin  and
Philippe Robaey
Russell J. Schachar*
Affiliation:
Neurosciences and Mental Health Programme, Research Institute and the Department of Psychiatry, The Hospital for Sick Children & University of Toronto, Toronto, Canada
Nadine Forget-Dubois
Affiliation:
Groupe de recherche sur l'inadaptation psychosociale chez l'enfant (GRIP) and École de Psychologie, Université Laval, Quebec, Canada
Ginette Dionne
Affiliation:
Groupe de recherche sur l'inadaptation psychosociale chez l'enfant (GRIP) and École de Psychologie, Université Laval, Quebec, Canada
Michel Boivin
Affiliation:
Groupe de recherche sur l'inadaptation psychosociale chez l'enfant (GRIP) and École de Psychologie, Université Laval, Quebec, Canada
Philippe Robaey
Affiliation:
Department of Psychiatry, Research Center of Ste-Justine Hospital, University of Montreal, Montreal, Canada
*
Correspondence and reprint requests to: Russell J. Schachar, Department of Psychiatry, The Hospital for Sick Children, 555 University Avenue, Toronto, ON M5G 1X8. E-mail: [email protected]
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Abstract

We report the heritability of response inhibition, latency, and variability, which are potential markers of genetic risk in neuropsychiatric conditions. Genetic and environmental influences on cancellation and restraint, response latency, and variability measured in a novel variant of the stop signal task were studied in 139 eight-year-old twin pairs from a birth cohort. Cancellation (50%), restraint (27%), and response latency (41%) showed significant heritability, the balance being non-shared environmental influences and/or error. Response variability was not heritable, with 23% of the variance attributable to shared environmental influences and 77% to non-shared environmental risk or error. The phenotypic correlation between response cancellation and restraint was −.44 and between response latency and restraint was .21. These phenotypic correlations were entirely genetic in origin. The phenotypic correlation between response variability and % successful inhibition was .27, but was not genetic. Cancellation and restraint were heritable and shared genetic influences, indicating that they may be influenced by a common gene or genes. Response latency was moderately heritable and shared genetic influences with restraint, but was not correlated with cancellation. Response variability was not heritable. These results support the potential of response inhibition and latency as endophenotypes in genetic research. (JINS, 2011, 17, 238–247)

Keywords

Twin modelingEndophenotypeStop taskGo/no-goInhibitionHeritability
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 17 , Issue 2 , 28 February 2011 , pp. 238 - 247
Copyright
Copyright © The International Neuropsychological Society 2010

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References

REFERENCES

Almasy, L., Blangero, J. (2001). Endophenotypes as quantitative risk factors for psychiatric disease: Rationale and study design. American Journal of Medical Genetics, 105, 42–44.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Arking, D.E., Pfeufer, A., Post, W., Kao, W.H., Newton-Cheh, C., Ikeda, M., Chakravarti, A. (2006). A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nature Genetics, 38, 644–651.CrossRefGoogle ScholarPubMed
Aron, A.R., Poldrack, R.A. (2005). The cognitive neuroscience of response inhibition: Relevance for genetic research in attention-deficit/hyperactivity disorder. Biological Psychiatry, 57, 1285–1292.CrossRefGoogle ScholarPubMed
Aron, A.R., Poldrack, R.A. (2006). Cortical and subcortical contributions to Stop signal response inhibition: Role of the subthalamic nucleus. Journal of Neurosciences, 26, 2424–2433.CrossRefGoogle ScholarPubMed
Aron, A.R., Robbins, T.W., Poldrack, R.A. (2004). Inhibition and the right inferior frontal cortex. Trends in Cognitive Sciences, 8, 170–177.CrossRefGoogle ScholarPubMed
Band, G.P., Van Boxtel, G.J. (1999). Inhibitory motor control in stop paradigms: Review and reinterpretation of neural mechanisms. Acta Psychologica (Amsterdam), 101, 179–211.CrossRefGoogle ScholarPubMed
Bidwell, L.C., Willcutt, E.G., Defries, J.C., Pennington, B.F. (2007). Testing for neuropsychological endophenotypes in siblings discordant for attention-deficit/hyperactivity disorder. Biological Psychiatry, 62, 991–998.CrossRefGoogle ScholarPubMed
Cannon, T.D., Keller, M.C. (2006). Endophenotypes in the genetic analyses of mental disorders. Annual Review of Clinical Psychology, 2, 267–290.CrossRefGoogle ScholarPubMed
Chambers, C., Bellgrove, M., Gould, I., English, T., Garavan, H., McNaught, E., Mattingley, J. (2007). Dissociable mechanisms of cognitive control in prefrontal and premotor cortex. Journal of Neurophysiology, 98, 3638–3647.CrossRefGoogle ScholarPubMed
Chambers, C., Bellgrove, M., Stokes, M., Henderson, T., Garavan, H., Robertson, I., Mattingley, J. (2006). Executive “brake failure” following deactivation of human frontal lobe. Journal of Cognitive Neuroscience, 18, 444–455.Google ScholarPubMed
Chevrier, A.D., Noseworthy, M.D., Schachar, R. (2007). Dissociation of response inhibition and performance monitoring in the stop signal task using event-related fMRI. Human Brain Mapping, 28, 1347–1358.CrossRefGoogle ScholarPubMed
Crosbie, J., Perusse, D., Barr, C.L., Schachar, R.J. (2008). Validating psychiatric endophenotypes: Inhibitory control and attention deficit hyperactivity disorder. Neurosciences and Biobehavioral Review, 32, 40–55.CrossRefGoogle ScholarPubMed
Finkel, D., McGue, M. (1998). Age differences in the nature and origin of individual differences in memory: A behavior genetic analysis. International Journal of Aging and Human Development, 47, 217–239.CrossRefGoogle ScholarPubMed
Finkel, D., McGue, M. (2007). Genetic and environmental influences on intraindividual variability in reaction time. Experimental Aging Research, 33, 13–35.CrossRefGoogle ScholarPubMed
Friedman, N.P., Miyake, A., Young, S.E., Defries, J.C., Corley, R.P., Hewitt, J.K. (2008). Individual differences in executive functions are almost entirely genetic in origin. Journal of Experimental Psychology General, 137, 201–225.CrossRefGoogle ScholarPubMed
Gauggel, S., Rieger, M., Feghoff, T.A. (2004). Inhibition of ongoing responses in patients with Parkinson's disease. Journal of Neurology, Neurosurgery, and Psychiatry, 75, 539–544.CrossRefGoogle ScholarPubMed
Geurts, H.M., Grasman, R.P., Verte, S., Oosterlaan, J., Roeyers, H., van Kammen, S.M., Sergeant, J.A. (2008). Intra-individual variability in ADHD, autism spectrum disorders and Tourette's syndrome. Neuropsychologia, 46, 3030–3041.CrossRefGoogle ScholarPubMed
Gottesman, I.I., Gould, T.D. (2003). The endophenotype concept in psychiatry: Etymology and strategic intentions. American Journal of Psychiatry, 160, 636–645.CrossRefGoogle ScholarPubMed
Graham, J.W. (2009). Missing data analysis: Making it work in the real world. Annual Review of Psychology, 60, 549–576.CrossRefGoogle ScholarPubMed
Graham, J.W., Olchowski, A.E., Gilreath, T.D. (2007). How many imputations are really needed? Some practical clarifications of multiple imputation theory. Prevention Science, 8, 206–213.CrossRefGoogle ScholarPubMed
Groot, A.S., de Sonneville, L.M., Stins, J.F., Boomsma, D.I. (2004). Familial influences on sustained attention and inhibition in preschoolers. Journal of Child Psychology and Psychiatry, 45, 306–314.CrossRefGoogle ScholarPubMed
Harnishfeger, K.K., Pope, R.S. (1996). Intending to forget: The development of cognitive inhibition in directed forgetting. Journal of Experimental Child Psychology, 62, 292–315.CrossRefGoogle ScholarPubMed
Herbert, A., Gerry, N.P., McQueen, M.B., Heid, I.M., Pfeufer, A., Illig, T., Christman, M.F. (2006). A common genetic variant is associated with adult and childhood obesity. Science, 312, 279–283.CrossRefGoogle ScholarPubMed
Hetherington, C.R., Stuss, D.T., Finlayson, M.A. (1996). Reaction time and variability 5 and 10 years after traumatic brain injury. Brain Injury, 10, 473–486.CrossRefGoogle ScholarPubMed
Huang, B.E., Lin, D.Y. (2007). Efficient association mapping of quantitative trait loci with selective genotyping. American Journal of Human Genetics, 80, 567–576.CrossRefGoogle ScholarPubMed
Johnson, K.A., Kelly, S.P., Bellgrove, M.A., Barry, E., Cox, M., Gill, M., Robertson, I.H. (2007). Response variability in attention deficit hyperactivity disorder: Evidence for neuropsychological heterogeneity. Neuropsychologia, 45, 630–638.CrossRefGoogle ScholarPubMed
Kuntsi, J., Rogers, H., Swinard, G., Borger, N., van der Meere, J., Rijsdijk, F., Asherson, P. (2006). Reaction time, inhibition, working memory and ‘delay aversion’ performance: Genetic influences and their interpretation. Psychological Medicine, 36, 1613–1624.CrossRefGoogle ScholarPubMed
Lee, S.I., Schachar, R.J., Chen, S.X., Ornstein, T.J., Charach, A., Barr, C., Ickowicz, A. (2008). Predictive validity of DSM-IV and ICD-10 criteria for ADHD and hyperkinetic disorder. Journal of Child Psychology and Psychiatry, 49, 70–78.CrossRefGoogle ScholarPubMed
Lenroot, R.K., Schmitt, J.E., Ordaz, S.J., Wallace, G.L., Neale, M.C., Lerch, J.P., Giedd, J.N. (2009). Differences in genetic and environmental influences on the human cerebral cortex associated with development during childhood and adolescence. Human Brain Mapping, 30, 163–174.CrossRefGoogle ScholarPubMed
Leth-Steensen, C., Elbaz, Z.K., Douglas, V.I. (2000). Mean response times, variability, and skew in the responding of ADHD children: A response time distributional approach. Acta Psychologica (Amsterdam), 104, 167–190.Google ScholarPubMed
Lipszyc, J., Schachar, R. (2010). Inhibitory control and psychopathology: A meta-analysis of studies using the stop signal task. Journal of the International Neuropsychological Society, 19, 1–13.Google Scholar
Logan, G.D. (1994). On the ability to inhibit thought and action: A users’ guide to the stop signal paradigm. In D. Dagenbach & T.H. Carr (Eds.), Inhibitory processes in attention, memory, and language (pp. 189–239). San Diego: Academic Press.Google Scholar
Logan, G., Schachar, R., Tannock, R. (1997). Impulsivity and inhibitory control. Psychological Science, 8, 60–64.CrossRefGoogle Scholar
McCartney, K., Burchinal, M.R., Bub, K.L. (2006). Best practices in quantitative methods for developmentalists. Monographs of the Society for Research in Child Development, 71, 1–145.CrossRefGoogle ScholarPubMed
McKnight, P.E., McKnight, C.M., Sidani, S., Figueredo, A.J. (2007). Missing data: A gentle introduction. New York: Guilford Press.Google Scholar
Menzel, S., Thein, S.L. (2009). Genetic architecture of hemoglobin F control. Current Opinion in Hematology, 16, 179–186.CrossRefGoogle ScholarPubMed
Merikangas, K.R., Risch, N. (2003). Will the genomics revolution revolutionize psychiatry? American Journal of Psychiatry, 160, 625–635.CrossRefGoogle ScholarPubMed
Mesulam, M.M. (1998). From sensation to cognition. Brain, 121, 1013–1052.CrossRefGoogle ScholarPubMed
Miyake, A., Friedman, N.P., Emerson, M.J., Witzki, A.H., Howerter, A., Wager, T.D. (2000). The unity and diversity of executive functions and their contributions to complex “Frontal Lobe” tasks: A latent variable analysis. Cognitive Psychology, 41, 49–100.CrossRefGoogle ScholarPubMed
Neale, M.C., Boker, S.M., Xie, G., Maes, H.H. (1999). Mx: Statistical modeling (5th ed.). Richmond, VA: Department of Psychiatry.Google Scholar
Norman, D., Shallice, T. (1986). Attention to action: Willed and automatic control of behaviour. In R.J. Davidson, G.E. Schwartz, & D. Shapiro (Eds.), Consciousness and self-regulation (Vol. 4). New York: Plenum Press.Google Scholar
Plomin, R., Kosslyn, S.M. (2001). Genes, brain and cognition. Nature Neuroscience, 4, 1153–1154.CrossRefGoogle ScholarPubMed
Posthuma, D., Mulder, E.J., Boomsma, D.I., de Geus, E.J. (2002). Genetic analysis of IQ, processing speed and stimulus-response incongruency effects. Biological Psychology, 61, 157–182.CrossRefGoogle ScholarPubMed
Rommelse, N.N., Altink, M.E., Martin, N.C., Buschgens, C.J., Buitelaar, J.K., Sergeant, J.A., Oosterlaan, J. (2008). Neuropsychological measures probably facilitate heritability research of ADHD. Archives of Clinical Neuropsychology, 23, 579–591.CrossRefGoogle ScholarPubMed
Rommelse, N.N., Altink, M.E., Oosterlaan, J., Beem, L., Buschgens, C.J., Buitelaar, J., Sergeant, J.A. (2008). Speed, variability, and timing of motor output in ADHD: Which measures are useful for endophenotypic research? Behavior Genetics, 38, 121–132.CrossRefGoogle ScholarPubMed
Rommelse, N.N., Arias-Vasquez, A., Altink, M.E., Buschgens, C.J., Fliers, E., Asherson, P., Franke, B. (2008). Neuropsychological endophenotype approach to genome-wide linkage analysis identifies susceptibility loci for ADHD on 2q21.1 and 13q12.11. American Journal of Human Genetics, 83, 99–105.CrossRefGoogle ScholarPubMed
Rubia, K., Russell, T., Overmeyer, S., Brammer, M.J., Bullmore, E.T., Sharma, T., Taylor, E. (2001). Mapping motor inhibition: Conjunctive brain activations across different versions of go/no-go and stop tasks. Neuroimage, 13, 250–261.CrossRefGoogle ScholarPubMed
Sanders, R.D., Joo, Y.H., Almasy, L., Wood, J., Keshavan, M.S., Pogue-Geile, M.F., Nimgaonkar, V.L. (2006). Are neurologic examination abnormalities heritable? A preliminary study. Schizophrenia Research, 86, 172–180.CrossRefGoogle ScholarPubMed
Schachar, R.J., Crosbie, J., Barr, C.L., Ornstein, T.J., Kennedy, J., Malone, M., Pathare, T. (2005). Inhibition of motor responses in siblings concordant and discordant for attention deficit hyperactivity disorder. American Journal of Psychiatry, 162, 1076–1082.CrossRefGoogle ScholarPubMed
Schachar, R., Logan, G.D., Robaey, P., Chen, S., Ickowicz, A., Barr, C. (2007). Restraint and cancellation: Multiple inhibition deficits in attention deficit hyperactivity disorder. Journal of Abnormal Child Psychology, 35, 229–238.CrossRefGoogle ScholarPubMed
Seiss, E., Praamstra, P. (2004). The basal ganglia and inhibitory mechanisms in response selection: Evidence from subliminal priming of motor responses in Parkinson's disease. Brain, 127, 330–339.CrossRefGoogle ScholarPubMed
Sergeant, J. (2000). The cognitive-energetic model: An empirical approach to attention-deficit hyperactivity disorder. Neuroscience & Biobehavioral Reviews, 24, 7–12.CrossRefGoogle Scholar
Shallice, T., Burgess, P. (1996). The domain of supervisory processes and temporal organization of behaviour. Philosophical Transactions of the Royal Society London B, 351, 1405–1411.Google ScholarPubMed
Shaw, P., Eckstrand, K., Sharp, W., Blumenthal, J., Lerch, J.P., Greenstein, D., Rapoport, J.L. (2007). Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation. Proceedings of the National Academy of Sciences of the United States of America, 104, 19649–19654.CrossRefGoogle ScholarPubMed
Shaw, P., Kabani, N.J., Lerch, J.P., Eckstrand, K., Lenroot, R., Gogtay, N., Wise, S.P. (2008). Neurodevelopmental trajectories of the human cerebral cortex. Journal of Neuroscience, 28, 3586–3594.Google ScholarPubMed
Simonen, R.L., Videman, T., Battie, M.C., Gibbons, L.E. (1998). Determinants of psychomotor speed among 61 pairs of adult male monozygotic twins. Journal of Gerontology A Biological Sciences, 53, 228–234.CrossRefGoogle ScholarPubMed
Soreni, N., Crosbie, J., Ickowicz, A., Schachar, R. (2009). Stop signal and Conners’ continuous performance tasks: test–retest reliability of two inhibition measures in ADHD children. Journal of Attention Disorders, 13, 137–143.CrossRefGoogle ScholarPubMed
Stins, J.F., de Sonneville, L.M., Groot, A.S., Polderman, T.C., van Baal, C.G., Boomsma, D.I. (2005). Heritability of selective attention and working memory in preschoolers. Behavior Genetics, 35, 407–416.CrossRefGoogle ScholarPubMed
Tabachnick, B.G., Fidell, L.S. (1996). Using multivariate statistics (3rd ed.). New York: Harper and Row Publishers.Google Scholar
Tabachnick, B.G., Fidell, L.S. (2007). Using multivariate statistics (5th ed.). Boston: Allyn and Bacon.Google Scholar
Townsend, J., Harris, N.S., Courchesne, E. (1996). Visual attention abnormalities in autism: Delayed orienting to location. Journal of the International Neuropsychological Society, 2, 541–550.CrossRefGoogle ScholarPubMed
Turkheimer, E., Waldron, M. (2000). Nonshared environment: A theoretical, methodological, and quantitative review. Psychological Bulletin, 126, 78–108.CrossRefGoogle ScholarPubMed
Uebel, H., Albrecht, B., Asherson, P., Borger, N.A., Butler, L., Chen, W., Banaschewski, T. (2010). Performance variability, impulsivity errors and the impact of incentives as gender-independent endophenotypes for ADHD. Journal of Child Psychology and Psychiatry, 51, 210–218.CrossRefGoogle ScholarPubMed
van den Wildenberg, W.P., Burle, B., Vidal, F., van der Molen, M.W., Ridderinkhof, K.R., Hasbroucq, T. (2010). Mechanisms and dynamics of cortical motor inhibition in the stop-signal paradigm: A TMS study. Journal of Cognitive Neurosciences, 22, 225–239.CrossRefGoogle ScholarPubMed
Van Gestel, S., Houwing-Duistermaat, J.J., Adolfsson, R., van Duijn, C.M., Van Broeckhoven, C. (2000). Power of selective genotyping in genetic association analyses of quantitative traits. Behavior Genetics, 30, 141–146.CrossRefGoogle ScholarPubMed
Vaurio, R.G., Simmonds, D.J., Mostofsky, S.H. (2009). Increased intra-individual reaction time variability in attention-deficit/hyperactivity disorder across response inhibition tasks with different cognitive demands. Neuropsychologia, 47, 2389–2396.CrossRefGoogle ScholarPubMed
Verbruggen, F., Logan, G.D. (2008a). Automatic and controlled response inhibition: Associative learning in the go/no-go and stop-signal paradigms. Journal of Experimental Psychology General, 137, 649–672.CrossRefGoogle ScholarPubMed
Verbruggen, F., Logan, G.D. (2008b). Response inhibition in the stop-signal paradigm. Trends in Cognitive Science, 12, 418–424.CrossRefGoogle ScholarPubMed
Verbruggen, F., Schneider, D.W., Logan, G.D. (2008). How to stop and change a response: The role of goal activation in multitasking. Journal of Experimental Psychology Human Perception and Performance, 34, 1212–1228.CrossRefGoogle Scholar
Williams, B.R., Ponesse, J.S., Schachar, R.J., Logan, G.D., Tannock, R. (1999). Development of inhibitory control across the life span. Developmental Psychology, 35, 205–213.CrossRefGoogle ScholarPubMed
Young, S.E., Friedman, N.P., Miyake, A., Willcutt, E.G., Corley, R.P., Haberstick, B.C., Hewitt, J.K. (2009). Behavioral disinhibition: Liability for externalizing spectrum disorders and its genetic and environmental relation to response inhibition across adolescence. Journal of Abnormal Psychology, 118, 117–130.CrossRefGoogle ScholarPubMed
Zelazo, P., Carter, A., Reznick, S., Frye, D. (1997). Early development of executive function: A problem-solving framework. Review of General Psychology, 1, 1–41.CrossRefGoogle Scholar