Skip to main content Accessibility help
×
Home

A Hierarchical Factor Model of Executive Functions in Adolescents: Evidence of Gene-Environment Interplay

  • James J. Li (a1), Tammy A. Chung (a2), Michael M. Vanyukov (a3), D. Scott Wood (a2), Robert Ferrell (a3) (a4) and Duncan B. Clark (a2) (a4)...

Abstract

Executive functions (EF) are a complex set of neurodevelopmental, higher-ordered processes that are especially salient during adolescence. Disruptions to these processes are predictive of psychiatric problems in later adolescence and adulthood. The objectives of the current study were to characterize the latent structure of EF using bifactor analysis and to investigate the independent and interactive effects of genes and environments on EF during adolescence. Using a representative young adolescent sample, we tested the interaction of a polymorphism in the serotonin transporter gene (5-HTTLPR) and parental supervision for EF through hierarchical linear regression. To account for the possibility of a hierarchical factor structure for EF, a bifactor analysis was conducted on the eight subtests of the Delis-Kaplan Executive Functions System (D-KEFS). The bifactor analysis revealed the presence of a general EF construct and three EF subdomains (i.e., conceptual flexibility, inhibition, and fluency). A significant 5-HTTLPR by parental supervision interaction was found for conceptual flexibility, but not for general EF, fluency or inhibition. Specifically, youth with the L/L genotype had significantly lower conceptual flexibility scores compared to youth with S/S or S/L genotypes given low levels of parental supervision. Our findings indicate that adolescents with the L/L genotype were especially vulnerable to poor parental supervision on EF. This vulnerability may be amenable to preventive interventions. (JINS, 2014, 20, 62–73)

Copyright

Corresponding author

Correspondence and reprint requests to: James J. Li, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, 800 East Leigh Street, P.O. Box 980126, Richmond, VA 23298-0126. E-mail: jli9@vcu.edu

References

Hide All
Alarcón, M., Plomin, R., Fulker, D.W., Corley, R., & DeFries, J.C. (1998). Molarity not modularity: Multivariate genetic analysis of specific cognitive abilities in 16-year-old children in the Colorado Adoption Project. Cognitive Development, 14, 175193.
Anderson, V., Northam, E., Hendy, J., & Wrenall, J. (2001). Developmental neuropsychology: A clinical approach. New York: Psychology Press.
Ando, J., Ono, Y., & Wright, M.J. (2001). Genetic structure of spatial and verbal working memory. Behavior Genetics, 31, 615624.
Barkley, R.A. (1997). Behavioral inhibition, sustained attention, and executive functions: Constructing a unifying theory of ADHD. Psychological Bulletin, 121, 6594.
Belsky, J., & Pluess, M. (2009). Beyond diathesis stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885908.
Bertolino, A., Blasi, G., Latorre, V., Rubino, V., Rampino, A., Sinibaldi, L., & Dallapiccola, B. (2006). Additive effects of genetic variation in dopamine regulating genes on working memory cortical activity in human brain. The Journal of Neuroscience, 26, 39183922.
Best, J.R., Miller, P.H., & Naglieri, J.A. (2011). Relations between executive function and academic achievement from ages 5 to 17 in a large, representative national sample. Learning and Individual Differences, 21, 327336.
Birrell, J.M., & Brown, V.J. (2000). Medial frontal cortex mediates perceptual attentional set shifting in the rat. The Journal of Neuroscience, 20, 43204324.
Blakemore, S.J., & Choudhury, S. (2006). Development of the adolescent brain: Implications for executive function and social cognition. Journal of Child Psychology and Psychiatry, 47, 296312.
Blanchard, M.M., Chamberlain, S.R., Roiser, J., Robbins, T.W., & Müller, U. (2011). Effects of two dopamine-modulating genes (DAT1 9/10 and COMT Val/Met) on n-back working memory performance in healthy volunteers. Psychological Medicine, 41, 611618.
Bogenschneider, K., Wu, M.Y., Raffaelli, M., & Tsay, J.C. (1998). Parent influences on adolescent peer orientation and substance use: The interface of parenting practices and values. Child Development, 69, 16721688.
Borg, J., Henningsson, S., Saijo, T., Inoue, M., Bah, J., Westberg, L., & Farde, L. (2009). Serotonin transporter genotype is associated with cognitive performance but not regional 5-HT1A receptor binding in humans. The International Journal of Neuropsychopharmacology, 12, 783792.
Brody, G.H., Beach, S.R.H., Philibert, R.A., Chen, Y.F., & Murry, V.M. (2009). Prevention effects moderate the association of 5-HTTLPR and youth risk behavior initiation: Gene x environment hypotheses tested via a randomized prevention design. Child Development, 80, 645661.
Caspi, A., Hariri, A.R., Holmes, A., Uher, R., & Moffitt, T.E. (2010). Genetic sensitivity to the environment: The case of the serotonin transporter gene and its implications for studying complex diseases and traits. American Journal of Psychiatry, 167, 509527.
Chesler, E.J., Lu, L., Shou, S., Qu, Y., Gu, J., Wang, J., & Williams, R.W. (2005). Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function. Nature Genetics, 37, 233242.
Clark, C., Prior, M., & Kinsella, G. (2002). The relationship between executive function abilities, adaptive behaviour, and academic achievement in children with externalising behaviour problems. Journal of Child Psychology and Psychiatry, 43, 785796.
Clark, D.B., Thatcher, D.L., & Maisto, S.A. (2004). Adolescent neglect and alcohol use disorders in two-parent families. Child Maltreatment, 9, 357370.
Clark, D.B., Thatcher, D.L., & Maisto, S.A. (2005). Supervisory neglect and adolescent alcohol use disorders: Effects on AUD onset and treatment outcome. Addictive Behaviors, 30, 17371750.
Clark, D.B., Kirisci, L., Mezzich, A., & Chung, T. (2008). Parental supervision and alcohol use in adolescence: Developmentally specific interactions. Journal of Developmental and Behavioral Pediatrics, 29, 285292.
Clark, D.B., Chung, T., Pajtek, S., Zhai, Z., Long, E., & Hasler, B. (2013). Neuroimaging methods for adolescent substance use disorder prevention science. Prevention Science, 14, 300309.
Clarke, H.F., Dalley, J.W., Crofts, H.S., Robbins, T.W., & Roberts, A.C. (2004). Cognitive inflexibility after prefrontal serotonin depletion. Science, 304, 878880.
Collette, F., Van der Linden, M., Laureys, S., Delfiore, G., Degueldre, C., Luxen, A., & Salmon, E. (2005). Exploring the unity and diversity of the neural substrates of executive functioning. Human Brain Mapping, 25, 409423.
Conger, R.D., Ge, X., Elder, G.H., Lorenz, F.O., & Simons, R.L. (1994). Economic stress, coercive family process, and developmental problems of adolescents. Child Development, 65, 541561.
Coolidge, F.L., Thede, L.L., & Young, S.E. (2000). Heritability and the comorbidity of attention deficit hyperactivity disorder with behavioral disorders and executive function deficits: A preliminary investigation. Developmental Neuropsychology, 17, 273287.
Cools, R., Roberts, A.C., & Robbins, T.W. (2008). Serotoninergic regulation of emotional and behavioural control processes. Trends in Cognitive Sciences, 12, 3140.
Crean, J., Richards, J.B., & de Wit, H. (2002). Effect of tryptophan depletion on impulsive behavior in men with or without a family history of alcoholism. Behavioural Brain Research, 136, 349357.
Crone, E.A. (2009). Executive functions in adolescence: Inferences from brain and behavior. Developmental Science, 12, 825830.
Dean, F.B., Hosono, S., Fang, L., Wu, X., Faruqi, A.F., Bray-Ward, P., & Lasken, R.S. (2002). Comprehensive human genome amplification using multiple displacement amplification. Proceedings of the National Academy of Sciences of the United States of America, 99, 52615266.
Delis, D.C., Kaplan, E., & Kramer, J.H. (2001). Delis-Kaplan executive function system (D-KEFS). San Antonio, TX: Psychological Corporation.
Dishion, T.J., & McMahon, R.J. (1998). Parental monitoring and the prevention of child and adolescent problem behavior: A conceptual and empirical formulation. Clinical Child and Family Psychology Review, 1, 6175.
Ernst, M. (2014). The triadic model perspective for the study of adolescent motivated behavior. Brain and Cognition, 89, 104111.
Enge, S., Fleischhauer, M., Lesch, K.P., Reif, A., & Strobel, A. (2011). Serotonergic modulation in executive functioning: Linking genetic variations to working memory performance. Neuropsychologia, 49, 37763785.
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, 201225.
Fuster, J.M. (2001). The prefrontal cortex--An update: Time is of the essence. Neuron, 30, 319333.
Galambos, N.L., Barker, E.T., & Almeida, D.M. (2003). Parents do matter: Trajectories of change in externalizing and internalizing problems in early adolescence. Child Development, 74, 578594.
Gelernter, J., Cubells, J.F., Kidd, J.R., Pakstis, A.J., & Kidd, K.K. (1999). Population studies of polymorphisms of the serotonin transporter protein gene. American Journal of Medical Genetics, 88, 6166.
Ghahremani, D.G., Lee, B., Robertson, C.L., Tabibnia, G., Morgan, A.T., De Shetler, N., & London, E.D. (2012). Striatal dopamine D2/D3 receptors mediate response inhibition and related activity in frontostriatal neural circuitry in humans. The Journal of Neuroscience, 32, 73167324.
Giancola, P.R., & Tarter, R.E. (1999). Executive cognitive functioning and risk for substance abuse. Psychological Science, 10, 203205.
Gibb, B.E., Uhrlass, D.J., Grassia, M., Benas, J.S., & McGeary, J. (2009). Children’s inferential styles, 5-HTTLPR genotype, and maternal expressed emotion-criticism: An integrated model for the intergenerational transmission of depression. Journal of Abnormal Psychology, 118, 734745.
Gizer, I.R., Ficks, C., & Waldman, I.D. (2009). Candidate gene studies of ADHD: A meta-analytic review. Human Genetics, 126, 5190.
Goldman-Rakic, P.S. (1996). Regional and cellular fractionation of working memory. Proceedings of the National Academy of Sciences of the United States of America, 93, 1347313480.
Greenberg, B.D., Tolliver, T.J., Huang, S.J., Li, Q., Bengel, D., & Murphy, D.L. (1999). Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets. American Journal of Medical Genetics, 88, 8387.
Greve, K.W., Farrell, J.F., Besson, P.S., & Crouch, J.A. (1995). A psychometric analysis of the California Card Sorting Test. Archives of Clinical Neuropsychology, 10, 265278.
Hackman, D.A., Farah, M.J., & Meaney, M.J. (2010). Socioeconomic status and the brain: Mechanistic insights from human and animal research. Nature Reviews Neuroscience, 11, 651659.
Hankin, B.L., Nederhof, E., Oppenheimer, C.W., Jenness, J., Young, J.F., Abela, J.R.Z., & Oldehinkel, A.J. (2011). Differential susceptibility in youth: Evidence that 5-HTTLPR x positive parenting is associated with positive affect ‘for better and worse’. Translational Psychiatry, 1, e44.
Hirshorn, E.A., & Thompson-Schill, S.L. (2006). Role of the left inferior frontal gyrus in covert word retrieval: Neural correlates of switching during verbal fluency. Neuropsychologia, 44, 25472557.
Hobson, C.W., Scott, S., & Rubia, K. (2011). Investigation of cool and hot executive function in ODD/CD independently of ADHD. Journal of Child Psychology and Psychiatry, 52, 10351043.
Homberg, J.R., Schiepers, O.J., Schoffelmeer, A.N., Cuppen, E., & Vanderschuren, L.J. (2007). Acute and constitutive increases in central serotonin levels reduce social play behaviour in peri-adolescent rats. Psychopharmacology, 195, 175182.
Hu, X.Z., Lipsky, R.H., Zhu, G., Akhtar, L.A., Taubman, J., Greenberg, B.D., & Goldman, D. (2006). Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder. American Journal of Human Genetics, 78, 815826.
Hughes, C.H., & Ensor, R.A. (2009). How do families help or hinder the emergence of early executive function? New Directions for Child and Adolescent Development, 3550.
Huizinga, M., Dolan, C.V., & van der Molen, M.W. (2006). Age-related change in executive function: Developmental trends and a latent variable analysis. Neuropsychologia, 44, 20172036.
Jacob, T., Moser, R.P., Windle, M., Loeber, R., & Stouthamer-Loeber, M. (2000). A new measure of parenting practices involving preadolescent-and adolescent-aged children. Behavior Modification, 24, 611634.
Jaffee, S., & Price, T. (2007). Gene–environment correlations: A review of the evidence and implications for prevention of mental illness. Molecular Psychiatry, 12, 432442.
Jedema, H.P., Gianaros, P.J., Greer, P.J., Kerr, D.D., Liu, S., Higley, J.D., & Bradberry, C.W. (2010). Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission. Molecular Psychiatry, 15, 512522.
Jurado, M.B., & Rosselli, M. (2007). The elusive nature of executive functions: A review of our current understanding. Neuropsychology Review, 17, 213233.
Kalin, N.H., Shelton, S.E., Fox, A.S., Rogers, J., Oakes, T.R., & Davidson, R.J. (2008). The serotonin transporter genotype is associated with intermediate brain phenotypes that depend on the context of eliciting stressor. Molecular Psychiatry, 13, 10211027.
Karg, K., Burmeister, M., Shedden, K., & Sen, S. (2011). The serotonin transporter promoter variant (5-HTTLPR), stress, and depression meta-analysis revisited: Evidence of genetic moderation. Archives of General Psychiatry, 68, 444454.
Kaufman, J., Yang, B.Z., Douglas-Palumberi, H., Houshyar, S., Lipschitz, D., Krystal, J.H., & Gelernter, J. (2004). Social supports and serotonin transporter gene moderate depression in maltreated children. Proceedings of the National Academy of Sciences of the United States of America, 101, 1731617321.
Kerr, A., & Zelazo, P.D. (2004). Development of “hot” executive function: The children's gambling task. Brain and Cognition, 55, 148157.
King, I.B., Satia-Abouta, J., Thornquist, M.D., Bigler, J., Patterson, R.E., Kristal, A.R., & White, E. (2002). Buccal cell DNA yield, quality, and collection costs: Comparison of methods for large-scale studies. Cancer Epidemiology, Biomarkers, and Prevention, 11, 11301133.
Krämer, U.M., Rojo, N., Schüle, R., Cunillera, T., Schöls, L., Marco-Pallarés, J., & Münte, T.F. (2009). ADHD candidate gene (DRD4 exon III) affects inhibitory control in a healthy sample. BMC Neuroscience, 10, 150.
Kuntsi, J., Rogers, H., Swinard, G., Börger, N., Meere, J.V.D., Rijsdijk, F., & Asherson, P. (2006). Reaction time, inhibition, working memory and delay aversion performance: Genetic influences and their interpretation. Psychological Medicine, 36, 16131624.
Lapiz‐Bluhm, M.D.S., Bondi, C.O., Doyen, J., Rodriguez, G.A., Bédard‐Arana, T., & Morilak, D.A. (2008). Behavioural assays to model cognitive and affective dimensions of depression and anxiety in rats. Journal of Neuroendocrinology, 20, 11151137.
Latzman, R.D., & Markon, K.E. (2010). The factor structure and age-related factorial invariance of the Delis-Kaplan Executive Function System (D-KEFS). Assessment, 17, 172184.
Lee, K., Bull, R., & Ho, R.M. (2013). Developmental changes in executive functioning. Child Development, 84, 19331953.
Lesch, K.P., Bengel, D., Heils, A., Sabol, S.Z., Greenberg, B.D., Petri, S., & Murphy, D.L. (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274, 15271531.
Li, H., Walker, R., & Armstrong, D. (2014). International note: Parenting, academic achievement and problem behaviour among Chinese adolescents. Journal of Adolescence, 37, 387389.
Li, J.J., & Lee, S.S. (2010). Latent class analysis of antisocial behavior: Interaction of serotonin transporter genotype and maltreatment. Journal of Abnormal Child Psychology, 38, 789801.
Li, J.J., Berk, M.S., & Lee, S.S. (2013). Differential susceptibility in longitudinal models of gene–environment interaction for adolescent depression. Development and Psychopathology, 25, 9911003.
Little, K.Y., McLaughlin, D.P., Zhang, L., Livermore, C.S., Dalack, G.W., McFinton, P.R., & Cook, E.H. (1998). Cocaine, ethanol, and genotype effects on human midbrain serotonin transporter binding sites and mRNA levels. American Journal of Psychiatry, 155, 207213.
Loeber, R., Farrington, D.P., Stouthamer-Loeber, M., & Van Kammen, W.B. (1998). Antisocial behavior and mental health problems: Explanatory factors in childhood and adolescence. Mahwah, NJ: L. Erlbaum.
Logan, G.D., Schachar, R.J., & Tannock, R. (1997). Impulsivity and inhibitory control. Psychological Science, 8, 6064.
Logue, S.F., & Gould, T.J. (2014). The neural and genetic basis of executive function: Attention, cognitive flexibility, and response inhibition. Pharmacology, Biochemistry, and Behavior, 123, 4554.
Matthys, W., Vanderschuren, L.J., & Schutter, D.J. (2013). The neurobiology of oppositional defiant disorder and conduct disorder: Altered functioning in three mental domains. Development and Psychopathology, 25, 193207.
Mau, W.C. (1997). Parental influences on the high school students' academic achievement: A comparison of Asian immigrants, Asian Americans, and White Americans. Psychology in the Schools, 34, 267277.
Mier, D., Kirsch, P., & Meyer-Lindenberg, A. (2010). Neural substrates of pleiotropic action of genetic variation in COMT: A meta-analysis. Molecular Psychiatry, 15, 918927.
Miyake, A., Friedman, N.P., Rettinger, D.A., Shah, P., & Hegarty, M. (2001). How are visuospatial working memory, executive functioning, and spatial abilities related? A latent-variable analysis. Journal of Experimental Psychology: General, 130, 621640.
Monchi, O., Petrides, M., Strafella, A.P., Worsley, K.J., & Doyon, J. (2006). Functional role of the basal ganglia in the planning and execution of actions. Annals of Neurology, 59, 257264.
Monsell, S. (1996). Control of mental processes. In V. Bruce (Ed.), Unsolved mysteries of the mind: Tutorial essays in cognition (pp 93148). New York, NY: Erlbaum.
Murray, J., & Farrington, D.P. (2010). Risk factors for conduct disorder and delinquency: Key findings from longitudinal studies. Canadian Journal of Psychiatry, 55, 633642.
Muthén, B.O., & Muthén, L.K. (2010). Mplus (Version 6). Los Angeles. CA: Muthen & Muthen.
Periáñez, J.A., Maestú, F., Barceló, F., Fernández, A., Amo, C., & Ortiz Alonso, T. (2004). Spatiotemporal brain dynamics during preparatory set shifting: MEG evidence. Neuroimage, 21, 687695.
Plomin, R., Haworth, C.M., & Davis, O.S. (2009). Common disorders are quantitative traits. Nature Reviews Genetics, 10, 872878.
Preacher, K.J., Curran, P.J., & Bauer, D.J. (2006). Computational tools for probing interactions in multiple linear regression, multilevel modeling, and latent curve analysis. Journal of Educational and Behavioral Statistics, 31, 437448.
Prencipe, A., Kesek, A., Cohen, J., Lamm, C., Lewis, M.D., & Zelazo, P.D. (2011). Development of hot and cool executive function during the transition to adolescence. Journal of Experimental Child Psychology, 108, 621637.
Puig, M.V., & Gulledge, A.T. (2011). Serotonin and prefrontal cortex function: Neurons, networks, and circuits. Molecular Neurobiology, 44, 449464.
Rankin, B.H., & Quane, J.M. (2002). Social contexts and urban adolescent outcomes: The interrelated effects of neighborhoods, families, and peers on African-American youth. Social Problems, 49, 79100.
Reif, A., Rösler, M., Freitag, C.M., Schneider, M., Eujen, A., Kissling, C., & Retz, W. (2007). Nature and nurture predispose to violent behavior: Serotonergic genes and adverse childhood environment. Neuropsychopharmacology, 32, 23752383.
Reise, S.P., Morizot, J., & Hays, R.D. (2007). The role of the bifactor model in resolving dimensionality issues in health outcomes measures. Quality of Life Research, 16, 1931.
Retz, W., Freitag, C.M., Retz-Junginger, P., Wenzler, D., Schneider, M., Kissling, C., & Rösler, M. (2008). A functional serotonin transporter promoter gene polymorphism increases ADHD symptoms in delinquents: Interaction with adverse childhood environment. Psychiatry Research, 158, 123131.
Roiser, J.P., Rogers, R.D., Cook, L.J., & Sahakian, B.J. (2006). The effect of polymorphism at the serotonin transporter gene on decision-making, memory and executive function in ecstasy users and controls. Psychopharmacology, 188, 213227.
Satorra, A. (2003). Power of χ2 goodness-of-fit tests in structural equation models: The case of non-normal data. In: New developments in psychometrics (pp. 5768). Tokyo: Springer.
Soenens, B., Vansteenkiste, M., Luyckx, K., & Goossens, L. (2006). Parenting and adolescent problem behavior: An integrated model with adolescent self-disclosure and perceived parental knowledge as intervening variables. Developmental Psychology, 42, 305318.
Stattin, H., & Kerr, M. (2000). Parental monitoring: A reinterpretation. Child Development, 71, 10721085.
Steinberg, L., & Silk, J.S. (2002). Parenting adolescents. Handbook of Parenting, 1, 103133.
Stuss, D.T., & Alexander, M.P. (2000). Executive functions and the frontal lobes: A conceptual view. Psychological Research, 63, 289298.
Taylor, S.F., Welsh, R.C., Wager, T.D., Luan Phan, K., Fitzgerald, K.D., & Gehring, W.J. (2004). A functional neuroimaging study of motivation and executive function. Neuroimage, 21, 10451054.
Tucker‐Drob, E.M., & Harden, K.P. (2012). Intellectual interest mediates Gene× Socioeconomic Status interaction on adolescent academic achievement. Child Development, 83, 743757.
van der Sluis, S., de Jong, P.F., & van der Leij, A. (2007). Executive functioning in children, and its relations with reasoning, reading, and arithmetic. Intelligence, 35, 427449.
Walker, S.C., Mikheenko, Y.P., Argyle, L.D., Robbins, T.W., & Roberts, A.C. (2006). Selective prefrontal serotonin depletion impairs acquisition of a detour‐reaching task. European Journal of Neuroscience, 23, 31193123.
Wang, Q., Pomerantz, E.M., & Chen, H. (2007). The role of parents’ control in early adolescents’ psychological functioning: A longitudinal investigation in the United States and China. Child Development, 78, 15921610.
Weikum, W.M., Brain, U., Chau, C.M., Grunau, R.E., Boyce, W.T., Diamond, A., & Oberlander, T.F. (2013). Prenatal serotonin reuptake inhibitor (SRI) antidepressant exposure and serotonin transporter promoter genotype (SLC6A4) influence executive functions at 6 years of age. Frontiers in Cellular Neuroscience, 7, 112.
Weiss, L.H., & Schwarz, J.C. (1996). The relationship between parenting types and older adolescents' personality, academic achievement, adjustment, and substance use. Child Development, 67, 21012114.
Wendland, J.R., Martin, B.J., Kruse, M.R., Lesch, K.P., & Murphy, D.L. (2006). Simultaneous genotyping of four functional loci of human SLC6A4, with a reappraisal of 5-HTTLPR and rs25531. Molecular Psychiatry, 11, 224226.
Zelazo, P.D., Craik, F.I., & Booth, L. (2004). Executive function across the life span. Acta Psychologica, 115, 167183.

Keywords

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed