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The brain-derived neurotrophic factor Val66Met polymorphism moderates early deprivation effects on attention problems

Published online by Cambridge University Press:  15 October 2012

Megan R. Gunnar*
Affiliation:
University of Minnesota
Jennifer A. Wenner
Affiliation:
University of Minnesota
Kathleen M. Thomas
Affiliation:
University of Minnesota
Charles E. Glatt
Affiliation:
Cornell University
Morgan C. Mckenna
Affiliation:
Cornell University
Andrew G. Clark
Affiliation:
Cornell University
*
Address correspondence and reprint requests to: Megan R. Gunnar, Institute of Child Development, University of Minnesota, 51 East River Road, Minneapolis, MN 55455; Email: gunnar@umn.edu.

Abstract

Adverse early care is associated with attention regulatory problems, but not all so exposed develop attention problems. In a sample of 612 youth (girls = 432, M = 11.82 years, SD = 1.5) adopted from institutions (e.g., orphanages) in 25 countries, we examined whether the Val66Met polymorphism of the brain-derived neurotrophic factor gene moderates attention problems associated with the duration of institutional care. Parent-reported attention problem symptoms were collected using the MacArthur Health and Behavior Questionnaire. DNA was genotyped for the brain-derived neurotrophic factor Val66Met (rs6265) single nucleotide polymorphism. Among youth from Southeast (SE) Asia, the predominant genotype was valine/methionine (Val/Met), whereas among youth from Russia/Europe and Caribbean/South America, the predominant genotype was Val/Val. For analysis, youth were grouped as carrying Val/Val or Met/Met alleles. Being female, being from SE Asia, and being younger when adopted were associated with fewer attention regulatory problem symptoms. Youth carrying at least one copy of the Met allele were more sensitive to the duration of deprivation, yielding an interaction that followed a differential susceptibility pattern. Thus, youth with Val/Met or Met/Met genotypes exhibited fewer symptoms than Val/Val genotypes when adoption was very early and more symptoms when adoption occurred later in development. Similar patterns were observed when SE Asian youth and youth from other parts of the world were analyzed separately.

Type
Articles
Copyright
Copyright © Cambridge University Press 2012

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References

Ablow, J. C., Measelle, J. R., Kraemer, H. C., Harrington, R., Luby, J., & Smider, N. (1999). The MacArthur three-city outcome study: Evaluating multi-informant measures of young children's symptomatology. Journal of American Academy of Child & Adolescent Psychiatry, 38, 15801590.Google Scholar
Aguilera, M. B., Arias, B., Wichers, M., Barrantes-Vidal, N., Moya, J., Villa, H., et al. (2009). Early adversity and 5-HTT/BDNF genes: New evidence of gene–environment interactions on depressive symptoms in a general population. Psychological Medicine, 39, 14251432.Google Scholar
Aiken, L. S., & West, S. G. (1991). Multiple regression: Testing and interpreting interactions Newbury Park, CA: Sage.Google Scholar
Bartkowska, K., Turlejski, K., & Djavadian, R. L. (2010). Neurotrophins and their receptors in early development of the mammalian nervous system. Acta Neurobiologiae Experimentalis (Wars), 70, 454467.Google Scholar
Belsky, J., Bakermans-Kranenburg, M., & van IJzendoorn, M. (2007). For better and for worse: Differential susceptibility to environmental influences. Current Directions in Psychological Science, 16, 305309.CrossRefGoogle Scholar
Belsky, J., Jonassaint, C., Pluess, M., Stanton, M., Brummet, B., & Williams, R. (2009). Vulnerability genes or plasticity genes? Molecular Psychiatry, 14, 746754.Google Scholar
Belsky, J., & Pluess, M. (2009). Beyond diathesis-stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885908.Google Scholar
Bock, J., Gruss, M., Becker, S., & Braun, K. (2005). Experience-induced changes of dendritic spine densities in the prefrontal and sensory cortex: Correlations with developmental time windows. Cerebral Cortex, 15, 802808.CrossRefGoogle ScholarPubMed
Boyle, M. H., Offord, D. R., Racine, Y., Szatmari, P., & Sanford, M. (1993). Evaluation of the revised Ontario Health Study Scales. Journal of Child Psychology and Psychiatry, 34, 189213.Google Scholar
Branaschewski, T., Becker, K., Scherag, S., Franke, B., & Coghill, D. (2010). Molecular genetics of attention deficit/hyperactivity disorder: An overview. European Child and Adolescent Psychiatry, 19, 237257.Google Scholar
Braun, K., Lange, E., Metzger, M., & Poegoel, G. (2000). Maternal separation followed by early social deprivation afffects the development of monoaminergic fiber systems in the medial prefrontal cortex of Octodon degus. Neuroscience, 95, 309318.CrossRefGoogle Scholar
Bruce, J., Tarullo, A. R., & Gunnar, M. R. (2009). Disinhibited social behavior among internationally adopted children. Development and Psychopathology, 21, 151171.Google Scholar
Calabrese, F., Molteni, R., Racagni, G., & Riva, M. A. (2009). Neuronal plasticity: A link between stress and mood disorders. Psychoneuoendocrinology, 341(Suppl. 1), S208S216.Google Scholar
Carlson, M., & Earls, F. (1997). Psychological and neuroendocrinological sequelae of early social deprivation in institutionalized children in Romania. Annals of the New York Academy of Sciences, 807, 419428.Google Scholar
Colvert, E., Rutter, M., Beckett, C., Castle, J., Groothues, C., Hawkins, A., et al. (2008). Emotional difficulties in early adolescence following severe early deprivation: Findings from the English and Romanian Adoptees Study. Development and Psychopathology, 20, 547567.CrossRefGoogle ScholarPubMed
Drury, S. S., Gleason, M. M., Theall, K. P., Smyke, A. T., Nelson, C. A., Fox, N. A., et al. (2011). Genetic sensitivity to the caregiving context: The influence of 5HTTLPR and BDNF Val66Met on indiscriminate social behavior. Physiology & Behavior.Google Scholar
Egan, M. F., Kojima, M., Callicott, J. H., Goldberg, T. E., Kolachana, B. S., Bertolino, A., et al. (2003). The BDNF Val66Met polymorphism affects activity dependent secretion of BDNF and human memory and hippocampal function. Cell, 112, 257269.Google Scholar
Essex, M. J., Boyce, T., Goldstein, L. H., Armstrong, J. M., Kraemer, H. C., & Kupfer, D. (2002). The confluence of mental, physical, social, and academic difficulties in middle childhood. II: Developing the MacArthur Health and Behavior Questionnaire. Journal of the American Academy of Child & Adolescent Psychiatry, 41, 588603.Google Scholar
Faraone, S. V., Perlis, R. H., Doyle, A. E., Smoller, J. W., Goralnick, J. J., Holmgren, M. A., et al. (2005). Molecular genetics of attention-deficit/hyperactivity disorder. Biological Psychiatry, 57, 13131323.CrossRefGoogle ScholarPubMed
Gatt, J. M., Nemeroff, C. B., Dobson-Stone, C., Paul, R. H., Bryant, R. A., Schofield, P. R., et al. (2009). Interactions between BDNF Val66Met polymorphism and early life stress predict brain and arousal pathways to syndromal depression and anxiety. Molecular Psychiatry, 14, 681695.Google Scholar
Gunnar, M. R. (2001). Effects of early deprivation: Findings from orphanage-reared infants and children. In Nelson, C. A. & Luciana, M. (Eds.), Handbook of developmental cognitive neuroscience (pp. 617629). Cambridge, MA: MIT Press.Google Scholar
Gunnar, M. R., & van Dulmen, M. (2007). Behavior problems in postinstitutionalized internationally adopted children. Development and Psychopathology, 19, 129148.CrossRefGoogle ScholarPubMed
Hayden, E. P., Klein, D. N., Dougherty, L. R., Olino, T. M., Dyson, M. W., Durbin, C. E., et al. (2010). The role of brain-derived neurotrophic factor genotype, parental depression, and relationship discord in predicting early-emerging negative emotionality. Psychological Science, 21, 16781685.Google Scholar
Hellerstedt, W. L., Madsen, N. J., Gunnar, M. R., Grotevant, H. D., Lee, R. M., & Johnson, D. E. (2008). The international adoption project: Population-based surveillance of Minnesota parents who adopted children internationally. Maternal and Child Health Journal, 12, 162171.Google Scholar
Hildyard, K. L., & Wolfe, D. A. (2002). Child neglect: Developmental issues and outcomes. Child Abuse & Neglect, 26, 679695.CrossRefGoogle ScholarPubMed
Johnson, D. E. (2000). Medical and developmental sequale of early childhood institutionalization in Eastern European adoptees. Minnesota Symposium on Child Psychology, 31, 113162.Google Scholar
Johnson, A. E., Bruce, J., Tarullo, A. R., & Gunnar, M. R. (2011). Growth delay as an index of allostatic load in young children: Predictions to disinhibited social approach and diurnal cortisol activity. Development and Psychopathology, 23, 859871.Google Scholar
Kaufman, J., Yang, B. Z., Douglas-Palumberi, H., Grasso, D., Lipschitz, D., Houshyar, S., et al. (2006). Brain-derived neurotrophic factor–5HTTLPR gene interactions and environmental modifiers of depression in children. Biological Psychiatry, 59, 673680.Google Scholar
Kreppner, J. A., O'Connor, T. G., & Rutter, M. (2001). Can inattention/overactivity be an institutional deprivation syndrome? Journal of Abnormal Child Psychology, 29, 513528.Google Scholar
Kuczewski, N., Porcher, C., & Gaiarsa, J. L. (2010). Activity-dependent dendritic secretion of brain-derived neurotrophic factor modulates synaptic plasticity. European Journal of Neuroscience, 32, 12391244.Google Scholar
Laucht, M., Skowronek, M. H., Becker, K., Schmidt, M. H., Esser, G., & Schulze, T. G. (2007). Interacting effects of the dopamine transporter gene and psychosocial adversity on attention-deficit/hyperactivity disorder symptoms among 15-year-olds from a high-risk community sample. Archives of General Psychiatry, 64, 585590.Google Scholar
Lemery-Chalfant, K., Schreiber, J. E., Schmidt, N. L., Van Hulle, C. A., Essex, M. J., & Goldsmith, H. H. (2007). Assessing internalizing, externalizing, and attention problems in young children: Validation of the MacArthur HBQ. Journal American Academy of Child & Adolescent Psychiatry, 46, 13151323.Google Scholar
Lippmann, M., Bress, A., Nemeroff, C. B., Plotsky, P. M., & Monteggia, L. M. (2007). Long-term behavioural and molecular alterations associated with maternal separation in rats. European Journal of Neuroscience, 25, 30913098.Google Scholar
Nederhof, E., Bouma, E. M., Riese, H., Laceulle, O. M., Ormel, J., & Oldehinkel, A. J. (2010). Evidence for plasticity genotypes in a gene–gene environment interaction: The TRAILS study. Genes, Brain, and Behavior, 9, 968973.CrossRefGoogle Scholar
Numakawa, T., Yokomaku, D., Richards, M., Hori, H., Adachi, N., & Kunugi, H. (2010). Functional interactions between steroid hormones and neurotrophin BDNF. World Journal of Biological Chemistry, 1, 133143.Google Scholar
Oh, S., & Lewis, C. (2008). Korean preschoolers’ advanced inhibitory control and its relation to other executive skills and mental state understanding. Child Development, 79, 8099.Google Scholar
Petryshen, T. L., Sabeti, P. C., Aldinger, K. A., Fry, B., Fan, J. B., Schaffner, S. F., et al. (2010). Population genetic study of the brain-derived neurotrophic factor (BDNF) gene. Molecular Psychiatry, 15, 810815.Google Scholar
Pluess, M., & Belsky, J. (2010). Differential susceptibility to parenting and quality child care. Developmental Psychology, 46, 379390.Google Scholar
Poelmans, G., Pauls, D. L., Buitelaar, J. K., & Franke, B. (2011). Integrated genome-wide association study findings: Identification of a neurodevelopmental network for attention-deficit/hyperacticity disorder. American Journal of Psychiatry, 168, 365377.Google Scholar
Polanczyk, G., de Lima, M. S., Horta, B. L., Biederman, J., & Rohde, L. A. (2007). The worldwide prevalence of ADHD: A systematic review and metaregression analysis. American Journal of Psychiatry, 164, 942948.Google Scholar
Pollak, S. D., Nelson, C. A., Schlaak, M. F., Roeber, B. J., Wewerka, S. S., Wiik, K. L., et al. (2010). Neurodevelopmental effects of early deprivation in postinstitutionalized children. Child Development, 81, 224236.Google Scholar
Roceri, M., Cirulli, F., Pessina, C., Peretto, P., Racagni, G., & Riva, M. A. (2004). Postnatal repeated maternal deprivation produces age-dependent changes in brain-derived neurotrophic factor expression in selected rat brain regions. Biological Psychiatry, 55, 708714.Google Scholar
Roceri, M., Hendriks, W., Racagni, G., Ellenbroek, B. A., & Riva, M. A. (2002). Early maternal deprivation reduces the expression of BDNF and NMDA receptor subunits in rat hippocampus. Molecular Psychiatry, 7, 609616.Google Scholar
Roth, T. L., Lubin, F. D., Funk, A. J., & Sweatt, J. D. (2009). Lasting epigenetic influence of early-life adversity on the BDNF gene. Biological Psychiatry, 65, 760769.CrossRefGoogle ScholarPubMed
Roth, T. L., & Sweatt, J. D. (2011). Epigenetic marking of the BDNF gene by early-life adverse experience. Hormones and Behavior, 59, 315320.Google Scholar
Roy, P., Rutter, M., & Pickels, A. (2000). Institutional care: Risk from family background or pattern of rearing? Journal of Child Psychology and Psychiatry, 41, 139149.Google Scholar
Rutter, M. L., Kreppner, J. M., & O'Connor, T. G. (2001). Specificity and heterogeneity in children's responses to profound institutional privation. British Journal of Psychiatry, 179, 97103.Google Scholar
Sakata, K., Woo, N. H., Martinowich, K., Greene, J. S., Schloesser, R. J., Shen, L., et al. (2009). Critical role of promoter IV-driven BDNF transcription in GABAergic tranmission and synaptic platicity in the prefrontal cortex. Proceedings of the National Academy of Science, 106, 59425947.Google Scholar
Shirtcliff, E. A., & Essex, M. J. (2008). Concurrent and longitudinal associations of basal and diurnal cortisol with mental health symptoms in early adolescence. Developmental Psychobiology, 50, 690703.CrossRefGoogle ScholarPubMed
Stevens, S., Kumsta, R., Kreppner, J., Brookes, K., Rutter, M., & Sonuga-Barke, E. J. S. (2009). Dopamine transporter gene polymorphism moderates the effects of severe deprivation on ADHD symptoms: Developmental continuities in gene environment inter-play. American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics, 150B, 753761.Google Scholar
Stevens, S. E., Sonuga-Barke, E. J., Kreppner, J. M., Beckett, C., Castle, J., Colvert, E., et al. (2008). Inattention/overactivity following early severe institutional deprivation: Presentation and associations in early adolescence. Journal of Abnormal Child Psychology, 36, 385398.CrossRefGoogle ScholarPubMed
Suzuki, A., Matsumoto, Y., Shibuya, N., Sadahiro, R., Kamata, M., Goto, K., et al. (2011). The brain-derived neurotrophic factor Val66Met polymorphism modulates the effects of parental rearing on personality traits in healthy subjects. Genes, Brain, and Behavior, 10, 385391.CrossRefGoogle ScholarPubMed
Wermter, A. K., Laucht, M., Schimmelmann, B. G., Banaschweski, T., Sonuga-Barke, E. J., Rietschel, M., et al. (2010). From nature versus nurture, via nature and nurture, to Gene × Environment interaction in mental disorders. European Child and Adolescent Psychiatry, 19, 199210.CrossRefGoogle ScholarPubMed