Skip to main content Accessibility help
×
Home

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
Corresponding
E-mail address:

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

Access options

Get access to the full version of this content by using one of the access options below.

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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle 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 ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Belsky, J., & Pluess, M. (2009). Beyond diathesis-stress: Differential susceptibility to environmental influences. Psychological Bulletin, 135, 885908.CrossRefGoogle ScholarPubMed
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 Scholar
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle 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.CrossRefGoogle ScholarPubMed
Calabrese, F., Molteni, R., Racagni, G., & Riva, M. A. (2009). Neuronal plasticity: A link between stress and mood disorders. Psychoneuoendocrinology, 341(Suppl. 1), S208S216.CrossRefGoogle 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.CrossRefGoogle ScholarPubMed
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 ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
Pluess, M., & Belsky, J. (2010). Differential susceptibility to parenting and quality child care. Developmental Psychology, 46, 379390.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle 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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle 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.CrossRefGoogle 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 Scholar
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

Full text views

Full text views reflects PDF downloads, PDFs sent to Google Drive, Dropbox and Kindle and HTML full text views.

Total number of HTML views: 6
Total number of PDF views: 89 *
View data table for this chart

* Views captured on Cambridge Core between September 2016 - 3rd December 2020. This data will be updated every 24 hours.

Hostname: page-component-6c64649b67-qq8cg Total loading time: 0.389 Render date: 2020-12-03T12:13:11.773Z Query parameters: { "hasAccess": "0", "openAccess": "0", "isLogged": "0", "lang": "en" } Feature Flags last update: Thu Dec 03 2020 11:15:45 GMT+0000 (Coordinated Universal Time) Feature Flags: { "metrics": true, "metricsAbstractViews": false, "peerReview": true, "crossMark": true, "comments": true, "relatedCommentaries": true, "subject": true, "clr": false, "languageSwitch": true }

Send article to Kindle

To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

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

Send article to Dropbox

To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

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

Send article to Google Drive

To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

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

Reply to: Submit a response


Your details


Conflicting interests

Do you have any conflicting interests? *