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Are serum brain-derived neurotrophic factor concentrations related to brain structure and psychopathology in late childhood and early adolescence?

Published online by Cambridge University Press:  17 December 2019

Celia Maria de Araujo Open the ORCID record for Celia Maria de Araujo [Opens in a new window] ,
Walter Swardfager ,
Andre Zugman ,
Hugo Cogo-Moreira ,
Sintia I. Belangero ,
Vanessa K. Ota ,
Leticia M. Spindola ,
Hakon Hakonarson ,
Renata Pellegrino  and
Ary Gadelha
...Show all authors
Celia Maria de Araujo*
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada
Walter Swardfager
Affiliation:
Department of Pharmacology & Toxicology, University of Toronto, Toronto, Canada Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Canada
Andre Zugman
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada
Hugo Cogo-Moreira
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil
Sintia I. Belangero
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil
Vanessa K. Ota
Affiliation:
Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil
Leticia M. Spindola
Affiliation:
Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada Department of Morphology and Genetics, Universidade Federal de São Paulo, São Paulo, Brazil
Hakon Hakonarson
Affiliation:
Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Renata Pellegrino
Affiliation:
Center for Applied Genomics, Children’s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Ary Gadelha
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada
Giovanni A. Salum
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Pedro M. Pan
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada
Rodrigo B. Mansur
Affiliation:
Mood Disorders Psychopharmacology Unit, University of Toronto, Toronto, ONCanada Department of Psychiatry, University of Toronto, Toronto, ONCanada
Marcelo Hoexter
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department & Institute of Psychiatry, Universidade de São Paulo, São Paulo, Brazil
Felipe Picon
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
João R. Sato
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Mathematics & Statistics Institute, Universidade Federal do ABC, Santo André, Brazil
Elisa Brietzke
Affiliation:
Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada
Rodrigo Grassi-Oliveira
Affiliation:
Developmental Cognitive Neuroscience Laboratory (DCNL), Pontifical Catholic University of Rio Grande do Sul, Porto Alegre, Brazil
Luis A. P. Rohde
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil
Euripedes C. Miguel
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, University of Toronto, Toronto, ONCanada
Rodrigo A. Bressan
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil
Andrea P. Jackowski
Affiliation:
National Institute of Developmental Psychiatry for Children and Adolescents (INCTCNPq), São Paulo, Brazil Department of Psychiatry, Queen’s University School of Medicine, Kingston ON, Canada
*
*Celia M de Araujo, Email: [email protected]
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Abstract

Objective

Mental disorders can have a major impact on brain development. Peripheral blood concentrations of brain-derived neurotrophic factor (BDNF) are lower in adult psychiatric disorders. Serum BDNF concentrations and BDNF genotype have been associated with cortical maturation in children and adolescents. In 2 large independent samples, this study tests associations between serum BDNF concentrations, brain structure, and psychopathology, and the effects of BDNF genotype on BDNF serum concentrations in late childhood and early adolescence.

Methods

Children and adolescents (7-14 years old) from 2 cities (n = 267 in Porto Alegre; n = 273 in São Paulo) were evaluated as part of the Brazilian high-risk cohort (HRC) study. Serum BDNF concentrations were quantified by sandwich ELISA. Genotyping was conducted from blood or saliva samples using the SNParray Infinium HumanCore Array BeadChip. Subcortical volumes and cortical thickness were quantified using FreeSurfer. The Development and Well-Being Behavior Assessment was used to identify the presence of a psychiatric disorder.

Results

Serum BDNF concentrations were not associated with subcortical volumes or with cortical thickness. Serum BDNF concentration did not differ between participants with and without mental disorders, or between Val homozygotes and Met carriers.

Conclusions

No evidence was found to support serum BDNF concentrations as a useful marker of developmental differences in brain and behavior in early life. Negative findings were replicated in 2 of the largest independent samples investigated to date.

Keywords

BDNFMRICortical ThicknessPsychiatric DisordersChildrenAdolescents
Type
Original Research
Information
CNS Spectrums , Volume 25 , Issue 6 , December 2020 , pp. 790 - 796
Copyright
© Cambridge University Press 2019

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References

Ninan, I. Synaptic regulation of affective behaviors; role of BDNF. Neuropharmacology. 2014;76(Pt C):684–695.Google ScholarPubMed
Cohen, S, Greenberg, ME. Communication between the synapse and the nucleus in neuronal development, plasticity, and disease. Annu Rev Cell Dev Biol. 2008;24:183–209.CrossRefGoogle Scholar
Lubin, FD, Roth, TL, Sweatt, JD. Epigenetic regulation of BDNF gene transcription in the consolidation of fear memory. J Neurosci. 2008;28(42):10576–10586.CrossRefGoogle ScholarPubMed
McAllister, AK, Katz, LC, Lo, DC. Neurotrophins and synaptic plasticity. Annu Rev Neurosci. 1999;22:295–318.CrossRefGoogle ScholarPubMed
Bocchio-Chiavetto, L, Bagnardi, V, Zanardini, R, et al. Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry. 2010;11(6):763–773.CrossRefGoogle ScholarPubMed
Sen, S, Duman, R, Sanacora, G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry. 2008;64(6):527–532.CrossRefGoogle ScholarPubMed
Brunoni, AR, Lopes, M, Fregni, F. A systematic review and meta-analysis of clinical studies on major depression and BDNF levels: implications for the role of neuroplasticity in depression. Int J Neuropsychopharmacol. 2008;11(8):1169–1180.Google ScholarPubMed
Molendijk, ML, Spinhoven, P, Polak, M, Bus, BA, Penninx, BW, Elzinga, BM. Serum BDNF concentrations as peripheral manifestations of depression: evidence from a systematic review and meta-analyses on 179 associations (N = 9484). Mol Psychiatry. 2014;19(7):791–800.CrossRefGoogle Scholar
Fernandes, BS, Molendijk, ML, Kohler, CA, et al. Peripheral brain-derived neurotrophic factor (BDNF) as a biomarker in bipolar disorder: a meta-analysis of 52 studies. BMC Med. 2015;13:289.CrossRefGoogle ScholarPubMed
Green, MJ, Matheson, SL, Shepherd, A, Weickert, CS, Carr, VJ. Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis. Mol Psychiatry. 2011;16(9):960–972.CrossRefGoogle ScholarPubMed
Simsek, S, Gencoglan, S, Yuksel, T, Kaplan, I, Alaca, R. Cortisol and brain-derived neurotrophic factor levels prior to treatment in children with obsessive–compulsive disorder. J Clin Psychiatry. 2016;77(7):e855–e859.CrossRefGoogle ScholarPubMed
Shim, SH, Hwangbo, Y, Kwon, YJ, et al. Increased levels of plasma brain-derived neurotrophic factor (BDNF) in children with attention deficit-hyperactivity disorder (ADHD). Progr Neuro-Psychopharmacol Biol Psychiatry. 2008;32(8):1824–1828.CrossRefGoogle Scholar
Pallavi, P, Sagar, R, Mehta, M, et al. Serum neurotrophic factors in adolescent depression: gender difference and correlation with clinical severity. J Affect Disord. 2013;150(2):415–423.CrossRefGoogle ScholarPubMed
Colak Sivri, R, Bilgic, A, Kilinc, I. Cytokine, chemokine and BDNF levels in medication-free pediatric patients with obsessive–compulsive disorder. Eur Child Adolesc Psychiatry. 2018;27(8):977–984.CrossRefGoogle ScholarPubMed
Cevher Binici, N, Inal Emiroglu, FN, Resmi, H, Ellidokuz, H. Serum brain-derived neurotrophic factor levels among euthymic adolescents with bipolar disorder type I. Noro Psikiyatri Arsivi. 2016;53(3):267–271.CrossRefGoogle ScholarPubMed
Bilgic, A, Toker, A, Isik, U, Kilinc, I. Serum brain-derived neurotrophic factor, glial-derived neurotrophic factor, nerve growth factor, and neurotrophin-3 levels in children with attention-deficit/hyperactivity disorder. Eur Child Adolesc Psychiatry. 2017;26(3):355–363.CrossRefGoogle ScholarPubMed
Yee, JY, Lee, TS, Lee, J. Levels of serum brain-derived neurotropic factor in individuals at ultra-high risk for psychosis—findings from the Longitudinal Youth at Risk Study (LYRIKS). Int J Neuropsychopharmacol. 2018;21(8):734.CrossRefGoogle Scholar
Inal-Emiroglu, FN, Resmi, H, Karabay, N, et al. Decreased right hippocampal volumes and neuroprogression markers in adolescents with bipolar disorder. Neuropsychobiology. 2015;71(3):140–148.CrossRefGoogle ScholarPubMed
Mansur, RB, Brietzke, E, McIntyre, RS, et al. BDNF and BMI effects on brain structures of bipolar offspring: results from the global mood and brain science initiative. Acta Psychiatr Scand. 2017;136(6):607–614.CrossRefGoogle ScholarPubMed
Zugman, A, Pedrini, M, Gadelha, A, et al. Serum brain-derived neurotrophic factor and cortical thickness are differently related in patients with schizophrenia and controls. Psychiatry Res. 2015;234(1):84–89.CrossRefGoogle ScholarPubMed
Rizos, E, Papathanasiou, MA, Michalopoulou, PG, et al. A longitudinal study of alterations of hippocampal volumes and serum BDNF levels in association to atypical antipsychotics in a sample of first-episode patients with schizophrenia. PLoS ONE. 2014;9(2):e87997.CrossRefGoogle Scholar
Lauxen Peruzzolo, T, Anes, M, Kohmann Ade, M, et al. Correlation between peripheral levels of brain-derived neurotrophic factor and hippocampal volume in children and adolescents with bipolar disorder. Neural Plast. 2015;2015:324825.CrossRefGoogle ScholarPubMed
Poletti, S, Aggio, V, Hoogenboezem, TA, et al. Brain-derived Neurotrophic Factor (BDNF) and gray matter volume in bipolar disorder. Eur Psychiatry. 2017;40:33–37.CrossRefGoogle ScholarPubMed
de Araujo, CM, Zugman, A, Swardfager, W, et al. Effects of the brain-derived neurotropic factor variant Val66Met on cortical structure in late childhood and early adolescence. J Psychiatric Res. 2018;98:51–58.CrossRefGoogle ScholarPubMed
Hashimoto, T, Fukui, K, Takeuchi, H, et al. Effects of the BDNF Val66Met polymorphism on gray matter volume in typically developing children and adolescents. Cereb Cortex. 2016;26(4):1795–1803.CrossRefGoogle ScholarPubMed
Jasinska, KK, Molfese, PJ, Kornilov, SA, et al. The BDNF Val(66)Met polymorphism is associated with structural neuroanatomical differences in young children. Behav Brain Res. 2017;328:48–56.CrossRefGoogle ScholarPubMed
Wheeler, AL, Felsky, D, Viviano, JD, et al. BDNF-dependent effects on amygdala-cortical circuitry and depression risk in children and youth. Cereb Cortex. 2018;28(5):1760–1770.CrossRefGoogle ScholarPubMed
Terracciano, A, Piras, MG, Lobina, M, et al. Genetics of serum BDNF: meta-analysis of the Val66Met and genome-wide association study. World J Biol Psychiatry. 2013;14(8):583–589.CrossRefGoogle ScholarPubMed
Bus, BA, Arias-Vasquez, A, Franke, B, Prickaerts, J, de Graaf, J, Voshaar, RC. Increase in serum brain-derived neurotrophic factor in met allele carriers of the BDNF Val66Met polymorphism is specific to males. Neuropsychobiology. 2012;65(4):183–187.CrossRefGoogle ScholarPubMed
Caldieraro, MA, McKee, M, Leistner-Segal, S, et al. Val66Met polymorphism association with serum BDNF and inflammatory biomarkers in major depression. World J Biol Psychiatry. 2018;19(5):402–409.CrossRefGoogle ScholarPubMed
Moreira, FP, Fabiao, JD, Bittencourt, G, et al. The Met allele of BDNF Val66Met polymorphism is associated with increased BDNF levels in generalized anxiety disorder. Psychiatric Genet. 2015;25(5):201–207.CrossRefGoogle ScholarPubMed
Lotrich, FE, Albusaysi, S, Ferrell, RE. Brain-derived neurotrophic factor serum levels and genotype: association with depression during interferon-alpha treatment. Neuropsychopharmacology. 2013;38(6):985–995.CrossRefGoogle ScholarPubMed
Ozan, E, Okur, H, Eker, C, Eker, OD, Gonul, AS, Akarsu, N. The effect of depression, BDNF gene Val66met polymorphism and gender on serum BDNF levels. Brain Res Bull. 2010;81(1):61–65.CrossRefGoogle ScholarPubMed
Salum, GA, Gadelha, A, Pan, PM, et al. High risk cohort study for psychiatric disorders in childhood: rationale, design, methods and preliminary results. Int J Methods Psychiatric Res. 2015;24(1):58–73.CrossRefGoogle ScholarPubMed
Weissman, MM, Wickramaratne, P, Adams, P, Wolk, S, Verdeli, H, Olfson, M. Brief screening for family psychiatric history: the family history screen. Arch Gen Psychiatry. 2000;57(7):675–682.Google ScholarPubMed
Fleitlich-Bilyk, B, Goodman, R. Prevalence of child and adolescent psychiatric disorders in southeast Brazil. J Am Acad Child Adolesc Psychiatry. 2004;43(6):727–734.CrossRefGoogle ScholarPubMed
Goodman, R, Ford, T, Richards, H, Gatward, R, Meltzer, H. The Development And Well-Being Assessment: description and initial validation of an integrated assessment of child and adolescent psychopathology. J Child Psychol Psychiatry Allied Discipl. 2000;41(5):645–655.CrossRefGoogle ScholarPubMed
Wechsler, D. WISC-III: Escala de Inteligência Wechsler para Crianças: Manual. São Paulo, Brazil: Casa do Psicólogo; 2002.Google Scholar
Tellegen, A, Briggs, PF. Old wine in new skins: grouping Wechsler subtests into new scales. J Consult Psycol. 1967;31(5):499–506.CrossRefGoogle ScholarPubMed
Figueiredo, VLM. Uma adaptação brasileira do teste de inteligência WISC-III. Brasília, DF: Curso de Pós-Graduação em Psicologia, Instituto de Psicologia – Universidade de Brasília; 2001.Google Scholar
Purcell, S, Neale, B, Todd-Brown, K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81(3):559–575.CrossRefGoogle ScholarPubMed
Fischl, B. FreeSurfer. NeuroImage. 2012;62(2):774–781.CrossRefGoogle ScholarPubMed
Soliman, F, Glatt, CE, Bath, KG, et al. A genetic variant BDNF polymorphism alters extinction learning in both mouse and human. Science. 2010;327(5967):863–866.CrossRefGoogle ScholarPubMed
Casey, BJ, Glatt, CE, Tottenham, N, et al. Brain-derived neurotrophic factor as a model system for examining gene by environment interactions across development. Neuroscience. 2009;164(1):108–120.CrossRefGoogle ScholarPubMed
Green, CR, Corsi-Travali, S, Neumeister, A. The role of BDNF-TrkB signaling in the pathogenesis of PTSD. J Depress Anxiety. 2013;2013:S4.Google ScholarPubMed
Song, X, Quan, M, Lv, L, et al. Decreased cortical thickness in drug naive first episode schizophrenia: in relation to serum levels of BDNF. J Psychiatric Res. 2015;60:22–28.CrossRefGoogle ScholarPubMed
Altman, DG, Bland, JM. Absence of evidence is not evidence of absence. BMJ. 1995;311(7003):485.CrossRefGoogle Scholar
Yoshida, T, Ishikawa, M, Niitsu, T, et al. Decreased serum levels of mature brain-derived neurotrophic factor (BDNF), but not its precursor proBDNF, in patients with major depressive disorder. PLoS ONE. 2012;7(8):e42676.CrossRefGoogle Scholar