Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression

Johannes Schumacher, Rami Abou Jamra, Tim Becker, Stephanie Ohlraun, Norman Klopp, Elisabeth B. Binder, Thomas G. Schulze, Monika Deschner, Christine Schmäl, Susanne Höfels, Astrid Zobel, Thomas Illig, Peter Propping, Florian Holsboer, Marcella Rietschel, Markus M. Nöthen, Sven Cichon

Research output: Contribution to journalArticle

Abstract

Background: Previous genetic studies investigating a possible involvement of variations at the brain derived neurotrophic factor (BDNF) gene locus in major depressive disorder (MDD), bipolar affective disorder (BPAD), and schizophrenia have provided inconsistent results. Methods: We performed single-marker and haplotype analyses using three BDNF polymorphisms in 2,376 individuals (465 MDD, 281 BPAD, 533 schizophrenia, and 1,097 control subjects). Results: Single-marker analysis did not provide strong evidence for association. Haplotype analysis of marker combination rs988748-(GT)n-rs6265 produced nominally significant associations for all investigated phenotypes (global p values: MDD p = .00006, BPAD p = .0057, schizophrenia p = .016). Association with MDD was the most robust finding and could be replicated in a second German sample of MDD patients and control subjects (p = .0092, uncorrected). Stratification of our schizophrenia sample according to the presence or absence of a lifetime history of depressive symptoms showed that our finding in schizophrenia might be attributable mainly to the presence of depressive symptoms. Conclusions: Association studies of genetic variants of the BDNF gene with various psychiatric disorders have been published with reports of associations and nonreplications. Our findings suggest that BDNF may be a susceptibility gene for MDD and schizophrenia - in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.

Original languageEnglish (US)
Pages (from-to)307-314
Number of pages8
JournalBiological Psychiatry
Volume58
Issue number4
DOIs
StatePublished - Aug 15 2005
Externally publishedYes

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Brain-Derived Neurotrophic Factor
Major Depressive Disorder
Schizophrenia
Depression
Mood Disorders
Bipolar Disorder
Haplotypes
Genes
Genetic Association Studies
Psychiatry
Phenotype

Keywords

  • Association
  • BDNF
  • Bipolar affective disorder
  • Haplotype analysis
  • Schizophrenia
  • Unipolar depression

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression. / Schumacher, Johannes; Jamra, Rami Abou; Becker, Tim; Ohlraun, Stephanie; Klopp, Norman; Binder, Elisabeth B.; Schulze, Thomas G.; Deschner, Monika; Schmäl, Christine; Höfels, Susanne; Zobel, Astrid; Illig, Thomas; Propping, Peter; Holsboer, Florian; Rietschel, Marcella; Nöthen, Markus M.; Cichon, Sven.

In: Biological Psychiatry, Vol. 58, No. 4, 15.08.2005, p. 307-314.

Research output: Contribution to journalArticle

Schumacher, J, Jamra, RA, Becker, T, Ohlraun, S, Klopp, N, Binder, EB, Schulze, TG, Deschner, M, Schmäl, C, Höfels, S, Zobel, A, Illig, T, Propping, P, Holsboer, F, Rietschel, M, Nöthen, MM & Cichon, S 2005, 'Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression', Biological Psychiatry, vol. 58, no. 4, pp. 307-314. https://doi.org/10.1016/j.biopsych.2005.04.006
Schumacher, Johannes ; Jamra, Rami Abou ; Becker, Tim ; Ohlraun, Stephanie ; Klopp, Norman ; Binder, Elisabeth B. ; Schulze, Thomas G. ; Deschner, Monika ; Schmäl, Christine ; Höfels, Susanne ; Zobel, Astrid ; Illig, Thomas ; Propping, Peter ; Holsboer, Florian ; Rietschel, Marcella ; Nöthen, Markus M. ; Cichon, Sven. / Evidence for a relationship between genetic variants at the brain-derived neurotrophic factor (BDNF) locus and major depression. In: Biological Psychiatry. 2005 ; Vol. 58, No. 4. pp. 307-314.
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AU - Schumacher, Johannes

AU - Jamra, Rami Abou

AU - Becker, Tim

AU - Ohlraun, Stephanie

AU - Klopp, Norman

AU - Binder, Elisabeth B.

AU - Schulze, Thomas G.

AU - Deschner, Monika

AU - Schmäl, Christine

AU - Höfels, Susanne

AU - Zobel, Astrid

AU - Illig, Thomas

AU - Propping, Peter

AU - Holsboer, Florian

AU - Rietschel, Marcella

AU - Nöthen, Markus M.

AU - Cichon, Sven

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Y1 - 2005/8/15

N2 - Background: Previous genetic studies investigating a possible involvement of variations at the brain derived neurotrophic factor (BDNF) gene locus in major depressive disorder (MDD), bipolar affective disorder (BPAD), and schizophrenia have provided inconsistent results. Methods: We performed single-marker and haplotype analyses using three BDNF polymorphisms in 2,376 individuals (465 MDD, 281 BPAD, 533 schizophrenia, and 1,097 control subjects). Results: Single-marker analysis did not provide strong evidence for association. Haplotype analysis of marker combination rs988748-(GT)n-rs6265 produced nominally significant associations for all investigated phenotypes (global p values: MDD p = .00006, BPAD p = .0057, schizophrenia p = .016). Association with MDD was the most robust finding and could be replicated in a second German sample of MDD patients and control subjects (p = .0092, uncorrected). Stratification of our schizophrenia sample according to the presence or absence of a lifetime history of depressive symptoms showed that our finding in schizophrenia might be attributable mainly to the presence of depressive symptoms. Conclusions: Association studies of genetic variants of the BDNF gene with various psychiatric disorders have been published with reports of associations and nonreplications. Our findings suggest that BDNF may be a susceptibility gene for MDD and schizophrenia - in particular, in a subgroup of patients with schizophrenia with a lifetime history of depressive symptoms.

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