Association of a functional BDNF polymorphism and anxiety-related personality traits

RationaleConverging lines of evidence point to brain-derived neurotrophic factor (BDNF) as a factor in the pathophysiology of depression. Recently, it was shown that the Val allele of the BDNF Val66Met substitution polymorphism showed a significant association with higher mean neuroticism scores of the NEO-Five Factor Inventory (NEO-FFI) in healthy subjects, and previous studies suggested the Val allele to be increased in bipolar disorder families. The association to anxiety-related traits has not been investigated so far.MethodsWe tested a total of 343 unrelated subjects of German descent (171 male, 172 female, age: 39.0±14.6 years) who were carefully screened for psychiatric health. The self-ratable State–Trait Anxiety Inventory (STAI), which allows anxiety to be quantified as a comparatively stable personality trait, and the NEO-Five Factor Inventory (NEO-FFI) was applied.ResultsIn the trait-related anxiety score, a significant (F=3.2, df=2, p<0.042) effect of the genotype was observed with higher levels of trait anxiety in Val/Val (35.0±7.4) compared to Val/Met (33.4±6.5) and Met/Met (32.0±4.6) genotypes. The NEO neuroticism scores were also higher in Val/Val (29.5±7.0) than in Val/Met (28.4±6.5) or Met/Met (26.8±5.8) genotype, but not at a significant rate.ConclusionsOur findings support the hypothesis that anxiety- and depression-related personality traits are associated with the BDNF polymorphism although the explained variance is low.

[1]  S. Gabriel,et al.  Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus. Brain-derived neutrophic factor. , 2002, Molecular psychiatry.

[2]  Margit Burmeister,et al.  A BDNF Coding Variant is Associated with the NEO Personality Inventory Domain Neuroticism, a Risk Factor for Depression , 2003, Neuropsychopharmacology.

[3]  K. Lesch,et al.  Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region , 1996, Science.

[4]  K. Livak,et al.  Oligonucleotides with fluorescent dyes at opposite ends provide a quenched probe system useful for detecting PCR product and nucleic acid hybridization. , 1995, PCR methods and applications.

[5]  D. Sheehan,et al.  The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. , 1998, The Journal of clinical psychiatry.

[6]  D. Senkowski,et al.  Evidence for disturbed cortical signal processing and altered serotonergic neurotransmission in generalized anxiety disorder , 2003, Biological Psychiatry.

[7]  S. Stoltenberg,et al.  Recent progress in psychiatric genetics-some hope but no hype. , 2000, Human molecular genetics.

[8]  C. Cotman,et al.  The influence of specific noradrenergic and serotonergic lesions on the expression of hippocampal brain-derived neurotrophic factor transcripts following voluntary physical activity , 2003, Neuroscience.

[9]  J. Aubry,et al.  Decreased serum brain-derived neurotrophic factor levels in major depressed patients , 2002, Psychiatry Research.

[10]  Daniel Senkowski,et al.  Frontal and Temporal Dysfunction of Auditory Stimulus Processing in Schizophrenia , 2002, NeuroImage.

[11]  E. Lander,et al.  Genetic dissection of complex traits science , 1994 .

[12]  Cloninger Cr.  A systematic method for clinical description and classification of personality variants: A proposal. , 1987 .

[13]  J. Gorman,et al.  SSRIs and SNRIs: broad spectrum of efficacy beyond major depression. , 1999, The Journal of clinical psychiatry.

[14]  J. Gallinat,et al.  BDNF Serum Concentrations in Healthy Volunteers are Associated with Depression-Related Personality Traits , 2004, Neuropsychopharmacology.

[15]  M. Antony,et al.  The State-Trait Anxiety Inventory, Trait version: structure and content re-examined. , 1998, Behaviour research and therapy.

[16]  S. Tsai,et al.  Association study of a brain‐derived neurotrophic‐factor genetic polymorphism and major depressive disorders, symptomatology, and antidepressant response , 2003, American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics.

[17]  E. Lander,et al.  Characterization of single-nucleotide polymorphisms in coding regions of human genes , 1999 .

[18]  S. Tsai,et al.  Association Study of a Brain-Derived Neurotrophic-Factor Genetic Polymorphism and Mood Disorders, Age of Onset and Suicidal Behavior , 2003, Neuropsychobiology.

[19]  Henry Kranzler,et al.  Serotonin transporter protein (SLC6A4) allele and haplotype frequencies and linkage disequilibria in African- and European-American and Japanese populations and in alcohol-dependent subjects , 1997, Human Genetics.

[20]  A. Russo-Neustadt.  Brain-derived neurotrophic factor, behavior, and new directions for the treatment of mental disorders. , 2003, Seminars in clinical neuropsychiatry.

[21]  Michael Geyer,et al.  Das NEO-Fünf-Faktoren Inventar (NEO-FFI) , 2002 .

[22]  Jürgen Gallinat,et al.  Association of BDNF Serum Concentrations with Central Serotonergic Activity: Evidence from Auditory Signal Processing , 2005, Neuropsychopharmacology.

[23]  G. MacQueen,et al.  Increased hippocampal bdnf immunoreactivity in subjects treated with antidepressant medication , 2001, Biological Psychiatry.

[24]  P. Hrdina,et al.  Gender differences in association between serotonin transporter gene polymorphism and personality traits. , 2000, Psychiatric genetics.

[25]  H. Ujike,et al.  Association study of the brain-derived neurotrophic factor (BDNF) gene with bipolar disorder , 2003, Neuroscience Letters.

[26]  L. Almasy,et al.  Endophenotypes as quantitative risk factors for psychiatric disease: rationale and study design. , 2001, American journal of medical genetics.

[27]  T. Hergueta,et al.  The mini international neuropsychiatric interview , 1998, European Psychiatry.

[28]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[29]  M. Egan,et al.  The BDNF val66met Polymorphism Affects Activity-Dependent Secretion of BDNF and Human Memory and Hippocampal Function , 2003, Cell.

[30]  R. Lynn,et al.  Gender differences in extraversion, neuroticism, and psychoticism in 37 nations. , 1997, The Journal of social psychology.

[31]  K. Hashimoto,et al.  Alterations of serum levels of brain-derived neurotrophic factor (BDNF) in depressed patients with or without antidepressants , 2003, Biological Psychiatry.

[32]  P. Costa,et al.  Gender differences in personality traits across cultures: robust and surprising findings. , 2001, Journal of personality and social psychology.

[33]  Peter Borkenau,et al.  Das NEO Fünf-Faktoren-Inventar (NEO-FFI): Handanweisung , 1994 .

[34]  P. Sullivan,et al.  Genetic epidemiology of major depression: review and meta-analysis. , 2000, The American journal of psychiatry.

[35]  Steven C. Hunt,et al.  Multi-center genetic study of hypertension: The Family Blood Pressure Program (FBPP). , 2002, Hypertension.

[36]  K. Lesch,et al.  Serotonin transporter function is modulated by brain-derived neurotrophic factor (BDNF) but not nerve growth factor (NGF) , 2000, Neurochemistry International.

[37]  P. Silverstone,et al.  Defining Anxious Depression: Going beyond Comorbidity , 2003, Canadian journal of psychiatry. Revue canadienne de psychiatrie.

[38]  S. Tsai,et al.  Association Study of a Brain-Derived Neurotrophic Factor (BDNF) Val66Met Polymorphism and Personality Trait and Intelligence in Healthy Young Females , 2004, Neuropsychobiology.

[39]  P. Sham,et al.  Neuroticism: a vulnerability marker for depression evidence from a family study. , 1995, Journal of affective disorders.

[40]  P. Muglia,et al.  The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study. , 2002, American journal of human genetics.

[41]  C. Robert Cloninger.  A systematic method for clinical description and classification of personality variants. A proposal. , 1987, Archives of general psychiatry.

[42]  I. Gotlib,et al.  Gender differences in depression: the role of personality factors , 2004, Psychiatry Research.

[43]  C. Altar.  Neurotrophins and depression. , 1999, Trends in pharmacological sciences.

[44]  I. Sora,et al.  Experimental gene interaction studies with SERT mutant mice as models for human polygenic and epistatic traits and disorders , 2003, Genes, brain, and behavior.

[45]  Pt Jr Costa.  Revised NEO Personality Inventory and NEO Five-Factor Inventory , 1992 .

[46]  David R. Kaplan,et al.  BDNF Promotes the Regenerative Sprouting, But Not Survival, of Injured Serotonergic Axons in the Adult Rat Brain , 2000, The Journal of Neuroscience.

[47]  S. Gabriel,et al.  Family-based association study of 76 candidate genes in bipolar disorder: BDNF is a potential risk locus , 2002, Molecular Psychiatry.

[48]  T. Zetterström,et al.  Manipulations of brain 5-HT levels affect gene expression for BDNF in rat brain , 1999, Neuropharmacology.

[49]  M. Chen,et al.  Noradrenergic and serotonergic blockade inhibits BDNF mRNA activation following exercise and antidepressant , 2003, Pharmacology Biochemistry and Behavior.

[50]  Andrew Lemire,et al.  Electroconvulsive Seizures Regulate Gene Expression of Distinct Neurotrophic Signaling Pathways , 2004, The Journal of Neuroscience.