The Val66Met polymorphism of the brain-derived neurotrophic-factor gene is associated with geriatric depression

Brain-derived neurotrophic-factor (BDNF), the most abundant of the neurotrophins in the brain, has been implicated in both major depression and cognitive function. This study examines the association between the BDNF-gene Val66Met polymorphism and depression susceptibility and severity, age-of-onset, cognitive function and suicidal attempt history in an elderly Chinese sample population. We genotyped the BDNF-gene Val66Met polymorphism in 110 elderly inpatients diagnosed with major depression and 171 age- and sex-similar control subjects. All patients were assessed with the Hamilton Rating Scale for Depression (HAM-D) for depression severity and the Mini-Mental Status Examination (MMSE) for cognitive function after admission. Suicide attempt history and age-of-onset of depression were evaluated by interview and medical record. The BDNF Val66Met genotype distribution was significantly different between depressed patients and control subjects (P=0.003) and there was a significant excess of Met allele in the depressed patients compared to the control group (P=0.001). The BDNF polymorphism did not affect age-of-onset, depression severity, cognitive function or suicidal attempt history. The results suggest that the BDNF Val66Met polymorphism is a relevant risk factor for geriatric depression.

[1]  James R MacFall,et al.  Hippocampal volume in geriatric depression , 2000, Biological Psychiatry.

[2]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[3]  F. Taneli,et al.  Effect of treatment on serum brain–derived neurotrophic factor levels in depressed patients , 2005, European Archives of Psychiatry and Clinical Neuroscience.

[4]  M. Hamilton A RATING SCALE FOR DEPRESSION , 1960, Journal of neurology, neurosurgery, and psychiatry.

[5]  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.

[6]  Yogesh K. Dwivedi,et al.  Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. , 2003, Archives of general psychiatry.

[7]  S M de la Monte,et al.  Human and rat brain-derived neurotrophic factor and neurotrophin-3: gene structures, distributions, and chromosomal localizations. , 1991, Genomics.

[8]  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.

[9]  J. Siuciak,et al.  Antidepressant-Like Effect of Brain-derived Neurotrophic Factor (BDNF) , 1997, Pharmacology Biochemistry and Behavior.

[10]  M. Riva,et al.  Association between the BDNF 196 A/G polymorphism and sporadic Alzheimer's disease , 2002, Molecular Psychiatry.

[11]  R. Duman Synaptic plasticity and mood disorders , 2002, Molecular Psychiatry.

[12]  N. Gervasoni,et al.  Partial Normalization of Serum Brain-Derived Neurotrophic Factor in Remitted Patients after a Major Depressive Episode , 2005, Neuropsychobiology.

[13]  S. Cichon,et al.  Evidence for a Relationship Between Genetic Variants at the Brain-Derived Neurotrophic Factor (BDNF) Locus and Major Depression , 2005, Biological Psychiatry.

[14]  D Robinson,et al.  Brain-derived neurotrophic factor Val66met polymorphism and volume of the hippocampal formation , 2005, Molecular Psychiatry.

[15]  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.

[16]  C. Crombie,et al.  BDNF gene is a risk factor for schizophrenia in a Scottish population , 2005, Molecular Psychiatry.

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

[18]  Philip B. Ward,et al.  Reduced hippocampal volumes and memory loss in patients with early- and late-onset depression , 2005, British Journal of Psychiatry.

[19]  M. Murer,et al.  Brain-derived neurotrophic factor in the control human brain, and in Alzheimer’s disease and Parkinson’s disease , 2001, Progress in Neurobiology.

[20]  R. Duman,et al.  Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[22]  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.

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