Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression.

CONTEXT Brain-derived neurotrophic factor (BDNF) is suspected of being a causative factor in psychiatric disorders based on case reports or studies involving large structural anomalies. OBJECTIVE To determine the involvement of BDNF in human psychopathology DESIGN Case- Control study SETTING Microarray-based comparative genomic hybridization (aCGH) data from seven molecular diagnostic centers including 38, 550 affected subjects and 28, 705 unaffected subjects. PATIENTS Subjects referred to diagnostic screening centers for aCGH for physical or cognitive impairment. MAIN OUTCOME MEASURE Genomic copy number gains and losses RESULTS We report five individuals with psychopathology and genomic deletion of a critical region including BDNF. The defined critical region was never disrupted in control subjects or diagnostic cases without developmental abnormalities. CONCLUSION Hemizygosity of the BDNF region contributes to variable psychiatric phenotypes including anxiety, behavioral, and mood disorders.

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Highly Penetrant Alterations of a Critical Region Including BDNF in Human Psychopathology and Obesity

Ernst

Marshall

Shen

et al. 2012

Arch Gen Psychiatry

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Brain-derived neurotrophic factor

Laske

Eschweiler

2006

Nervenarzt

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Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family and plays an important role in neuronal survival and plasticity in the CNS. The proform of BDNF (pro-BDNF) is secreted and cleaved extracellularly by the serine protease plasmin to mature BDNF, which potentiates synaptic plasticity and long-term potentiation. Recent findings in animal models suggest an involvement of BDNF and its genetic functional single nucleotide polymorphism in the pathogenesis of different psychiatric diseases including depression, mania, schizophrenia, eating disorders, dementia, and Huntington's disease. In the brain and serum, BDNF is modulated by different factors. It is downregulated by stress and upregulated by learning processes, several antidepressive treatments, physical activity, and dietary restriction. Measurement of BDNF serum concentrations may be of diagnostic value. Additionally, the influence of different strategies for BDNF allocation seems to be relevant for the treatment and prevention of the above psychiatric disorders.

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Forced swimming test in mice: a review of antidepressant activity

Petit-Demoulière¹,

Chenu²,

Bourin³

2004

Psychopharmacology

844

531

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Performance of heterozygous brain-derived neurotrophic factor knockout mice on behavioral analogues of anxiety, nociception, and depression.

Cited by 53 publications

References 43 publications

Highly Penetrant Alterations of a Critical Region Including BDNF in Human Psychopathology and Obesity

Highly Penetrant Alterations of a Critical Region Including BDNF in Human Psychopathology and Obesity

Brain-derived neurotrophic factor

Forced swimming test in mice: a review of antidepressant activity

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