ArticleMolecular psychiatry2013
Brain-derived neurotrophic factor (BDNF) Val(66)Met polymorphism differentially predicts hippocampal function in medication-free patients with schizophrenia.
Article in Molecular psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Molecular and Cellular Mechanisms Linking Mood Disorders, HPA Axis Dysregulation, and Neurocognitive Inflammation to Perioperative Neurocognitive Disorders.Biomolecules · 2026Review
- The Role of BDNF on Neural Plasticity in Depression.Frontiers in cellular neuroscience · 2020Article
- Brain-derived neurotrophic factor and schizophrenia.Psychiatric genetics · 2019Review
- Brain-derived neurotrophic factor signaling mitigates the impact of acute social stress.Neuropharmacology · 2019Article
- Mapping the Schizophrenia Genes by Neuroimaging: The Opportunities and the Challenges.International journal of molecular sciences · 2018Review
- BDNF ValNeuroImage · 2017Article
- The schizophrenia risk gene ZNF804A: clinical associations, biological mechanisms and neuronal functions.Molecular psychiatry · 2017Review
- Mechanisms and regulation of neurotrophin synthesis and secretion.Neurosciences (Riyadh, Saudi Arabia) · 2016Review
- The BDNF gene Val66Met polymorphism as a modifier of psychiatric disorder susceptibility: progress and controversy.Molecular psychiatry · 2015Review
- Neurodevelopment, GABA system dysfunction, and schizophrenia.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2015Review
- Targeted deletion of the C-terminus of the mouse adenomatous polyposis coli tumor suppressor results in neurologic phenotypes related to schizophrenia.Molecular brain · 2014Article
- Dosage effects of BDNF Val66Met polymorphism on cortical surface area and functional connectivity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- The effects of olanzapine on genome-wide DNA methylation in the hippocampus and cerebellum.Clinical epigenetics · 2014Article
- Mice with altered BDNF signaling as models for mood disorders and antidepressant effects.Frontiers in behavioral neuroscience · 2014Review
- Olanzapine induced DNA methylation changes support the dopamine hypothesis of psychosis.Journal of molecular psychiatry · 2013Article
- BDNF and schizophrenia: from neurodevelopment to neuronal plasticity, learning, and memory.Frontiers in psychiatry · 2013Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
A Val(66)Met single-nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene impairs activity-dependent BDNF release in cultured hippocampal neurons and predicts impaired memory and exaggerated basal hippocampal activity in healthy humans. Several clinical genetic association studies along with multi-modal evidence for hippocampal dysfunction in schizophrenia indirectly suggest a relationship between schizophrenia and genetically determined BDNF function in the hippocampus. To directly test this hypothesized relationship, we studied 47 medication-free patients with schizophrenia or schizoaffective disorder and 74 healthy comparison individuals with genotyping for the Val(66)Met SNP and [(15)O]H(2)O positron emission tomography (PET) to measure resting and working memory-related hippocampal regional cerebral blood flow (rCBF). In patients, harboring a Met allele was associated with significantly less hippocampal rCBF. This finding was opposite to the genotype effect seen in healthy participants, resulting in a significant diagnosis-by-genotype interaction. Exploratory analyses of interregional resting rCBF covariation revealed a specific and significant diagnosis-by-genotype interaction effect on hippocampal-prefrontal coupling. A diagnosis-by-genotype interaction was also found for working memory-related hippocampal rCBF change, which was uniquely attenuated in Met allele-carrying patients. Thus, both task-independent and task-dependent hippocampal neurophysiology accommodates a Met allelic background differently in patients with schizophrenia than in control subjects. Potentially consistent with the hypothesis that cellular sequelae of the BDNF Val(66)Met SNP interface with aspects of schizophrenic hippocampal and frontotemporal dysfunction, these results warrant future investigation to understand the contributions of unique patient trait or state variables to these robust interactions.
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