Cognitive and magnetic resonance imaging brain morphometric correlates of brain-derived neurotrophic factor Val66Met gene polymorphism in patients with schizophrenia and healthy volunteers.

Department of Psychiatry, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, USA.
Archives of General Psychiatry (Impact Factor: 13.75). 08/2006; 63(7):731-40. DOI: 10.1001/archpsyc.63.7.731
Source: PubMed

ABSTRACT Relatively little is known about genetic determinants of cognitive dysfunction in schizophrenia. Recent studies suggest that a brain-derived neurotrophic factor (BDNF) prodomain single nucleotide polymorphism resulting in a valine (Val)-to-methionine (Met) substitution is associated with impaired declarative memory in healthy volunteers and patients with schizophrenia. These studies indicate that the BDNF(Met) variant may mediate hippocampal cognitive functions by modulating intracellular trafficking and activity-dependent BDNF release. To our knowledge, the way in which this functional single nucleotide polymorphism affects other neurocognitive measures has not been examined. Its role in determining cognitive deficits in schizophrenia has also not been systematically studied.
To characterize the neurocognitive and brain morphometric phenotypic correlates of the BDNF Val66Met polymorphism and to test the specificity of the BDNF(Met) variant on cognitive dysfunction in schizophrenia.
A comprehensive battery of standardized neuropsychological tests was administered to 144 healthy volunteers and 293 patients with schizophrenia spectrum disorder at a tertiary care university hospital. Approximately two thirds of the sample also underwent high-resolution magnetic resonance imaging brain scans.
Genotype effects (in Met allele carriers vs Val homozygotes) on 5 cognitive domain z scores and magnetic resonance imaging gray matter brain volume measures (Talairach atlas-based cerebral lobes and optimized voxel-based morphometry) were examined using general linear models.
On verbal memory, there was a significant genotype effect but no genotype x diagnosis effects. In both patients with schizophrenia and healthy volunteers, Met allele carriers had poorer verbal memory performance than their Val-homozygous counterparts. On visuospatial abilities, there were significant genotype and genotype x diagnosis effects. Met allele-associated visuospatial impairment was specific to patients with schizophrenia but not healthy volunteers. There were significant genotype effects on gray matter volumes within brain regions known to subserve these 2 cognitive domains, with Met allele carriers having smaller temporal and occipital lobar gray matter volumes. Optimized voxel-based morphometry further suggests that parietal heteromodal cortical gray matter deficits may underlie visuospatial impairment in patients with schizophrenia carrying the Met allele.
We replicated the association between the BDNF(Met) variant and poor medial temporal lobe-related memory performance. The consonance of our cognitive and brain morphology findings further suggests that the BDNF(Met) variant may have a specific role in conferring visuospatial dysfunction in schizophrenia.

1 Follower
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Research evidence points to abnormal brain-derived neurotrophic factor (BDNF) signaling being a common and vital participant in the etiology and pathophysiology of many psychiatric disorders, including depression, schizophrenia, and bipolar disorder. To increase BDNF levels in patients is therefore a necessary goal of any treatment. This review explores the various therapeutic strategies that can increase BDNF brain expression and recover mental health disturbances. From environmental enrichment and exercise to dietary intake, it is apparent that a healthy lifestyle significantly influences BDNF signaling and mental health. We conclude that in order to combat the inefficiency of current treatment methods, more attention should be focused on holistic approaches to achieve this goal, as BDNF is proven to have dynamic responses to environmental influences.
    Journal of Receptor, Ligand and Channel Research 01/2014; 20147:61-79. DOI:10.2147/JRLCR.S50404
  • Source
    European Psychiatry 01/2014; 29:1. DOI:10.1016/S0924-9338(14)78142-8 · 3.21 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Schizophrenia is believed to arise from complex gene-environment interactions. Brain-Derived Neurotrophic Factor (BDNF) is involved in neuronal development, differentiation and plasticity. A functional single nucleotide polymorphism that results in a Valine (Val) to Methionine (Met) substitution at codon 66 (Val66Met) results in the aberrant sorting and release of mature BDNF through the activity-dependent secretion pathway. The Val66Met polymorphism has been linked to impaired neurocognitive function in healthy adults, and identified as a locus of risk for a range of neuropsychiatric disorders including schizophrenia. Here we provide a comprehensive review of the relationship between the BDNF Val66Met polymorphism and schizophrenia, integrating evidence from the fields of genetic epidemiology, clinical psychiatry, behavioral neuroscience and neuroimaging. We argue that while the Val66Met polymorphism may not be a major risk-conferring agent for the development of schizophrenia per se, there is mounting evidence that the polymorphism modulates a range of clinical features of the illness, including age of onset, symptoms, therapeutic responsiveness, neurocognitive function and brain morphology.
    Neuroscience & Biobehavioral Reviews 01/2015; 51. DOI:10.1016/j.neubiorev.2014.12.016 · 10.28 Impact Factor

Full-text (2 Sources)

Available from
Sep 8, 2014