Association between BDNF Val(66)Met genotype and episodic memory

Section of Molecular Genetics, Division of Psychological Medicine, Institute of Psychiatry, London, United Kingdom.
American Journal of Medical Genetics Part B Neuropsychiatric Genetics (Impact Factor: 3.27). 04/2005; 134B(1):73-5. DOI: 10.1002/ajmg.b.30150
Source: PubMed

ABSTRACT The val66 met polymorphism of brain derived neurotrophic factor (BDNF) has been associated with variability in episodic memory [Egan et al., 2003]. In an attempt to replicate this finding, we genotyped 206 individuals (92 affected with schizophrenia or a related disorder and 114 unaffected relatives) from the Maudsley Family Study for the BDNF val66 met polymorphism. We analyzed the effect of this polymorphism on episodic memory using the Wechsler Memory Scale, revised version (WMS-R) by regression analysis between the WMS delayed score of logical memory and genotype (corrected for age, sex, and IQ). We found the met66 allele conferred a lower score on the WMS delayed measure (R2 = 0.014 P = 0.09), which was not significant. When cases and unaffected relatives were analyzed separately, met66 was associated with a lower score on the WMS delayed measure in the relatives only (R2 = 0.077 P = 0.01), which is consistent with previous findings.

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    • "Cognitive deficits are recognized as forming part of the core psychopathology of schizophrenia, with impairments in learning, memory and attention being common (Weickert et al. 2000; Palmer et al. 2009). Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors that potentiates synaptic strength and plasticity underlying learning and memory (Lu & Chow, 1999; Poo, 2001; Egan et al. 2003; Hariri et al. 2003; Lu, 2003; Dempster et al. 2005). A single nucleotide polymorphism in the human BDNF gene produces a valine to methionine substitution in the protein prodomain that influences intracellular trafficking, activitydependent release of BDNF, learning and brain activity (Egan et al. 2003; Hariri et al. 2003). "
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    ABSTRACT: Background. Brain-derived neurotrophic factor (BDNF) is an important regulator of synaptogenesis and synaptic plasticity underlying learning. However, a relationship between circulating BDNF levels and brain activity during learning has not been demonstrated in humans. Reduced brain BDNF levels are found in schizophrenia and functional neuroimaging studies of probabilistic association learning in schizophrenia have demonstrated reduced activity in a neural network that includes the prefrontal and parietal cortices and the caudate nucleus. We predicted that brain activity would correlate positively with peripheral BDNF levels during probabilistic association learning in healthy adults and that this relationship would be altered in schizophrenia. Method. Twenty-five healthy adults and 17 people with schizophrenia or schizo-affective disorder performed a probabilistic association learning test during functional magnetic resonance imaging (fMRI). Plasma BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA). Results. We found a positive correlation between circulating plasma BDNF levels and brain activity in the parietal cor-tex in healthy adults. There was no relationship between plasma BDNF levels and task-related activity in the prefrontal, parietal or caudate regions in schizophrenia. A direct comparison of these relationships between groups revealed a sign-ificant diagnostic difference. Conclusions. This is the first study to show a relationship between peripheral BDNF levels and cortical activity during learning, suggesting that plasma BDNF levels may reflect learning-related brain activity in healthy humans. The lack of relationship between plasma BDNF and task-related brain activity in patients suggests that circulating blood BDNF may not be indicative of learning-dependent brain activity in schizophrenia.
    Psychological Medicine 08/2014; 45(04). DOI:10.1017/S0033291714001925 · 5.43 Impact Factor
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    • "The current study found that within the high schizotypy group, val homozygotes perform significantly better than met homozygotes, which suggests that when there is more releasable BDNF protein (e.g., in vals), there is better learning in those with more schizotypal traits relative to met homozygotes with more schizotypal traits. This is supported by previous studies demonstrating that the met allele is detrimental for learning and memory [5] [6] as well as IQ [50] in healthy adults. However, in the current study the exact opposite effect was found in those individuals with low SPQ scores, where the met allele appeared to be beneficial (although not significantly greater) for frontal–striatal learning relative to BDNF val homozygotes. "
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    ABSTRACT: The brain derived neurotrophic factor (BDNF) val66met polymorphism rs6265 influences learning and may represent a risk factor for schizophrenia. Healthy people with high schizotypal personality traits display cognitive deficits that are similar to but not as severe as those observed in schizophrenia and they can be studied without confounds of antipsychotics or chronic illness. How genetic variation in BDNF may impact learning in individuals falling along the schizophrenia spectrum is unknown. We predicted that schizotypal personality traits would influence learning and that schizotypal personality-based differences in learning would vary depending on the BDNF val66met genotype. Eighty-nine healthy adults completed the Schizotypal Personality Questionnaire (SPQ) and a probabilistic association learning test. Blood samples were genotyped for the BDNF val66met polymorphism. An ANOVA was performed with BDNF genotype (val homozygotes and met-carriers) and SPQ score (high/low) as grouping variables and probabilistic association learning as the dependent variable. Participants with low SPQ scores (fewer schizotypal personality traits) showed significantly better learning than those with high SPQ scores. BDNF met-carriers displaying few schizotypal personality traits performed best, whereas BDNF met-carriers displaying high schizotypal personality traits performed worst. Thus, the BDNF val66met polymorphism appears to influence probabilistic association learning differently depending on the extent of schizotypal personality traits displayed.
    Behavioural Brain Research 08/2014; 174:137-142. DOI:10.1016/j.bbr.2014.07.041 · 3.39 Impact Factor
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    • "In the USA, Goldberg et al. (2008) enrolled 48 normal adults and found that Val homozygote subjects performed better than Met carriers in identifying previously encoded stimuli. In the UK, Dempster et al. (2005) found that the Met allele was associated with poor episodic memory in 114 non-psychotic relatives of schizophrenia patients aged 17–70 years. However, no significant differences were found for either the genotype or allele distribution of the BDNF Val66Met polymorphism between amnestic mild cognitive impairment patients and control subjects in the Chinese Han population (Yu et al. 2008). "
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    ABSTRACT: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is common and influences the activity-dependent secretion of BDNF, which is critical for neuronal plasticity and survival. This study investigated the genetic effect of the BDNF Val66Met polymorphism on cognitive function and regional gray matter (GM) volume in a healthy Chinese population (n = 330). Voxel-based morphometry (VBM)-optimized analysis was used. There was no significant difference in the neuropsychological performances among the three BDNF genotypic groups. VBM analyses demonstrated that Met homozygotes had greater GM volumes than Val homozygotes in the left medial frontal gyrus, the left middle temporal gyrus, the left cerebellum, and the right middle temporal gyrus, and had larger GM volumes than Val/Met heterozygotes in the left middle temporal gyrus, the left inferior temporal gyrus, and the right superior frontal gyrus. Our findings suggest that the presence of two Met alleles has a protective effect on regional GM volumes in the Chinese population.
    Neuromolecular medicine 12/2013; DOI:10.1007/s12017-013-8265-7 · 3.89 Impact Factor