Brain-derived Neurotrophic Factor Val66Met Single Nucleotide Polymorphism Research Articles

Acute stress induces an aberrant increase of presynaptic release of glutamate and cellular activation in the hippocampus of BDNFVal/Met mice.

Stressful life events are considered major risk factors for the development of several psychiatric disorders, though people differentially cope with stress. The reasons for this are still largely unknown but could be accounted for by individual genetic variants, previous life events, or the kind of stressors. The human brain-derived neurotrophic factor (BDNF) Val66Met variant, which was found to impair intracellular trafficking and activity-dependent secretion of BDNF, has been associated with increased susceptibility to develop several neuropsychiatric disorders, although there is still some controversial evidence. On the other hand, acute stress has been consistently demonstrated to promote the release of glutamate in cortico-limbic regions and altered glutamatergic transmission has been reported in psychiatric disorders. However, it is not known if the BDNF Val66Met single-nucleotide polymorphism (SNP)affects the stress-induced presynaptic glutamate release. In this study, we exposed adult male BDNFVal/Val and BDNFVal/Met knock-in mice to 30 min of acute restraint stress. Plasma corticosterone levels, glutamate release, protein, and gene expression in the hippocampus were analyzed immediately after the end of the stress session. Acute restraint stress similarly increased plasma corticosterone levels and nuclear glucocorticoid receptor levels and phosphorylation in both BDNFVal/Val and BDNFVal/Met mice. However, acute restraint stress induced higher increases in hippocampal presynaptic release of glutamate, phosphorylation of cAMP-response element binding protein(CREB), and levels of the immediate early gene c-fos of BDNFVal/Met compared to BFNFVal/Val mice. Moreover, acute restraint stress selectively increased phosphorylation levels of synapsin I at Ser9 and at Ser603 in BDNFVal/Val and BDNFVal/Met mice, respectively. In conclusion, we reporthere that the BDNF Val66Met SNP knock-in mice display an altered response to acute restraint stress in terms of hippocampal glutamate release, CREB phosphorylation, and neuronal activation, compared to wild-type animals. Taken together, these results could partially explain the enhanced vulnerability to stressful events of Met carriers reported in both preclinical and clinical studies.

The brain-derived neurotrophic factor Val66Met polymorphism increases segregation of structural correlation networks in healthy adult brains.

BackgroundAlthough structural correlation network (SCN) analysis is an approach to evaluate brain networks, the neurobiological interpretation of SCNs is still problematic. Brain-derived neurotrophic factor (BDNF) is well-established as a representative protein related to neuronal differentiation, maturation, and survival. Since a valine-to-methionine substitution at codon 66 of the BDNF gene (BDNF Val66Met single nucleotide polymorphism (SNP)) is well-known to have effects on brain structure and function, we hypothesized that SCNs are affected by the BDNF Val66Met SNP. To gain insight into SCN analysis, we investigated potential differences between BDNF valine (Val) homozygotes and methionine (Met) carriers in the organization of their SCNs derived from inter-regional cortical thickness correlations.MethodsForty-nine healthy adult subjects (mean age = 41.1 years old) were divided into two groups according to their genotype (n: Val homozygotes = 16, Met carriers = 33). We obtained regional cortical thickness from their brain T1 weighted images. Based on the inter-regional cortical thickness correlations, we generated SCNs and used graph theoretical measures to assess differences between the two groups in terms of network integration, segregation, and modularity.ResultsThe average local efficiency, a measure of network segregation, of BDNF Met carriers’ network was significantly higher than that of the Val homozygotes’ (permutation p-value = 0.002). Average shortest path lengths (a measure of integration), average local clustering coefficient (another measure of network segregation), small-worldness (a balance between integration and segregation), and modularity (a representative measure for modular architecture) were not significantly different between group (permutation p-values ≧ 0.01).Discussion and ConclusionOur results suggest that the BDNF Val66Met polymorphism may potentially influence the pattern of brain regional morphometric (cortical thickness) correlations. Comparing networks derived from inter-regional cortical thickness correlations, Met carrier SCNs have denser connections with neighbors and are more distant from random networks than Val homozygote networks. Thus, it may be necessary to consider potential effects of BDNF gene mutations in SCN analyses. This is the first study to demonstrate a difference between Val homozygotes and Met carriers in brain SCNs.

BDNF Val66Met polymorphism alters food intake and hypothalamic BDNF expression in mice.

Obesity, a rising public health burden, is a multifactorial disease with an increased risk for patients to develop several pathological conditions including type 2 diabetes mellitus, hypertension, and cardiovascular disease. Increasing evidence suggests a relationship between the human brain-derived neurotrophic factor (BDNF) Val66Met single-nucleotide polymorphism (SNP) and obesity, although the underlying mechanisms of this connection are still not completely understood. In the present study, we found that homozygous knock-in BDNFMet/Met mice were overweight and hyperphagic compared to wildtype BDNFVal/Val mice. Increased food intake was associated withreduction of total BDNF and BDNF1, BDNF4 and BDNF6 transcripts in the hypothalamus of BDNFMet/Met mice. Incontrast, in the white adipose tissue total BDNF and Glut4 expression levels were augmented, while sirtuin 1 and leptin receptor (Ob-R) expression levels were reduced in BDNFMet/Met mice. Moreover, plasmatic leptin levels were decreased in BDNFMet/Met mice. However, BDNFVal/Val and BDNFMet/Met mice showed a similar response to the insulin tolerance test and glucose tolerance test. Altogether, these results suggest that BDNF Val66Met SNP strongly contributes to adipose tissue pathophysiology, resulting in reduced circulating leptin levels and hypothalamic expression of BDNF, which, in turn, promote increased food intake and overweight in BDNFMet/Met mice.

Impact of BDNF Val66Met Polymorphism on Myocardial Infarction: Exploring the Macrophage Phenotype.

Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin growth factor family, well known for its role in the homeostasis of the cardiovascular system. Recently, the human BDNF Val66Met single nucleotide polymorphism has been associated with the increased propensity for arterial thrombosis related to acute myocardial infarction (AMI). Using cardiac magnetic resonance imaging and immunohistochemistry analyses, we showed that homozygous mice carrying the human BDNF Val66Met polymorphism (BDNFMet/Met) undergoing left anterior descending (LAD) coronary artery ligation display an adverse cardiac remodeling compared to wild-type (BDNFVal/Val). Interestingly, we observed a persistent presence of pro-inflammatory M1-like macrophages and a reduced accumulation of reparative-like phenotype macrophages (M2-like) in the infarcted heart of mutant mice. Further qPCR analyses showed that BDNFMet/Met peritoneal macrophages are more pro-inflammatory and have a higher migratory ability compared to BDNFVal/Val ones. Finally, macrophages differentiated from circulating monocytes isolated from BDNFMet/Met patients with coronary heart disease displayed the same pro-inflammatory characteristics of the murine ones. In conclusion, the BDNF Val66Met polymorphism predisposes to adverse cardiac remodeling after myocardial infarction in a mouse model and affects macrophage phenotype in both humans and mice. These results provide a new cellular mechanism by which this human BDNF genetic variant could influence cardiovascular disease.

BDNF Val66Met genetic variation and its plasma level in patients with morbid obesity: A case-control study

Obesity is a major public health concern worldwide. Genetic, behavioral, and environmental factors contribute to the multifactorial etiology of obesity. Evidence suggests an association between human Brain-Derived Neurotrophic Factor (BDNF) Val66Met single nucleotide polymorphism (SNP) and obesity. Reduced plasma BDNF levels have also been reported in patients with eating disorders and obesity. We aimed to evaluate the BDNF Val66Met (rs6265) SNP and also plasma BDNF levels in morbidly obese patients compared with healthy normal controls in southern Iran. One hundred morbidly obese patients and one hundred eight healthy normal controls were enrolled. Blood-derived DNA samples were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and confirmed by DNA sequencing. Plasma BDNF levels were evaluated using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit for human BDNF. Data analysis was performed by SPSS software, version 18.0. Genotype distribution was not significantly different between obese patients and controls. However, plasma BDNF levels were significantly lower in obese patients compared with controls. Interestingly, a significant association was found between BDNF Val66Met SNP and plasma BDNF levels. No relationship was observed between BDNF Val66Met SNP and all assessed demographic and clinical characteristics of obese patients. It seems that plasma BDNF levels were associated with both obesity and BDNF Val66Met SNP. However, this association was not found between BDNF Val66Met SNP and obesity. Further studies with larger sample sizes are needed for more detailed assessment of this genetic variation as a potential biomarker for obesity.

Interactions of BDNF Val66Met Polymorphism and Menstrual Pain on Brain Complexity.

The irregularity and uncertainty of neurophysiologic signals across different time scales can be regarded as neural complexity, which is related to the adaptability of the nervous system and the information processing between neurons. We recently reported general loss of brain complexity, as measured by multiscale sample entropy (MSE), at pain-related regions in females with primary dysmenorrhea (PDM). However, it is unclear whether this loss of brain complexity is associated with inter-subject genetic variations. Brain-derived neurotrophic factor (BDNF) is a widely expressed neurotrophin in the brain and is crucial to neural plasticity. The BDNF Val66Met single-nucleotide polymorphism (SNP) is associated with mood, stress, and pain conditions. Therefore, we aimed to examine the interactions of BDNF Val66Met polymorphism and long-term menstrual pain experience on brain complexity. We genotyped BDNF Val66Met SNP in 80 PDM females (20 Val/Val, 31 Val/Met, 29 Met/Met) and 76 healthy female controls (25 Val/Val, 36 Val/Met, 15 Met/Met). MSE analysis was applied to neural source activity estimated from resting-state magnetoencephalography (MEG) signals during pain-free state. We found that brain complexity alterations were associated with the interactions of BDNF Val66Met polymorphism and menstrual pain experience. In healthy female controls, Met carriers (Val/Met and Met/Met) demonstrated lower brain complexity than Val/Val homozygotes in extensive brain regions, suggesting a possible protective role of Val/Val homozygosity in brain complexity. However, after experiencing long-term menstrual pain, the complexity differences between different genotypes in healthy controls were greatly diminished in PDM females, especially in the limbic system, including the hippocampus and amygdala. Our results suggest that pain experience preponderantly affects the effect of BDNF Val66Met polymorphism on brain complexity. The results of the present study also highlight the potential utilization of resting-state brain complexity for the development of new therapeutic strategies in patients with chronic pain.

The BDNF Val66Met polymorphism is associated with the functional connectivity dynamics of pain modulatory systems in primary dysmenorrhea.

Primary dysmenorrhea (PDM), menstrual pain without an organic cause, is a prevailing problem in women of reproductive age. We previously reported alterations of structure and functional connectivity (FC) in the periaqueductal gray (PAG) of PDM subjects. Given that the brain derived neurotrophic factor (BDNF) acts as a pain modulator within the PAG and the BDNF Val66Met polymorphism contributes towards susceptibility to PDM, the present study of imaging genetics set out to investigate the influence of, firstly, the BDNF Val66Met single nucleotide polymorphism and, secondly, the genotype-pain interplays on the descending pain modulatory systems in the context of PAG-seeded FC patterning. Fifty-six subjects with PDM and 60 controls participated in the current study of resting-state functional magnetic resonance imaging (fMRI) during the menstruation and peri-ovulatory phases; in parallel, blood samples were taken for genotyping. Our findings indicate that the BDNF Val66Met polymorphism is associated with the diverse functional expressions of the descending pain modulatory systems. Furthermore, PAG FC patterns in pain-free controls are altered in women with PDM in a genotype-specific manner. Such resilient brain dynamics may underpin the individual differences and shed light on the vulnerability for chronic pain disorders of PDM subjects.

Connectivity across recognition memory circuits is reduced in carriers of the BDNF Val66Met single nucleotide polymorphism.

Event Abstract Back to Event Connectivity across recognition memory circuits is reduced in carriers of the BDNF Val66Met single nucleotide polymorphism. Nicole Mckay1* and Ian Kirk1 1 University of Auckland, Psychology, New Zealand A common single nucleotide polymorphism (SNP) within the gene for brain derived neurotrophic factor (BDNF) is known to impact both brain structure and memory performance. One area that has not been extensively researched is whether the BDNF genotype influences recognition memory performance and related brain structures. Recognition memory is comprised of two subcomponents, familiarity and recollection, that are dependent upon related but distinct neural circuits. The network that underlies processing of familiarity-based recognition judgments is dependent upon the medial dorsal thalamic nucleus, while the anterior thalamic nucleus has been linked to the circuit that underlies recollection-based processing. Carriers of at least one copy of the BDNF SNP were compared with non-carriers on two recognition memory tasks. Connectivity analyses were conducted to determine whether differences exist in white matter connectivity across familiarity- or recollection-associated tracts seeded from the relevant thalamic nuclei. In order to do this, probabilistic tractography was conducted. No performance differences were observed between SNP carriers and non-carriers on either recognition memory task. However, connectivity differences were found across both familiarity- and recollection-associated tracts: carriers of the BDNF SNP displayed lower connectivity compared to non-carriers. This result is consistent with the findings of previous studies that have shown carriers of the BDNF SNP to perform worse on memory tasks, and to have abnormal gray matter structure. Furthermore, white matter microstructural differences might help to explain the mechanism through which behavioural differences might occur in these two genetic groups. It is possible that performance on tasks that recruit these pathways might be reduced in those who have less connectivity across these tracts. Keywords: Diffusion Tensor Imaging, recognition memory, Probabilistic Tractography, structural MRI, brain derived neurotrophic factor Conference: XII International Conference on Cognitive Neuroscience (ICON-XII), Brisbane, Queensland, Australia, 27 Jul - 31 Jul, 2014. Presentation Type: Poster Topic: Memory and Learning Citation: Mckay N and Kirk I (2015). Connectivity across recognition memory circuits is reduced in carriers of the BDNF Val66Met single nucleotide polymorphism.. Conference Abstract: XII International Conference on Cognitive Neuroscience (ICON-XII). doi: 10.3389/conf.fnhum.2015.217.00287 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 19 Feb 2015; Published Online: 24 Apr 2015. * Correspondence: Ms. Nicole Mckay, University of Auckland, Psychology, Auckland, New Zealand, nicole.mckay@auckland.ac.nz Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Nicole Mckay Ian Kirk Google Nicole Mckay Ian Kirk Google Scholar Nicole Mckay Ian Kirk PubMed Nicole Mckay Ian Kirk Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism differentially predicts hippocampal function in medication-free patients with schizophrenia

A Val66Met 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 Val66Met SNP and [15O]H2O 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 Val66Met 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.

Impact of the BDNF Val66Met Polymorphism on Regional Brain Gray Matter Volumes: Relevance to the Stress Response

ObjectiveGenetic imaging is used to investigate the mechanism by which genetic variants influence brain structure. In a previous study, a structural change of the dorsolateral prefrontal cortex was associated with symptom modulation in post-traumatic stress disorder patients. This study examined the effect of a polymorphism in the gene encoding brain-derived neurotrophic factor (BDNF) on regional gray matter (GM) volumes and the correlations between the dorsolateral prefrontal GM volume and the stress level in healthy volunteers.MethodsSixty-one volunteers underwent genotyping for the BDNF Val66Met single nucleotide polymorphism (SNP) and completed the Stress Response Inventory (SRI). Magnetic resonance images were also acquired, and the effect of each subject's BDNF genotype and SRI subscore on his or her dorsolateral prefrontal GM volume was evaluated.ResultsThe Val/Val homozygotes had significantly larger GM volumes in the prefrontal cortex and the precuneus, the uncus, and the superior temporal and occipital cortices than Met carriers. The Met homozygotes demonstrated a higher stress response in depression domain than Val/Val and Val/Met groups. A negative correlation between the middle frontal cortex GM volume and the SRI depression subscore was found.ConclusionThese findings indicate an interaction between genes and brain structure, and they suggest that differences in dorsolateral prefrontal GM volume related to the BDNF Val66Met SNP are associated with resilience to stressful life events, particularly in the dimension of emotion.

Variant Brain-Derived Neurotrophic Factor (Valine66Methionine) Polymorphism Contributes to Developmental and Estrous Stage-Specific Expression of Anxiety-Like Behavior in Female Mice

Most anxiety and depressive disorders are twice as common in women compared with men, and the sex difference in prevalence typically emerges during adolescence. Hormonal changes across the menstrual cycle and during the postpartum and perimenopausal periods are associated with increased risk for anxiety and depression symptoms. In humans and animals, reduced brain-derived neurotrophic factor (BDNF) has been associated with increased expression of affective pathology. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (BDNF Valine66Methionine [Val66Met]), which reduces BDNF bioavailability, has been identified in humans and associated with a variety of neuropsychiatric disorders. Although BDNF expression can be directly influenced by estrogen and progesterone, the potential impact of the BDNF Val66Met SNP on sensitivity to reproductive hormone changes remains an open question. As a predictive model, we used female mice in which the human SNP (BDNF Val66Met) was inserted into the mouse BDNF gene. Using standard behavioral paradigms, we tested the impact of this SNP on age and estrous-cycle-specific expression of anxiety-like behaviors. Mice homozygous for the BDNF Val66Met SNP begin to exhibit increased anxiety-like behaviors over prepubertal and early adult development, show significant fluctuations in anxiety-like behaviors over the estrous cycle, and, as adults, differ from wild-type mice by showing significant fluctuations in anxiety-like behaviors over the estrous cycle-specifically, more anxiety-like behaviors during the estrus phase. These findings have implications regarding the potential role of this SNP in contributing to developmental and reproductive hormone-dependent changes in affective disorders in humans.

BDNF Val66Met Impairs Fluoxetine-Induced Enhancement of Adult Hippocampus Plasticity

Recently, a single-nucleotide polymorphism (SNP) in the brain-derived neurotrophic factor (BDNF) gene (BDNF Val66Met) has been linked to the development of multiple forms of neuropsychiatric illness. This SNP, when genetically introduced into mice, recapitulates core phenotypes identified in human BDNF Val66Met carriers. In mice, this SNP also leads to elevated expression of anxiety-like behaviors that are not rescued with the prototypic selective serotonin reuptake inhibitor (SSRI), fluoxetine. A prominent hypothesis is that SSRI-induced augmentation of BDNF protein expression and the beneficial trophic effects of BDNF on neural plasticity are critical components for drug response. Thus, these mice represent a potential model to study the biological mechanism underlying treatment-resistant forms of affective disorders. To test whether the BDNF Val66Met SNP alters SSRI-induced changes in neural plasticity, we used wild-type (BDNF(Val/Val)) mice, and mice homozygous for the BDNF Val66Met SNP (BDNF(Met/Met)). We assessed hippocampal BDNF protein levels, survival rates of adult born cells, and synaptic plasticity (long-term potentiation, LTP) in the dentate gyrus either with or without chronic (28-day) fluoxetine treatment. BDNF(Met/Met) mice had decreased basal BDNF protein levels in the hippocampus that did not significantly increase following fluoxetine treatment. BDNF(Met/Met) mice had impaired survival of newly born cells and LTP in the dentate gyrus; the LTP effects remained blunted following fluoxetine treatment. The observed effects of the BDNF Val66Met SNP on hippocampal BDNF expression and synaptic plasticity provide a possible mechanistic basis by which this common BDNF SNP may impair efficacy of SSRI drug treatment.

Variant brain‐derived neurotrophic factor Val66Met endophenotypes: implications for posttraumatic stress disorder

Recently, a common single nucleotide polymorphism (SNP) has been identified in the gene encoding brain-derived neurotrophic factor (BDNF). The variant BDNF(Met) has been shown to have decreased activity-dependent BDNF secretion from neurons and to lead to impairments in specific forms of learning and altered susceptibility to stress. A mouse model containing BDNF(Met) has also been linked to increased anxiety-like behavior. In a translational study, mice and human carriers of the BDNF(Met) allele were compared in their ability to extinguish a learned fear memory. Both showed slower suppression of the learned fear response. In humans, the neural correlates of this behavior were validated using fMRI. As anxiety and fear extinction lie at the core of symptoms and therapeutic approaches to posttraumatic stress disorder (PTSD), we propose that BDNF genotype and neuroimaging may be useful as biomarkers to provide guidance for more customized therapeutic directions. The aim of this paper is to review the available knowledge on the BDNF Val66Met SNP, with emphasis on anxiety- and fear-related endophenotypes and its potential implications for PTSD.

Identification of pro- and mature brain-derived neurotrophic factor in human saliva

Objective Growth factors, including brain-derived neurotrophic factor (BDNF), are polypeptides that are involved in the maintenance, survival, and death of central and peripheral cells. Numerous growth factors have been identified in saliva and are thought to promote wound healing and maintenance of the oral epithelium. The aim of this study was to determine if BDNF is also found in human saliva. Methods Whole, unstimulated saliva samples ( n = 30) were analyzed by SDS-PAGE and Western blot using an anti-human BDNF antibody. Proteolytic cleavage products were similarly assessed following the incubation of pooled saliva with N-glycanase F and plasmin. Subjects were also genotyped for the BDNF Val66Met single nucleotide polymorphism (SNP). Results These experiments revealed the presence of immunoreactive bands at 14, 32 and 34 kDa, corresponding to mature (mBDNF) and proBDNF, as well as a truncated pro-form at 24 kDa. Not every sample contained all forms of BDNF. Treatment with N-glycanase and plasmin reduced the size of the higher molecular weight bands, confirming the glycosylated pro-form of BDNF. mBDNF was detected significantly less often in subjects with the Val66Met SNP, compared to those without the polymorphism ( χ 2 = 4.05; P < 0.05). Conclusions While the function of salivary BDNF still requires elucidation, these findings suggest that it may be possible to use saliva in lieu of blood in future studies of BDNF and the Val66Met polymorphism.

BDNF and COMT Polymorphisms: Relation to Memory Phenotypes in Young Adults With Childhood-Onset Mood Disorder

Recent investigations in several species have suggested a role for brain-derived neurotrophic factor (BDNF) in memory, which may be mediated by the influence of BDNF on neuronal plasticity in the hippocampus. BDNF polymorphisms have also been associated with mood disorders. Catechol-O-methyltransferase (COMT) metabolizes dopamine and has been implicated in prefrontal function, another area of the brain relevant for memory. In a sample of 63 young adults with a history of childhood-onset mood disorder, we typed three BDNF polymorphisms, including the BDNF Val66Met single nucleotide polymorphism (SNP), and the COMT Val108/158Met SNP. Multivariate analysis of variance was used to test the association between BDNF and COMT markers and measures of declarative memory. Variants at the three BDNF markers and one COMT marker were not associated with declarative memory function p-values ranged from 0.25 to 0.98. Higher IQ (F = 6.18, df = 4, 58, p = 0.0003) and female gender (F = 4.41, df = 4, 58, p = 0.0035) were associated with more optimal performance on the memory tasks. This study did not provide evidence supporting an association between BDNF and COMT genes and declarative memory phenotypes.