Alteration of the Centromedial Amygdala Glutamatergic Synapses by the BDNF Val66Met Polymorphism

Fear expression is mediated by an activation of the centromedial amygdala (CEm), the major output nucleus of the amygdaloid complex. Consistently, fear extinction is associated with an increased synaptic inhibition as well as a suppression of the excitability of the CEm neurons. However, little is known about the role of CEm glutamatergic synapses in fear regulation and anxiety-like behaviors. The BDNF Val66Met, a single-nucleotide polymorphism in the human BDNF gene, impairs fear extinction and leads to anxiety-like symptoms. To determine whether the BDNF Val66Met polymorphism affects the CEm excitatory synapses, we examined basal glutamatergic synaptic transmission and plasticity in the CEm neurons of BDNF Val66Met knock-in (BDNF^Met/Met) mice. The BDNF Val66Met single-nucleotide polymorphism exerted an opposite effect on non-NMDA and NMDA receptor transmission with a potentiation of the former and a suppression of the latter. In addition, the decay time of NMDA currents was decreased in BDNF^Met/Met mice, suggesting a modification of NMDA receptor subunit composition. Unlike the wild-type mice that exhibited a potentiation of non-NMDA receptor transmission following fear conditioning and a depotentiation upon fear extinction, BDNF^Met/Met mice failed to show this experience-dependent synaptic plasticity in the CEm neurons. Our results suggest that the elevated non-NMDA receptor transmission, the suppression of NMDA receptor transmission, and an impairment of synaptic plasticity in the CEm neurons might contribute to the fear extinction deficit and increased anxiety-like symptoms in BDNF Val66Met carriers.     

Impact of variation in the BDNF gene on social stress sensitivity and the buffering impact of positive emotions: Replication and extension of a gene–environment interaction

A previous study reported that social stress sensitivity is moderated by the brain-derived-neurotrophic-factor^Val66Met (BDNF rs6265) genotype. Additionally, positive emotions partially neutralize this moderating effect. The current study aimed to: (i) replicate in a new independent sample of subjects with residual depressive symptoms the moderating effect of BDNF^Val66Met genotype on social stress sensitivity, (ii) replicate the neutralizing impact of positive emotions, (iii) extend these analyses to other variations in the BDNF gene in the new independent sample and the original sample of non-depressed individuals.Previous findings were replicated in an experience sampling method (ESM) study. Negative Affect (NA) responses to social stress were stronger in “Val/Met” carriers of BDNF^Val66Met compared to “Val/Val” carriers. Positive emotions neutralized the moderating effect of BDNF^Val66Met genotype on social stress sensitivity in a dose–response fashion. Finally, two of four additional BDNF SNPs (rs11030101, rs2049046) showed similar moderating effects on social stress-sensitivity across both samples. The neutralizing effect of positive emotions on the moderating effects of these two additional SNPs was found in one sample.In conclusion, ESM has important advantages in gene–environment (GxE) research and may attribute to more consistent findings in future GxE research. This study shows how the impact of BDNF genetic variation on depressive symptoms may be explained by its impact on subtle daily life responses to social stress. Further, it shows that the generation of positive affect (PA) can buffer social stress sensitivity and partially undo the genetic susceptibility.     

BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms: A prospective study

Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val⁶⁶Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val⁶⁶Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val⁶⁶Met and 5-HTTLPR genotype.     

Sublingual buprenorphine/naloxone treatment is not affected by OPRM1 A118G and BDNF Va66Met polymorphisms,but alters the plasma beta-endorphin and BDNF levels in individuals with opioid use disorder

The study aimed to examine the genetic contribution to buprenorphine (BUP) treatment in individuals with opioid use disorder (OUD), with a specific focus on BDNF and OPRM1 genes. A total of 113 controls and 111 OUD patients receiving sublingual BUP/naloxone were enrolled. OPRM1 A118G and BDNF Val66Met polymorphisms were investigated by PCR-FRLP. Plasma BDNF and beta-endorphin levels were assessed by ELISA kits in both groups. Blood BUP levels were measured by LC-MS/MS and normalized with daily BUP dose (BUP/D). OPRM1 A118G and BDNF Val66Met polymorphisms didn’t have an effect on plasma beta-endorphin and BDNF levels in OUD patients, respectively. Interestingly, OUD patients had significantly higher plasma BDNF and lower beta-endorphin levels compared to the controls (p < 0.001). A negative and significant correlation between plasma BUP/D and BDNF levels was found. Age onset of first use was associated with OPRM1 A118G polymorphism. The findings indicated that sublingual BUP/naloxone may increase plasma BDNF levels, but may decrease beta-endorphin levels in individuals with OUD. Plasma BDNF level seemed to be decreased in a BUP/D concentration-dependent manner.     

Val66Met functional polymorphism and serum protein level of brain-derived neurotrophic factor (BDNF) in acute episode of schizophrenia and depression

Background

Brain-derived neurotrophic factor (BDNF) influences neuron differentiation during development as well as the synaptic plasticity and neuron survival in adulthood. BDNF has been implicated in the pathogenesis of schizophrenia and depression. Val66Met polymorphism and BDNF serum level are potential biomarkers in neuropsychiatric disorders. The aim of this study was to determine the effect of BDNF gene Val66Met functional polymorphism on serum BDNF concentration in patients with schizophrenia, during depression episode and in healthy control group.

Antidepressants that inhibit both serotonin and norepinephrine reuptake impair long-term potentiation in hippocampus

Rationale

Monoamine reuptake inhibitors can stimulate expression of brain-derived neurotrophic factor (BDNF) and alter long-term potentiation (LTP), a widely used model for the synaptic mechanisms that underlie memory formation. BDNF expression is upregulated during LTP, and BDNF in turn positively modulates LTP. Previously, we found that treatment with venlafaxine, a serotonin and norepinephrine reuptake inhibitor (SNRI), but not citalopram, a selective serotonin reuptake inhibitor (SSRI), reduced LTP in hippocampal area CA1 without changing hippocampal BDNF protein expression.

Objectives

We tested the hypothesis that combined serotonin and norepinephrine reuptake inhibition is necessary for LTP impairment, and we reexamined the potential role of BDNF by testing for region-specific changes in areas CA1, CA3, and dentate gyrus. We also tested whether early events in the LTP signaling pathway were altered to impair LTP.

Methods

Animals were treated for 21 days with venlafaxine, imipramine, fluoxetine, or maprotiline. In vitro hippocampal slices were used for electrophysiological measurements. Protein expression was measured by enzyme-linked immunosorbent assay (ELISA) and Western blotting.

Results

LTP was impaired only following treatment with combined serotonin and norepinephrine reuptake inhibitors (venlafaxine, imipramine) but not with selective serotonin (fluoxetine) or norepinephrine (maprotiline) reuptake inhibitors. BDNF protein expression was not altered by venlafaxine or imipramine treatment, nor were postsynaptic depolarization during LTP inducing stimulation or synaptic membrane NMDA receptor subunit expression affected.

Conclusions

LTP is impaired by chronic treatment with antidepressant that inhibit both serotonin and norepinephrine reuptake; this impairment results from changes that are downstream of postsynaptic depolarization and calcium influx.     

BDNF Val66Met is Associated with Introversion and Interacts with 5-HTTLPR to Influence Neuroticism

Brain-derived neurotrophic factor (BDNF) regulates synaptic plasticity and neurotransmission, and has been linked to neuroticism, a major risk factor for psychiatric disorders. A recent genome-wide association (GWA) scan, however, found the BDNF Val66Met polymorphism (rs6265) associated with extraversion but not with neuroticism. In this study, we examine the links between BDNF and personality traits, assessed using the Revised NEO Personality Inventory (NEO-PI-R), in a sample from SardiNIA (n=1560) and the Baltimore Longitudinal Study of Aging (BLSA; n=1131). Consistent with GWA results, we found that BDNF Met carriers were more introverted. By contrast, in both samples and in a meta-analysis inclusive of published data (n=15251), we found no evidence for a main effect of BDNF Val66Met on neuroticism. Finally, on the basis of recent reports of an epistatic effect between BDNF and the serotonin transporter, we explored a Val66Met × 5-HTTLPR interaction in a larger SardiNIA sample (n=2333). We found that 5-HTTLPR LL carriers scored lower on neuroticism in the presence of the BDNF Val variant, but scored higher on neuroticism in the presence of the BDNF Met variant. Our findings support the association between the BDNF Met variant and introversion and suggest that BDNF interacts with the serotonin transporter gene to influence neuroticism.     

Three-way interaction effect of 5-HTTLPR,BDNF Val66Met,and childhood adversity on depression: A replication study

Both the serotonin transporter linked promoter region (5-HTTLPR) and the brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms have been shown to interact with unfavourable environment in relation to depression symptoms and to depression diagnosis. Several attempts have been made to study a three-way interaction effect of these factors on depression, however with contradictory results. We aimed to test the hypothesis of a three-way interaction effect and to attempt at replication in an independent population-based sample. Family maltreatment, sexual abuse and depression were self-reported by an adolescent population-based cohort (N=1393) from the county of Västmanland, Sweden. DNA was isolated from saliva, and used for genotyping of the 5-HTTLPR and BDNF Val66Met polymorphisms. Neither 5-HTTLPR or BDNF genotypes separately, nor in interaction with each other had any relation to depression, however in an environment adjusted model a two-way interaction and a three-way interaction effect was found. Both 5-HTTLPR and BDNF Val66Met interacted with unfavourable environment in relation to depressive symptoms (Adj R²=0.19). Depressive symptoms and depression were more common among carriers of either the ss/sl+Val/Val or the ll+Met genotypes in the presence of early-life adversities. This three-way effect was more pronounced among girls. The current study, with a virtually similar set-up compared to previous studies, can partially confirm previous findings and their generalizability. The study also shows the importance of genetic plasticity in individuals with different environmental exposure, for different phenotypic expression.     

Genotypes Do Not Confer Risk For Delinquency ut Rather Alter Susceptibility to Positive and Negative Environmental Factors: Gene-Environment Interactions of BDNF Val66Met, 5-HTTLPR,and MAOA-uVNTR

Background:

Previous evidence of gene-by-environment interactions associated with emotional and behavioral disorders is contradictory. Differences in findings may result from variation in valence and dose of the environmental factor, and/or failure to take account of gene-by-gene interactions. The present study investigated interactions between the brain-derived neurotrophic factor gene (BDNF Val66Met), the serotonin transporter gene-linked polymorphic region (5-HTTLPR), the monoamine oxidase A (MAOA-uVNTR) polymorphisms, family conflict, sexual abuse, the quality of the child-parent relationship, and teenage delinquency.

Methods:

In 2006, as part of the Survey of Adolescent Life in Västmanland, Sweden, 1 337 high-school students, aged 17–18 years, anonymously completed questionnaires and provided saliva samples for DNA analyses.

Results:

Teenage delinquency was associated with two-, three-, and four-way interactions of each of the genotypes and the three environmental factors. Significant four-way interactions were found for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × family conflicts and for BDNF Val66Met × 5-HTTLPR×MAOA-uVNTR × sexual abuse. Further, the two genotype combinations that differed the most in expression levels (BDNF Val66Met Val, 5-HTTLPR LL, MAOA-uVNTR LL [girls] and L [boys] vs BDNF Val66Met Val/Met, 5-HTTLPR S/LS, MAOA-uVNTR S/SS/LS) in interaction with family conflict and sexual abuse were associated with the highest delinquency scores. The genetic variants previously shown to confer vulnerability for delinquency (BDNF Val66Met Val/Met × 5-HTTLPR S × MAOA-uVNTR S) were associated with the lowest delinquency scores in interaction with a positive child-parent relationship.

Conclusions:

Functional variants of the MAOA-uVNTR, 5-HTTLPR, and BDNF Val66Met, either alone or in interaction with each other, may be best conceptualized as modifying sensitivity to environmental factors that confer either risk or protection for teenage delinquency.     

Association between the brain-derived neurotrophic factor Val66Met polymorphism and therapeutic response to olanzapine in schizophrenia patients

Rationale

Brain-derived neurotrophic factor (BDNF) is a neurotrophin that plays a major role in neurogenesis and neuroplasticity, and in the modulation of several neurotransmitter systems including the dopaminergic system. There are mixed reports about the association between the BDNF Val66Met polymorphism, schizophrenia, and treatment response to antipsychotic drugs.

Objectives

The present study evaluated the association of the BDNF Val66Met polymorphism with treatment response to atypical antipsychotic olanzapine in schizophrenia and the possible predictive value of the BDNF Val66Met genotype status in treatment response to antipsychotic medication.

Methods

The study included 590 ethnically homogenous Caucasian patients with schizophrenia (diagnosed using the SCID), 40.2?±?12.0 years old, treated with olanzapine monotherapy (10–20 mg/day), or with other antipsychotics such as risperidone (3–6 mg/day), clozapine (100–500 mg/day), haloperidol (3–115 mg/day), fluphenazine (4–25 mg/day), and quetiapine (50–800 mg/day). Patients were subdivided into responders and non-responders according to a 50 % reduction in the Positive and Negative Syndrome Scale (PANSS) total and subscale scores after 8 weeks of treatment.

Results

The results, corrected for possible effects of gender and age, showed a significant association between the BDNF Val66Met polymorphism and treatment response to olanzapine in patients. The Val/Val genotype was observed more frequently in treatment responders to olanzapine, and this genotype was associated with an improvement in clinical symptoms.

Conclusions

Our results suggest that BDNF Val66Met variants might influence the response to 8 weeks of monotherapy with olanzapine, in a relatively large sample of patients with schizophrenia.     

Brain-derived neurotrophic factor gene polymorphisms: influence on treatment response phenotypes of major depressive disorder

Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor family of neurotrophins, has pivotal roles in neuronal survival, proliferation, and synaptic plasticity in the brain. Both clinical and pharmacological studies have implicated the common single nucleotide polymorphism (SNP) at position 196, Val66Met in the pathophysiology of major depressive disorder (MDD), and antidepressant response. However, inconsistent results were found between Val66Met (rs6265) polymorphism and treatment response phenotypes in genetic association studies. The functional Val66Met polymorphism and seven other tagging SNP markers selected to capture the major allelic variations across BDNF locus were analyzed in depressed patients, treated with antidepressants, and 76 control patients. Two hundred and six patients with Diagnostic and Statistical Manual of Mental Disorders-IV MDD were recruited for this study and genotyped for eight BDNF tagging SNPs (rs11030096, rs925946, rs10501087,rs6265, rs12273363, rs908867, rs1491850, and rs1491851)to investigate the functional impact of genotypes/haplotypes in the susceptibility of depression and on treatment response. None of the eight SNPs, including the rs6265, were significantly associated with MDD after permutation correction. However, we found an association for rs10501087, rs6265 with nonresponse to antidepressant treatment (corrected permutation P:0.03599; 0.0399 and power: 0.1420; 0.1492, respectively).Analysis of each two-marker, three-marker, and four-marker sliding window haplotypes showed significance in haplotype combinations. Especially rs10501087 (C), rs6265 (A), and rs149,1850 (C) together or with the other SNP haplotypes showed a similar pattern in all treatment response phenotypes. Despite the limited power of analysis, our results suggest that these three SNPs may play a role in antidepressant treatment response phenotypes in MDD.     

The functional BDNF Val66Met polymorphism affects functions of pre-attentive visual sensory memory processes

The brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, is involved in nerve growth and survival. Especially, a single nucleotide polymorphism (SNP) in the BDNF gene, Val66Met, has gained a lot of attention, because of its effect on activity-dependent BDNF secretion and its link to impaired memory processes. We hypothesize that the BDNF Val66Met polymorphism may have modulatory effects on the visual sensory (iconic) memory performance. Two hundred and eleven healthy German students (106 female and 105 male) were included in the data analysis. Since BDNF is also discussed to be involved in the pathogenesis of depression, we additionally tested for possible interactions with depressive mood. The BDNF Val66Met polymorphism significantly influenced iconic-memory performance, with the combined Val/Met-Met/Met genotype group revealing less time stability of information stored in iconic memory than the Val/Val group. Furthermore, this stability was positively correlated with depressive mood exclusively in the Val/Val genotype group. Thus, these results show that the BDNF Val66Met polymorphism has an effect on pre-attentive visual sensory memory processes.     

Repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity

Rationale: Recent studies have implicated intracellular transduction pathways and neurotrophic factors in the action of antidepressants. Adaptation in these pathways may ultimately affect electrophysiological and morphological properties of neurones. We have previously shown that repeated electroconvulsive stimulation, a safe and effective antidepressant treatment, has profound effects on hippocampal synaptic connectivity and plasticity in the rat. Here, we investigated whether these electrophysiological properties were shared by the chemical antidepressant, fluoxetine. Objectives: To compare the electrophysiological and cognitive effects of two very different antidepressant treatments: repeated electroconvulsive stimulation (rECS); and chronic administration of the serotonin specific re-uptake inhibitor (SSRI), fluoxetine. Methods: Rats were exposed to either rECS or daily fluoxetine administration for 15 days. The animals were then anaesthetised and dentate field excitatory post-synaptic potential (fEPSP) characteristics were measured before and after the induction of long-term potentiation (LTP) by high frequency perforant path stimulation. In a separate experiment, the effects of rECS and chronic fluoxetine administration on acquisition and retention of a spatial learning task in the Morris watermaze were determined. Results: Chronic fluoxetine administration and rECS produced equivalent increases in dentate fEPSP compared to respective control groups. LTP induction was attenuated in both groups. Spatial learning was, in contrast, unaffected by fluoxetine treatment but significantly impaired following rECS. Conclusions: Given that fluoxetine and rECS share antidepressant properties, but differ in their effects on learning and memory, we propose that the common effects on dentate connectivity and synaptic plasticity described here are more likely to relate to affective rather than cognitive function. This result is consistent with other experiments showing that a reduction in dentate connectivity correlates with stress susceptibility in animals. Received: 17 February 1999 / Final version: 23 August 1999     

Meta-analysis of BDNF Val66Met polymorphism association with treatment response in patients with major depressive disorder

The aim of our meta-analysis was to assess the association between BDNF Val66Met polymorphism and treatment response in patients with MDD. 8 studies that included data from 1115 subjects were identified. We tested two phenotypes: response rate and remission rate. OR was used as a measure of the effect of the association in a fixed/random effect model. Meta-analysis was performed for genotypes Met/Met versus Val/Val, Val/Met versus Val/Val, Met/Met versus Val/Met, Val/Met + Met/Met versus Val/Val, Met/Met versus Val/Val + Val/Met, and Met allele versus Val allele. When all groups were pooled, a significant association of Val/Met genotype and increased response rate was found in comparison to Val/Val in overall population (OR = 1.66, 95%CI = 1.07–2.57, P = 0.02). In the subgroup analysis, similar result was shown in Asian population (OR = 1.83, 95%CI = 1.03–3.26, P = 0.04), but not in Caucasian population. We didn't observe a significant association of BDNF Val66Met polymorphism with remission rate. This meta-analysis demonstrates the association between BDNF Val66Met polymorphism and treatment response in patients with MDD, and Val66Met heterozygous patients have a better response rate in comparison to Val/Val homozygote patients, especially in Asian population.     

Epistasis of the DRD2/ANKK1 Taq Ia and the BDNF Val66Met Polymorphism Impacts Novelty Seeking and Harm Avoidance

Mounting evidence from animal studies show that the mesolimbic dopaminergic pathways are modulated by the brain-derived neurotrophic factor (BDNF). This study investigates in N=768 healthy Caucasian participants the influence of two prominent functional single-nucleotide polymorphisms (SNPs) on the BDNF gene (BDNF Val66Met SNP) and the ankyrin repeat and kinase domain containing 1 (ANKK1) gene (DRD2 Taq Ia/ANKK1 SNP) on the personality traits of Novelty Seeking and Harm Avoidance, which are mediated, in part, through dopaminergic mesolimbic circuitry. Carriers of the 66Met+/A1+ variant scored lowest on Novelty Seeking and highest on Harm Avoidance, compared to all other genotype groups. These participants are characterized by a relatively low D₂ receptor density in the striatum and an impaired activity-dependent secretion of BDNF. This is one of the first genetic association studies to show a modulatory role for BDNF genetic variation on genetically mediated differences in the mesolimbic dopaminergic system in the context of human personality.     

Interaction between BDNF Val66Met and dopamine transporter gene variation influences anxiety-related traits.

The involvement in neural plasticity and the mediation of effects of repeated stress exposure and long-term antidepressant treatment on hippocampal neurogenesis supports a critical role of brain-derived neurotrophic factor (BDNF) in the pathophysiology of affective and other stress-related disorders. A previously reported valine to methionine substitution at amino-acid position 66 (BDNF Val66Met) seems to account for memory disturbance and hippocampal dysfunction. In the present study, we evaluated the impact of the BDNF Val66Met polymorphism on individual differences in personality traits in a sample of healthy volunteers in relation to other common gene variants thought to be involved in the pathophysiology of affective disorders, such as the serotonin transporter promoter polymorphism (5-HTTLPR) and a variable number of tandem repeat polymorphism of the dopamine transporter gene (DAT VNTR). Personality traits were assessed using the NEO personality inventory (NEO-PI-R) and Tridimensional Personality Questionnaire (TPQ). There was a significant DAT VNTR-dependent association between NEO-PI-R Neuroticism and the BDNF Val66Met polymorphism. Among individuals with at least one copy of the DAT 9-repeat allele, carriers of the BDNF Met allele exhibited significantly lower Neuroticism scores than noncarriers. This interaction was also observed for TPQ Harm Avoidance, a personality dimension related to Neuroticism. Our results support the notion that allelic variation at the BDNF locus--in interaction with other gene variants--influences anxiety- and depression-related personality traits.     

Association between the Val66Met polymorphism (rs6265/G196A) of the BDNF gene and cognitive performance with SSRI use in Arab Alzheimer’s disease patients

Brain derived neutrophic factor (BDNF) is a protein and a member of the neurotrophin family of growth factors, supports the survival of existing neurons and encourages the growth and differentiation of new neurons and synapses. The BDNF gene Val66Met polymorphism (rs6265/G196A) is responsible for BDNF synthesis that impact BDNF function that includes memory and cognition.This study investigated whether the BDNF gene Val66Met polymorphism (rs6265/G196A) is associated with cognitive function changes in both Alzheimer disease (AD) patients and elderly participants. In addition the impact of SSRI use on cognition improvement will be assessed. Healthy young, middle ages (25–59 years old) and elderly (more than 60 years old) participants (140) as well as 40 AD patients of whom are both of Saudi Arabian origin were recruited. The genotyping for the association study was performed by real-time PCR using Taqman chemistry in the ABI Prism 7900HT Sequence Detection System. Both Mini-Mental Status Examination (MMSE) and Clinical Dementia Rating (CDR) were used to assess cognitive function of healthy and AD participants, respectively.The findings showed that the BDNF Val66Met genotype distributions and allele frequencies have significant association with cognitive performance in both elderly control group and AD patients. The main findings showed that carriers of GG homozygotes (Val/Val) have superior cognitive performance among AD patients and elderly control subjects. In addition the use of SSRIs in 13 AD patients and 17 elderly participants positively improved cognitive function in elderly (p > 0.001) but not in AD patients (p = 0.1).     

Association study between BDNF gene variants and Mexican patients with obsessive–compulsive disorder

Obsessive–compulsive disorder (OCD) is a psychiatric disorder whose etiology is not yet known. We investigate the role of three variants of the BDNF gene (rs6265, rs1519480 and rs7124442) by single SNP and haplotype analysis in OCD Mexican patients using a case–control and family-based association design. BDNF gene variants were genotyped in 283 control subjects, 232 OCD patients and first degree relatives of 111 OCD subjects. Single SNP analysis in case–control study showed an association between rs6265 and OCD with a high frequency of Val/Val genotype and Val allele (p=0.0001 and p=0.0001, respectively). Also, genotype and allele analysis of rs1519480 showed significant differences (p=0.0001, p=0.0001; respectively) between OCD and control groups. Haplotype analysis showed a high frequency of A–T (rs6265–rs1519480) in OCD patients compared with the control group (OR=2.06 [1.18–3.59], p=0.0093) and a low frequency of haplotype A–C in the OCD patients (OR=0.04 [0.01–0.16], p=0.000002). The family-based association study showed no significant differences in the transmission of any variant. Our study replicated the association between BDNF Val66Met gene polymorphism and OCD. Also, we found a significant association of rs1519480 in OCD patients compared with a control group, region that has never been analyzed in OCD. In conclusion, our findings suggest that BDNF gene could be related to the development of OCD.     

Influence of BDNF and COMT polymorphisms on emotional decision making

Decision making is an important brain function. Although little is known about the genetic basis of decision making, it has been suggested that it is mediated by the modulation of neurotransmitter systems. We investigated how the BDNF Val66Met and COMT Val158Met polymorphisms affect emotional decision making using the Iowa Gambling Task (IGT). One hundred sixty-eight healthy Korean college students (93 males, 75 females) with a complete dataset were included in the data analysis. The IGT and genotyping for the polymorphisms of BDNF Val66Met and COMT Val158Met were performed. Both Met/Met and Val/Met of the BDNF Val66Met polymorphism were significantly associated with a lower mean score of blocks 3-5 of the IGT and with less improvement from block 1 to block 3-5 than the Val/Val. However, the BDNF was not significantly associated with the score of block 1, and the COMT Val158Met polymorphism produced no significant effect on IGT performance. No interaction effect was observed between the BDNF and the COMT for the IGT. These findings suggest the BDNF Val66Met may affect the emotional decision making performance.