Brain-derived Neurotropic Factor Val66Met Research Articles

1 The Impact of APOzA and BDNF val66met on Executive Function in Older Veterans with Post-traumatic Stress Disorder

Objective:Both Apolipoprotein z4 (APOz4) and Brain-Derived Neurotropic Factor val66met (BDNF-met) have been implicated as cognitive risk polymorphisms and may signal a more rapid trajectory of cognitive decline (Boots et al., 2017; Lim et al., 2015). The presence of both risk alleles may additively result in greater cognitive difficulties (Cechova et al., 2020), specifically executive functioning (Sapkota et al., 2017). As executive functioning difficulties can be associated with Posttraumatic Stress Disorder (PTSD; Woon et al., 2017), individuals with PTSD who carry these polymorphisms may be at higher risk for decline in executive functioning. In this study, we examined the cross-sectional and longitudinal impact of these alleles on executive functioning performance in Veterans with PTSD.Participants and Methods:Seventy community-dwelling male Veterans were enrolled as part of a larger study at VAPAHCS and consented to genetic analysis. A current or lifetime history of PTSD (score > 40 on the CAPS-IV; Blake et al., 1995) was required for study participation. Trail Making Test B (TMT-B; Army Individual Test Battery, 1994) was used to assess executive functioning. TMT-B was part of a comprehensive neuropsychological battery administered at baseline and yearly over the following three years. Mean age and education were 61 years old (SD = 4.5; range = 55-78) and 14 years (SD = 2.3; range = 8-20), respectively.The majority of the sample was White (71%) and were from the Korean and Vietnam War eras.Results:APOz4 and BDNF-met were present in 29% and 27% of the sample, respectively; both were present in six participants. Regression models were fitted separately for TMT-B raw time-to-complete and number of errors, both cross-sectionally at screening and then longitudinally. The presence of BDNF-met was a significant predictor of TMT-B time and number of errors in both models (Time: ß = 0.09, p = 0.03 and ß = 0.11, p < 0.01; Errors: IRR = 2.4, p = 0.01 and IRR = 1.9, p = 0.01), while APOz4 only predicted errors longitudinally (IRR = 1.8, p = 0.03). There was no significant allelic interaction; however, the presence of both alleles additively multiplied TMT-B errors by approximately 3.7 times at screening (IRR = 3.7; p = 0.01) and 3.3 times longitudinally (IRR = 3.3; p < 0.01).Conclusions:Altogether, these results are suggestive of an adverse, additive, effect of the APOz4 and BDNF-met polymorphisms on executive functioning, in particular error-proneness, with their combined presence tripling the errors made on TMT-B cross-sectionally and longitudinally. Consistent with previous research, the TMT-B error analysis increases detection of cognitive impairment, similar to other clinical samples (Varjacic et al., 2018). While TMT-B errors are typically interpreted qualitatively, the strong effect of these established risk alleles on error rates further support this metric as a clinically useful indicator of executive dysfunction in a PTSD population. In keeping with the Boston Process approach, these findings support the importance of error analysis in clinical interpretation of neuropsychological performance.

Aerobic exercise improves executive functions in females, but not males, without the BDNF Val66Met polymorphism

BackgroundAerobic exercise promotes cognitive function in older adults; however, variability exists in the degree of benefit. The brain-derived neurotropic factor (BDNF) Val66Met polymorphism and biological sex are biological factors that have been proposed as important modifiers of exercise efficacy. Therefore, we assessed whether the effect of aerobic exercise on executive functions was dependent on the BDNFval66met genotype and biological sex.MethodsWe used data from a single-blind randomized controlled trial in older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Fifty-eight older adults were randomly assigned to either the 6 months, three times per week progressive aerobic training (AT) group or the usual care plus education control (CON) group. The secondary aim of the parent study included executive functions which were assessed with the Trail Making Test (B–A) and the Digit Symbol Substitution Test at baseline and trial completion at 6 months.ResultsAnalysis of covariance, controlling for baseline global cognition and baseline executive functions performance (Trail Making Test or Digit Symbol Substitution Test), tested the three-way interaction between experimental group (AT, CON), BDNFval66met genotype (Val/Val carrier, Met carrier), and biological sex (female, male). Significant three-way interactions were found for the Trail Making Test (F(1,48) = 4.412, p < 0.04) and Digit Symbol Substitution Test (F(1,47) = 10.833, p < 0.002). Posthoc analyses showed female Val/Val carriers benefited the most from 6 months of AT compared with CON for Trail Making Test and Digit Symbol Substitution Test performance. Compared with CON, AT did not improve Trail Making Test performance in male Val/Val carriers or Digit Symbol Substitution Test performance in female Met carriers.ConclusionsThese results suggest that future randomized controlled trials should take into consideration BDNF genotype and biological sex to better understand the beneficial effects of AT on cognitive function in vascular cognitive impairment to maximize the beneficial effects of exercise and help establish exercise as medicine for cognitive health.

Brain-derived Neurotropic Factor val66met is a Strong Predictor of Decision Making and Attention Performance on the CONVIRT Virtual Reality Cognitive Battery

The val66met polymorphism of the brain-derived neurotrophic factor gene has been associated with changes in components of executive functioning such as decision making; however, this relationship remains unclear. Val66met-related changes in attention and visual processing speed may explain potential changes in decision making. Furthermore, chronic stress disrupts executive functions and alters autonomic activity. Because the relationship between val66met and cognition has not been investigated in the context of chronic stress or stress-related autonomic changes, in this study 55 healthy university students completed self-report measures of chronic stress and mental health. Participants then completed a virtual reality cognitive test battery (CONVIRT) measuring decision making, attention, and visual processing reaction times. To measure autonomic activity, saliva alpha amylase and heart rate variability (HRV) were assessed at baseline and after CONVIRT testing. Saliva samples were used to identify val66met genotype. Regression analyses demonstrated that val66met was the strongest predictor of decision making and attention, but not visual processing, where valine/methionine (Val/met) participants had faster reaction times than Val/val participants. Val/met participants also had higher perceived chronic stress and heightened increases in sympathetic activity, but not parasympathetic activity. Neither stress nor autonomic activity moderated the effect of val66met on decision making or attention. This study is the first to investigate the role of val66met in decision making, attention, and visual processing while taking into account chronic stress and autonomic activity. This multifactorial approach revealed that carriers of the Val/met genotype may have better decision making and attention than Val/val carriers.

The BDNF Val66Met polymorphism impacts victim's moral emotions following interpersonal transgression.

Immoral behaviors make individuals abominate and punish transgressors. Inspired by the associations between the Val66Met polymorphism of brain-derived neurotropic factor (BDNF) gene and emotional responses following negative events, we investigated whether this polymorphism was also associated moral emotions such as punishment and forgiveness following interpersonal transgression. To do so, we categorized 340 individuals according to the BDNF Val66Met and assessed moral emotions by using 12 hypothetic scenarios in different conditions of intention and interpersonal consequence. The results indicated that this polymorphism was significantly associated with moral aversion and punishment towards transgressors. Victims with the Val/Val genotype expressed less aversion and punishment than the Met carriers, regardless of intention and interpersonal consequence. Moreover, this polymorphism was associated with forgiveness. Victims with the Val/Val genotype expressed more forgiveness than the Met carriers. Taken together, these findings highlight the importance of the BDNF Val66Met to moral emotions.

Working memory moderates the relation between the brain-derived neurotropic factor (BDNF) and psychotherapy outcome for depression

BackgroundInsight into patient characteristics that predict response to treatment for major depressive disorder (MDD) may help to personalize treatment and improve outcomes. One mechanism that has been linked to the success of treatment for MDD is brain-derived neurotropic factor (BDNF). BDNF is implicated in learning and memory and may play a role in the effects of psychotherapy that involves changing cognitions and behaviors. In addition, only in individuals with low BDNF, low working memory capacity has been associated with increased symptoms of depression. However, the role of BDNF and working memory capacity in psychotherapy outcome is unclear. The aim of this study was to investigate the role of BDNF and its interaction with working memory capacity in psychotherapy outcomes for MDD. MethodAdult patients with MDD were randomized to weekly or twice weekly sessions of cognitive behavioral therapy or interpersonal psychotherapy. BDNF Val66Met polymorphism (rs6265) (n = 138) was defined and serum BDNF was quantified before (n = 138) and after psychotherapy (n = 82). ResultsBaseline serum BDNF and the Val66Met polymorphism were not associated with outcome and associations did not differ between treatment conditions. Working memory capacity significantly moderated the relation between baseline serum BDNF and outcome: high serum BDNF at baseline was related to less depressive symptoms following psychotherapy in the presence of high working memory capacity, but not low working memory capacity. DiscussionThese findings, if replicated, might indicate that while BDNF may not be related to psychotherapy outcomes in general, they may play a role in the presence of specific learning processes such as working memory capacity.

The BDNF Val66Met Polymorphism Modulates Resilience of Neurological Functioning to Brain Ageing and Dementia: A Narrative Review.

Brain-derived neurotropic factor (BDNF) is an abundant and multi-function neurotrophin in the brain. It is released following neuronal activity and is believed to be particularly important in strengthening neural networks. A common variation in the BDNF gene, a valine to methionine substitution at codon 66 (Val66Met), has been linked to differential expression of BDNF associated with experience-dependent plasticity. The Met allele has been associated with reduced production of BDNF following neuronal stimulation, which suggests a potential role of this variation with respect to how the nervous system may respond to challenges, such as brain ageing and related neurodegenerative conditions (e.g., dementia and Alzheimer’s disease). The current review examines the potential of the BDNF Val66Met variation to modulate an individual’s susceptibility and trajectory through cognitive changes associated with ageing and dementia. On balance, research to date indicates that the BDNF Met allele at this codon is potentially associated with a detrimental influence on the level of cognitive functioning in older adults and may also impart increased risk of progression to dementia. Furthermore, recent studies also show that this genetic variation may modulate an individual’s response to interventions targeted at building cognitive resilience to conditions that cause dementia.

Depression and Cognitive Dysfunction in Older U.S. Military Veterans: Moderating Effects of BDNF Val66Met Polymorphism and Physical Exercise

ObjectiveDepression is associated with increased risk for cognitive dysfunction, yet little is known about genetic and behavioral factors that may moderate this association. Using data from a nationally representative sample of older U.S. military veterans, we examined the direct and interactive effects of depression, brain-derived neurotropic factor (BDNF) Val66Met genotype, and physical exercise on cognitive functioning. MethodsOne thousand three hundred eighty-six older European-American U.S. military veterans (mean age = 63) completed a web-based survey and cognitive assessment. Analyses of covariance were conducted to evaluate the effects of depression, BDNF Met allele carrier status, and physical exercise on these measures. ResultsDepressed veterans scored worse than nondepressed veterans on subjective measures of cognitive functioning (Cohen d's = 0.34–0.57) and objective measures of visual learning (d = 0.39) and working memory (d = 0.28). Among depressed veterans, those who were Met allele carriers scored worse than Val/Val homozygotes on subjective cognitive measures (d's = 0.52–0.97) and an objective measure of visual learning (d = 0.36). Engagement in physical exercise moderated the association between depression and cognitive function, with depressed exercisers scoring better than depressed nonexercisers on a subjective measure of reasoning, and objective measures of processing speed, attention, and visual learning (d = 0.58–0.99): further, in depressed Met allele carriers, exercisers scored better than nonexercisers on subjective cognitive (d's = 0.80–1.92), and objective measures of visual learning (d = 0.8–1.31) and working memory (d = 0.67). ConclusionDepression is associated with moderate decrements in cognitive functioning in older U.S. military veterans, and this association is moderated by BDNF Val66Met genotype and physical exercise. Prevention and treatment efforts designed to promote physical exercise may help preserve cognitive functioning in at-risk veterans.

Inhibition of the CD36 receptor reduces visceral fat accumulation and improves insulin resistance in obese mice carrying the BDNF-Val66Met variant

Obesity-induced metabolic dysfunctions increase the risk for vascular diseases, including type II diabetes and stroke. Managing obesity is of interest to address the worldwide health problem; however, the role of genetic variability in human obesity development and specific targets for obesity-related metabolic disease have not been thoroughly studied. A SNP in the brain-derived neurotropic factor (BDNF) gene that results in the substitution of a valine with a methionine at codon 66 (Val66Met) occurs with a high frequency in humans. This study addressed the effect of genetic variability in developing obesity and the efficacy of the inhibition of cluster of differentiation 36 (CD36), a multifunctional receptor implicated in obesity and insulin resistance, in WT mice and mice with the BDNF Val66Met variant. CD36 inhibition by salvionolic acid B (SAB) in diet-induced obese WT mice reduced visceral fat accumulation and improved insulin resistance. The benefit of SAB was abrogated in CD36 knockout mice, showing the specificity of SAB. In addition, mice with the Val66Met variant in both alleles (BDNFM/M) fed a high-fat diet exhibited extreme obesity with increased CD36 gene and protein levels in macrophages. Chronic SAB treatment in BDNFM/M mice significantly decreased visceral fat accumulation and improved insulin resistance. Notably, the effect of SAB was greater in the extremely obese BDNFM/M mice compared with the WT mice. The study demonstrated a link between BDNF Val66Met and elevated CD36 expression and suggested that CD36 inhibition may be a potential strategy to improve metabolic dysfunctions and to normalize risk factors for vascular diseases in the obese population.

Potential Role of Brain-Derived Neurotrophic Factor and Dopamine Receptor D2 Gene Variants as Modifiers for the Susceptibility and Clinical Course of Wilson's Disease.

Wilson's disease (WD), an inborn error of copper metabolism caused by mutations in the ATPase copper transporting beta (ATP7B) gene, manifests variable age of onset and different degrees of hepatic and neurological disturbances. This complex phenotypical outcome of a classical monogenic disease can possibly be explained by modifier loci regulating the clinical course of the disease. The brain-derived neurotropic factor (BDNF), critical for the survival, morphogenesis, and plasticity of the neurons, and the dopamine receptor D2 (DRD2), one of the most abundant dopamine receptors in the brain, have been highlighted in the pathophysiology of various neuropsychiatric diseases. This study aims to identify the potential association between BDNF and DRD2 gene polymorphisms and WD and its clinical characteristics. A total of 164 WD patients and 270 controls from India were included in this study. Two BDNF polymorphisms [p.Val66Met (c.G196A) and c.C270T] and the DRD2 Taq1A (A2/A1 or C/T) polymorphism were examined for their association with WD and some of its clinical attributes, using polymerase chain reaction, restriction fragment length digestion, and bidirectional sequencing. The C allele and CC genotype of BDNF C270T were significantly overrepresented among controls compared to WD patients. In addition, a significantly higher proportion of the allele coding for Val and the corresponding homozygous genotype of BDNF Val66Met polymorphism was found among WD patients with age of onset later than 10years. Furthermore, the A1A1 genotype of DRD2 Taq1A polymorphism was significantly more common among WD patients with rigidity. Our data suggest that both BDNF and DRD2 may act as potential modifiers of WD phenotype in the Indian context.

The Involvement of Genes in Adolescent Depression: A Systematic Review.

Numerous studies have reported on the roles of genetic factors in the development of depression in adolescents and young adults. However, there are few systematic reviews that update our understanding of adolescent depression with the biological findings identifying the roles of gene expression and/or polymorphism(s). This review systematically summarized the findings that clearly identified the contribution of a gene to the risk of depression in adolescents between the ages of 10 and 19 years old and young adults between the ages of 20 and 25 years old. Data were obtained through searching PubMed, Embase, and Web of Science. A total of 47 studies on early adolescence and three studies on young adults were included in the current review. Most articles studied genes in the serotonergic system (n = 26), dopaminergic system (n = 3), and the Brain-derived neurotropic factor (BDNF) gene (n = 12). 92.3% of studies (24/26) identified positive associations of 5-HTTLPR polymorphism with depressive illness or depressive symptoms. 83.3% of studies (10/12) found positive association between BDNF Val66Met genotype and adolescent depressive symptoms. More studies should be conducted on the 18 genes reported in a few studies to clarify their roles in the risk for adolescent depression.

Brain-derived neurotropic factor polymorphisms, traumatic stress, mild traumatic brain injury, and combat exposure contribute to postdeployment traumatic stress.

BackgroundIn addition to experiencing traumatic events while deployed in a combat environment, there are other factors that contribute to the development of posttraumatic stress disorder (PTSD) in military service members. This study explored the contribution of genetics, childhood environment, prior trauma, psychological, cognitive, and deployment factors to the development of traumatic stress following deployment.MethodsBoth pre‐ and postdeployment data on 231 of 458 soldiers were analyzed. Postdeployment assessments occurred within 30 days from returning stateside and included a battery of psychological health, medical history, and demographic questionnaires; neurocognitive tests; and blood serum for the D2 dopamine receptor (DRD2), apolipoprotein E (APOE), and brain‐derived neurotropic factor (BDNF) genes.ResultsSoldiers who screened positive for traumatic stress at postdeployment had significantly higher scores in depression (d = 1.91), anxiety (d = 1.61), poor sleep quality (d = 0.92), postconcussion symptoms (d = 2.21), alcohol use (d = 0.63), traumatic life events (d = 0.42), and combat exposure (d = 0.91). BDNF Val66 Met genotype was significantly associated with risk for sustaining a mild traumatic brain injury (mTBI) and screening positive for traumatic stress. Predeployment traumatic stress, greater combat exposure and sustaining an mTBI while deployed, and the BDNF Met/Met genotype accounted for 22% of the variance of postdeployment PTSD scores (R 2 = 0.22, P < 0.001). However, predeployment traumatic stress, alone, accounted for 17% of the postdeployment PTSD scores.ConclusionThese findings suggest predeployment traumatic stress, genetic, and environmental factors have unique contributions to the development of combat‐related traumatic stress in military service members.

Differential effects of BDNF val66met in repetitive associative learning paradigms

In healthy young subjects, the brain derived neurotropic factor (BDNF) val66met polymorphism negatively affects behavioural outcome in short-term motor cortex or hippocampus-based learning paradigms. In repetitive training paradigms over several days this effect can be overcome, in tests involving other brain areas even positive effects were found.To further specify the role of this polymorphism in cognitive processes, we used an associative vocabulary learning paradigm over four consecutive days and tested 38 young healthy subjects and 29 healthy elderly subjects. As a control paradigm, we designed a nonverbal haptic Braille letter-learning paradigm based on the same principles. Behavioural outcome was then associated with the BDNF-genotype.In the vocabulary learning task, met carrier (met/val and met/met) benefitted more from the repetitive training than val/val subjects. This was paralleled by a higher reduction of delayed answers during the course of the study, an effect that was also present in the haptic paradigm. However, in a group of healthy elderly subjects, no similar tendency was found.We conclude that the BDNF val66met polymorphism alters highly circumscribed answer behaviours in young healthy subjects. This might partly explain the high variability of previously published results.

Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism influences the association of the methylome with maternal anxiety and neonatal brain volumes.

Early life environments interact with genotype to determine stable phenotypic outcomes. Here we examined the influence of a variant in the brain-derived neurotropic factor (BDNF) gene (Val66Met), which underlies synaptic plasticity throughout the central nervous system, on the degree to which antenatal maternal anxiety associated with neonatal DNA methylation. We also examined the association between neonatal DNA methylation and brain substructure volume, as a function of BDNF genotype. Infant, but not maternal, BDNF genotype dramatically influences the association of antenatal anxiety on the epigenome at birth as well as that between the epigenome and neonatal brain structure. There was a greater impact of antenatal maternal anxiety on the DNA methylation of infants with the methionine (Met)/Met compared to both Met/valine (Val) and Val/Val genotypes. There were significantly more cytosine-phosphate-guanine sites where methylation levels covaried with right amygdala volume among Met/Met compared with both Met/Val and Val/Val carriers. In contrast, more cytosine-phosphate-guanine sites covaried with left hippocampus volume in Val/Val infants compared with infants of the Met/Val or Met/Met genotype. Thus, antenatal Maternal Anxiety × BDNF Val66Met Polymorphism interactions at the level of the epigenome are reflected differently in the structure of the amygdala and the hippocampus. These findings suggest that BDNF genotype regulates the sensitivity of the methylome to early environment and that differential susceptibility to specific environmental conditions may be both tissue and function specific.

Identification of BDNF sensitive electrophysiological markers of synaptic activity and their structural correlates in healthy subjects using a genetic approach utilizing the functional BDNF Val66Met polymorphism.

Increasing evidence suggests that synaptic dysfunction is a core pathophysiological hallmark of neurodegenerative disorders. Brain-derived neurotropic factor (BDNF) is key synaptogenic molecule and targeting synaptic repair through modulation of BDNF signalling has been suggested as a potential drug discovery strategy. The development of such “synaptogenic” therapies depend on the availability of BDNF sensitive markers of synaptic function that could be utilized as biomarkers for examining target engagement or drug efficacy in humans. Here we have utilized the BDNF Val66Met genetic polymorphism to examine the effect of the polymorphism and genetic load (i.e. Met allele load) on electrophysiological (EEG) markers of synaptic activity and their structural (MRI) correlates. Sixty healthy adults were prospectively recruited into the three genetic groups (Val/Val, Val/Met, Met/Met). Subjects also underwent fMRI, tDCS/TMS, and cognitive assessments as part of a larger study. Overall, some of the EEG markers of synaptic activity and brain structure measured with MRI were the most sensitive markers of the polymorphism. Met carriers showed decreased oscillatory activity and synchrony in the neural network subserving error-processing, as measured during a flanker task (ERN); and showed increased slow-wave activity during resting. There was no evidence for a Met load effect on the EEG measures and the polymorphism had no effects on MMN and P300. Met carriers also showed reduced grey matter volume in the anterior cingulate and in the (left) prefrontal cortex. Furthermore, anterior cingulate grey matter volume, and oscillatory EEG power during the flanker task predicted subsequent behavioural adaptation, indicating a BDNF dependent link between brain structure, function and behaviour associated with error processing and monitoring. These findings suggest that EEG markers such as ERN and resting EEG could be used as BDNF sensitive functional markers in early clinical development to examine target engagement or drug related efficacy of synaptic repair therapies in humans.

The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic factor levels in Han Chinese patients with bipolar disorder and schizophrenia

Brain-derived neurotropic factor (BDNF) is widely distributed in the peripheral and central nervous systems. BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of several mental illnesses. To elucidate the role of BDNF, we compared the plasma BDNF levels and the BDNF Val66Met gene variants effect in several mental disorders. We enrolled 644 participants: 177 patients with bipolar I disorder (BP-I), 190 with bipolar II disorder (BP-II), 151 with schizophrenia, and 126 healthy controls. Their plasma BDNF levels and BDNF Val66Met single nucleotide polymorphisms (SNP) were checked before pharmacological treatment. Plasma levels of BDNF were significantly lower in patients with schizophrenia than in healthy controls and patients with bipolar disorder (F = 37.667, p<0.001); the distribution of the BDNF Val66Met SNP was not different between groups (χ(2) = 5.289, p = 0.507). Nor were plasma BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not influence plasma BDNF levels in our participants. Plasma BDNF levels were, however, significantly negatively correlated with depression scores in patients with bipolar disorder and with negative symptoms in patients with schizophrenia. We conclude that plasma BDNF profiles in different mental disorders are not affected by BDNF Val66Met gene variants, but by the process and progression of the illness itself.

Late cortical plasticity in motor and auditory cortex: role of met-allele in BDNF Val66Met polymorphism

The brain-derived neurotropic factor (BDNF) Val66Met polymorphism has been associated with abnormalities of synaptic plasticity in animal models, and abnormalities in motor cortical plasticity have also been described in humans using transcranial direct current stimulation. No study has yet been done on plasticity in non-motor regions, and the effect of two Met alleles (i.e. 'Met dose') is not well understood. We studied the effect of the BDNF Val66Met polymorphism on the after-effects of transcranial direct current stimulation and tetanic auditory stimulation in 65 subjects (23; Val66Val, 22; Val66Met and 20; Met66Met genotypes). In the first session, motor evoked potentials (MEP) were recorded under stereotaxic guidance for 90 min after 9 min of anodal transcranial direct current stimulation (TDCS). In the second session, auditory-evoked potentials (AEP) were recorded before and after 2 min of auditory 13 Hz tetanic stimulation. There was a difference in MEP facilitation post-TDCS comparing Met carriers with non-Met carriers, with Met carriers having a modest late facilitation at 30-90 min. There was no difference in responses between Val66Met genotype and Met66Met genotype subjects. Tetanic auditory stimulation also produced late facilitation of N1-P2 AEP at 25 min, but there was no apparent effect of genetic status. This study indicates that Met66Met carriers behave like Val66Met carriers for TDCS-induced plasticity, and produce a late facilitation of MEPs. Auditory cortical plasticity was not affected by the BDNF Val66Met polymorphism. This study sheds light on the differences between auditory and motor cortical plasticity and the role of the BDNF Val66Met polymorphism.

The influence of the brain-derived neurotropic factor Val66Met genotype and HMG-CoA reductase inhibitors on insulin resistance in the schizophrenia and bipolar populations.

The brain-derived neurotrophic factor (BDNF) Val66Met variant and HMG-COA reductase inhibitors (statins) have been implicated in insulin resistance with a possible increased risk of diabetes. We sought to determine the effect of the BDNF Met variant and statin medication use on insulin resistance in schizophrenia and bipolar disorder using the homeostasis model assessment of insulin resistance (HOMA-IR). A cross-sectional design was used and patients with diabetes or on any medications affecting glucose regulation were -excluded. Associations between insulin resistance and genotype were then analyzed by ANOVA and regression analysis. Subjects were grouped by BDNF genotype as well as presence of statin. Two hundred fifty-two subjects with a mean age of 44 years were included. The group was 53% male and 41% had a diagnosis of bipolar disorder; 78% and 19% were receiving atypical antipsychotics (AAPs) and statin medications, respectively. Analysis showed schizophrenia subjects with the BDNF met allele as well as schizophrenia subjects with both the BDNF met allele and were receiving a statin had significantly higher HOMA-IR values compared to the other groups (p= 0.046 and p= 0.016, respectively). Our results suggest that in the metabolically high-risk population of schizophrenia the BDNF met allele alone and in combination with statin medications is associated with higher insulin resistance values. This was not seen in the bipolar population. Further validation of these associations remains necessary.

The brain-derived neurotropic factor Val66Met polymorphism and cingulate gray matter volume in healthy Koreans

The brain-derived neurotropic factor Val66Met polymorphism and cingulate gray matter volume in healthy Koreans