Sex-specific association of brain-derived neurotrophic factor (BDNF) Val66Met polymorphism and plasma BDNF with attention-deficit/hyperactivity disorder in a drug-naïve Han Chinese sample

A functional polymorphism of the brain derived neurotrophic factor gene (BDNF) (Val66Met) has been suggested to be involved in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD). It also has an impact on peripheral BDNF levels in psychiatric disorders. This study examined the association of Val66Met with plasma BDNF level of ADHD in Han Chinese children (170 medication – naïve ADHD patients and 155 unaffected controls, aged 6–16 years). The Val allele was showed a higher frequency in females with ADHD (n=84) than controls (P=0.029) from the case-control association study. The analysis of covariance (ANCOVA) indicated that the mean plasma BDNF levels of ADHD patients were significantly higher than that of controls (P=0.001). We performed both total sample and sex stratified analyses to investigate the effect of Val66Met genotype on the plasma BDNF levels, but only a trend of association was found in females with ADHD (n=84), with a tendency of lower plasma BDNF level in Val allele carriers than Met/Met genotype carriers (P=0.071). Our results suggested a sex-specific association between BDNF and ADHD. Furthermore, there was a possible sex-specific relationship between the BDNF Val66Met genotype and plasma BDNF levels. However, further studies are required to elucidate the role of BDNF in ADHD.     

Val66Met polymorphism association with serum BDNF and inflammatory biomarkers in major depression

Objectives: Current evidence supports participation of neurotrophic and inflammatory factors in the pathogenesis of major depressive disorder (MDD). Some studies reported an association between the Val66Met polymorphism (rs6265) of brain-derived neurotrophic factor (BDNF) gene with MDD and peripheral BDNF levels. However, no previous studies have examined the association of this polymorphism with inflammation. The present study assessed the association of the Val66Met polymorphism with serum levels of BDNF and inflammatory markers among depressed outpatients.

Methods: All participants (n?=?73) met DSM-IV criteria for a unipolar depressive episode. The serum levels of BDNF and inflammatory biomarkers (IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ) were compared between individuals presenting with at least one Met allele (Met-carriers) and those homozygous for the Val allele.

Results: In our sample (84.9% female, mean age 52.4?±?10.3 years), 24.7% (n?=?18) were Met-carriers. After Bonferroni correction, the Met allele was significantly associated with higher BDNF and lower TNF-α. These associations persisted after adjusting for potential confounders.

Conclusions: The pattern of low BDNF and high inflammation in MDD may be influenced by the Val66Met polymorphism. The association of a polymorphism in the BDNF gene with inflammatory markers in addition to BDNF levels suggests an interaction between these systems.     

Structural correlates of COMT Val158Met polymorphism in childhood ADHD: a voxel-based morphometry study

Objectives. The Val158-allele of the catechol-O-methyltransferase (COMT) Val158Met (rs4680) functional polymorphism has been identified as a risk factor for antisocial behaviour in attention-deficit/hyperactivity disorder (ADHD). Here, we used voxel-based morphometry to investigate the effects of Val158Met polymorphism on grey matter (GM) volumes in a sample of 7–13-year-old children. Methods. MRI and genotype data were obtained for 38 children with combined-type ADHD and 24 typically developing (TD) children. Four regions of interest were identified: striatum, cerebellum, temporal lobe and inferior frontal gyrus (IFG). Results. When compared to TD children, those with ADHD had a significant decrease of GM volume in the IFG. Volume in this region was negatively correlated with ratings of hyperactivity/impulsivity symptoms. Furthermore, the smaller GM volume in the IFG was attributed to the presence of the Met158-allele, as only children with ADHD carrying a Met158-allele exhibited such decrease in the IFG. Children with ADHD homozygotes for the Val158-allele presented increased GM volume in the caudate nucleus when compared with TD children. Conclusions. This study provides the first evidence of a modulation of ADHD-related GM volume alterations by Val158Met in two key regions, possibly mediating the relationship between Val158Met polymorphism and antisocial behaviour in children with ADHD.     

Childhood trauma,BDNF Val66Met and subclinical psychotic experiences. Attempt at replication in two independent samples

Childhood trauma exposure is a robust environmental risk factor for psychosis. However, not all exposed individuals develop psychotic symptoms later in life. The Brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been suggested to moderate the psychosis-inducing effects of childhood trauma in clinical and nonclinical samples. Our study aimed to explore the interaction effect between childhood trauma and the BDNF Val66Met polymorphism on subclinical psychotic experiences (PEs). This was explored in two nonclinical independent samples: an undergraduate and technical-training school student sample (n = 808, sample 1) and a female twin sample (n = 621, sample 2). Results showed that childhood trauma was strongly associated with positive and negative PEs in nonclinical individuals. A BDNF Val66Met x childhood trauma effect on positive PEs was observed in both samples. These results were discordant in terms of risk allele: while in sample 1 Val allele carriers, especially males, were more vulnerable to the effects of childhood trauma regarding PEs, in sample 2 Met carriers presented higher PEs scores when exposed to childhood trauma, compared with Val carriers. Moreover, in sample 2, a significant interaction was also found in relation to negative PEs. Our study partially replicates previous findings and suggests that some individuals are more prone to develop PEs following childhood trauma because of a complex combination of multiple factors. Further studies including genetic, environmental and epigenetic factors may provide insights in this field.     

Interaction of the DRD3 and BDNF gene variants in subtyped bipolar disorder

Objectives

Bipolar disorder is a severe mental disorder with prominent genetic etiologic factors. Dopaminergic dysfunction has been implicated in the pathogenesis of bipolar disorder, which suggests that the dopamine D3 receptor gene (DRD3) is a strong candidate gene. The brain-derived neurotrophic factor (BDNF) gene has been implicated in the etiology of bipolar disorder. We examined the association between the BDNF Val66Met and DRD3 Ser9Gly polymorphisms with two subtypes of bipolar disorder: bipolar-I and -II. Because BDNF regulates DRD3 expression (1), we also examined possible interactions between these genes.

Methods

We recruited 964 participants: 268 with bipolar-I, 436 with bipolar-II, and 260 healthy controls. The genotypes of the BDNF Val66Met and DRD3 Ser9Gly polymorphisms were determined using polymerase chain reactions plus restriction fragment length polymorphism analysis.

Results

Logistic regression analysis showed a significant main effect for the Val/Val genotype of the BDNF Val66Met polymorphism (P = 0.020), which predicted bipolar-II patients. Significant interaction effects for the BDNF Val66Met Val/Val genotype and both DRD3 Ser9Gly Ser/Ser and Ser/Gly genotypes were found only in bipolar-II patients (P = 0.027 and 0.006, respectively).

Conclusion

We provide initial evidence that the BDNF Val66Met and DRD3 Ser9Gly genotypes interact only in bipolar-II disorder and that bipolar-I and bipolar-II may be genetically distinct.     

A common polymorphism in the brain-derived neurotrophic factor gene in patients with adult-onset primary focal and segmental dystonia

Brain-derived neurotrophic factor (BDNF) modulates neuroplasticity. A functional polymorphism [Val66Met (G196A)] in BDNF has been reported to modify cortical plasticity in humans. Physiologic investigations have revealed that dystonia might be a consequence of the pathologic plasticity of the sensorimotor cortex. We aimed to investigate the role of the Val66Met polymorphism in a cohort of Serbian patients with adult-onset primary focal and segmental dystonia (PTD). One hundred and forty-nine patients with primary adult-onset PTD, 194 patients with Parkinson’s disease (PD), and 366 healthy control subjects were recruited for the study. Patients with PTD and PD, as well as healthy controls had a similar distribution of genotypes and allele frequencies. There was no any significant difference in the allelic distribution at the Val66Met SNP of the BDNF gene among patients with adult-onset PTD, PD, and healthy volunteers from the same geographic areas. In addition, the presence of the Met allele did not influence the clinical characteristics of PTD patients. Patients with the Met variant did not differ by age at onset, number of affected regions, and efficacy of a sensory trick. Met66Met is not associated with an increased risk of dystonia.     

Emotional fronto‐cingulate cortex activation and brain derived neurotrophic factor polymorphism in premenstrual dysphoric disorder

Premenstrual dysphoric disorder (PMDD) is the prototypical sex‐specific disorder in which symptom onset and offset require a particular hormonal milieu and for which there is moderate heritability. The present study investigated brain emotion processing in PMDD and healthy controls, as well as functional polymorphisms in two candidate genes for PMDD, the serotonin transporter (5‐HTT) and brain derived neurotrophic factor (BDNF). The 5‐HTT linked polymorphic region (5‐HTTLPR) and BDNF Val66Met polymorphisms were genotyped in 31 patients with PMDD and 31 healthy controls. A subset of 16 patients and 15 controls participated in two functional magnetic resonance imaging‐sessions performing an emotion processing task; once in the mid‐follicular, and once in the late luteal phase which corresponds with maximum severity of mood symptoms. Genotypes were not directly associated with PMDD. A main effect of group was found in the whole brain analysis, with patients having lower activation of the pre‐genual anterior cingulate and ventro‐medial prefrontal cortex, independent of menstrual cycle phase. Post‐hoc functional ROI analyses in the fronto‐cingulate cluster showed no effect of 5‐HTTLPR genotype but a genotype‐by‐group‐by‐phase interaction effect of BDNF Val66Met. Women with PMDD who were carriers of the Met‐allele had lower fronto‐cingulate cortex activation in the luteal phase compared to Met‐allele carrying controls. The results provide suggestive evidence of impaired emotion‐induced fronto‐cingulate cortex activation in PMDD patients. Although limited by a small sample, the potential influence of BDNF Val66Met in PMDD is in line with preclinical findings. Hum Brain Mapp 35:4450–4458, 2014. © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.     

Lack of association between brain-derived neurotrophic factor Val66Met polymorphism and aggressive behavior in schizophrenia

We investigated the association of the Val66Met gene polymorphism in the Brain-Derived Neurotrophic Factor (BDNF) gene with aggressive behavior among Southern Han Chinese schizophrenia patients. We used polymerase chain reaction-restriction fragment length polymorphism to determine the genotypes and the Modified Overt Aggression Scale (MOAS) to measure aggressive behavior. No significant differences in genotype or allele distribution of Val66Met were identified between aggressive and non-aggressive schizophrenia patients.     

Smoking and BDNF Val66Met polymorphism in male schizophrenia: A case-control study

Some recent studies show an association between a functional polymorphism of BDNF gene (Val66Met) and the susceptibility to nicotine dependence and we hypothesized that this polymorphism was associated with smoking in both schizophrenia patients and healthy controls. The BDNF Val66Met gene polymorphism was genotyped in 690 chronic male schizophrenia patients (smoker/nonsmoker = 522/169) and 628 male controls (smoker/nonsmoker = 322/306) using a case-control design. Nicotine dependence (ND) was assessed by the cigarettes smoked per day (CPD), the Heaviness of Smoking Index (HSI), and the Fagerstrom Test for ND (FTND). Patients also were rated on the Positive and Negative Syndrome Scale (PANSS). The results showed no significant differences in BDNF Val66Met genotype and allele distributions between the patients and healthy controls or between smokers and nonsmokers in either patients or healthy controls alone. In patient groups, however, the smokers with the Met allele had significantly higher HSI scores (Met/Met: 2.8 ± 1.7 vs. Met/Val: 2.2 ± 1.7 vs. Val/Val: 2.0 ± 1.6, p < 0.01) and a trend toward a significantly higher FTND score (p = 0.09) than those with the Val/Val genotype. In addition, the smokers showed significantly lower PANSS negative symptom and total scores, longer duration of illness and more hospitalizations (all p < 0.05). In the control group, the smokers with the Met allele started smoking significantly earlier than those with the Val/Val genotype (both p < 0.05). These results suggest that the BDNF Val66Met polymorphism may affect a smoker's response to nicotine in both schizophrenia and healthy controls from a Chinese Han population, but with differential effects in different aspects of smoking behaviors.     

Human BDNF rs6265 polymorphism as a mediator for the generalization of contextual anxiety

The Met allele of the human brain-derived neurotrophic factor (BDNF) gene might be a risk factor for anxiety disorders and is associated with reduced hippocampal volume. Notably, hippocampus plays a crucial role in contextual learning and generalization. The role of the BDNF gene variation in human context-conditioning and generalization is still unknown. We investigated 33 carriers of the Met allele (18 females) and 32 homozygous carriers of the Val allele (15 females) with a virtual-reality context-conditioning paradigm. Electric stimulations (unconditioned stimulus, US) were unpredictably delivered in one virtual office (CTX+), but never in another virtual office (CTX-). During generalization, participants revisited CTX+ and CTX- and a generalization office (G-CTX), which was a mix of the other two. Rating data indicated successful conditioning (more negative valence, higher arousal, anxiety and contingency ratings for CTX+ than CTX-), and generalization of conditioned anxiety by comparable ratings for G-CTX and CTX+. The startle data indicated discriminative learning for Met allele carriers, but not for Val homozygotes. Moreover, a trend effect suggests that startle responses of only the Met carriers were slightly potentiated in G-CTX versus CTX-. In sum, the BDNF polymorphism did not affect contextual learning and its generalization on a verbal level. However, the physiological data suggest that Met carriers are characterized by fast discriminative contextual learning and a tendency to generalize anxiety responses to ambiguous contexts. We propose that such learning may be related to reduced hippocampal functionality and the basis for the risk of Met carriers to develop anxiety disorders.     

Is the Val66Met polymorphism of the brain‐derived neurotrophic factor gene associated with panic disorder? A meta‐analysis

Although emerging evidence has suggested an association between the Val66Met (rs6265) polymorphisms in brain‐derived neurotrophic factor (BDNF) gene and the panic disorder, the conclusion is inclusive given the mixed results. This meta‐analysis reviewed and analyzed the recent studies addressing the potential association between the Val66Met polymorphisms and panic disorder susceptibility. Related case–control studies were retrieved by database searching and selected according to established inclusion criteria. Six articles were identified, which explored the association between the BDNF Val66Met polymorphism and panic disorder. Statistical analyses revealed no association for the allele contrast and the dominant model. However, the recessive model showed a significant association between the BDNF Val66Met polymorphism and panic disorder (odds ratio = 1.26, 95% confidence interval = 1.04–1.52, z = 2.39, P = 0.02). Despite of some limitations, this meta‐analysis suggests that the Val66Met polymorphism of BDNF gene is a susceptibility factor for panic disorder.     

Ethnic differences in COMT genetic effects on striatal grey matter alterations associated with childhood ADHD: A voxel-based morphometry study in a Japanese sample

Objectives: Attention deficit/hyperactivity disorder (ADHD) is associated with deficits in the dopaminergic fronto-striatal systems mediating higher-level cognitive functions. We hypothesised that a dopamine-regulating gene, catechol-O-methyltransferase (COMT), would have differential effects on the neural systems of different ethnic samples with ADHD. In Caucasian children with ADHD, the COMT Val-homozygotes have been previously shown to be associated with striatal grey matter volume (GMV) alterations. By using voxel-based morphometry, we examined whether Asian children with ADHD would exhibit a pattern opposite to that found in Caucasian samples. Methods: Structural brain images were obtained for Japanese children with ADHD (n?=?17; mean age?=?10.3 years) and typically developing (TD) children (n?=?15; mean age?=?12.8 years). COMT Val158Met genotype data were also obtained for the ADHD group. Results: Reduced GMV in the left striatum was observed in the ADHD group versus the TD group. This reduced GMV was modulated by COMT polymorphism; Met-carriers exhibited smaller striatal GMV than the Val/Val genotype. Conclusions: Contrasting with previous findings in Caucasians, the COMT Met allele was associated with striatal GMV alterations in Japanese children with ADHD. These results suggest the existence of ethnic differences in the COMT genetic effect on ADHD-related striatal abnormalities.     

The BDNF Val66Met polymorphism is an independent risk factor for high lethality in suicide attempts of depressed patients

Some authors have reported an association of BDNF Val66Met polymorphism with suicidal behavior and/or clinical aspects of suicidal attempts. We evaluated, here, the impact of BDNF Val66Met polymorphism on the clinical characteristics of suicide attempts. The study was conducted on a cohort of 120 consecutive patients who were admitted to the Emergency Hospital of Porto Alegre, Brazil, due to a suicide attempt. Variables of univariate analyses were included in a logistic regression model to test whether the risk factors had independent effect. In univariate analyses, sex, BDNF genotype, intent and method of suicide attempt were all risk factors for high lethality in suicide attempts. After logistic regression analysis, male sex (O.R. = 3.03; 95% C.I = 1.34–6.84; 0.008) and the presence of BDNF 66Met allele (O.R. = 2.62; 95% C.I = 1.04–6.57; 0.04) were significantly and independently associated with the high lethality in suicide attempts. The present study showed that BDNF 66Met allele is an independent predictor of high lethality in suicide attempts of depressed patients. This finding is important because it might allow earlier identification of patients at high risk for suicide, perhaps providing better tools for clinical care of these patients in the future.     

Association of the Catechol O-Methyltransferase Val158-Met Polymorphism and Reduced Interference Control in Korean Children with Attention-Deficit Hyperactivity Disorder

Objective

We tested for association of the catechol-O-methyltransferase (COMT) Val¹⁵⁸-Met (rs4680) polymorphism with attention-deficit hyperactivity disorder (ADHD) using family-based test in Korean trios.

Methods

A total of 181 subjects with ADHD along with both of their biological parents were recruited from University Hospitals in Korea. We performed a transmission disequilibrium test (TDT) on 181 trios.

Results

In the TDT, we found the over-transmission of the Val allele in children with ADHD (χ²=4.21, p=0.040).

Conclusion

These results suggest that the COMT Val158-Met polymorphism is associated with ADHD among the Korean population. However, this study must be replicated in larger populations.     

Brain-Derived Neurotrophic Factor Gene Val66Met Polymorphism Is a Risk Factor for Attention-Deficit Hyperactivity Disorder in a Turkish Sample

ObjectiveAttention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder that negatively affects different areas of life. We aimed to evaluate the associations between the Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) and ADHD and to assess the effect of the BDNF polymorphism on the neurocognitive profile and clinical symptomatology in ADHD.MethodsTwo hundred one ADHD cases and 99 typically developing subjects (TD) between the ages of 8 and 15 years were involved in the study. All subjects were evaluated using a complete neuropsychological battery, Child Behavior Checklist, the Teacher''s Report Form (TRF) and the DSM-IV Disruptive Behavior Disorders Rating Scale-teacher and parent forms.ResultsThe GG genotype was significantly more frequent in the patients with ADHD than in the TD controls, and the GG genotype was also significantly more frequent in the ADHD-combined (ADHD-C) subtype patients than in the TDs. However, there were no significant associations of the BDNF polymorphism with the ADHD subtypes or neurocognitive profiles of the patients. The teacher-assessed hyperactivity and inattention symptom count and the total score were higher, and the appropriately behaving subtest score of the TRF was lower in the GG genotypes than in the GA and AA (i.e., the A-containing) genotypes.ConclusionWe found a positive association between the BDNF gene Val66Met polymorphism and ADHD, and this association was observed specifically in the ADHD-C subtype and not the ADHD-predominantly inattentive subtype. Our findings support that the Val66Met polymorphism of BDNF gene might be involved in the pathogenesis of ADHD. Furthermore Val66Met polymorphism of BDNF gene may be more closely associated with hyperactivity rather than inattention.     

The association between brain-derived neurotrophic factor Val66Met variants and psychotic symptoms in posttraumatic stress disorder

Abstract

Objectives. Psychotic symptoms frequently occur in veterans with combat-related posttraumatic stress disorder (PTSD). Brain-derived neurotrophic factor (BDNF) plays a major role in neurodevelopment, neuro-regeneration, neurotransmission, learning, regulation of mood and stress responses. The Met allele of the functional polymorphism, BDNF Val66Met, is associated with psychotic disorders. This study intended to assess whether the Met allele is overrepresented in unrelated Caucasian male veterans with psychotic PTSD compared to veteran controls. Methods. The BDNF Val66Met variants were genotyped in 576 veterans: 206 veterans without PTSD and 370 veterans with PTSD subdivided into groups with or without psychotic features. Results. Veterans with psychotic PTSD were more frequently carriers of one or two Met alleles of the BDNF Val66Met polymorphism than veterans with PTSD without psychotic features and veterans without PTSD. Conclusions. The study shows that veterans with psychotic PTSD carried more Met alleles of the BDNF Val66Met than non-psychotic veterans with PTSD or veterans without PTSD. The results might add further support to the hypothesis that psychotic PTSD is a more severe subtype of PTSD.     

Differential modulation of motor cortex excitability in BDNF Met allele carriers following experimentally induced and use-dependent plasticity

The purpose of this study was to investigate how healthy young subjects with one of three variants of the brain‐derived neurotrophic factor (BDNF) gene modulate motor cortex excitability following experimentally induced and use‐dependent plasticity interventions. Electromyographic recordings were obtained from the right first dorsal interosseous (FDI) muscle of 12 Val/Val, ten Val/Met and seven Met/Met genotypes (aged 18–39 years). Transcranial magnetic stimulation of the left hemisphere was used to assess changes in FDI motor‐evoked potentials (MEPs) following three separate interventions involving paired associative stimulation, a simple ballistic task and complex visuomotor tracking task using the index finger. Val/Val subjects increased FDI MEPs following all interventions (≥ 25%, P < 0.01), whereas the Met allele carriers only showed increased MEPs after the simple motor task (≥ 26%, P < 0.01). In contrast to the simple motor task, there was no significant change in MEPs for the Val/Met subjects (7%, P = 0.50) and a reduction in MEPs for the Met/Met group (?38%, P < 0.01) following the complex motor task. Despite these differences in use‐dependent plasticity, the performance of both motor tasks was not different between BDNF genotypes. We conclude that modulation of motor cortex excitability is strongly influenced by the BDNF polymorphism, with the greatest differences observed for the complex motor task. We also found unique motor cortex plasticity in the rarest form of the BDNF polymorphism (Met/Met subjects), which may have implications for functional recovery after disease or injury to the nervous system in these individuals.     

Effects of BDNF Val66Met polymorphisms on brain structures and behaviors in adolescents with conduct disorder

Accumulating evidence suggests that neural abnormalities in conduct disorder (CD) may be subject to genetic influences, but few imaging studies have taken genetic variants into consideration. The Val66Met polymorphism of brain-derived neurotrophic factor (BDNF) has emerged as a high-interest genetic variant due to its importance in cortical maturation, and several studies have implicated its involvement in neurodevelopmental disorders. Thus, it is unclear how this polymorphism may influence brain anatomy and aberrant behaviors in CD. A total of 65 male adolescents with CD and 69 gender-, IQ- and socioeconomic status-matched healthy controls (HCs) (age range 13–17 years) were enrolled in this study. Analyses of variance (ANOVAs) were used to assess the main effects of CD diagnosis, BDNF genotype, and diagnosis–genotype interactions on brain anatomy and behaviors. We detected a significant main effect of BDNF genotype on temporal gyrification and antisocial behaviors, but not on CD symptoms. Diagnosis–genotype interactive effects were found for cortical thickness of the superior temporal and adjacent areas. These results suggest that the BDNF Val66Met polymorphism may exert its influence both on neural alterations and delinquent behaviors in CD patients. This initial evidence highlights the importance of elucidating potentially different pathways between BDNF genotype and cortical alterations or delinquent behaviors in CD patients.

     

Plasma BDNF levels are correlated with aggressiveness in patients with amnestic mild cognitive impairment or Alzheimer disease

In the present study, we examined whether neuropsychiatric symptoms were correlated with plasma brain-derived neurotrophic factor (BDNF) levels as a state marker or were associated with the BDNF polymorphism Val66Met in patients with amnestic mild cognitive impairment (A-MCI) or Alzheimer disease (AD). One hundred and seventy-six outpatients with AD (n = 129) or A-MCI (n = 47) were selected and their plasma BDNF concentrations measured. Next, we investigated the correlation between the plasma BDNF level and the Behavioral Pathology in Alzheimer Disease (Behave-AD) subscale scores, which reflect neuropsychiatric symptoms. We also compared the plasma BDNF level and the Behave-AD subscale scores among the BDNF Val66Met genotypic groups. Among the seven Behave-AD subscale scores, aggressiveness was positively correlated with the plasma BDNF level (ρ = 0.237, P < 0.005), but did not differ significantly among the three BDNF Val66Met genotypic groups. The Behave-AD total and other subscale scores did not differ significantly among the BDNF Val66Met genotypic groups and were not associated with the plasma BDNF level. Moreover, the plasma BDNF level did not differ significantly among the three BDNF Val66Met genotypic groups or between patients with A-MCI and those with AD. The plasma BDNF level was robustly correlated with aggressiveness, implying that the plasma BDNF level might be useful as a behavioral state marker in patients with AD or A-MCI.     

Brain‐derived neurotrophic factor gene polymorphism predicts interindividual variation in the sleep electroencephalogram

Previous studies have suggested that brain‐derived neurotrophic factor (BDNF) participates in the homeostatic regulation of sleep. The objective of this study was to investigate the influence of the Val66Met functional polymorphism of the BDNF gene on sleep and sleep EEG parameters in a large population‐based sample. In total 337 individuals participating in the São Paulo Epidemiologic Sleep Study were selected for analysis. None of the participants had indications of a sleep disorder, as measured by full‐night polysomnography and questionnaire. Spectral analysis of the EEG was carried out in all individuals using fast Fourier transformation of the oscillatory signals for each EEG electrode. Sleep and sleep EEG parameters in individuals with the Val/Val genotype were compared with those in Met carriers (Val/Met and Met/Met genotypes). After correction for multiple comparisons and for potential confounding factors, Met carriers showed decreased spectral power in the alpha band in stage one and decreased theta power in stages two and three of nonrapid‐eye‐movement sleep, at the central recording electrode. No significant influence on sleep macrostructure was observed among the genotype groups. Thus, the Val66Met polymorphism seems to modulate the electrical activity of the brain, predicting interindividual variation of sleep EEG parameters. Further studies of this and other polymorphic variants in potential candidate genes will help the characterization of the molecular basis of sleep. © 2014 Wiley Periodicals, Inc.