BDNF Polymorphism Research Articles

Effects of transcranial direct current stimulation on cognition in MCI with Alzheimer's disease risk factors using Bayesian analysis

Despite the growing interest in precision medicine-based therapies for Alzheimer's disease (AD), little research has been conducted on how individual AD risk factors influence changes in cognitive function following transcranial direct current stimulation (tDCS). This study evaluates the cognitive effects of sequential tDCS on 63 mild cognitive impairment (MCI) patients, considering AD risk factors such as amyloid-beta deposition, APOE ε4, BDNF polymorphism, and sex. Using both frequentist and Bayesian methods, we assessed the interaction of tDCS with these risk factors on cognitive performance. Notably, we found that amyloid-beta deposition significantly interacted with tDCS in improving executive function, specifically Stroop Word-Color scores, with strong Bayesian support for this finding. Memory enhancements were differentially influenced by BDNF Met carrier status. However, sex and APOE ε4 status did not show significant effects. Our results highlight the importance of individual AD risk factors in modulating cognitive outcomes from tDCS, suggesting that precision medicine may offer more effective tDCS treatments tailored to individual risk profiles in early AD stages.

Correlation between human BDNF rs6265 gene polymorphism and type-2 diabetes and diabetic peripheral neuropathy

Background & objective: Diabetes mellitus is quite common and globally prevalent condition affecting patients’ quality of life. Patients who have type 2 diabetes mellitus (T2DM), are more likely to get diabetic peripheral neuropathy (DPN), which may affect feet, legs, hand, and arm. A BDNF gene rs6265 polymorphism in humans results in the substitution of valine with methionine at codon 66 (Val66Met). We aimed to find the possible link between human BDNF rs6265 gene polymorphism and T2DM with and without peripheral neuropathy and compare it with healthy subjects in Kirkuk City, Iraq. Methodology: One hundred subjects were chosen to participate in this research, aged from 35 to 75 y and divided into three groups: 35 DPN, 35 T2DM patients, and 30 healthy controls were selected randomly for BDNF gene rs6265 SNP screening by using conventional PCR with specific sets of primers. Products of PCR for patients and control groups were run on the gel electrophoresis to detect the SNP rs6265 fragment. A nerve-conducting study was used to examine DPN. Results: The observed results demonstrated the presence of two types of alleles identified as genotypic variants (GG and GA) among all participants in this investigation. By applying the Hardy-Weinberg Equilibrium principle (HWE) for both patient and control groups, the results proved that there was a statistically significant variance (P < 0.05) in the genotypic frequencies between each of the groups that had been studied. The wild homozygous GG genotype in type 2 diabetic without neuropathy, with DPN, and healthy control group were 51.4%, 40% and 80% respectively. The heterozygous GA genotype were 48.6%, 60% and 20%, respectively in the three groups. Conclusion: The present study showed that the BDNF (Val66Met) rs6265 polymorphism is associated with type 2 diabetes mellitus and diabetic peripheral neuropathy in heterozygous allele G/A (Met/Met) and homozygous allele GG (Val/Val) genotype. Also, the current study found the absence of the mutant genotype AA, possibly due to the evidence that the distribution of the BDNF polymorphisms varies widely among different ethnic groups. Abbreviations: BDNF - Brain-derived neurotrophic factor; DPN - Diabetic peripheral neuropathy Keywords: Type2 diabetes mellitus; Diabetic peripheral neuropathy; Brain-Derived Neurotrophic Factor; BDNF rs6265 SNP; BDNF Val66Met polymorphism. Citation: Hamid R, Al-Wasiti E, Jabbar AM. Correlation between human BDNF rs6265 gene polymorphism and type-2 diabetes and diabetic peripheral neuropathy. Anaesth. pain intensive care 2024;28(4):752−756. DOI: 10.35975/apic.v28i4.2517 Received: March 08, 2024; Reviewed: April 20, 2024; Accepted: April 28, 2024

Using Precision Medicine to Disentangle Genotype-Phenotype Relationships in Twins with Rett Syndrome: A Case Report.

Rett syndrome (RTT) is a paediatric neurodevelopmental disorder spanning four developmental stages. This multi-system disorder offers a unique window to explore genotype-phenotype relationships in a disease model. However, genetic prognosticators of RTT have limited clinical value due to the disorder's heterogeneity on multiple levels. This case report used a precision medicine approach to better understand the clinical phenotype of RTT twins with an identical pathogenic MECP2 mutation and discordant neurodevelopmental profiles. Targeted genotyping, objective physiological monitoring of heart rate variability (HRV) parameters, and clinical severity were assessed in a RTT twin pair (5 years 7 months old) with an identical pathogenic MECP2 mutation. Longitudinal assessment of autonomic HRV parameters was conducted using the Empatica E4 wristband device, and clinical severity was assessed using the RTT-anchored Clinical Global Impression Scale (RTT-CGI) and the Multi-System Profile of Symptoms Scale (MPSS). Genotype data revealed impaired BDNF function for twin A when compared to twin B. Twin A also had poorer autonomic health than twin B, as indicated by lower autonomic metrics (autonomic inflexibility). Hospitalisation, RTT-CGI-S, and MPSS subscale scores were used as measures of clinical severity, and these were worse in twin A. Treatment using buspirone shifted twin A from an inflexible to a flexible autonomic profile. This was mirrored in the MPSS scores, which showed a reduction in autonomic and cardiac symptoms following buspirone treatment. Our findings showed that a combination of a co-occurring rs6265 BDNF polymorphism, and worse autonomic and clinical profiles led to a poorer prognosis for twin A compared to twin B. Buspirone was able to shift a rigid autonomic profile to a more flexible one for twin A and thereby prevent cardiac and autonomic symptoms from worsening. The clinical profile for twin A represents a departure from the disorder trajectory typically observed in RTT and underscores the importance of wider genotype profiling and longitudinal objective physiological monitoring alongside measures of clinical symptoms and severity when assessing genotype-phenotype relationships in RTT patients with identical pathogenic mutations. A precision medicine approach that assesses genetic and physiological risk factors can be extended to other neurodevelopmental disorders to monitor risk when genotype-phenotype relationships are not so obvious.

Interaction of childhood trauma with BDNF and FKBP5 gene polymorphisms in predicting burnout in general occupational groups

Interaction of childhood trauma with BDNF and FKBP5 gene polymorphisms in predicting burnout in general occupational groups

The association between serum BDNF levels, BDNF polymorphisms, and tardive dyskinesia: A review of current evidence

The association between serum BDNF levels, BDNF polymorphisms, and tardive dyskinesia: A review of current evidence

The influence of hippocampal dopamine D2 receptor losses on episodic-memory decline across 5 years is moderated by BDNF and KIBRA polymorphisms

Losses in dopamine (DA) functioning may contribute to aging-related decline in cognition. Hippocampal DA is necessary for successful episodic memory formation. Previously, we reported that higher DA D2 receptor (D2DR) availability in hippocampus is beneficial for episodic memory only in older carriers of more advantageous genotypes of well-established plasticity-related genetic variations, the brain-derived neurotrophic factor (BDNF, rs6265) and the kidney and brain expressed protein (KIBRA, rs17070145) polymorphisms. Extending our observations to the longitudinal level, the current data show that individuals with one or no beneficial BDNF and KIBRA genotype (n = 80) decline more in episodic memory across five years, without any contribution of losses in hippocampal D2DR availability to memory decline. Although carriers of two beneficial genotypes (n = 39) did not decline overall in episodic memory, losses of hippocampal D2DR availability were predictive of episodic-memory decline among these individuals. Our findings have implications for interventions targeting DA modulation to enhance episodic memory in aging, which may not benefit all older individuals.

Mild behavioral impairment in early Alzheimer’s disease and its association with APOE and BDNF risk genetic polymorphisms

BackgroundMild behavioral impairment (MBI) has been commonly reported in early Alzheimer’s disease (AD) but rarely using biomarker-defined samples. It is also unclear whether genetic polymorphisms influence MBI in such individuals. We thus aimed to examine the association between the cognitive status of participants (amnestic mild cognitive impairment (aMCI-AD) vs cognitively normal (CN) older adults) and MBI severity. Within aMCI-AD, we further examined the association between APOE and BDNF risk genetic polymorphisms and MBI severity.MethodsWe included 62 aMCI-AD participants and 50 CN older adults from the Czech Brain Aging Study. The participants underwent neurological, comprehensive neuropsychological examination, APOE and BDNF genotyping, and magnetic resonance imaging. MBI was diagnosed with the Mild Behavioral Impairment Checklist (MBI-C), and the diagnosis was based on the MBI-C total score ≥ 7. Additionally, self-report instruments for anxiety (the Beck Anxiety Inventory) and depressive symptoms (the Geriatric Depression Scale-15) were administered. The participants were stratified based on the presence of at least one risk allele in genes for APOE (i.e., e4 carriers and non-carriers) and BDNF (i.e., Met carriers and non-carriers). We used linear regressions to examine the associations.ResultsMBI was present in 48.4% of the aMCI-AD individuals. Compared to the CN, aMCI-AD was associated with more affective, apathy, and impulse dyscontrol but not social inappropriateness or psychotic symptoms. Furthermore, aMCI-AD was related to more depressive but not anxiety symptoms on self-report measures. Within the aMCI-AD, there were no associations between APOE e4 and BDNF Met and MBI-C severity. However, a positive association between Met carriership and self-reported anxiety appeared.ConclusionsMBI is frequent in aMCI-AD and related to more severe affective, apathy, and impulse dyscontrol symptoms. APOE and BDNF polymorphisms were not associated with MBI severity separately; however, their combined effect warrants further investigation.

Body index mass not associated with DRD4, DAT1, BDNF, and COMT gene polymorphisms in young adults without depression or anxiety disorders

Body index mass not associated with DRD4, DAT1, BDNF, and COMT gene polymorphisms in young adults without depression or anxiety disorders

Risk Polymorphisms of FNDC5, BDNF, and NTRK2 and Poor Education Interact and Aggravate Age-Related Cognitive Decline.

Cognitive abilities tend to decline with aging, with variation between individuals, and many studies seek to identify genetic biomarkers that more accurately anticipate risks related to pathological aging. We investigated the influence of BDNF, NTRK2, and FNDC5 single nucleotide polymorphisms (SNPs) on the cognitive performance of young and older adults with contrasting educational backgrounds. We addressed three questions: (1) Is education associated with reduced age-related cognitive decline? (2) Does the presence of SNPs explain the variation in cognitive performance observed late in life? (3) Is education differentially associated with cognition based on the presence of BDNF, NTRK2, or FNDC5 polymorphisms? We measured the cognitive functions of young and older participants, with lower and higher education, using specific and sensitive tests of the Cambridge Automated Neuropsychological Test Assessment Battery. A three-way ANOVA revealed that SNPs were associated with differential performances in executive functions, episodic memory, sustained attention, mental and motor response speed, and visual recognition memory and that higher educational levels improved the affected cognitive functions. The results revealed that distinct SNPs affect cognition late in life differentially, suggesting their utility as potential biomarkers and emphasizing the importance of cognitive stimulation that advanced education early in life provides.

DAT1 and BDNF polymorphisms interact to predict cross‐sectional and longitudinal amyloid and tau pathology in cognitively normal older adults

AbstractBackgroundDysfunctional dopamine signaling and disruptions in neurotrophic support are potential exacerbators of Alzheimer’s disease (AD) pathophysiology. A single nucleotide polymorphism (SNP) in the dopamine transporter gene (rs6347 in DAT1/SLC6A3) is associated with greater ventricular expansion and lower scores on the Mini Mental State Exam (MMSE; Roussotte et al., 2015). A polymorphism in the brain derived neurotrophic factor gene (Val66Met in BDNF) is related to greater hippocampal atrophy and more severe episodic memory decline for amyloid positive Met carriers (Lim et al., 2013). However, it is unclear whether and how these polymorphisms directly relate to AD pathology.MethodWe tested a moderated mediation model (Fig. 1) involving both BDNF and DAT1 polymorphisms in a sample of cognitively normal older adults (n = 321) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). This mediation involved DAT1 (independent variable), b‐amyloid (Ab; mediator), and tau pathology (dependent variable) with BDNF as a moderator. Ab and tau were measured both cross‐sectionally and longitudinally with positron emission tomography (PET) tracers [18F]Florbetapir/[18F]Florbetaben and [18F]Flortaucipir, respectively.ResultA significant moderated mediation demonstrated that DAT1 and BDNF interacted to predict cross‐sectional Ab‐PET (p = .02) and tau‐PET (p = .04), such that carriers of both DAT1 C and BDNF Met alleles demonstrated greater pathology (Fig. 2), consistent with previous research associating these variants with AD symptoms. Longitudinal analyses replicated these cross‐sectional results, with DAT1 C and BDNF Met carriers exhibiting greater accumulation of tau pathology (p = .0002) and marginally increased Ab accumulation (p = .07).ConclusionOur analyses revealed novel interaction effects between genetic polymorphisms in the DAT1 and BDNF genes. These results suggest that carrying DAT1 CC and BDNF Met results in higher Ab, which then contributes to higher tau pathology. While our analyses do not demonstrate causality, these findings are consistent with current hypotheses of AD in which Ab drives increases in tau pathology (Karran et al., 2011).

DAT1 and BDNF polymorphisms interact to predict cross‐sectional and longitudinal amyloid and tau pathology in cognitively normal older adults

AbstractBackgroundDysfunctional dopamine signaling and disruptions in neurotrophic support are potential exacerbators of Alzheimer’s disease (AD) pathophysiology. A single nucleotide polymorphism (SNP) in the dopamine transporter gene (rs6347 in DAT1/SLC6A3) is associated with greater ventricular expansion and lower scores on the Mini Mental State Exam (MMSE; Roussotte et al., 2015). A polymorphism in the brain derived neurotrophic factor gene (Val66Met in BDNF) is related to greater hippocampal atrophy and more severe episodic memory decline for amyloid positive Met carriers (Lim et al., 2013). However, it is unclear whether and how these polymorphisms directly relate to AD pathology.MethodWe tested a moderated mediation model (Fig. 1) involving both BDNF and DAT1 polymorphisms in a sample of cognitively normal older adults (n = 321) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). This mediation involved DAT1 (independent variable), b‐amyloid (Ab; mediator), and tau pathology (dependent variable) with BDNF as a moderator. Ab and tau were measured both cross‐sectionally and longitudinally with positron emission tomography (PET) tracers [18F]Florbetapir/[18F]Florbetaben and [18F]Flortaucipir, respectively.ResultA significant moderated mediation demonstrated that DAT1 and BDNF interacted to predict cross‐sectional Ab‐PET (p = .02) and tau‐PET (p = .04), such that carriers of both DAT1 C and BDNF Met alleles demonstrated greater pathology (Fig. 2), consistent with previous research associating these variants with AD symptoms. Longitudinal analyses replicated these cross‐sectional results, with DAT1 C and BDNF Met carriers exhibiting greater accumulation of tau pathology (p = .0002) and marginally increased Ab accumulation (p = .07).ConclusionOur analyses revealed novel interaction effects between genetic polymorphisms in the DAT1 and BDNF genes. These results suggest that carrying DAT1 CC and BDNF Met results in higher Ab, which then contributes to higher tau pathology. While our analyses do not demonstrate causality, these findings are consistent with current hypotheses of AD in which Ab drives increases in tau pathology (Karran et al., 2011).

OPRM1 and BDNF polymorphisms associated with a compensatory neurophysiologic signature in knee osteoarthritis patients

ObjectiveThe present study investigated the relationship between three genetic polymorphisms of OPRM1 (rs1799971 - A118G and rs1799972 - C17T) and BDNF (rs6265 - C196T) and EEG-measured brain oscillations in Knee Osteoarthritis (KOA) patients. Materials and MethodsWe performed a cross-sectional analysis of a cohort study (DEFINE cohort), KOA arm, with 66 patients, considering demographic (age, sex, and education), clinical (pain intensity and duration), OPRM1 (rs1799971 - A118G and rs1799972 - C17T) and BDNF (rs6265 - C196T) genotypes, and electrophysiological measures. Brain oscillations relative power from Delta, Theta, Alpha, Low Alpha, High Alpha, Beta, Low Beta and High Beta oscillations were measured during resting state EEG. Multivariate regression models were used to explore the main brain oscillation predictors of the three genetic polymorphisms. ResultsOur findings demonstrate that Theta and Low Beta oscillations are associated with the variant allele of OPRM1-rs1799971 (A118G) on left frontal and left central regions, respectively, while Alpha brain oscillation is associated with variant genotypes (CT/TT) of BDNF-rs6265 on frontal (decrease of oscillation power) and left central (increase of oscillation power) regions. No significant model was found for OPRM1-rs1799972 (C17T) in addition to the inclusion of pain intensity as a significant predictor of this last model. ConclusionOne potential interpretation for these findings is that polymorphisms of OPRM1 – that is involved with endogenous pain control - lead to increased compensatory oscillatory mechanisms, characterized by increased theta oscillations. Along the same line, polymorphisms of the BDNF lead to decreased alpha oscillations in the frontal area, likely also reflecting the disruption of resting states to also compensate for the increased injury associated with knee OA. It is possible that these polymorphisms require additional brain adaption to the knee OA related injury.

DAT1 and BDNF polymorphisms interact to predict Aβ and tau pathology

Previous work has associated polymorphisms in the dopamine transporter gene (rs6347 in DAT1/SLC6A3) and brain derived neurotrophic factor gene (Val66Met in BDNF) with atrophy and memory decline. However, it is unclear whether these polymorphisms relate to atrophy and cognition through associations with Alzheimer’s disease pathology. We tested for effects of DAT1 and BDNF polymorphisms on cross-sectional and longitudinal β-amyloid (Aβ) and tau pathology (measured with positron emission tomography (PET)), hippocampal volume, and cognition. We analyzed a sample of cognitively normal older adults (cross-sectional n = 321) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). DAT1 and BDNF interacted to predict Aβ-PET, tau-PET, and hippocampal atrophy. Carriers of both “non-optimal” DAT1 C and BDNF Met alleles demonstrated greater pathology and atrophy. Our findings provide novel links between dopamine and neurotrophic factor genes and AD pathology, consistent with previous research implicating these variants in greater risk for developing AD.

Interaction of Val66Met BDNF and 5-HTTLPR polymorphisms with prevalence of post-earthquake 27-F PTSD in Chilean population.

Post-traumatic stress (PTSD) disorder is a mental health condition that can occur after experiencing or witnessing a traumatic event. The 27-F earthquake that struck Chile in 2010 was one such event that had a significant impact on the mental health of the population. A study was conducted to investigate the prevalence of PTSD and its associated factors among survivors of this earthquake. The study was a longitudinal design, involving a sample of 913 patients aged 18 to 75 years who attended 10 Primary Care Centers in Concepción, Chile. The Composite International Diagnostic Interview (CIDI) was used to assess both depressive episodes (DE) and PTSD before and after the earthquake. The study also involved genotyping studies using saliva samples from the participants, specifically focusing on the Val66Met and 5-HTTLPR polymorphisms. Statistical analysis was performed to examine the association between different variables and the presence of PTSD. These variables included demographic factors, family history of psychiatric disorders, DE, childhood maltreatment experiences, and critical traumatic events related to the earthquake. The results showed that the incidence of post-earthquake PTSD was 11.06%. No significant differences were found between the groups of participants who developed post-earthquake PTSD regarding the Val66Met or 5-HTTLPR polymorphisms. However, a significant association was found between the concomitant diagnosis of DE and the development of post-earthquake PTSD. The presence of DE doubled the risk of developing post-earthquake PTSD. The number of traumatic events experienced also had a statistically significant association with an increased risk of developing post-earthquake PTSD. The study's limitations include the potential interference of different DE subtypes, the complexity of quantifying the degree of earthquake exposure experienced by each individual, and events entailing social disruption, such as looting, that can profoundly influence distress. In conclusion, the study found that PTSD following the 27-F earthquake in Chile was associated with a concomitant diagnosis of DE and the number of traumatic events experienced. The study did not find a significant association between PTSD and the Val66Met or 5-HTTLPR polymorphisms. The researchers recommend that mental health professionals should prioritize the detection and treatment of concomitant depressive episodes and exposure to critical traumatic events in survivors of disasters. They also suggest that further research is needed to better understand the relationship between genetic factors and post-disaster PTSD.

STUDY OF THE CONTRIBUTION OF GENES NERVOUS SYSTEM RELATED TO HEART FAILURE

Objective: Heart Failure (HF) is a complex syndrome that can be amplified by pathology associated with the nervous system. This study aims to investigate the contribution of genetic polymorphisms of Brain Derived Neurotrophic Factor (BDNF, rs6265), Neurotrophic Receptor Tyrosine Kinase 2 (NTRK2, rs2289656) and Neural Growth Factor (NGF, rs6330) genes in the development of HF. Design and method: A case-control study was conducted with a population of 261 individuals, of which 131 had HF (66 women and 65 men) with a median age of 77 years (Min = 31 years and Max = 96 years) and a BMI median of 25,00 Kg/m2 (Min = 17,80 Kg/m2 and Max = 47,30 Kg/m2), and 130 controls (113 women and 17 men) with a median of age 60,50 years (Min = 44 years and Max = 84 years) and a median BMI of 29,09 Kg/m2 (Min = 14,19 Kg/m2 and Max = 47,30 Kg/m2). Analyses of the 3 polymorphisms were performed using the Genotyping Endpoint PCR technique. Statistical analysis was performed using IBM software® SPSS® Statistics 28.0, with a statistical significance level set at p < 0,05. Results: For the rs2289656 polymorphism of the NTRK2 gene, the GG genotype was found to be a risk factor for HF [OR (CI, 95%) = 3.029 (1.053 – 8.718); p = 0.040]. The association between the presence of the A allele of the NTRK2 gene and HF [OR (CI, 95%) = 0.330 (0.115 – 0.950); p = 0.040] was also verified, with this allele constituting a protection factor. Regarding BDNF and NGF gene polymorphisms, no statistically significant differences were found. These results were adjusted for age, BMI and gender. Conclusions: These results show an association between the NTRK2 gene and HF, suggesting that this gene variation may enhance the development of HF. The identification of genetic polymorphisms that may somehow influence the development and severity of HF may allow its faster diagnosis and the application of methodologies for disease prevention. Moreover, our results will contribute to define a genomic profile associated with the role of the nervous system in HF.

Association Study of BDNF, SLC6A4, and FTO Genetic Variants with Schizophrenia Spectrum Disorders.

Schizophrenia spectrum disorders (patients with a diagnosis of schizophrenia, schizotypal, and delusional disorders: F20-F29 according to International Classification of Diseases 10th revision (ICD-10)) are considered highly heritable heterogeneous psychiatric conditions. Their pathophysiology is multifactorial with involved dysregulated serotonergic neurotransmission and synaptic plasticity. The present study aimed to evaluate the association of SLC6A4 (5-HTTLPR), FTO (rs9939609), and BDNF (rs6265, rs962369) polymorphisms with schizophrenia spectrum disorders in Slovak patients. We analyzed the genotypes of 150 patients with schizophrenia, schizotypal, and delusional disorders and compared them with genotypes from 178 healthy volunteers. We have found a marginally protective effect of LS + SS genotypes of 5-HTTLPR variant of the serotonin transporter SLC6A4 gene against the development of schizophrenia spectrum disorders, but the result failed to remain significant after Bonferroni correction. Similarly, we have not proven any significant association between other selected genetic variants and schizophrenia and related disorders. Studies including a higher number of subjects are warranted to reliably confirm the presence or absence of the studied associations.

The Impact of BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 Genetic Polymorphisms in Antidepressant Treatment Response Phenotypes

This study aimed to investigate the influence of genetic variants in neuroplasticity-related genes on antidepressant treatment phenotypes. The BDNF-TrkB signaling pathway, as well as the downstream kinases Akt and ERK and the mTOR pathway, have been implicated in depression and neuroplasticity. However, clinicians still struggle with the unpredictability of antidepressant responses in depressed patients. We genotyped 26 polymorphisms in BDNF, NTRK2, NGFR, CREB1, GSK3B, AKT, MAPK1, MTOR, PTEN, ARC, and SYN1 in 80 patients with major depressive disorder treated according to the Texas Medical Algorithm for 27 months at Hospital Magalhães Lemos, Porto, Portugal. Our results showed that BDNF rs6265, PTEN rs12569998, and SYN1 rs1142636 SNP were associated with treatment-resistant depression (TRD). Additionally, MAPK1 rs6928 and GSK3B rs6438552 gene polymorphisms were associated with relapse. Moreover, we found a link between the rs6928 MAPK1 polymorphism and time to relapse. These findings suggest that the BDNF, PTEN, and SYN1 genes may play a role in the development of TRD, while MAPK1 and GSK3B may be associated with relapse. GO analysis revealed enrichment in synaptic and trans-synaptic transmission pathways and glutamate receptor activity with TRD-associated genes. Genetic variants in these genes could potentially be incorporated into predictive models of antidepressant response.

The complex influence of the combination of the BDNF (rs6265), VDR (rs2228570), and NMDA (rs4880213) genotypes on the development of cognitive disorders in patients with autoimmune thyroiditis andhypothyroidism

Background. Numerous studies have demonstrated that thyroid conditions can affect cognitive function. Gene polymorphisms associated with pathology of the endocrine and nervous system have ethnic and population specificity, which determines the need to study them in a certain region. The purpose of the study was to investigate the combined impact of the BDNF (rs6265), VDR (rs2228570), and NMDA (rs4880213) gene polymorphisms on cognitive impairment in patients with autoimmune thyroiditis and hypothyroidism among the population of Western regions of Ukraine, and to predict the onset of cognitive disorders. Materials and methods. The study involved a total of 153 patients with autoimmune thyroiditis and hypothyroidism. Genotyping of the VDR (rs2228570), BDNF (rs6265), and NMDA (rs4880213) gene polymorphism using TaqMan probes and TaqMan Genotyping Master Mix (4371355) was performed on CFX96™ Real-Time PCR Detection System (Bio-Rad Laboratories, Inc., USA). Polymerase chain reaction for TaqMan genotyping was carried out according to the kit instructions (Applied Biosystems, USA). We detect a decline in cognitive function using the Mini-Mental State Examination. Results. Carrying a combination of CC/AG/CC genotypes significantly reduces the risk of developing cognitive impairment (odds ratio (OR)=0.1410; 95% confidence interval (CI) 0.0181–1.0965; p=0.0416). At the same time, carrying a combination of CT/AG/CT genotypes increases the risk of cognitive impairment by more than 5 times (OR=5.1915; 95% CI 1.2471–21.6107; p=0.0214) and a combination of CT/AG/TT genotypes — by 10 times (OR=10.1224; 95% CI 1.1037–92.8401; p=0.0281). Carriers of the CT/AA/CT genotype combination have a 6.4-fold increased risk of cognitive impairment (OR=6.4062; 95% CI 1.2019–34.1471; p=0.0253). Conclusions. Among patients with autoimmune thyroiditis and hypothyroidism, carriers of the CC/AG/CC genotype combination of the BDNF (rs6265), VDR (rs2228570) and NMDA (rs4880213) genes have a reduced risk of developing cognitive disorders, while carriers of the CT/AG/CT, CT/AG/TT and CT/AA/CT have an increased risk of cognitive impairment.

Association of HTTLPR, BDNF, and FTO Genetic Variants with Completed Suicide in Slovakia.

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. The aim of this case-control study was to evaluate the associations between completed suicide and polymorphisms in genes BDNF (rs6265, rs962369), SLC6A4 (5-HTTLPR), and FTO (rs9939609) in relation to sex and BMI. We genotyped 119 completed suicide victims and 137 control subjects that were age, sex, and ethnicity matched. A significant association with completed suicide was found for BDNF rs962369. This variant could play a role in completed suicide, as individuals with the CC genotype were more often found among suicides than in control subjects. After sex stratification, the association remained significant only in males. A nominally significant association between the gene variant and BMI was observed for BDNF rs962369 under the overdominant model. Heterozygotes with the TC genotype showed a lower average BMI than homozygotes with TT or CC genotypes. FTO polymorphism (rs9939609) did not affect BMI in the group of Slovak suicide completers, but our findings follow an inverse association between BMI and completed suicide.

The effect of brain-derived neurotrophic factor Val66Met polymorphism on adolescent activity and rest rhythms, circadian preferences and attentional performance

BackgroundVariations in circadian regulating mechanisms generate different individual preferences in respect of sleep and activity timing, which are known as chronotypes. In this sense, specifically during adolescence, there is a greater tendency for an eveningness chronotype. One factor that has been shown to have an impact on circadian rhythm patterns, as well as on some aspects of cognitive function, is the relatively common Val66Met (rs6265) polymorphism in the human brain-derived neurotrophic factor gene. ObjectiveThis study aimed to evaluate the effect of the BDNF Val66Met polymorphism on the performance of adolescents in attentional tests, circadian preferences and activity-rest rhythm. Methods85 healthy high school students completed the Morningness-Eveningness Questionnaire to assess their circadian preferences; were evaluated using the Psychological Battery for Attention Assessment; and were categorized as carriers and non-carriers of the rs6265 polymorphism using the TaqMan rt-PCR technique. A subsample of 42 students had their activity/rest rhythm recorded by actigraphy for nine days from which sleep parameters were estimated. ResultsCircadian preference did not affect attentional performance (p > 0.1), but the time that the students attended school had an impact on all types of attention with morning shift students scoring higher, regardless of chronotype (p < 0.05). The presence of the BDNF Val66Met polymorphism was associated only with alternate attention performance (p < 0.05). Regarding actigraphy evaluation, the carriers of the polymorphism demonstrated significantly higher total time in bed, total sleep time, social jetlag, and earlier sleep onset. ConclusionsThe results indicate some degree of adaptation in the students' attentional performance, according to their school schedules. The presence of BDNF polymorphism demonstrated a counterintuitive impact on attentional performance, comparing to previous findings. The findings reinforce the effect of genetic traits on sleep-wake rhythm parameters, when objectively evaluated.