The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Clement C Zai - One of the best experts on this subject based on the ideXlab platform.
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neurostructural correlates of bdnf Rs6265 genotype in youth bipolar disorder
Bipolar Disorders, 2021Co-Authors: Kody G Kennedy, Zaid Shahatit, Mikaela K Dimick, Lisa Fiksenbaum, Natalie Freeman, Clement C ZaiAbstract:Objective Brain-derived neurotrophic factor (BDNF) Rs6265 single-nucleotide polymorphism has been associated with bipolar disorder (BD), and with brain structure among adults with BD. We set out to investigate the association of the BDNF Rs6265 Met allele with neurostructural phenotypes in youth BD. Methods Caucasian youth (N = 99; 13-20 years; n = 56 BD, n = 43 age and sex-matched healthy controls) underwent 3-Tesla Magnetic Resonance Imaging and genotyping for BDNF Rs6265. Region of interest (ROI) analyses of the ventromedial prefrontal cortex (vmPFC), anterior cingulate cortex (ACC), and hippocampus were complemented by vertex-wise analyses examining cortical thickness, surface area (SA) and volume. Multivariable models included the main effects of diagnosis and gene, and a diagnosis-by-genotype interaction term, controlling for age, sex, and intracranial volume. Results There were no significant gene main effects or diagnosis-by-gene interaction effects in ROI analyses. The vertex-wise analysis yielded a significant gene main effect whereby Met allele carriers had greater middle temporal gyrus SA (p = 0.001) and supramarginal gyrus volume (p = 0.03) than Val/Val individuals. Significant interaction effects were found on lateral occipital lobe SA (p = 0.03), whereby the Met allele was associated with increased SA in BD only. Interaction effects were also found on postcentral gyrus SA (p = 0.049) and supramarginal gyrus SA (p = 0.04), with smaller SA in BD Met carriers versus healthy control Met carriers. Conclusion These findings suggest that BDNF Rs6265 is differentially associated with regional SA in youth BD. Further investigation is warranted to evaluate whether BDNF protein levels mediate the observed effects, and to evaluate Rs6265-related developmental changes.
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an examination of genes stress and suicidal behavior in two first nations communities the role of the brain derived neurotropic factor gene
Psychiatry Research-neuroimaging, 2019Co-Authors: Clement C Zai, Julie George, Sheraz Y Cheema, Gwyneth Zai, Trehani M Fonseka, Michael Danesi, Sajid A Shaikh, David IrwinAbstract:Abstract Suicide claims over 800,000 lives each year worldwide. Suicide rates in indigenous populations in Canada are about double that of the national average, making it a serious public health issue. Numerous factors are involved in suicide risk, including genetic factors, as well as various psychosocial stressors, such as historical experience with the Indian Residential School system for Indigenous populations, as well as protective variables such as social support. Here, we report the first genetic study of suicidal behaviors that includes multiple measures of stress and social supports. We investigated the role of the functional Val66Met marker (Rs6265) in the Brain-Derived Neurotropic Factor (BDNF) gene in suicidal ideation and suicide attempt in a First Nations community sample (N = 278). We did not find a significant association between the BDNF Rs6265 marker and suicidal behaviors. We found childhood adversities, recent life stress, chronic stress, perceived stress, difficulties, and hazardous alcohol use to be associated with both suicidal ideation and suicide attempt. Thus, while additional studies with larger samples are required to elucidate the genetic component of suicide, addressing environmental stressors may be important for suicide prevention.
David Irwin - One of the best experts on this subject based on the ideXlab platform.
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an examination of genes stress and suicidal behavior in two first nations communities the role of the brain derived neurotropic factor gene
Psychiatry Research-neuroimaging, 2019Co-Authors: Clement C Zai, Julie George, Sheraz Y Cheema, Gwyneth Zai, Trehani M Fonseka, Michael Danesi, Sajid A Shaikh, David IrwinAbstract:Abstract Suicide claims over 800,000 lives each year worldwide. Suicide rates in indigenous populations in Canada are about double that of the national average, making it a serious public health issue. Numerous factors are involved in suicide risk, including genetic factors, as well as various psychosocial stressors, such as historical experience with the Indian Residential School system for Indigenous populations, as well as protective variables such as social support. Here, we report the first genetic study of suicidal behaviors that includes multiple measures of stress and social supports. We investigated the role of the functional Val66Met marker (Rs6265) in the Brain-Derived Neurotropic Factor (BDNF) gene in suicidal ideation and suicide attempt in a First Nations community sample (N = 278). We did not find a significant association between the BDNF Rs6265 marker and suicidal behaviors. We found childhood adversities, recent life stress, chronic stress, perceived stress, difficulties, and hazardous alcohol use to be associated with both suicidal ideation and suicide attempt. Thus, while additional studies with larger samples are required to elucidate the genetic component of suicide, addressing environmental stressors may be important for suicide prevention.
Gwyneth Zai - One of the best experts on this subject based on the ideXlab platform.
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an examination of genes stress and suicidal behavior in two first nations communities the role of the brain derived neurotropic factor gene
Psychiatry Research-neuroimaging, 2019Co-Authors: Clement C Zai, Julie George, Sheraz Y Cheema, Gwyneth Zai, Trehani M Fonseka, Michael Danesi, Sajid A Shaikh, David IrwinAbstract:Abstract Suicide claims over 800,000 lives each year worldwide. Suicide rates in indigenous populations in Canada are about double that of the national average, making it a serious public health issue. Numerous factors are involved in suicide risk, including genetic factors, as well as various psychosocial stressors, such as historical experience with the Indian Residential School system for Indigenous populations, as well as protective variables such as social support. Here, we report the first genetic study of suicidal behaviors that includes multiple measures of stress and social supports. We investigated the role of the functional Val66Met marker (Rs6265) in the Brain-Derived Neurotropic Factor (BDNF) gene in suicidal ideation and suicide attempt in a First Nations community sample (N = 278). We did not find a significant association between the BDNF Rs6265 marker and suicidal behaviors. We found childhood adversities, recent life stress, chronic stress, perceived stress, difficulties, and hazardous alcohol use to be associated with both suicidal ideation and suicide attempt. Thus, while additional studies with larger samples are required to elucidate the genetic component of suicide, addressing environmental stressors may be important for suicide prevention.
Trehani M Fonseka - One of the best experts on this subject based on the ideXlab platform.
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an examination of genes stress and suicidal behavior in two first nations communities the role of the brain derived neurotropic factor gene
Psychiatry Research-neuroimaging, 2019Co-Authors: Clement C Zai, Julie George, Sheraz Y Cheema, Gwyneth Zai, Trehani M Fonseka, Michael Danesi, Sajid A Shaikh, David IrwinAbstract:Abstract Suicide claims over 800,000 lives each year worldwide. Suicide rates in indigenous populations in Canada are about double that of the national average, making it a serious public health issue. Numerous factors are involved in suicide risk, including genetic factors, as well as various psychosocial stressors, such as historical experience with the Indian Residential School system for Indigenous populations, as well as protective variables such as social support. Here, we report the first genetic study of suicidal behaviors that includes multiple measures of stress and social supports. We investigated the role of the functional Val66Met marker (Rs6265) in the Brain-Derived Neurotropic Factor (BDNF) gene in suicidal ideation and suicide attempt in a First Nations community sample (N = 278). We did not find a significant association between the BDNF Rs6265 marker and suicidal behaviors. We found childhood adversities, recent life stress, chronic stress, perceived stress, difficulties, and hazardous alcohol use to be associated with both suicidal ideation and suicide attempt. Thus, while additional studies with larger samples are required to elucidate the genetic component of suicide, addressing environmental stressors may be important for suicide prevention.
Caryl E Sortwell - One of the best experts on this subject based on the ideXlab platform.
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bdnf Rs6265 genotype influences outcomes of pharmacotherapy and subthalamic nucleus deep brain stimulation in early stage parkinson s disease
Neuromodulation, 2021Co-Authors: Caryl E Sortwell, Mallory L Hacker, David Luke Fischer, Peter E Konrad, Thomas L Davis, Joseph S Neimat, Lily Wang, Yanna Song, Zach R MattinglyAbstract:Introduction The efficacy of pharmacotherapy and deep brain stimulation of the subthalamic nucleus in treating Parkinson's disease motor symptoms is highly variable and may be influenced by patient genotype. The relatively common (prevalence about one in three) and protein-altering Rs6265 single nucleotide polymorphism (C > T) in the gene BDNF has been associated with different clinical outcomes with levodopa. Objective We sought to replicate this reported association in early-stage Parkinson's disease subjects and to examine whether a difference in clinical outcomes was present with subthalamic nucleus deep brain stimulation. Materials and methods Fifteen deep brain stimulation and 13 medical therapy subjects were followed for 24 months as part of the Vanderbilt DBS in Early Stage PD clinical trial (NCT00282152, FDA IDE #G050016). Primary outcome measures were the Unified Parkinson's Disease Rating Scale (UPDRS) and Parkinson's Disease Questionnaire-39. Results Outcomes with drug therapy in subjects carrying the Rs6265 T allele were significantly worse following 12 months of treatment compared to C/C subjects (UPDRS: +20 points, p = 0.019; PDQ-39: +16 points, p = 0.018). In contrast, Rs6265 genotype had no effect on overall motor response to subthalamic nucleus deep brain stimulation at any time point; further, Rs6265 C/C subjects treated with stimulation were associated with worse UPDRS part II scores at 24 months compared to medical therapy. Conclusions Genotyping for the Rs6265 polymorphism may be useful for predicting long-term response to drug therapy and counseling Parkinson's disease patients regarding whether to consider earlier subthalamic nucleus deep brain stimulation. Validation in a larger cohort of early-stage Parkinson's disease subjects is warranted.
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the bdnf val66met polymorphism Rs6265 enhances dopamine neuron graft efficacy and side effect liability in Rs6265 knock in rats
Neurobiology of Disease, 2021Co-Authors: Natosha M Mercado, Jennifer A Stancati, Caryl E Sortwell, Rebecca L Mueller, Samuel A Boezwinkle, Megan F Duffy, Luke D Fischer, Ivette M SandovalAbstract:Abstract Prevalent in approximately 20% of the worldwide human population, the Rs6265 (also called ‘Val66Met’) single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor (BDNF) is a common genetic variant that can alter therapeutic responses in individuals with Parkinson’s disease (PD). Possession of the variant Met allele results in decreased activity-dependent release of BDNF. Given the resurgent worldwide interest in neural transplantation for PD and the biological relevance of BDNF, the current studies examined the effects of the Rs6265 SNP on therapeutic efficacy and side-effect development following primary dopamine (DA) neuron transplantation. Considering the significant reduction in BDNF release associated with Rs6265, we hypothesized that Rs6265-mediated dysfunctional BDNF signaling contributes to the limited clinical benefit observed in a subpopulation of PD patients despite robust survival of grafted DA neurons, and further, that this mutation contributes to the development of aberrant graft-induced dyskinesias (GID). To this end, we generated a CRISPR knock-in rat model of the Rs6265 BDNF SNP to examine for the first time the influence of a common genetic polymorphism on graft survival, functional efficacy, and side-effect liability, comparing these parameters between wild-type (Val/Val) rats and those homozygous for the variant Met allele (Met/Met). Counter to our hypothesis, the current research indicates that Met/Met rats show enhanced graft-associated therapeutic efficacy and a paradoxical enhancement of graft-derived neurite outgrowth compared to wild-type rats. However, consistent with our hypothesis, we demonstrate that the Rs6265 genotype in the host rat is strongly linked to development of GID, and that this behavioral phenotype is significantly correlated with neurochemical signatures of atypical glutamatergic neurotransmission by grafted DA neurons.
