Genetic Predictors of Lithium Response in Bipolar Disorder
双相情感障碍锂反应的遗传预测因素
基本信息
- 批准号:8586871
- 负责人:
- 金额:--
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-10-01 至 2015-09-30
- 项目状态:已结题
- 来源:
- 关键词:AdoptedAffectBipolar DisorderCandidate Disease GeneClinical TrialsCodeCommunitiesDNADataDisease PathwayDouble-Blind MethodDrug TargetingFamily history ofFundingGenesGeneticGenetic VariationGenotypeGoalsGoldIndividualIraqLeadLithiumMaintenanceManicMeasuresMental DepressionMental disordersMoodsNTRK2 geneNeurotrophic Tyrosine Kinase Receptor Type 2Outcome MeasurePatientsPharmaceutical PreparationsPharmacogeneticsPhasePhenotypeProcessProtocols documentationPsychiatryRandomizedRecruitment ActivityRelapseSamplingSeriesStagingTestingTherapeuticTimeVeteransabstractingbasecombatdesigndisorder later incidence preventionnovelphosphodiesterase 11aprimary outcomeprospectivepublic health relevanceresponsestandard care
项目摘要
DESCRIPTION (provided by applicant):
Project Abstract Bipolar Disorder is a major psychiatric disorder characterized by alternation between the extreme mood states of mania and depression. Many efficacious treatments exist; however, there is a high degree of variability in individual response. This frequently results in a lengthy trial and error process of treatment optimization which may take years. Lithium was the first mood stabilizing medication and is still the gold standard for treatment. Existing data suggests that lithium responsive bipolar disorder may be a distinct form of illness. There is a subset of patients who have a remarkably good response to lithium. These patients tend to have a family history of bipolar disorder and present with euphoric rather than irritable mania. Lithium response has also been shown to be familial. The goal of this project has been the identification of genes associated with response to lithium in bipolar disorder. In the last funding period, we studied a series of candidate genes in our retrospectively assessed sample of 184 patients. These studies found evidence for two genes predicting response to lithium. NTRK2 codes for the trkb receptor which is the receptor for BDNF also implicated in bipolar disorder. We found SNPs in the NTRK2 gene that were associated with response to lithium in those with euphoric mania but not associated in those with irritable mania. Conversely, the gene for the phosphodiesterase PDE11A was associated with response for all forms of mania. These data support the idea that lithium responsive bipolar disorder is genetically distinct. Retrospective data has numerous limitations. For this reason, we have also conducted a prospective clinical trial of lithium in bipolar disorder. Patients with bipolar disorder are first stabilized on lithium monotherapy over a three month period and then entered into the maintenance phase of the study. Patients are then followed for 2 years in order to detect relapse into mania or depression. SNPs are tested for association to response measured as time to relapse using a survival curve analysis. 75 subjects have entered the protocol to date. In this renewal, we propose to: 1) expand the retrospective sample to 500 subjects; 2) genotype the retrospective sample at an additional 50 genes; 3) recruit an additional 125 subjects into the prospective sample for a total of 200 and 4) replicate the most significant SNPs from the retrospective sample in the prospective sample.
PUBLIC HEALTH RELEVANCE:
Project Narrative: Bipolar disorder is a common psychiatric disorder characterized by alternation between the extreme mood states of mania and depression. Though it affects 1 - 3% of veterans overall, the rate may be several fold higher for combat exposed veterans returning from Iraq. Several good treatments exist, but there is a high variability in response to different medications in that treatment is often a lengthy trial and error process. The goal of this study is to identify genetic variation that is associated with a good therapeutic response to lithium in bipolar disorder. The results of this study could be used to develop a DNA based predictor of response to different medications. This could aid clinicians in the selection of medications and lead to faster stabilization and reduced suffering of veterans.
描述(由申请人提供):
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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John R. Kelsoe其他文献
92. Synaptic Protein Expression in Bipolar Disorder Patient-Derived Glutamatergic Neurons Implicates PSD-95 as a Marker of Lithium Response
双相情感障碍患者来源的谷氨酸能神经元中的突触蛋白表达表明PSD - 95可作为锂反应的标志物
- DOI:
10.1016/j.biopsych.2025.02.329 - 发表时间:
2025-05-01 - 期刊:
- 影响因子:9.000
- 作者:
Johansen Amin;Kayla E. Rohr;Himanshu K. Mishra;Timothy Nakhla;John R. Kelsoe;Michael J. McCarthy - 通讯作者:
Michael J. McCarthy
Circadian Rhythms in Bipolar Disorder Patient-Derived Neurons Predict Lithium Response
- DOI:
10.1016/j.biopsych.2021.02.193 - 发表时间:
2021-05-01 - 期刊:
- 影响因子:
- 作者:
Himanshu Mishra;Noelle Ying;Angelica Luis;Heather Wei;Metta Nguyen;Timothy Nakhla;John R. Kelsoe;David Welsh;Michael McCarthy - 通讯作者:
Michael McCarthy
Lithium-Responsiveness in Bipolar Depression Patients Attenuates Circadian Rhythm Disturbances
- DOI:
10.1016/j.biopsych.2021.02.834 - 发表时间:
2021-05-01 - 期刊:
- 影响因子:
- 作者:
Monica Federoff;Mike McCarthy;John R. Kelsoe - 通讯作者:
John R. Kelsoe
A gene for impulsivity
一个冲动的基因
- DOI:
10.1038/4681049a - 发表时间:
2010-12-22 - 期刊:
- 影响因子:48.500
- 作者:
John R. Kelsoe - 通讯作者:
John R. Kelsoe
Synaptotagmin-7 is a key factor for bipolar-like behavioral abnormalities in mice
- DOI:
doi: 10.1073/pnas.1918165117. - 发表时间:
2020 - 期刊:
- 影响因子:
- 作者:
Wei Shen;Qiu-Wen Wang;Yao-Nan Liu;Maria C. Marchetto;Sara Linker;Si-Yao Lu;Yun Chen;Chuihong Liu;Chongye Guo;Zhikai Xing;Wei Shi;John R. Kelsoe;Martin Alda;Hongwei Wang;Yi Zhong;Sen-Fang Sui;Mei Zhao;Yiming Yang;Shuangli Mi;Liping Cao;Fred H. Gage;Jun Yao - 通讯作者:
Jun Yao
John R. Kelsoe的其他文献
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{{ truncateString('John R. Kelsoe', 18)}}的其他基金
Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder
双相情感障碍情绪稳定剂反应的药物基因组学
- 批准号:
8509307 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Genetic Predictors of Lithium Response in Bipolar Disorder
双相情感障碍锂反应的遗传预测因素
- 批准号:
8196309 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder
双相情感障碍情绪稳定剂反应的药物基因组学
- 批准号:
8492162 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder
双相情感障碍情绪稳定剂反应的药物基因组学
- 批准号:
8307029 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder
双相情感障碍情绪稳定剂反应的药物基因组学
- 批准号:
8695486 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Genetic Predictors of Lithium Response in Bipolar Disorder
双相情感障碍锂反应的遗传预测因素
- 批准号:
8391087 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder
双相情感障碍情绪稳定剂反应的药物基因组学
- 批准号:
7867605 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Pharmacogenomics of Mood Stabilizer Response in Bipolar Disorder
双相情感障碍情绪稳定剂反应的药物基因组学
- 批准号:
8139260 - 财政年份:2010
- 资助金额:
-- - 项目类别:
Genetic Predictors of Lithium Response in Bipolar Disorder
双相情感障碍锂反应的遗传预测因素
- 批准号:
7931543 - 财政年份:2010
- 资助金额:
-- - 项目类别:
ROLE OF DOPAMINE METABOLISM IN ANTIDEPRESSANT EFFECT OF SLEEP DEPRIVATION
多巴胺代谢在睡眠剥夺的抗抑郁作用中的作用
- 批准号:
7724899 - 财政年份:2007
- 资助金额:
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