Treatment-Resistant Depression, Hippocampus Atrophy and Serotonin Genetic Polymorphism
关键词
抽象
描述
Individuals who are defined as having treatment-resistant major depression (failure of at least 2 trials of an antidepressant at an adequate dose) and currently meet DSM-IV criteria for depression qualify for this study. At the initial visit, each subject is given an MRI in order to perform a volumetric analysis of their hippocampus and a blood sample is taken in order to determine their genotype for the 5-HT1a(serotonin) promoter. Each patient is then aggressively treated (open label) for depression with the goal of remission. A second MRI scan is completed 6 months after sustained remission or 12 months from baseline if remission is not met or sustained.
The investigators will select healthy volunteer controls with no personal or first relative history of depression and match with the subjects based on age and handedness. Genotyping and and MRI scan will be performed on the healthy subjects in order to compare all parameters.
Hypothesis: It is anticipated that the hippocampal volume will be smaller than those of matched controls. It is also anticipated that the Homozygous G(-1019) genotype will be more prevalent in the patient group than in the healthy subjects.
In addition, it is hypothesized that the investigators should find a small increase in hippocampal volume after long-term treatment. Also, most non-responders will be of homozygous G(-1019) 5-HT1a genotype and will have the greatest degree of hippocampal atrophy. Moreover, it is hypothesized that patients carrying a long allele of 5-HTTLPR polymorphism for 5-HTT might show a better response to antidepressants in general. Finally, it is anticipated that the TPH*A variant of the gene coding for tryptophan hydroxylase will be associated with poorer outcome.
日期
| 最后验证: | 01/31/2009 |
| 首次提交: | 06/17/2008 |
| 提交的预估入学人数: | 06/22/2008 |
| 首次发布: | 06/24/2008 |
| 上次提交的更新: | 01/17/2011 |
| 最近更新发布: | 01/18/2011 |
| 实际学习开始日期: | 01/31/2005 |
| 预计主要完成日期: | 10/31/2009 |
| 预计完成日期: | 11/30/2010 |
状况或疾病
干预/治疗
Other: TR
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: TR TR- Subjects defined as having treatment resistant depression, who have failed at least 2 adequate trials of an antidepressant. Subjects will be treated in an open label trial for their depression, with the goal of sustained remission. | Other: TR Dosage and drug types change based on patients need and response.
doxepin, clomipramine, amoxapine, amitriptyline, maprotiline, desipramine, nortriptyline, trimipramine, imipramine, protriptyline, isocarboxazid, phenelzine, tranylcypromine, moclobemide, fluvoxamine, paroxetine, fluoxetine, sertraline, citalopram, escitalopram, venlafaxine, atomoxetine, pramipexole, bromocriptine, quetiapine, clozapine, olanzapine, ziprasidone, aripiprazole, paliperidone, Risperidone, bupropion, mirtazapine, pindolol, topiramate, trazodone, Lithium, |
资格标准
| 有资格学习的年龄 | 18 Years 至 18 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria: - Male or female between ages of 18 to 65 years of age. - A diagnosis of Major Depression according to the DSM-IV criteria - Failing to achieve remission while receiving at least two different antidepressants at adequate dosage for at least 6 weeks. - Initial score of at least 18 on the HAMD-17 item rating scale Exclusion Criteria: - A diagnosis of substance abuse or dependence in the last 6 months or a lifetime diagnosis of substance abuse according to the DSM-IV criteria, elicited by inquiry. - A diagnosis of post-traumatic stress disorder, schizophrenia, schizo-affective disorder and other psychotic disorders, anorexia nervosa or a history of a manic or mixed episode - Major medical illnesses including endocrine and neurological disorders, as well as a history of significant head trauma - Exposure to oral or intravenous steroids - Contraindications to magnetic resonance imaging - An IQ less than 80 |
结果
主要结果指标
1. Sustained Remission from Depression and Hippocampal Atrophy [6 months]
次要成果指标
1. 5-HT1a Genetic Markers [Baseline Visit]
