Neural Circuits in Women with Abuse and PTSD

遭受虐待和创伤后应激障碍 (PTSD) 的女性的神经回路

基本信息

批准号：
8080404
负责人：
James Douglas Bremner
金额：
$ 64.99万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1999
资助国家：
美国
起止时间：
1999-04-10 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8080404
关键词：
Affect African American Amygdaloid structure Animals Anterior Antidepressive Agents Area Brain Brain region Child Abuse Child Sexual Abuse Chronic Clinical Research Creatinine Data Development Disease Dose Double-Blind Method Extinction (Psychology)Failure Fright Funding Hippocampus (Brain)Magnetic Resonance Imaging Magnetic Resonance Spectroscopy Measurement Measures Medial Mediating Memory N-acetylaspartate Neurobiology Neuropsychological Tests Paroxetine Patients Pharmaceutical Preparations Pilot Projects Placebos Positron-Emission Tomography Post-Traumatic Stress Disorders Prefrontal Cortex Public Health Randomized Research Resolution Sampling Schedule Selective Serotonin Reuptake Inhibitor Specificity Stress Structure Symptoms Temporal Lobe Water Woman Workplace conditioned fear early childhood flexibility improved neural circuit neurogenesis open label pre-clinical research response treatment effect treatment response

项目摘要

DESCRIPTION (provided by applicant): Early childhood sexual abuse is an important public health problem that affects 16% of women before their 18th birthday and leads to chronic symptoms of posttraumatic stress disorder (PTSD) in as many as a third of women. Preclinical and clinical research has established a network of brain regions that are sensitive to stress and mediate PTSD symptoms, including decreased function in the hippocampus and anterior cingulate/medial prefrontal cortex, and increased function in the amygdala. During prior funding periods in women with early abuse related PTSD we have shown smaller hippocampal volume, a failure of hippocampal activation with declarative memory tasks, deficits in verbal declarative memory on neuropsychological testing, decreased anterior cingulate, medial prefrontal and hippocampal function, and increased amygdala function during fear acquisition, as well as smaller anterior cingulate volume. Little is known about the effects of treatment for PTSD on the brain. Such information may be useful in the development of better treatments for this disorder. Studies in animals have shown that treatment with antidepressants, including selective serotonin reuptake inhibitors (SSRI), promote neurogenesis in the hippocampus, which may even represent the mechanism of treatment response for these medications. Our pilot data has shown a 5% increase in hippocampal volume and improvements in neuropsychological testing of memory in patients with PTSD treated with paroxetine, as well as increases in medial temporal NAA. The current project assesses the effects of paroxetine on memory, brain structure and function in women with early childhood abuse related PTSD. Women with PTSD undergo baseline assessment with neuropsychological testing of memory, magnetic resonance imaging (MRI) for assessment of hippocampal volume and NAA, and high resolution positron emission tomography (PET) with PET O-15 water during verbal declarative memory and traumatic memory tasks. Women are then treated in a randomized double- blind fashion with paroxetine or placebo on a flexible dose schedule for three months, followed by a repeat of these assessments. All subjects then receive open label paroxetine for nine months followed by a repeat of all assessments. We hypothesize that paroxetine will result in an improvement in memory function, increased hippocampal volume and NAA, and increased frontal and hippocampal function

描述（由申请人提供）：幼儿期性虐待是一个重要的公共卫生问题，在18岁生日之前会影响16％的妇女，并导致多达三分之一的女性的慢性后应激障碍（PTSD）慢性症状。临床前和临床研究已经建立了一个对压力和介导PTSD症状敏感的大脑区域网络，包括海马的功能降低和前扣带回/内侧前额叶皮层以及杏仁核的功能增加。 During prior funding periods in women with early abuse related PTSD we have shown smaller hippocampal volume, a failure of hippocampal activation with declarative memory tasks, deficits in verbal declarative memory on neuropsychological testing, decreased anterior cingulate, medial prefrontal and hippocampal function, and increased amygdala function during fear acquisition, as well as smaller anterior cingulate volume.关于PTSD治疗对大脑的影响知之甚少。此类信息可能在开发该疾病的更好治疗方法上很有用。在动物中的研究表明，抗抑郁药的治疗，包括选择性5-羟色胺再摄取抑制剂（SSRI），促进海马中的神经发生，这甚至可能代表了这些药物治疗反应的机制。我们的试点数据显示，海马体积增加了5％，并改善了用帕罗西汀治疗的PTSD患者的记忆力测试，并增加了内侧颞NAA。当前的项目评估了帕罗西汀对与儿童早期虐待与PTSD相关的幼年女性的记忆，大脑结构和功能的影响。具有PTSD的妇女接受了基线评估，对记忆的神经心理学测试，用于评估海马体积和NAA的磁共振成像（MRI），以及在言语声明记忆和创伤性记忆任务期间用PET O-15水评估的高分辨率正电子发射断层扫描（PET）。然后，以柔性剂量时间表以帕罗西汀或安慰剂为例，以随机的双盲方式治疗女性三个月，然后重复这些评估。然后，所有受试者都会收到九个月的开放标签帕罗西汀，然后重复所有评估。我们假设Paroxetine将改善记忆功能，海马体积和NAA增加，以及额叶和海马功能的增加

项目成果

期刊论文数量（85）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Script-driven imagery of self-injurious behavior in patients with borderline personality disorder: a pilot FMRI study.

DOI：
10.1111/j.1600-0447.2009.01417.x
发表时间：
2010-01
期刊：
Acta psychiatrica Scandinavica
影响因子：
6.7
作者：
Kraus A;Valerius G;Seifritz E;Ruf M;Bremner JD;Bohus M;Schmahl C
通讯作者：
Schmahl C

Heritability of flow-mediated dilation: a twin study.

血流介导的扩张的遗传性：一项双胞胎研究。

DOI：
10.1111/j.1538-7836.2007.02760.x
发表时间：
2007
期刊：
Journal of thrombosis and haemostasis : JTH
影响因子：
0
作者：
Zhao,J;Cheema,FA;Reddy,U;Bremner,JD;Su,S;Goldberg,J;Snieder,H;Vaccarino,V
通讯作者：
Vaccarino,V

Common genes contribute to depressive symptoms and heart rate variability: the Twins Heart Study.

DOI：
10.1375/twin.13.1.1
发表时间：
2010-02
期刊：
Twin research and human genetics : the official journal of the International Society for Twin Studies
影响因子：
0
作者：
Su S;Lampert R;Lee F;Bremner JD;Snieder H;Jones L;Murrah NV;Goldberg J;Vaccarino V
通讯作者：
Vaccarino V

The impact of the 1991 Gulf War on the mind and brain: findings from neuropsychological and neuroimaging research.

1991 年海湾战争对思想和大脑的影响：神经心理学和神经影像学研究的发现。

DOI：
10.1098/rstb.2006.1819
发表时间：
2006
期刊：
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
影响因子：
0
作者：
Vasterling,JenniferJ;Bremner,JDouglas
通讯作者：
Bremner,JDouglas

Behavioral therapy, sertraline, or both in childhood anxiety.