TREATMENT OF AGGRESSION, ANGER & EMOTIONAL DYSREGULATION IN BPD

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 9/21/2007 这项拟议的研究将探索生物参数作为治疗反应的预测因素，并探索与12个月辩证行为疗法(DBT)治疗反应相关的这些指标的变化。辩证行为疗法是一种专门针对改善边缘性人格障碍(BPD)情绪调节障碍的治疗方法。评估将包括基线、6个月和12个月惊恐眨眼调制(SEM)以及基线和治疗后的功能磁共振成像，每一项都使用不愉快和中性的词语作为情绪探测器。扫描电子显微镜将提供一种客观的、非语言的情感加工测量方法，并将用于预测治疗反应和测量DBT治疗后的心理生理变化。功能磁共振成像将被用来检测治疗前对不愉快的词语或图片呈现的区域的大胆激活，并探索特定的激活模式是否预测治疗反应，以及临床反应是否与特定的激活模式相关。 具体目标：(礼宾，第2页) 1)在36例BPD(PI Hazlett资助的研究)和26例正常对照(NC)中，检测对阴性和中性BPD特定词语反应的扫描电子显微镜。 假设：与正常受试者相比，BPD受试者会表现出a)在不愉快的词语时惊吓反应幅度被夸大，b)在以后的探测位置对不愉快词语的惊吓反应的情感调节减少，c)对负面词语的习惯性降低。 2)在DBT治疗6个月和12个月后，对17个BPD中的负性和中性BPD特定词汇重复扫描结构评估。扫描电子显微镜的参数包括波幅、时程和习得率。 假设：通过6个月和12个月时间点Zan-BPD的变化来衡量BPD症状的改善将显著地与a)在不愉快的词期间夸张的惊吓反应幅度的减弱，b)在以后的探测位置对不愉快的词进行更大的情感调节c)在试验中增加负面情绪的习惯化。 3)检查PFC中基线fMRI大胆反应幅度、时间进程和习惯化的差异 和杏仁核到阴性和中性的BPD特异性词语来预测治疗反应，通过 将Zan-BPD改为12个月的DBT试验。 假设：以ZAN-BPD变化分数衡量的DBT治疗反应将与PFC的基线fMRI BOLD激活(不愉快-中性词汇条件)显着相关，而与杏仁核基线fMRI BOLD激活显着负相关。此外，DBT的治疗反应将与基线习惯性反应显著相关，杏仁核激活较少，随着时间的推移反复暴露于负面词汇中证明了这一点。 探索性假设： 4)于DBT后12个月对17个BPD患者进行fMRI检查，观察(治疗前)PFC和杏仁核对阴性和中性BPD特异性词语的fMRI大胆反应幅度、时程和习惯化程度的差异及其与治疗反应的相关性。结果将与16名正常对照组在基线和12个月时的fMRI结果进行比较。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 9/21/2007 The proposed study will explore biological parameters as predictors of treatment response and explore changes in these measures associated with treatment response to 12 months of dialectical behavioral therapy (DBT), a treatment approach specifically targeted for improvement of emotional dysregulation in Borderline Personality Disorder (BPD). Assessments will include baseline, six and twelve month startle eye blink modulation (SEM) and baseline and post-treatment fMRI, each employing unpleasant and neutral words as emotional probes. SEM will provide an objective, nonverbal measure of affective processing and will be used both to predict treatment response and measure psychophysiologic change after DBT treatment. fMRI will be employed to examine pretreatment regional BOLD activation to the presentation of unpleasant versus neutral words or pictures and explore whether specific patterns of activation predict treatment response and whether clinical response is associated with specific patterns of activation. Specific aims: (Protocol, p. 2) 1) To examine SEM in response to negative versus neutral BPD specific words in 36 BPD (ROI (PI Hazlett- funded study) and 26 normal controls (NC). Hypothesis: BPD subjects compared to NC will demonstrate an a) exaggerated startle response amplitude during unpleasant words, b) reduced affective modulation of the startle response to unpleasant words at later probe positions and c) reduced habituation to negative words. 2) To repeat the SEM assessment in response to negative and neutral BPD specific words in 17 BPD after six and twelve months of DBT. Parameters of SEM will include amplitude, time course, and habituation rate. Hypothesis: Improvement of BPD symptomatology as measured by changes in the ZAN-BPD at six and twelve month time points will significantly correlate with a) an attenuation of the exaggerated startle response amplitude during unpleasant words, b) greater affective modulation of unpleasant words at later probe positions c) increased habituation of negative emotion across trials. 3) To examine differences in baseline fMRI BOLD response magnitude, time course and habituation in PFC and amygdala to negative and neutral BPD-specific words to predict treatment response, as measured by changes in the ZAN-BPD, to a 12 month DBT trial. Hypothesis: DBT treatment response as measured by ZAN-BPD change scores will significantly correlate with baseline fMRI BOLD activation (unpleasant- neutral word conditions) in PFC and significantly inversely correlate with baseline fMRI BOLD activation in the amygdala. Additionally, DBT treatment response will significantly correlate with baseline habituation response as demonstrated by less amygdala activation with repeated exposure to negative words over time. Exploratory hypothesis: 4) To repeat fMRI after 12 months DBT in 17 BPD to examine differences (post-pre) fMRI BOLD response magnitude, time course and habituation in PFC and amygdala to negative and neutral BPD-specific words and correlate with treatment response. Results will be compared to fMRI findings in 16 normal controls at baseline and 12 months.