TREATMENT OF AGGRESSION, ANGER & EMOTIONAL DYSREGULATION IN BPD

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者的研究机构。 9/21/2007 这项拟议的研究将探讨生物学参数作为治疗反应的预测因子，并探讨这些指标与12个月辩证行为疗法（DBT）治疗反应相关的变化，DBT是一种专门针对改善边缘型人格障碍（BPD）情绪失调的治疗方法。 评估将包括基线、6个月和12个月的惊吓眨眼调制（SEM）以及基线和治疗后的功能磁共振成像（fMRI），每种评估都采用不愉快和中性的词语作为情绪探针。 SEM将提供情感处理的客观、非语言测量，并将用于预测治疗反应和测量DBT治疗后的心理生理变化。fMRI将被用来检查预处理区域BOLD激活的不愉快与中性的话或图片的介绍，并探讨是否特定模式的激活预测治疗反应和临床反应是否与特定模式的激活。 具体目标：（议定书，第2页） 第一章 在36名BPD（ROI）（PI Hazlett资助的研究）和26名正常对照（NC）中检查SEM对阴性与中性BPD特定词汇的反应。 假设：与NC相比，BPD受试者将表现出a）在不愉快的词语期间夸大的惊吓反应幅度，B）在稍后的探测位置处对不愉快的词语的惊吓反应的情感调节降低，以及c）对负面词语的习惯化降低。 （二） 在DBT治疗6个月和12个月后，对17例BPD患者的阴性和中性BPD特定词汇进行重复SEM评估。SEM的参数将包括振幅、时程和习惯化速率。 假设：通过在6个月和12个月时间点的ZAN-BPD的变化测量的BPD行为学的改善将与a）在不愉快的词语期间夸大的惊吓反应幅度的衰减，B）在稍后的探测位置处不愉快的词语的更大的情感调节，c）在试验中增加的负面情绪习惯化显著相关。 第三章 检查PFC中基线fMRI BOLD反应幅度、时程和习惯化的差异 和杏仁核对阴性和中性BPD特异性词语的反应，以预测治疗反应， ZAN-BPD的变化，到12个月的DBT试验。 假设：通过ZAN-BPD变化评分测量的DBT治疗反应将与PFC中的基线fMRI BOLD激活（不愉快-中性词条件）显著相关，并与杏仁核中的基线fMRI BOLD激活显著负相关。 此外，DBT治疗反应将与基线习惯化反应显著相关，如随着时间的推移反复暴露于负面词语的杏仁核激活减少所证明的。 探索性假设： 四、 在17例BPD患者接受12个月DBT后重复fMRI，以检查PFC和杏仁核对阴性和中性BPD特异性词语的fMRI BOLD反应幅度、时程和习惯化的差异，并与治疗反应相关。 结果将与fMRI结果进行比较， 基线和12个月时有16名正常对照。

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.