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.
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