Janice R. Kuo

Neural Mechanisms Underlying 5-HTTLPR-Related Sensitivity to Acute Stress

OBJECTIVE Many studies have shown that 5-HTTLPR genotype interacts with exposure to stress in conferring risk for psychopathology. However, the specific neural mechanisms through which this gene-by-environment interaction confers risk remain largely unknown, and no study to date has directly examined the modulatory effects of 5-HTTLPR on corticolimbic circuit responses during exposure to acute stress. METHOD An acute laboratory stressor was administered to 51 healthy women during blood-oxygen-level-dependent functional magnetic resonance imaging. In this task, participants were threatened with electric shocks of uncertain intensity, which were unpredictably delivered to the wrist after a long anticipatory cue period of unpredictable duration. RESULTS Relative to women carrying the L allele, those with the SS genotype showed enhanced activation during threat anticipation in a network of regions, including the amygdala, hippocampus, anterior insula, thalamus, pulvinar, caudate, precuneus, anterior cingulate cortex, and medial prefrontal cortex. Individuals with the SS genotype also displayed enhanced positive coupling between medial prefrontal cortex activation and anxiety experience, whereas enhanced negative coupling between insula activation and perceived success at regulating anxiety was observed in individuals carrying the L allele. CONCLUSIONS These findings suggest that during stress exposure, neural systems that enhance fear and arousal, modulate attention toward threat, and perseverate on emotional salience of the threat may be engaged preferentially in individuals with the SS genotype. This may be one mechanism underlying the risk for psychopathology conferred by the S allele upon exposure to life stressors.

Amygdala Volume in Combat-Exposed Veterans With and Without Posttraumatic Stress Disorder: A Cross-sectional Study

CONTEXT Data from animal models demonstrate a link between stress exposure and hypertrophic changes in the amygdala; however, studies of adults with posttraumatic stress disorder (PTSD) have failed to find analogous structural alterations. OBJECTIVES To compare amygdala volumes between a sample of combat veterans with and without PTSD (analysis 1) and examine whether our observation of larger amygdala volume in individuals with PTSD could be accounted for by the presence of trauma exposure in childhood and the severity of combat exposure in adulthood (analysis 2). DESIGN Cross-sectional magnetic resonance imaging. SETTING Veterans Affairs Palo Alto Health Care System Inpatient Trauma Recovery Program and Veterans Affairs New England Health Care System Outpatient PTSD program. PARTICIPANTS Ninety-nine combat-exposed veterans from the Vietnam Conflict or the Persian Gulf War who had been exposed to substantial military operational stress. MAIN OUTCOME MEASURES Amygdala volume adjusted for total cerebral volume, Life Events Checklist, and the Combat Exposure Scale. RESULTS Analysis 1 indicated that combat-exposed individuals with PTSD exhibited larger total amygdala volume compared with their non-PTSD counterparts (99 individuals, P = .047). Analysis 2 indicated that greater severity of combat exposure (87 individuals, P = .02), as well as the interaction between the presence of early life trauma and the severity of combat exposure (87 individuals, P = .008), were significantly associated with smaller total amygdala volume. The PTSD diagnosis continued to explain larger amygdala volume (87 individuals, P = .006). CONCLUSIONS Posttraumatic stress disorder is associated with enlarged amygdala volume, above the variance accounted for by a history of early life trauma and severity of adult trauma exposure. The discrepancy between our and prior findings may be explained by variability in these trauma indices in previous investigations. These findings support additional study of amygdala structure in human stress disorders and further delineation of the role of early and adult trauma on associated neurologic changes.

An examination of the relationship between childhood emotional abuse and borderline personality disorder features: The role of difficulties with emotion regulation

Childhood abuse has been consistently linked with borderline personality disorder (BPD) and recent studies suggest that some forms of childhood abuse might be uniquely related to both BPD and BPD features. In addition, difficulties with emotion regulation have been found to be associated with childhood abuse, BPD, as well as BPD features. The present study examined (1) whether frequency of childhood emotional abuse is uniquely associated with BPD feature severity when controlling for other forms of childhood abuse and (2) whether difficulties with emotion regulation accounts for the relationship between childhood emotional abuse and BPD feature severity. A sample of undergraduates (n=243) completed the Childhood Trauma Questionnaire - Short Form, Difficulties in Emotion Regulation Scale, and Borderline Symptom List-23. Multiple regression analyses and Structural Equation Modeling were conducted. Results indicated that frequency of childhood emotional abuse (and not sexual or physical abuse) was uniquely associated with BPD feature severity. In addition, while there was no direct path between childhood emotional abuse, childhood physical abuse, or childhood sexual abuse and BPD features, there was an indirect relationship between childhood emotional abuse and BPD features through difficulties with emotion regulation. These findings suggest that, of the different forms of childhood abuse, emotional abuse specifically, may have a developmental role in BPD pathology. Prevention and treatment of BPD pathology might benefit from the provision of emotion regulation strategies.

A multi-method laboratory investigation of emotional reactivity and emotion regulation abilities in borderline personality disorder.

BACKGROUND AND OBJECTIVES Borderline personality disorder (BPD) is conceptualized as a disorder of heightened emotional reactivity and difficulties with emotion regulation. However, findings regarding emotional reactivity in BPD are mixed and there are limited studies examining emotion regulation capabilities in this population. METHODS Twenty-five individuals with BPD and 30 healthy controls (HCs) engaged in a baseline assessment followed by the presentation of neutral and BPD-relevant negative images. Participants were instructed to react as they naturally would to the image, or to use a mindfulness-based or distraction-based strategy to feel less negative. Self-reported and physiological (i.e., heart rate, electrodermal activity, and respiratory sinus arrhythmia) measures were collected. RESULTS Compared with the HCs, the BPD group exhibited elevated heart rate and reduced respiratory sinus arrhythmia at baseline. However, there were no differences in emotional reactivity in self-report or physiological indices between the two groups. In addition, the BPD group did not exhibit deficits in the ability to implement either emotion regulation strategy, with the exception that the BPD group reported less positive emotions while distracting compared with the HCs. LIMITATIONS This study is limited by a small sample size and the inclusion of a medicated BPD sample. CONCLUSIONS Emotion dysregulation in BPD might be better accounted for by abnormal baseline emotional functioning rather than heightened emotional reactivity or deficits in emotion regulation. Treatments for BPD might be enhanced by directly targeting resting state emotional functioning rather than emotional reactions or regulatory attempts.

A psychophysiological investigation of emotion regulation in chronic severe posttraumatic stress disorder

There have been few direct examinations of the volitional control of emotional responses to provocative stimuli in PTSD. To address this gap, an emotion regulation task was administered to 27 Operation Enduring Freedom/Operation Iraqi Freedom combat veterans and 23 healthy controls. Neutral and aversive photographs were presented to participants who did or did not employ emotion regulation strategies. Objective indices included corrugator electromyogram, the late positive potential, and the electrocardiogram. On uninstructed trials, participants with PTSD exhibited blunted cardiac reactivity rather than the exaggerated cardioacceleratory responses seen in trauma cue reactivity studies. On interleaved regulation trials, no measure evidenced group differences in voluntary emotion regulation. Persons with PTSD may not differ from normals in their capacity to voluntarily regulate normative emotional responses to provocative stimuli in the laboratory, though they may nevertheless respond differentially on uninstructed trials and endorse symptoms of dyscontrol pathognomonic of the disorder outside of the laboratory.

Early adversity and combat exposure interact to influence anterior cingulate cortex volume in combat veterans

Objective Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach. Method Anterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis. Results As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes. Conclusions In the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma.

The impact of stimulus arousal level on emotion regulation effectiveness in borderline personality disorder.

Basic emotion theory suggests that the effectiveness of different emotion regulation strategies vary with the intensity of the emotionally-salient stimulus. Although findings from studies using healthy samples are concordant with what is proposed by theory, it is unclear whether these relationships hold true among individuals with borderline personality disorder (BPD). Twenty-five individuals with BPD and 30 HCs were exposed to negative images of varying levels of emotional arousal and were instructed to either react as they normally would, distract, or use mindful awareness. Self-reported negativity ratings, heart rate, and skin conductance level (SCL) were monitored throughout. SCL data indicated that increases in image arousal resulted in larger reductions in SCL when distracting but not when implementing mindful awareness. Self-report data suggested that, in HCs, the effectiveness of mindful awareness decreased to a greater extent than distraction when image arousal increased. These findings are consistent with basic emotion research and suggest that some forms of emotion regulation (distraction) are more suited to high emotion arousal contexts than others (mindful awareness) and that, compared with HCs, individuals with BPD may be more resilient to the deteriorating effectiveness of mindful awareness with respect to increasing emotional arousal.

Examining the relationship between emotion regulation deficits and borderline personality disorder features: A daily diary study

This study used a six-day daily diary methodology to precisely specify the nature of emotion regulation deficits associated with borderline personality disorder (BPD) features. Three possibilities were explored: that BPD features are associated with (1) the overall underuse of emotion regulation strategies; (2) the overuse of dysfunctional and the underuse of functional strategies; and (3) the lower perceived effectiveness of emotion regulation strategies. One hundred and fifty-four undergraduate participants completed self-report measures of BPD feature severity, and then reported their daily negative emotional intensity, whether or not they used various emotion regulation strategies, and whether or not the strategies that they used were effective across a six-day period. Higher BPD features were associated with (a) higher total frequency use of emotion regulation strategies; (b) higher frequency use of dysfunctional and functional emotion regulation strategies; and (c) less self-reported effectiveness of functional strategies. BPD features may be characterized by increased attempts to regulate emotions, without corresponding increases in perceived effectiveness.

How do you choose and how well does it work?: the selection and effectiveness of emotion regulation strategies and their relationship with borderline personality disorder feature severity

ABSTRACT There is little research examining whether the selection of emotion regulation strategies is compromised among individuals characterised by emotion dysregulation. In a sample of 149 undergraduates, we examined the selection and effectiveness of 2 emotion regulation strategies (reappraisal or distraction) in response to emotionally evocative stimuli, and their relationship with emotion dysregulation, measured by borderline personality disorder (BPD) feature severity. Stimulus intensity and self-reported negative emotional intensity were also compared as predictors of strategy selection. Results indicated that self-reported negative emotional intensity was a stronger predictor of strategy selection than stimulus intensity, and participants generally selected reappraisal over distraction. However, increases in self-reported negative emotional intensity was associated with an increased likelihood of choosing distraction, particularly among individuals higher in BPD features. In general, distraction exhibited less effectiveness than reappraisal, and higher BPD features did not differentially impact such effectiveness. Our findings indicate that individuals higher in emotion dysregulation prefer to use distraction as self-reported negative emotional intensity increases, a strategy which, overall, may not be as effective as reappraisal. Selection, rather than effectiveness of emotion regulation strategy might be a key feature of individuals characterised by emotion dysregulation.

The unique contribution of acceptance without judgment in predicting nonsuicidal self-injury after 20-weeks of dialectical behaviour therapy group skills training

The current research tested whether four dimensions of mindfulness - acceptance without judgment, observing, describing and acting with awareness - predicted frequency of nonsuicidal self-injury (NSSI) and mediate the relationship with NSSI outcomes during 20-weeks of Dialectical Behaviour Therapy (DBT) skills training for borderline personality disorder (BPD). Eighty-four self-harming individuals with BPD were randomized to either DBT skills training or to a waitlist control group. A series of regressions revealed no relationship between dimensions of mindfulness and NSSI at baseline. There was a significant effect of DBT skills training on NSSI. As well, mediation analysis indicated that acceptance without judgment, specifically, mediated the relation between DBT skills training and change in frequency of NSSI.