Classical conditioning in borderline personality disorder: an fMRI study.

Previous research suggests disturbed emotional learning and memory in borderline personality disorder (BPD). Studies investigating the neural correlates of aversive differential delay conditioning in BPD are currently lacking. We aimed to investigate acquisition, within-session extinction, between-session extinction recall, and reacquisition. We expected increased activation in the insula, amygdala, and anterior cingulate, and decreased prefrontal activation in BPD patients. During functional magnetic resonance imaging, 27 medication-free female BPD patients and 26 female healthy controls (HC) performed a differential delay aversive conditioning paradigm. An electric shock served as unconditioned stimulus, two neutral pictures as conditioned stimuli (CS+/CS-). Dependent variables were blood-oxygen-level-dependent response, skin conductance response (SCR), and subjective ratings (valence, arousal). No significant between-group differences in brain activation were found [all p(FDR) > 0.05]. Within-group comparisons for CS+unpaired > CS- revealed increased insula activity in BPD patients but not in HC during early acquisition; during late acquisition, both groups recruited fronto-parietal areas [p(FDR) < 0.05]. During extinction, BPD patients rated both CS+ and CS- as significantly more arousing and aversive than HC and activated the amygdala in response to CS+. In contrast, HC showed increased prefrontal activity in response to CS+ > CS during extinction. During extinction recall, there was a trend for stronger SCR to CS+ > CS in BPD patients. Amygdala habituation to CS+paired (CS+ in temporal contingency with the aversive event) during acquisition was found in HC but not in patients. Our findings suggest altered temporal response patterns in terms of increased vigilance already during early acquisition and delayed extinction processes in individuals with BPD.

Evaluation of naltrexone for dissociative symptoms in borderline personality disorder.

Data from a pilot study suggest that naltrexone might reduce dissociative symptoms in patients with borderline personality disorder. However, the interpretation of these data is limited by the lack of a control group and by the nonblind nature of this study. Hence, we examined the effects of naltrexone using a more rigorous design that controlled for major confounders such as spontaneous reduction of dissociation over time and placebo effects. Unmedicated patients with BPD [according to Diagnostic and Statistical Manual of Mental Disorders-IVth edition (DSM-IV)] were included in two small double-blind placebo-controlled randomized trials (total n=29). Patients received both 3 weeks of naltrexone (50 or 200 mg/day) and 3 weeks of placebo in a randomized order. Twenty-five patients completed the study according to protocol. Dissociation under naltrexone and placebo, respectively, was compared by repeated-measures analyses of variance. In either trial, both the intensity and duration of dissociative symptoms were numerically lower under naltrexone than under placebo. However, the effects were too small to reach statistical significance. Our data provide the first estimate of the pure pharmacological antidissociative efficacy of naltrexone from a rigorously designed trial.

Reducing unwanted trauma memories by imaginal exposure or autobiographical memory elaboration: an analogue study of memory processes.

Unwanted memories of traumatic events are a core symptom of post-traumatic stress disorder. A range of interventions including imaginal exposure and elaboration of the trauma memory in its autobiographical context are effective in reducing such unwanted memories. This study explored whether priming for stimuli that occur in the context of trauma and evaluative conditioning may play a role in the therapeutic effects of these procedures. Healthy volunteers (N = 122) watched analogue traumatic and neutral picture stories. They were then randomly allocated to 20 min of either imaginal exposure, autobiographical memory elaboration, or a control condition designed to prevent further processing of the picture stories. A blurred picture identification task showed that neutral objects that preceded traumatic pictures in the stories were subsequently more readily identified than those that had preceded neutral stories, indicating enhanced priming. There was also an evaluative conditioning effect in that participants disliked neutral objects that had preceded traumatic pictures more. Autobiographical memory elaboration reduced the enhanced priming effect. Both interventions reduced the evaluative conditioning effect. Imaginal exposure and autobiographical memory elaboration both reduced the frequency of subsequent unwanted memories of the picture stories.

Dissociation predicts poor response to Dialectial Behavioral Therapy in female patients with Borderline Personality Disorder.

A substantial proportion of Borderline Personality Disorder (BPD) patients respond by a marked decrease of psychopathology when treated with Dialectical Behavioral Therapy (DBT). To further enhance the rate of DBT-response, it is useful to identify characteristics related to unsatisfactory response. As DBT relies on emotional learning, we explored whether dissociation-which is known to interfere with learning- predicts poor response to DBT. Fifty-seven Borderline Personality Disorder (BPD) patients (DSM-IV) were prospectively observed during a three-month inpatient DBT program. Pre-post improvements in general psychopathology (SCL-90-R) were predicted from baseline scores of the Dissociative Experiences Scale (DES) by regression models accounting for baseline psychopathology. High DES-scores were related to poor pre-post improvement (ß = -0.017 ± 0.006, p = 0.008). The data yielded no evidence that some facets of dissociation are more important in predicting DBT-response than others. The results suggest that dissociation in borderline-patients should be closely monitored and targeted during DBT. At this stage, research on treatment of dissociation (e.g., specific skills training) is warranted.

Increased psychological and attenuated cortisol and alpha-amylase responses to acute psychosocial stress in female patients with borderline personality disorder.

OBJECTIVE: Borderline personality disorder (BPD) is characterized by increased self-reported stress and emotional responding. Knowledge about the psychological and physiological mechanisms that underlie these experiences in BPD patients is scarce. The objective was to assess both psychological and endocrinological responses to a standardized psychosocial stressor in female BPD patients and healthy controls. METHODS: A total of 15 female BPD patients and 17 healthy control subjects were included in a case-control study. All subjects were free of any medication, had a regular menstrual cycle, and were investigated during the luteal phase of their menstrual cycle. Co-occurring current major depression, current substance abuse/dependence, and lifetime schizophrenia or bipolar I disorder were excluded. Psychological measures of stress, salivary cortisol, salivary alpha-amylase, plasma ACTH, plasma norepinephrine and epinephrine concentrations were measured before, during, and after exposure to a standardized psychosocial stress protocol. RESULTS: BPD patients displayed maladaptive cognitive appraisal processes regarding the upcoming stressor as well as significantly higher subjective stress, coupled with a substantial cortisol and alpha-amylase hyporeactivity to the stressor in comparison to the controls. No significant differences for ACTH and catecholaminergic responses were observed, while the ACTH:cortisol ratio was higher in BPD patients than in controls. CONCLUSIONS: Attenuated cortisol responsiveness in BPD patients might in part be explained by decreased adrenal responsiveness to endogenous ACTH and altered central noradrenergic activation as reflected by alpha-amylase.

The latest neuroimaging findings in borderline personality disorder.

This review provides an overview of the most recent neuroimaging findings in borderline personality disorder. The contributions of the structural and functional imaging studies of the past 3 years are presented to help us better understand this severe psychiatric disorder. There are three domains of functional imaging findings: 1) affective dysregulation; 2) the complex of dissociation, self-injurious behavior, and pain processing; and 3) social interaction. Knowledge of the neurobiological basis of borderline personality disorder has grown considerably. Therefore, these findings convey a good impression of the current findings from neuroimaging research in this disorder and also of the necessary next steps with regard to content and methodology.

Pain sensitivity and neural processing during dissociative states in patients with borderline personality disorder with and without comorbid posttraumatic stress disorder: a pilot study.

BACKGROUND: Stress-induced dissociative states involving analgesia are a common feature of borderline personality disorder (BPD) and posttraumatic stress disorder (PTSD). Our aim was to investigate the psychologic, somatosensory (pain sensitivity) and neural correlates of dissociative states in patients with these disorders. METHODS: We included 15 women with BPD who were not taking medication; 10 of these women had comorbid PTSD. While undergoing functional magnetic resonance imaging at 1.5 Tesla, participants were exposed to a script describing a personalized dissociation-inducing situation and a personalized script describing a neutral situation. We assessed dissociative psychopathology and pain sensitivity. RESULTS: Dissociative psychopathology scores were significantly higher and pain sensitivity was lower after the dissociation-inducing script was read compared with the neutral script. The blood oxygen level-dependent (BOLD) signal was significantly increased in the left inferior frontal gyrus (Brodmann area [BA] 9) during the presentation of the dissociation-inducing script. Regression analyses revealed positive correlations between BOLD signal and dissociative psychopathology in the left superior frontal gyrus (BA 6) and negative correlations in the right middle (BA 21) and inferior temporal gyrus (BA 20). In the subgroup of participants with comorbid PTSD, we also found increased activity in the left cingulate gyrus (BA 32) during script-driven imagery-induced dissociation, a positive correlation between dissociation scores and activity in the right and left insula (BA 13) and a negative correlation in the right parahippocampal gyrus (BA 35). LIMITATIONS: The main limitation of this pilot study is the absence of a control group. Therefore, the results may also reflect the neural correlates of non-BPD/PTSD specific dissociative states or the neural correlates of emotionally stressful or "loaded" memories. Another limitation is the uncorrected statistical level of the functional magnetic resonance imaging results. CONCLUSION: Our results showed that the script-driven imagery method is capable of inducing dissociative states in participants with BPD with and without comorbid PTSD. These states were characterized by reduced pain sensitivity and a frontolimbic activation pattern, which resembles the findings in participants with PTSD while in dissociative states.

Emotional learning during dissociative states in borderline personality disorder.

BACKGROUND: Neurobiological findings and clinical data suggest that dissociative experience inhibits conditioning processes, but experimental studies are lacking. The aim of our study was to determine whether high states of dissociative experience would specifically alter emotional learning, but not declarative knowledge. METHODS: We used an aversive differential delay conditioning procedure in 33 unmedicated patients with borderline personality disorder (BPD) and 35 healthy controls. RESULTS: Patients with BPD who had high state dissociative experiences (BPD D+) showed diminished acquisition of differential aversive delay conditioning with respect to emotional learning compared with those who did not experience dissociative symptoms (BPD D-) and healthy controls (skin conductance response; interaction dissociation x quadratic time x type, p = 0.009). Specifically, the control group and the BPD D- subgroup showed an increase in valence and arousal to the conditioned stimulus (CS+) during the conditioning procedure (all p < 0.012) and demonstrated differential skin conductance responses in the acquisition and extinction phases. In contrast, the BPD D+ subgroup showed no increase in valence and arousal to CS+ or differential response regarding skin conductance. We examined general psychopathology, trauma history, perceptual differences and posttraumatic stress disorder as confounding factors, but we found no evidence of bias. LIMITATIONS: Subdividing the BPD group reduced power. In addition, because our sample included only women, the generalizability of our results is constrained. Furthermore, we performed no separate analysis of the influence of different aspects of dissociation on the learning process. CONCLUSION: Emotional, amygdala-based learning processes seem to be inhibited during state dissociative experience. State dissociative experience may alter acquisition and extinction processes and should be closely monitored in exposure-based psychotherapy.