Charles A. Sanislow

Amygdala Hyperreactivity in Borderline Personality Disorder: Implications for Emotional Dysregulation.

BACKGROUND Disturbed interpersonal relations and emotional dysregulation are fundamental aspects of borderline personality disorder (BPD). The amygdala plays important roles in modulating vigilance and generating negative emotional states and is often abnormally reactive in disorders of mood and emotion. The aim of this study was to assess amygdala reactivity in BPD patients relative to normal control subjects. We hypothesized that amygdala hyperreactivity contributes to hypervigilance, emotional dysregulation, and disturbed interpersonal relations in BPD. METHODS Using functional magnetic resonance imaging, we examined neural responses to 20-sec blocks of neutral, happy, sad, and fearful facial expression (or a fixation point) in 15 BPD and 15 normal control subjects. The DSM IV-diagnosed BPD patients and the normal control subjects were assessed by a clinical research team in a medical school psychiatry department. RESULTS Borderline patients showed significantly greater left amygdala activation to the facial expressions of emotion (vs. a fixation point) compared with normal control subjects. Post-scan debriefing revealed that some borderline patients had difficulty disambiguating neutral faces or found them threatening. CONCLUSIONS Pictures of human emotional expressions elicit robust differences in amygdala activation levels in borderline patients, compared with normal control subjects, and can be used as probes to study the neuropathophysiologic basis of borderline personality disorder.

Developing constructs for psychopathology research: Research domain criteria.

There exists a divide between findings from integrative neuroscience and clinical research focused on mechanisms of psychopathology. Specifically, a clear correspondence does not emerge between clusters of complex clinical symptoms and dysregulated neurobiological systems, with many apparent redundancies. For instance, many mental disorders involve multiple disruptions in putative mechanistic factors (e.g., excessive fear, deficient impulse control), and different disrupted mechanisms appear to play major roles in many disorders. The Research Domain Criteria (RDoC) framework is a heuristic to facilitate the incorporation of behavioral neuroscience in the study of psychopathology. Such integration might be achieved by shifting the central research focus of the field away from clinical description to more squarely examine aberrant mechanisms. RDoC first aims to identify reliable and valid psychological and biological mechanisms and their disruptions, with an eventual goal of understanding how anomalies in these mechanisms drive psychiatric symptoms. This approach will require new methods to ascertain samples, relying on hypothesized psychopathological mechanisms to define experimental groups instead of traditional diagnostic categories. RDoC, by design, uncouples research efforts from clinically familiar categories to focus directly on fundamental mechanisms of psychopathology. RDoC proposes a matrix of domains and levels of analyses and invites the field to test and refine the framework. If RDoC is successful, the domains will ultimately relate to familiar psychopathologies in ways that promote new knowledge regarding etiology and more efficient development of new preventive and treatment interventions.

Stability of functional impairment in patients with schizotypal, borderline, avoidant, or obsessive–compulsive personality disorder over two years

BACKGROUND A defining feature of personality disorder (PD) is an enduring pattern of inner experience and behavior that is stable over time. Follow-up and follow-along studies have shown considerable diagnostic instability of PDs, however, even over short intervals. What, then, about personality disorder is stable? The purpose of this study was to determine the stability of impairment in psychosocial functioning in patients with four different PDs, in contrast to patients with major depressive disorder (MDD) and no PD, prospectively over a 2-year period. METHOD Six hundred treatment-seeking or treated patients were recruited primarily from clinical services in four metropolitan areas of the Northeastern USA. Patients were assigned to one of five diagnostic groups: schizotypal (STPD) (n=81), borderline (BPD) (n=155), avoidant (AVPD) (n=137), or obsessive-compulsive (OCPD) (n=142) personality disorders or MDD and no PD (n=85), based on the results of semi-structured interview assessments and self-report measures. Impairment in psychosocial functioning was measured using the Longitudinal Interval Follow-up Evaluation (LIFE) at baseline and at three follow-up assessments. RESULTS Significant improvement in psychosocial functioning occurred in only three of seven domains of functioning and was largely the result of improvements in the MDD and no PD group. Patients with BPD or OCPD showed no improvement in functioning overall, but patients with BPD who experienced change in personality psychopathology showed some improvement in functioning. Impairment in social relationships appeared most stable in patients with PDs. CONCLUSION Impairment in functioning, especially social functioning, may be an enduring component of personality disorder.

Two-Year Stability and Change of Schizotypal, Borderline, Avoidant, and Obsessive-Compulsive Personality Disorders.

The authors examined the stability of schizotypal (STPD), borderline (BPD), avoidant (AVPD) and obsessive-compulsive (OCPD) personality disorders (PDs) over 2 years of prospective multiwave follow-up. Six hundred thirty-three participants recruited at 4 collaborating sites who met criteria for 1 or more of the 4 PDs or for major depressive disorder (MOD) without PD were assessed with semistructured interviews at baseline, 6, 12, and 24 months. Lifetable survival analyses revealed that the PD groups had slower time to remission than the MDD group. Categorically, PD remission rates range from 50% (AVPD) to 61% (STPD) for dropping below diagnostic threshold on a blind 24-month reassessment but range from 23% (STPD) to 38% (OCPD) for a more stringent definition of improvement. Dimensionally, these findings suggest that PDs may be characterized by maladaptive trait constellations that are stable in their structure (individual differences) but can change in severity or expression over time.

Gender differences in borderline personality disorder: findings from the collaborative longitudinal personality disorders study

A majority of the literature on borderline personality disorder (BPD) focuses on its occurrence in women or does not specifically assess for gender differences in clinical presentations. Some studies report that men with BPD may be more likely to be diagnosed with substance use disorders, as well as paranoid, passive-aggressive, narcissistic, sadistic, and antisocial personality disorders (PDs). Additionally, women with BPD appear to be more likely to report histories of adult physical and sexual abuse and to meet diagnostic criteria for post-traumatic stress disorder (PTSD) and eating disorders. The purpose of the present study was to further examine gender differences in BPD. Using baseline data from the Collaborative Longitudinal Personality Disorders Study (CLPS), men and women who met criteria for BPD were compared on current axis I and II disorders, BPD diagnostic criteria, childhood trauma histories, psychosocial functioning, temperament, and personality traits. Men with BPD were more likely to present with substance use disorders, and with schizotypal, narcissistic, and antisocial PDs, while women with BPD were more likely to present with PTSD, eating disorders, and the BPD criterion of identity disturbance. Generally speaking, women and men with BPD displayed more similarities than differences in clinical presentations. The differences that did emerge are consistent with those found in epidemiological studies of psychopathology and therefore do not appear unique to BPD. Additionally, many gender differences traditionally found in epidemiological samples did not emerge in BPD subjects. For example, no difference was found in rates of major depressive disorder, a condition that is more prevalent in females. Thus, BPD pathology may be a prevailing characterization that can attenuate usual gender-based distinctions.

When and how perfectionism impedes the brief Treatment of depression : Further analyses of the national institute of Mental Health Treatment of Depression Collaborative Research Program

Perfectionism has previously been identified as having a significant negative impact on therapeutic outcome at termination in the brief (16-week) treatment of depression (S. J. Blatt, D. M. Quinlan, P. A. Pilkonis, & T. Shea, 1995) as measured by the 5 primary outcome measures used in the National Institute of Mental Health Treatment of Depression Collaborative Research Program (TDCRP). The present analyses of other data from the TDCRP indicated that this impact of perfectionism on therapeutic outcome was also found in ratings by therapists, independent clinical evaluators, and the patients and that this effect persisted 18 months after termination. In addition, analyses of comprehensive, independent assessments made during the treatment process indicated that perfectionism began to impede therapeutic gain in approximately 2/3 of the sample, in the latter half of treatment, between the 9th and 12th sessions. Implications of these findings are discussed, including the possibility that more perfectionistic patients may be negatively impacted by anticipation of an arbitrary, externally imposed termination date.

Axis I and Axis II Disorders as Predictors of Prospective Suicide Attempts: Findings From the Collaborative Longitudinal Personality Disorders Study

This study examined diagnostic predictors of prospectively observed suicide attempts in a personality disorder (PD) sample. During 2 years of follow-up, 58 participants (9%) reported at least 1 definitive suicide attempt. Predictors that were examined include 4 PD diagnoses and selected Axis I diagnoses (baseline and course). Multivariate logistic regression analyses indicated that baseline borderline personality disorder (BPD) and drug use disorders significantly predicted prospective suicide attempts. Controlling for baseline BPD diagnosis, proportional hazards analyses showed that worsening in the course of major depressive disorder (MDD) and of substance use disorders in the month preceding the attempt were also significant predictors. Therefore, among individuals diagnosed with PDs, exacerbation of Axis I conditions, particularly MDD and substance use, heightens risk for a suicide attempt.

Associations in the Course of Personality Disorders and Axis I Disorders Over Time

In this study, the authors examined time-varying associations between schizotypal (STPD), borderline (BPD), avoidant (AVPD), or obsessive-compulsive (OCPD) personality disorders and co-occurring Axis I disorders in 544 adult participants from the Collaborative Longitudinal Personality Disorders Study. The authors tested predictions of specific longitudinal associations derived from a model of crosscutting psychobiological dimensions (L. J. Siever & K. L. Davis, 1991) with participants with the relevant Axis I disorders. The authors assessed participants at baseline and at 6-, 12-, and 24-month follow-up evaluations. BPD showed significant longitudinal associations with major depressive disorder and posttraumatic stress disorder. AVPD was significantly associated with anxiety disorders (specifically social phobia and obsessive-compulsive disorder). Two of the four personality disorders under examination (STPD and OCPD) showed little or no association with Axis I disorders.

Personality Assessment in DSM--5: Empirical support for rating Severity, Style, and Traits

Despite a general consensus that dimensional models are superior to the categorical representations of personality disorders in DSM-IV, proposals for how to depict personality pathology dimensions vary substantially. One important question involves how to separate clinical severity from the style of expression through which personality pathology manifests. This study empirically distinguished stylistic elements of personality pathology symptoms from the overall severity of personality disorder in a large, longitudinally assessed clinical sample (N = 605). Data suggest that generalized severity is the most important single predictor of current and prospective dysfunction, but that stylistic elements also indicate specific areas of difficulty. Normative personality traits tend to relate to the general propensity for personality pathology, but not stylistic elements of personality disorders. Overall, findings support a three-stage diagnostic strategy involving a global rating of personality disorder severity, ratings of parsimonious and discriminant valid stylistic elements of personality disorder, and ratings of normative personality traits.

Preliminary evidence for medication effects on functional abnormalities in the amygdala and anterior cingulate in bipolar disorder

RationaleAbnormal amygdala and frontocortical responses to emotional stimuli are implicated in bipolar disorder (BD) and have been proposed as potential treatment targets.ObjectivesThe aim of this study was to investigate amygdala and frontocortical responses to emotional face stimuli in BD and the influences of mood-stabilizing medications on these responses.MethodsFunctional magnetic resonance imaging was performed while 17 BD participants (5 unmedicated) and 17 healthy comparison (HC) participants viewed faces with happy, sad, fearful, or neutral expressions.ResultsThe group by stimulus-condition interaction was significant (p<0.01) for amygdala activation, with the greatest effects in the happy face condition. Relative to HC, amygdala increases were greater in unmedicated BD, but lower in medicated BD. Rostral anterior cingulate (rAC) activation was decreased in unmedicated BD compared to HC; however, BD participants taking medication demonstrated rAC activation similar to HC participants.ConclusionsAlthough the sample sizes were small, these preliminary results suggest that BD is associated with increased amygdala and decreased rAC response to emotional faces. The findings also provide preliminary evidence that mood-stabilizing medications may reverse abnormalities in BD in the response of an amygdala–frontal neural system to emotional stimuli.