Joseph Triebwasser

Laboratory induced aggression: a positron emission tomography study of aggressive individuals with borderline personality disorder.

BACKGROUND Borderline personality disorder (BPD) is often associated with symptoms of impulsive aggression, which poses a threat to patients themselves and to others. Preclinical studies show that orbital frontal cortex (OFC) plays a role in regulating impulsive aggression. Prior work has found OFC dysfunction in BPD. METHODS We employed a task to provoke aggressive behavior, the Point Subtraction Aggression Paradigm (PSAP), which has never previously been used during functional brain imaging. Thirty-eight BPD patients with intermittent explosive disorder (BPD-IED) and 36 age-matched healthy control subjects (HCs) received (18)fluoro-deoxyglucose positron emission tomography ((18)FDG-PET) on two occasions with a provocation and nonprovocation version of the PSAP. Mean relative glucose metabolism was measured throughout the cortex, and difference scores (provoked - nonprovoked) were calculated. A whole brain exploratory analysis for the double difference of BPD-IED - HC for provoked - nonprovoked was also conducted. RESULTS BPD-IED patients were significantly more aggressive than HCs on the PSAP. BPD-IED patients also increased relative glucose metabolic rate (rGMR) in OFC and amygdala when provoked, while HCs decreased rGMR in these areas. However, HCs increased rGMR in anterior, medial, and dorsolateral prefrontal regions during provocation more than BPD-IED patients. CONCLUSIONS Patients responded aggressively and showed heightened rGMR in emotional brain areas, including amygdala and OFC, in response to provocation but not in more dorsal brain regions associated with cognitive control of aggression. In contrast, HCs increased rGMR in dorsal regions of PFC during aggression provocation, brain regions involved in top-down cognitive control of aggression, and, more broadly, of emotion.

Recent advances in the biological study of personality disorders.

While it is premature to provide a simple model for the vulnerability to the development of either borderline (BPD) or schizotypal (SPD) personality disorder, it is clear that these heritable disorders lend themselves to fruitful neurobiological exploration. The most promising findings in BPD suggest that a diminished top-down control of affective responses, which is likely to relate to deceased responsiveness of specific midline regions of prefrontal cortex, may underlie the affective hyperresponsiveness in this disorder. In addition, genetic and neuroendocrine and molecular neuroimaging findings point to a role for serotonin in this affective disinhibition. Clearly SPD falls within the schizophrenia spectrum, but precisely the nature of what predicts full-blown schizophrenia as opposed to the milder symptoms of SPD is not yet clear.

The Case for Shifting Borderline Personality Disorder to Axis I

Through reviewing what is known about the nature, course, and heritability of borderline personality disorder (BPD), we argue for a reconceptualization of this disorder that would lead to its placement on Axis I. Borderline personality disorder is a prevalent and disabling condition, and yet the empirical research into its nature and treatment has not been commensurate with the seriousness of the illness. We not only review empirical evidence about the etiology, phenomenology, and course of the disorder in BPD but we also address fundamental misconceptions about BPD that we believe have contributed to misunderstanding and stigmatization of the disease. Finally, we suggest future directions for research that might permit the identification of core features of this disorder, with a focus on the importance of naturalistic assessments and of assessments through the course of development.

The Effects of Guanfacine on Context Processing Abnormalities in Schizotypal Personality Disorder

BACKGROUND The signature of impaired cognition in people with schizotypal personality disorder (SPD) may be centrally related to working memory impairments. Guanfacine, an alpha2A agonist that acts post-synaptically in the prefrontal cortex (PFC), has shown potential for reducing working memory limitations in other populations. This study examined the potential of guanfacine for improving context processing, a feature of working memory, in SPD. METHODS 29 individuals with SPD entered into a 4-week, randomized parallel-design, double-blind, placebo-controlled trial of guanfacine treatment, followed by a 4-week open-label extension. A modified version of the AX-Continuous Performance Test (AX-CPT) was administered. On this task, evidence of intact context processing includes few BX errors (false cue, correct probe) and higher levels of AY errors (correct cue, false probe). RESULTS At the end of double-blind treatment, participants treated with guanfacine demonstrated a significant reduction in BX errors and a small but significant increase in AY errors, a pattern that was not seen in the participants treated with placebo. CONCLUSIONS SPD participants improved in their context processing toward a normal response bias, making fewer BX and more AY errors, after being treated with guanfacine.

Pergolide Treatment of Cognitive Deficits Associated with Schizotypal Personality Disorder: Continued Evidence of the Importance of the Dopamine System in the Schizophrenia Spectrum

Cognitive deficits observed in schizophrenia are also frequently found in individuals with other schizophrenia spectrum disorders, such as schizotypal personality disorder (SPD). Dopamine appears to be a particularly important modulator of cognitive processes such as those impaired in schizophrenia spectrum disorders. In a double-blind, placebo-controlled clinical trial, we administered pergolide, a dopamine agonist targeting D1 and D2 receptors, to 25 participants with SPD and assessed the effect of pergolide treatment, as compared with placebo, on neuropsychological performance. We found that the pergolide group showed improvements in visual-spatial working memory, executive functioning, and verbal learning and memory. These results suggest that dopamine agonists may provide benefit for the cognitive abnormalities of schizophrenia spectrum disorders.

Evidence-based pharmacotherapy for personality disorders.

Patients with personality disorders are prescribed psychotropic medications with greater frequency than almost any other diagnostic group. Prescribing practices in these populations are often based on anecdotal evidence rather than rigorous data. Although evidence-based psychotherapy remains an integral part of treatment, Axis II psychopathology is increasingly conceptualized according to neurobiological substrates that correspond to specific psychopharmacological strategies. We summarize the best available evidence regarding medication treatment of personality disordered patients and provide optimal strategies for evidence-based practice. Most available evidence is concentrated around borderline and schizotypal personality disorders, with some additional evidence concerning the treatment of avoidant and antisocial personality disorders. Although maladaptive personality symptoms respond to antidepressants, antipsychotics, mood stabilizers, and other medications, evidence-based pharmacotherapy is most useful in treating circumscribed symptom domains and induces only partial improvement. Most available evidence supports use of medication in reducing impulsivity and aggression, characteristic of borderline and antisocial psychopathology. Efforts have also begun to reduce psychotic-like symptoms and improve cognitive deficits characteristic of schizotypy. Indirect evidence is also provided for psychopharmacological reduction of social anxiety central to avoidant personality disorder. Evidence-based practice requires attention to domains of expected clinical improvement associated with a medication, relative to the potential risks. The development of future rational pharmacotherapy will require increased understanding of the neurobiological underpinnings of personality disorders and their component dimensions. Increasing efforts to translate personality theory and social cognitive neuroscience into increasingly specific neurobiological substrates may provide more effective targets for pharmacotherapy.

Treatment utilization by gender in patients with borderline personality disorder.

Minimal data exist on treatment utilization by gender in borderline personality disorder (BPD). This study used an online questionnaire to investigate initial and lifetime patterns of utilization of multiple treatment modalities by patients with BPD, and parental satisfaction with treatment. Respondents were parents of probands diagnosed with BPD who completed a 100-question anonymous Internet survey. Of the 495 surveys that were analyzed, 409 pertained to female subjects with BPD and 86 to male subjects with BPD. Results for probands with BPD across gender were notable for similar high lifetime levels of use of care, including hospitalization, day programs, and halfway houses, but not similar levels of use of drug/alcohol rehabilitation services, which was greater among the male subjects with BPD. The male subjects with BPD received significantly less lifetime psychotherapy and pharmacotherapy than the female subjects with BPD, although the duration of medication and psychotherapy treatment did not differ by gender. These results highlight the need for more research to better understand what might account for these gender differences in treatment and improve strategies to provide appropriate care for male patients with BPD. (Journal of Psychiatric Practice 2010;16:155–163).

Schizotypal personality disorder.

Early phenomenological descriptions of schizophrenia have acknowledged the existence of milder schizophrenia spectrum disorders characterized by the presence of attenuated symptoms typically present in chronic schizophrenia. The investigation of the schizophrenia spectrum disorders offers an opportunity to elucidate the pathophysiological mechanisms giving rise to schizophrenia. Differences and similarities between subjects with schizotypal personality disorder (SPD), the prototypical schizophrenia personality disorder, and chronic schizophrenia have been investigated with genetic, neurochemical, imaging, and pharmacological techniques. Patients with SPD and the more severely ill patients with chronic schizophrenia share cognitive, social, and attentional deficits hypothesized to result from common neurodevelopmentally based cortical temporal and prefrontal pathology. However, these deficits are milder in SPD patients due to their capacity to recruit other related brain regions to compensate for dysfunctional areas. Individuals with SPD are also less vulnerable to psychosis due to the presence of protective factors mitigating subcortical DA hyperactivity. Given the documented close relationship to other schizophrenic disorders, SPD will be included in the psychosis section of DSM-5 as a schizophrenia spectrum disorder as well as in the personality disorder section.

Parental Burden associated with Borderline Personality disorder in Female oFFsPring

To identify aspects of parental burden associated with borderline personality disorder (BPD), an anonymous internet survey linked to BPD support websites was developed for parents to complete on their BPD offspring and unaffected siblings. The questions cover aspects of the childs life from pregnancy through young adulthood, and query about the impact of the childs BPD on six domains of the parents life, including physical and emotional health, marriage, job, standard of living, social life, and career trajectory. Additionally, financial burden was assessed with questions pertaining to insurance and out-of pocket costs associated with the BPD disorder. BPD offspring were identified by meeting diagnostic criteria embedded within the survey and having been given a diagnosis of BPD by a professional at some point in their life. We report on 233 female offspring meeting strict criteria for BPD. Parents of daughters with BPD endorsed varying levels of impact on the six domains comprising burden with the largest impact on emotional health which was impacted in over 88% of the respondents. Over 50% of parents endorsed four or greater of the six burden items. Particular aspects of the offsprings BPD symptom profile correlated with intensity of parental burden included including problems in adolescence with acting out behavior (p < .000), property destruction (.003), delusional symptoms (.007), and hallucinatory symptoms (.008). A subgroup of respondents provided data on specific financial expenses. The average and median out-of-pocket expense was

Pharmacotherapy of personality disorders

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