Luis H. Ripoll

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.

Striatal activity in borderline personality disorder with comorbid intermittent explosive disorder: sex differences.

Borderline Personality Disorder (BPD) is associated with behavioral and emotional dysregulation, particularly in social contexts; however, the underlying pathophysiology at the level of brain function is not well understood. Previous studies found abnormalities in frontal cortical and limbic areas suggestive of poor frontal regulation of downstream brain regions. However, the striatum, which is closely connected with the medial frontal cortices and plays an important role in motivated behaviors and processing of rewarding stimuli, has been understudied in BPD. Here we hypothesized that, in addition to frontal dysfunction, BPD patients may show abnormal striatal function. In this study, 38 BPD patients with intermittent explosive disorder (BPD-IED) and 36 healthy controls (HC) participated in the Point Subtraction Aggression Paradigm (PSAP), a computer game played with a fictitious other player. (18)Fluoro-deoxyglucose positron emission tomography (FDG-PET) measured relative glucose metabolism (rGMR) within caudate and putamen in response to aggression-provoking and non-provoking versions of the PSAP. Male BPD-IED patients had significantly lower striatal rGMR than all other groups during both conditions, although male and female BPD-IED patients did not differ in clinical or behavioral measures. These sex differences suggest differential involvement of frontal-striatal circuits in BPD-IED, and are discussed in relation to striatal involvement in affective learning and social decision-making.

The neurobiology of empathy in borderline personality disorder.

We present a neurobiological model of empathic dysfunction in borderline personality disorder (BPD) to guide future empirical research. Empathy is a necessary component of interpersonal functioning, involving two distinct, parallel neural networks. One form of empathic processing relies on shared representations (SR) of others’ mental states, while the other is associated with explicit mental state attribution (MSA). SR processing is visceral and automatic, contributing to attunement, but also emotional contagion. MSA processing contributes to deliberate, perspectival forms of empathic understanding. Empathic dysfunction in BPD may involve hyper-reactivity of SR networks and impairment of MSA networks. Nevertheless, this empathic dysfunction is subtle, but contributes to interpersonal difficulties. Interaction between genetic factors and traumatic attachment stressors may contribute to development of BPD, with painful attachment insecurity and disorganization affecting SR and MSA network functioning. Future avenues for BPD research will include developmental assessment of attachment and neurobiological functioning under varying conditions.

Empathic accuracy and cognition in schizotypal personality disorder

Interpersonal dysfunction contributes to significant disability in the schizophrenia spectrum. Schizotypal Personality Disorder (SPD) is a schizophrenia-related personality demonstrating social cognitive impairment in the absence of frank psychosis. Past research indicates that cognitive dysfunction or schizotypy may account for social cognitive dysfunction in this population. We tested SPD subjects and healthy controls on the Empathic Accuracy (EA) paradigm and the Reading of the Mind in the Eyes Test (RMET), assessing the impact of EA on social support. We also explored whether EA differences could be explained by intelligence, working memory, trait empathy, or attachment avoidance. SPD subjects did not differ from controls in RMET, but demonstrated lower EA during negative valence videos, associated with lower social support. Dynamic, multimodal EA paradigms may be more effective at capturing interpersonal dysfunction than static image tasks such as RMET. Schizotypal severity, trait empathy, and cognitive dysfunction did not account for empathic dysfunction in SPD, although attachment avoidance is related to empathic differences. Empathic dysfunction for negative affect contributes to decreased social support in the schizophrenia spectrum. Future research may shed further light on potential links between attachment avoidance, empathic dysfunction, and social support.

PET and SPECT in Personality Disorders

While neurobiological studies have focused primarily on DSM-IV Axis I disorders, there is an emerging neurobiology of personality disorders. Specific neurocircuitry alterations have been identified as the biological underpinnings of the dimensional traits that underlie personality disorders. In this chapter, we review the most significant neuroimaging findings using PET and SPECT in relation to personality disorders and dimensions.

Arginine vasopressin receptor gene variants associated with aggression, borderline and schizotypal personality disorder

M. Mercedes Perez-Rodriguez1,2, E. Rothstein1,2, L. Rimsky1,2, N. Hoque1,2, T. Lichtman1,2, A. McMaster1,2, S. Chowdury1,2, K. Mascitelli1,2, L. Bevilacqua3, A. Ungar1, L. Ripoll1, D. Goldman3, C. Hodgkinson3, M. Goodman1,2, A. S. New1,2, L. J. Siever1,2 1Mount Sinai School of Medicine, New York, NY, United States; 2MIRECC, James J. Peters Veterans Affairs Medical Center, Bronx, NY, United States; 3Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD

Empathic Accuracy and Borderline Personality Disorder

Borderline personality disorder (BPD) includes severe, refractory interpersonal dysfunction. One component of interpersonal dysfunction in BPD entails a distinct style of empathy (the ability to understand others’ mental states to guide subsequent interpersonal behavior), highlighted by clinical experience with such patients and associated phenomenology. Empathic processing involves two parallel neural networks: one involving implicit, relatively automatic mirroring and shared mental representations (SR); the other involving explicit, deliberate mental state attribution (MSA). One neurobiological model of BPD suggests that it involves hyperreactivity of SR networks and impairment in MSA processing, under the influence of dysregulated neuropeptide signaling. A complex interaction between genetics and development (particularly attachment stressors) contributes to the ontogeny of this neurobiological dysfunction. A neuropsychoanalytic approach provides the means by which future research can guide questions to test this model, further understand BPD etiology and psychopathology, and eventually improve treatment for this disorder.