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Research paper thumbnail of Evaluation of the dopamine βeta-hydroxylase (dβh) inhibitor nepicastat in participants who meet the criteria for cocaine use disorder

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2015

In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxyla... more In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxylase (DβH) inhibitor nepicastat would have minimal effects on cardiovascular and pharmacokinetic parameters associated with cocaine administration and would reduce the positive subjective effects produced by cocaine. We conducted a double-blind, placebo-controlled, inpatient study of oral nepicastat (0, 80 and 160mg) concurrent with intravenous (IV) cocaine (0, 10, 20 and 40mg) in non-treatment seeking participants who metcriteria for cocaine use disorder. Safety analyses revealed that nepicastat was well-tolerated and there were no differences in adverse events observed after nepicastat plus cocaine vs. cocaine alone. In addition, the pharmacokinetic properties of cocaine administration were not altered by nepicastat treatment. Cocaine-induced cardiovascular and subjective effects were evaluated for completers in the cohort randomized to nepicastat (n=13) using a within-subjects statistical analysis strategy. Specifically, the cardiovascular and subjective effects of cocaine were assessed in the presence of placebo (0mg), 80mg of nepicastat or 160mg of nepicastat on study Days 4, 8 and 12, respectively. Analyses revealed a main effect of nepicastat to reduce several cocaine-induced positive subjective effects. Taken together, these data indicate that nepicastat is safe when co-administered with cocaine and may suppress its positive subjective effects, and may be viable as a pharmacotherapy for treatment of cocaine use disorder.

Research paper thumbnail of Evaluation of the dopamine β-hydroxylase (DβH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder

Progress in Neuro Psychopharmacology and Biological Psychiatry, Jun 3, 2015

In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxyla... more In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxylase (DβH) inhibitor nepicastat would have minimal effects on cardiovascular and pharmacokinetic parameters associated with cocaine administration and would reduce the positive subjective effects produced by cocaine. We conducted a double-blind, placebo-controlled, inpatient study of oral nepicastat (0, 80 and 160mg) concurrent with intravenous (IV) cocaine (0, 10, 20 and 40mg) in non-treatment seeking participants who metcriteria for cocaine use disorder. Safety analyses revealed that nepicastat was well-tolerated and there were no differences in adverse events observed after nepicastat plus cocaine vs. cocaine alone. In addition, the pharmacokinetic properties of cocaine administration were not altered by nepicastat treatment. Cocaine-induced cardiovascular and subjective effects were evaluated for completers in the cohort randomized to nepicastat (n=13) using a within-subjects statistical analysis strategy. Specifically, the cardiovascular and subjective effects of cocaine were assessed in the presence of placebo (0mg), 80mg of nepicastat or 160mg of nepicastat on study Days 4, 8 and 12, respectively. Analyses revealed a main effect of nepicastat to reduce several cocaine-induced positive subjective effects. Taken together, these data indicate that nepicastat is safe when co-administered with cocaine and may suppress its positive subjective effects, and may be viable as a pharmacotherapy for treatment of cocaine use disorder.

Research paper thumbnail of Psychometric Investigation of the Childhood Interview for Borderline Personality Disorder in an Adolescent Inpatient Setting

Research paper thumbnail of The protective role of attachment security for adolescent borderline personality disorder features via enhanced positive emotion regulation strategies

Personality disorders, 2014

While studies have documented significant associations between insecure attachment, emotion dysre... more While studies have documented significant associations between insecure attachment, emotion dysregulation, and borderline personality disorder (BPD) features, no research to date has empirically delineated the specific mechanisms by which these constructs are related. The present study brings together 2 lines of research that have hitherto separately examined attachment disturbance and emotion dysregulation as they respectively manifest in the pathogenesis of BPD, and explores the complex relations between the 2 well-established correlates of borderline traits in a clinical sample of adolescents (N = 228). We examined the adolescents' use of positive and negative emotion regulation strategies, along with their maternal and paternal attachment security. Results indicated that positive and negative emotion regulation strategies were differentially implicated in the link between attachment insecurity and BPD features. Attachment security functioned as a buffer against adolescent BP...

Research paper thumbnail of Borderline personality disorder in adolescents: evidence in support of the Childhood Interview for DSM-IV Borderline Personality Disorder in a sample of adolescent inpatients

Comprehensive Psychiatry, 2012

Empirical evidence is increasing in support of the validity of the construct of borderline person... more Empirical evidence is increasing in support of the validity of the construct of borderline personality disorder (BPD) in adolescence. There is growing consensus that the early identification and treatment of emerging borderline traits may be an important focus. However, few diagnostic (questionnaire- or interview-based) measures specifically developed or adapted for adolescents and children exist. The Childhood Interview for DSM-IV Borderline Personality Disorder (CI-BPD) [Zanarini, 2003] is a promising interview-based measure of adolescent BPD. Currently, no studies have explicitly been designed to examine the psychometric properties of the CI-BPD. The aim of the current study was to examine various psychometric properties of the CI-BPD in an inpatient sample of adolescents (n = 245). A confirmatory factor analytic approach was used to examine the internal factor structure of the 9 CI-BPD items. In addition, internal consistency, interrater reliability, convergent validity (with clinician diagnosis and 2 questionnaire-based measures of BPD), and concurrent validity (with Axis I psychopathology and deliberate self-harm) were examined. Similar to several adult studies, the confirmatory factor analytic results supported a unidimensional factor structure for the CI-BPD, indicating that the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria on which the CI-BPD is based constitute a coherent combination of traits and symptoms even in adolescents. In addition, other validity criteria were excellent. Taken together, the current study provides strong evidence for the validity of the CI-BPD for use in adolescents.

Research paper thumbnail of Hypermentalizing in adolescent inpatients: treatment effects and association with borderline traits

Sharp et al. (2011) recently demonstrated that in adolescents with borderline traits the loss of ... more Sharp et al. (2011) recently demonstrated that in adolescents with borderline traits the loss of mentalization is more apparent in the emergence of unusual alternative strategies (excessive theory of mind or hypermentalizing) than in the loss of the capacity per se (no mentalizing or undermentalizing). This suggests that hypermentalizing could be a worthwhile social-cognitive treatment target in adolescents with borderline traits. The aim of the current study was to examine (1) whether a reduction in excessive theory of mind or hypermentalizing is achieved between admission and discharge for adolescent inpatients; (2) whether the hypothesized reduction is more apparent in adolescents meeting criteria for BPD compared with psychiatric controls; and (3) whether other forms of mentalizing would also be sensitive to and malleable by inpatient treatment in the same way we expected hypermentalizing to be. The "Movie for the Assessment of Social Cognition" Task (Dziobek et al., 2006) was administered to consecutive admissions to an adolescent inpatient setting (n = 164) at admission and discharge, alongside measures of borderline symptomology and interview-based diagnosis of BPD. Results demonstrated that 41% (n = 68) of the sample met full or intermediate criteria for BPD on an interview-based measure of BPD. A relation between borderline traits and hypermentalizing that appears to be independent of internalizing and externalizing problems was demonstrated. Hypermentalizing, but not other forms of social-cognitive reasoning (as measured by the Child Eyes Test, Basic Empathy Scale and the Mentalizing Stories Test for Adolescents), was found to be malleable through a milieu-based inpatient treatment. Clinical implications of the findings for the organization of treatment settings for adolescents are discussed. Several developmental theories have emerged to elucidate the origins of Borderline Personality Disorder (BPD). A mentalization-based theory of BPD was proposed by Fonagy and colleagues (Fonagy, 1989, 1991; Fona

Research paper thumbnail of Evaluation of the dopamine βeta-hydroxylase (dβh) inhibitor nepicastat in participants who meet the criteria for cocaine use disorder

Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2015

In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxyla... more In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxylase (DβH) inhibitor nepicastat would have minimal effects on cardiovascular and pharmacokinetic parameters associated with cocaine administration and would reduce the positive subjective effects produced by cocaine. We conducted a double-blind, placebo-controlled, inpatient study of oral nepicastat (0, 80 and 160mg) concurrent with intravenous (IV) cocaine (0, 10, 20 and 40mg) in non-treatment seeking participants who metcriteria for cocaine use disorder. Safety analyses revealed that nepicastat was well-tolerated and there were no differences in adverse events observed after nepicastat plus cocaine vs. cocaine alone. In addition, the pharmacokinetic properties of cocaine administration were not altered by nepicastat treatment. Cocaine-induced cardiovascular and subjective effects were evaluated for completers in the cohort randomized to nepicastat (n=13) using a within-subjects statistical analysis strategy. Specifically, the cardiovascular and subjective effects of cocaine were assessed in the presence of placebo (0mg), 80mg of nepicastat or 160mg of nepicastat on study Days 4, 8 and 12, respectively. Analyses revealed a main effect of nepicastat to reduce several cocaine-induced positive subjective effects. Taken together, these data indicate that nepicastat is safe when co-administered with cocaine and may suppress its positive subjective effects, and may be viable as a pharmacotherapy for treatment of cocaine use disorder.

Research paper thumbnail of Evaluation of the dopamine β-hydroxylase (DβH) inhibitor nepicastat in participants who meet criteria for cocaine use disorder

Progress in Neuro Psychopharmacology and Biological Psychiatry, Jun 3, 2015

In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxyla... more In the present study, we tested the hypothesis that the potent and selective dopamine-β-hydroxylase (DβH) inhibitor nepicastat would have minimal effects on cardiovascular and pharmacokinetic parameters associated with cocaine administration and would reduce the positive subjective effects produced by cocaine. We conducted a double-blind, placebo-controlled, inpatient study of oral nepicastat (0, 80 and 160mg) concurrent with intravenous (IV) cocaine (0, 10, 20 and 40mg) in non-treatment seeking participants who metcriteria for cocaine use disorder. Safety analyses revealed that nepicastat was well-tolerated and there were no differences in adverse events observed after nepicastat plus cocaine vs. cocaine alone. In addition, the pharmacokinetic properties of cocaine administration were not altered by nepicastat treatment. Cocaine-induced cardiovascular and subjective effects were evaluated for completers in the cohort randomized to nepicastat (n=13) using a within-subjects statistical analysis strategy. Specifically, the cardiovascular and subjective effects of cocaine were assessed in the presence of placebo (0mg), 80mg of nepicastat or 160mg of nepicastat on study Days 4, 8 and 12, respectively. Analyses revealed a main effect of nepicastat to reduce several cocaine-induced positive subjective effects. Taken together, these data indicate that nepicastat is safe when co-administered with cocaine and may suppress its positive subjective effects, and may be viable as a pharmacotherapy for treatment of cocaine use disorder.

Research paper thumbnail of Psychometric Investigation of the Childhood Interview for Borderline Personality Disorder in an Adolescent Inpatient Setting

Research paper thumbnail of The protective role of attachment security for adolescent borderline personality disorder features via enhanced positive emotion regulation strategies

Personality disorders, 2014

While studies have documented significant associations between insecure attachment, emotion dysre... more While studies have documented significant associations between insecure attachment, emotion dysregulation, and borderline personality disorder (BPD) features, no research to date has empirically delineated the specific mechanisms by which these constructs are related. The present study brings together 2 lines of research that have hitherto separately examined attachment disturbance and emotion dysregulation as they respectively manifest in the pathogenesis of BPD, and explores the complex relations between the 2 well-established correlates of borderline traits in a clinical sample of adolescents (N = 228). We examined the adolescents' use of positive and negative emotion regulation strategies, along with their maternal and paternal attachment security. Results indicated that positive and negative emotion regulation strategies were differentially implicated in the link between attachment insecurity and BPD features. Attachment security functioned as a buffer against adolescent BP...

Research paper thumbnail of Borderline personality disorder in adolescents: evidence in support of the Childhood Interview for DSM-IV Borderline Personality Disorder in a sample of adolescent inpatients

Comprehensive Psychiatry, 2012

Empirical evidence is increasing in support of the validity of the construct of borderline person... more Empirical evidence is increasing in support of the validity of the construct of borderline personality disorder (BPD) in adolescence. There is growing consensus that the early identification and treatment of emerging borderline traits may be an important focus. However, few diagnostic (questionnaire- or interview-based) measures specifically developed or adapted for adolescents and children exist. The Childhood Interview for DSM-IV Borderline Personality Disorder (CI-BPD) [Zanarini, 2003] is a promising interview-based measure of adolescent BPD. Currently, no studies have explicitly been designed to examine the psychometric properties of the CI-BPD. The aim of the current study was to examine various psychometric properties of the CI-BPD in an inpatient sample of adolescents (n = 245). A confirmatory factor analytic approach was used to examine the internal factor structure of the 9 CI-BPD items. In addition, internal consistency, interrater reliability, convergent validity (with clinician diagnosis and 2 questionnaire-based measures of BPD), and concurrent validity (with Axis I psychopathology and deliberate self-harm) were examined. Similar to several adult studies, the confirmatory factor analytic results supported a unidimensional factor structure for the CI-BPD, indicating that the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria on which the CI-BPD is based constitute a coherent combination of traits and symptoms even in adolescents. In addition, other validity criteria were excellent. Taken together, the current study provides strong evidence for the validity of the CI-BPD for use in adolescents.

Research paper thumbnail of Hypermentalizing in adolescent inpatients: treatment effects and association with borderline traits

Sharp et al. (2011) recently demonstrated that in adolescents with borderline traits the loss of ... more Sharp et al. (2011) recently demonstrated that in adolescents with borderline traits the loss of mentalization is more apparent in the emergence of unusual alternative strategies (excessive theory of mind or hypermentalizing) than in the loss of the capacity per se (no mentalizing or undermentalizing). This suggests that hypermentalizing could be a worthwhile social-cognitive treatment target in adolescents with borderline traits. The aim of the current study was to examine (1) whether a reduction in excessive theory of mind or hypermentalizing is achieved between admission and discharge for adolescent inpatients; (2) whether the hypothesized reduction is more apparent in adolescents meeting criteria for BPD compared with psychiatric controls; and (3) whether other forms of mentalizing would also be sensitive to and malleable by inpatient treatment in the same way we expected hypermentalizing to be. The "Movie for the Assessment of Social Cognition" Task (Dziobek et al., 2006) was administered to consecutive admissions to an adolescent inpatient setting (n = 164) at admission and discharge, alongside measures of borderline symptomology and interview-based diagnosis of BPD. Results demonstrated that 41% (n = 68) of the sample met full or intermediate criteria for BPD on an interview-based measure of BPD. A relation between borderline traits and hypermentalizing that appears to be independent of internalizing and externalizing problems was demonstrated. Hypermentalizing, but not other forms of social-cognitive reasoning (as measured by the Child Eyes Test, Basic Empathy Scale and the Mentalizing Stories Test for Adolescents), was found to be malleable through a milieu-based inpatient treatment. Clinical implications of the findings for the organization of treatment settings for adolescents are discussed. Several developmental theories have emerged to elucidate the origins of Borderline Personality Disorder (BPD). A mentalization-based theory of BPD was proposed by Fonagy and colleagues (Fonagy, 1989, 1991; Fona