Marc Ferrer

COMORBID ATTENTION-DEFICIT/ HYPERACTIVITY DISORDER IN BORDERLINE PATIENTS DEFINES AN IMPULSIVE SUBTYPE OF BORDERLINE PERSONALITY DISORDER

In order to examine the impulsive profile of a BPD sample with comorbid ADHD, adult patients who met criteria for BPD were assessed for ADHD with the CAADID and the WURS. A high rate of ADHD in the BPD sample was found, with sixty-nine (38.1%) BPD patients diagnosed as having comorbid adult ADHD. BPD-ADHD group had higher rates of general substance use disorder (59.4% vs. 38.4%), antisocial personality disorder (7.2% vs. 0.9%) and obsessive-compulsive personality disorder (21.7% vs. 6.3%). The BPD group without comorbid adult ADHD showed a higher rate of mood disorders (62.5% vs. 37.7%), panic disorders (54.5% vs. 23.1%) and benzodiazepine abuse (18.8% vs. 5.8%). Only in BPD patients without ADHD was comorbid avoidant personality disorder found. BPD patients could be distinguished in two clear subgroups related to the adult ADHD comorbidity. BPD-ADHD patients showed a more homogeneous and impulsive profile while BPD without ADHD comorbidity had more anxiety and depressive disorders.

Effect of Switching Drug Formulations from Immediate-Release to Extended-Release OROS Methylphenidate

AbstractBackground: The potential advantages of osmotic-release oral system (OROS) methylphenidate (Concerta®) over immediate-release (IR) methylphenidate (Rubifen®) in adults with attention-deficit hyperactivity disorder (ADHD), with respect to medication adherence, effectiveness and tolerability, are yet to be determined. Objective: To compare the adherence, effectiveness and tolerability of OROS methylphenidate versus IR methylphenidate in adults with ADHD. It was hypothesized (after data collection) that adherence and effectiveness would be higher with OROS methylphenidate than with the IR formulation. Study design: A chart review was carried out from April 2004 until April 2005. Setting: Adult ADHD outpatient program in a general hospital in Spain. Patients: Seventy adults with ADHD who met DSM-IV-TR criteria and who did not have any other current major psychiatric disorder. Intervention: Patients were treated with IR methylphenidate three times daily for 3 months and then switched to OROS methylphenidate once daily. Main outcome measure: Effectiveness was assessed by means of the ADHD rating scale-IV (ADHD-RS-IV) and the Clinical Global Impression-Improvement (CGI-I) scale at 3 months (coinciding with treatment switch) and at 6 months. The Simplified Medication Adherence Questionnaire (SMAQ) was used to assess treatment adherence, and was administered at both 3 and 6 months. Results: Seventy adult ADHD patients (mean age ± SD: 30 ± 9.6 years; n = 48 men [68.6%]) were included in this study. The mean baseline ADHD-RS-IV score was 34.6 (SD = 10.9). The mean daily dose of IR methylphenidate was 52.1 mg (SD = 13.8 mg) administered as three divided doses. After the treatment switch, the mean OROS methylphenidate daily dose was 57.9 mg (SD = 16.5 mg) administered once daily.The switch from IR methylphenidate to OROS methylphenidate was associated with a statistically significant improvement in all items of the SMAQ questionnaire. OROS methylphenidate was more effective than IR methylphenidate (p = 0.0005) in reducing symptoms of ADHD. The percentage of responders was 28.6% with IR methylphenidate and 91.4% with the OROS formulation (p = 0.0005). OROS methylphenidate was preferred by 97% of patients. The most common adverse events for each formulation were dry mouth (30% IR methylphenidate) and mood instability (31% OROS methylphenidate). No patients stopped treatment with methylphenidate because of adverse events. Conclusions: The switch from IR to OROS methylphenidate was associated with an improvement in both adherence and effectiveness. There were no differences between IR and OROS methylphenidate in terms of tolerability.

Association between methylation of the glucocorticoid receptor gene, childhood maltreatment, and clinical severity in borderline personality disorder.

The hypothalamus-pituitary-adrenal axis (HPA) is essential in the regulation of stress responses. Increased methylation of the promoter region of the glucocorticoid receptor gene (NR3C1) has been described both in subjects with history of childhood trauma and in patients with Borderline Personality Disorder (BPD). However, no data on the possible association between a higher methylation of this gene and clinical severity is available. The aim of this study was to evaluate the association between NR3C1 methylation status, the history of childhood trauma, and current clinical severity in subjects with BPD. A sample of 281 subjects with BPD (diagnosed by SCID-II and DIB-R semi-structured diagnostic interviews) was recruited. Clinical variables included previous hospitalizations, self-injurious behavior, and self-reported history of childhood trauma. DNA was extracted from peripheral blood. The results indicated a significant positive correlation between NR3C1 methylation status and childhood maltreatment (specifically physical abuse). In addition, a positive correlation between methylation status and clinical severity (DIB-R total score and hospitalizations) was observed. These findings suggest that NR3C1 methylation in subjects with BPD may be associated not only with childhood trauma but also with clinical severity, adding new evidence to the involvement of gene-environment interactions in this disorder.

Axis II comorbidity in borderline personality disorder is influenced by sex, age, and clinical severity.

Borderline personality disorder (BPD) is a severe psychiatric disorder that has a high clinical heterogeneity and frequent co-occurrence with other personality disorders (PDs). Although several studies have been performed to assess axis II comorbidity in BPD, more research is needed to clarify associated factors. The aim of this study was to determine the prevalence of co-occurrent axis II disorders in a large sample of patients with BPD and to investigate the influence of sex, age, and severity on this comorbidity. Data were collected from 484 patients with BPD through 2 semistructured interviews. We analyzed the frequency of axis II comorbidity and assessed differences regarding sex, age, and severity of BPD. About 74% of patients with BPD had at least 1 co-occurrent axis II disorder. The most common were paranoid, passive-aggressive, avoidant, and dependent PDs. Significant sex differences were found. Women presented more comorbidity with dependent PD, whereas men showed higher rates of comorbidity with antisocial PD. We also observed a significant positive correlation between age and the number of co-occurrent axis II disorders in women with BPD. Another finding was the positive correlation between BPD severity and the number of co-occurrent axis II disorders. These findings suggest that comorbidity with other axis II disorders and sex, age, and severity should be taken into account when developing treatment strategies and determining the prognosis of BPD.

Neuroticism and impulsivity: Their hierarchical organization in the personality characterization of drug-dependent patients from a decision tree learning perspective

OBJECTIVE Neuroticism and impulsivity are the personality variables most consistently associated with drug-dependent patients. To date, no data mining procedures have been applied to explore the differential role of personality variables in this population. METHODS The personality profile of 336 drug-dependent patients was compared with that of a sample of community participants in the context of a decision tree learning approach using the Alternative Five Factor Model. The resulting discriminant model was cross-validated. RESULTS Neuroticism and impulsivity were the most relevant variables in the resulting model, but their association appeared to be hierarchically organized. In the personality characterization of these patients, neuroticism became the main discriminant dimension, whereas impulsivity played a differential role, explained by means of an interaction effect. Decision tree learning models appear to be a heuristic theoretical and empirical approximation to the study of relevant variables, such as personality traits, in drug-dependency research.

Confirmatory Factor Analysis of Borderline Personality Disorder symptoms based on two different interviews: The Structured Clinical Interview for DSM-IV Axis II Disorder and the Revised Diagnostic Interview for Borderlines

The diagnostic criteria for Borderline Personality Disorder (BPD) are heterogeneous, and include an admixture of personality traits, behaviours, and symptoms. The BPD DSM factor structure has been extensively studied, even though results are not consistent. In this study we performed a confirmatory factor analysis (CFA) to compare the five-factor model reported by Oldham, a three-factor model, and a unidimensional model of BPD diagnosis criteria. This study validates the findings of previous studies by performing a CFA with the DSM-IV BPD criteria and information derived from the DIB-R. A sample of 338 patients referred to our outpatient BPD program participated in the study. Results of the CFA support both the hypothesized unidimensional and the three-factor models, whereas the five-factor model was not confirmed. However, the three-factor model fits better than the unidimensional model. Thus, although the DSM-IV BPD criteria conceptualize BPD as a unidimensional structure, our results give support to the idea that the three-factor model could offer a better approach to further improve the current treatment of BPD, as well as lead to a better understanding of its ethiopathogenesis and comorbidity analysis.

Psychometric Properties of the Spanish PID-5 in a Clinical and a Community Sample:

The Personality Inventory for DSM-5 (PID-5) measures the trait part (Criterion B) of the alternative model for personality disorders proposed in Section III of DSM-5. Although its psychometric properties have proven adequate thus far, evidence is limited in other languages and in clinical samples. The Spanish PID-5 was examined in two samples comprising 446 clinical and 1,036 community subjects. Facet scales showed good internal consistency in both samples (median α = .86 and .79) and were unidimensional under exploratory and confirmatory approaches. They were also able to distinguish between clinical and community subjects with a mean standardized difference of z = 0.81. All facets except for Risk Taking were unipolar, such that the upper poles indicated pathology and the lower poles reflected normality, rather than the opposite pole of abnormality. The entire PID-5 hierarchical structure, from one to five factors, was confirmed in both samples with Tucker’s congruence coefficients over .95.

Effectiveness of combined individual and group dialectical behavior therapy compared to only individual dialectical behavior therapy: a preliminary study.

Dialectical behavior therapy (DBT) is an effective therapy. However, treating borderline personality disorder (BPD) patients with standard DBT can be problematic in some institutions due to logistical or cost limitations. The aim of this preliminary study is to examine the efficacy of Individual DBT in 37 BPD patients, compared with Combined individual/Group DBT in 14 BPD patients. Outcome measures included suicide attempts, self-harm behaviors, and visits to emergency departments. These variables were examined at pretreatment, 12 months/end of treatment, and at an 18-month follow-up. In addition, dropout rates were examined. Significant improvements on the outcome measures were observed across both versions of DBT treatment, particularly at the 18-month follow-up assessment. No significant differences were observed between Individual DBT and Combined individual/Group DBT on any of the posttreatment evaluations. An individual version of DBT may be an effective and less costly option for BPD treatment. Larger controlled trials are needed to confirm the results.

Cortisol responses in children and adults with attention deficit hyperactivity disorder (ADHD): a possible marker of inhibition deficits

Attention deficit hyperactivity disorder (ADHD) is a heterogeneous disease whose neurobiological background is not completely understood. It has been proposed that deficits of the inhibitory function with an underactive behavioral inhibition system (BIS) may be in the core of ADHD. In this regard, this review summarizes all studies that examine the involvement of cortisol in ADHD. Differences in cortisol responses from different ADHD subtypes, hyperactive/impulsive, inattentive, and combined, are analyzed. In addition, we examine the role of comorbidities as confounding factors in the study of cortisol in ADHD, including comorbid disruptive behavioral disorder (DBD), as well as anxiety and depressive disorders. Because ADHD is a neurodevelopmental condition and approximately half of the children enter adulthood with the disorder, we review cortisol studies in adults and children separately. Two diverse patterns of cortisol have been reported both in children and adults with ADHD. Blunted cortisol responses to stress are associated with comorbid DBD, whereas high cortisol responses are associated to comorbid anxiety disorders. Nevertheless, the inhibitory deficits in ADHD do not appear to be related directly to cortisol deficits in either children or adults. This review increases our understanding of the heterogeneity of ADHD and could help in determining new strategies for the treatment of these patients. Future studies including gender and a more systematic methodology to study the cortisol response are needed.

Cannabis use and striatal D2 receptor density in untreated first-episode psychosis: An in vivo SPECT study

The biological basis of the association between cannabis-induced dopamine dysregulation and psychosis remains poorly understood. This (123)I-IBZM SPECT study assessed striatal dopamine D2 receptor (D2R) binding in 37 untreated first-episode psychosis (FEP) subjects, and 18 healthy controls. The aim was to examine if there were differences between FEP subjects with (n=14) and without (n=23) cannabis use in uptake ratios in the D2R. Striatal/Frontal cortex (S/F) uptake ratios were obtained. Healthy controls showed the lowest D2R binding ratios. No differences were found in S/F ratios between users and non-users, suggesting similar dopaminergic mechanisms underlying psychotic symptoms in both groups.