Rosetta Nicastro

Increased methylation of glucocorticoid receptor gene ( NR3C1 ) in adults with a history of childhood maltreatment: a link with the severity and type of trauma

Childhood maltreatment, through epigenetic modification of the glucocorticoid receptor gene (NR3C1), influences the hypothalamic–pituitary–adrenal axis (HPA axis). We investigated whether childhood maltreatment and its severity were associated with increased methylation of the exon 1F NR3C1 promoter, in 101 borderline personality disorder (BPD) and 99 major depressive disorder (MDD) subjects with, respectively, a high and low rate of childhood maltreatment, and 15 MDD subjects with comorbid post-traumatic stress disorder (PTSD). Childhood sexual abuse, its severity and the number of type of maltreatments positively correlated with NR3C1 methylation (P=6.16 × 10−8, 5.18 × 10−7 and 1.25 × 10−9, respectively). In BPD, repetition of abuses and sexual abuse with penetration correlated with a higher methylation percentage. Peripheral blood might therefore serve as a proxy for environmental effects on epigenetic processes. These findings suggest that early life events may permanently impact on the HPA axis though epigenetic modifications of the NR3C1. This is a mechanism by which childhood maltreatment may lead to adulthood psychopathology.

Response to psychotherapy in borderline personality disorder and methylation status of the BDNF gene

Downregulation of brain-derived neurotrophic factor (BDNF) gene expression with corresponding increased methylation at specific promoters has been associated with stressful experiences in early life and may explain later adulthood psychopathology. We measured the percentage of methylation at BDNF CpG exons I and IV as well as plasma BDNF protein levels in 115 subjects with borderline personality disorder (BPD) and 52 controls. BPD subjects then underwent a 4-week course of intensive dialectical behavior therapy (I-DBT). BDNF methylation status and protein levels were re-assessed at the end of treatment. BPD subjects had significantly higher methylation status in both CpG regions than controls. In addition, the higher the number of childhood trauma, the higher was the methylation status. In BPD subjects, BDNF methylation significantly increased after I-DBT. Nonresponders accounted for the majority of this increase, whereas responders showed a decrease in methylation status over time. Accordingly, the changes in methylation status over time were significantly associated with changes in depression scores, hopelessness scores and impulsivity. No association was found between protein levels and BDNF methylation status. We here found a relationship between child maltreatment and higher DNA methylation of BDNF. These results moreover support the idea that these epigenetic marks may be changed through psychotherapeutic approaches and that these changes underline changes in cognitive functions.

Distinguishing borderline personality disorder from adult attention deficit/hyperactivity disorder: A clinical and dimensional perspective

Adult attention deficit hyperactivity disorder (ADHD) is frequently associated with borderline personality disorder (BPD). As both disorders share some core clinical features they are sometimes difficult to distinguish from one another. The present work aimed to investigate differences in the expression of impulsivity, anger and aggression, quality of life as well as the number and severity of the comorbidities between ADHD, BPD, comorbid BPD-ADHD and control subjects. ADHD and BPD-ADHD patients showed a higher level of impulsivity than BPD and control subjects. BPD-ADHD patients had higher levels of substance abuse/dependence and higher levels of aggression than the other groups. Comorbid BPD-ADHD patients showed high levels of impulsivity and aggression, a characteristic that should draw the attention of clinicians on the necessity of providing an accurate diagnosis. The question also arises as to whether they represent a distinct clinical subgroup with specific clinical characteristics, outcomes and vulnerability factors.

Mindfulness skills in borderline personality disorder patients during dialectical behavior therapy: preliminary results.

Objective. One of the components of dialectical behavior therapy (DBT) is the use of mindfulness skills as a core component of treatment for subjects with borderline personality disorder (BPD). In this study, we investigated changes in and correlates of mindfulness skills over a 1-year follow-up including a 4-week session of intensive DBT followed by 10 months of standard DBT. Methods. Fifty-two BPD subjects were assessed several times using the Kentucky Inventory of Mindfulness Skills (KIMS) which describes mindfulness in four discrete dimensions: observing (Obs), describing (Des), acting with awareness (AwA) and accepting without judgment (AwJ). Results. AwJ was the only dimension that increased significantly over time after adjustment for potential confounding factors (β = 0.24; P = 0.0002). Increases in AwJ correlated with improvement in BPD symptoms. Conclusions. This study highlights the usefulness of investigating changes in mindfulness dimensions during DBT. AwJ is a possible mechanism for positive change. Encouraging this skill should lead to a more adaptive response to problematic situations and counteract impulsive and problematic behaviors. The lack of specific control groups means that these findings are preliminary and replication is required.

METHYLATION OF SEROTONIN RECEPTOR 3A IN ADHD, BORDERLINE PERSONALITY, AND BIPOLAR DISORDERS: LINK WITH SEVERITY OF THE DISORDERS AND CHILDHOOD MALTREATMENT

Serotonin 3A receptor (5‐HT3AR) is associated at the genetic and epigenetic levels with a variety of psychiatric disorders and interacts with early‐life stress such as childhood maltreatment. We studied the impact of childhood maltreatment on the methylation status of the 5‐HT3AR and its association with clinical severity outcomes in relation with a functional genetic polymorphism.

Borderline personality disorder and childhood maltreatment: a genome‐wide methylation analysis

Early life adversity plays a critical role in the emergence of borderline personality disorder (BPD) and this could occur through epigenetic programming. In this perspective, we aimed to determine whether childhood maltreatment could durably modify epigenetic processes by the means of a whole‐genome methylation scan of BPD subjects. Using the Illumina Infinium® HumanMethylation450 BeadChip, global methylation status of DNA extracted from peripheral blood leucocytes was correlated to the severity of childhood maltreatment in 96 BPD subjects suffering from a high level of child adversity and 93 subjects suffering from major depressive disorder (MDD) and reporting a low rate of child maltreatment. Several CpGs within or near the following genes (IL17RA, miR124‐3, KCNQ2, EFNB1, OCA2, MFAP2, RPH3AL, WDR60, CST9L, EP400, A2ML1, NT5DC2, FAM163A and SPSB2) were found to be differently methylated, either in BPD compared with MDD or in relation to the severity of childhood maltreatment. A highly relevant biological result was observed for cg04927004 close to miR124‐3 that was significantly associated with BPD and severity of childhood maltreatment. miR124‐3 codes for a microRNA (miRNA) targeting several genes previously found to be associated with BPD such as NR3C1. Our results highlight the potentially important role played by miRNAs in the etiology of neuropsychiatric disorders such as BPD and the usefulness of using methylome‐wide association studies to uncover such candidate genes. Moreover, they offer new understanding of the impact of maltreatments on biological processes leading to diseases and may ultimately result in the identification of relevant biomarkers.

PREDICTORS OF RESPONSE AND DROP-OUT DURING INTENSIVE DIALECTICAL BEHAVIOR THERAPY

The purpose of this study was to examine the effectiveness, and predictors of response and drop-out during a four-week course of intensive dialectical behavior therapy (I-DBT) in 447 outpatients suffering from borderline personality disorder (BPD), over a 10-year period. Assessments included a diagnostic interview, the International Personality Disorder Examination Screening Questionnaire, the Beck Depression Inventory, and the Beck Hopelessness Scale. Among these participants, 103 started a second course of treatment. In agreement with previous reports, I-DBT was effective in reducing levels of depression and hopelessness with a trend of increasing effectiveness over the study period. High schizoid scores and low narcissistic score predicted poor response. Treatment completion rate was high, and low education predicted dropout. A discussion on the usefulness of a second course of treatment should be held with patients and staff as it was not effective in reducing depression and hopelessness.

Assessment of Mindfulness With the French Version of the Kentucky Inventory of Mindfulness Skills in Community and Borderline Personality Disorder Samples

This article explores mindfulness skills in community and borderline personality disorder (BPD) samples. Study 1 includes 173 community volunteers and explores the psychometric properties of the French version of the Kentucky Inventory of Mindfulness Skills (KIMS). Study 2 explores the KIMS factor structure in 130 BPD patients and compares KIMS scores of this sample with those of the community sample from Study 1. Study 3 investigates the changes in KIMS scores in a BPD sample (n = 82) treated with Intensive Dialectical Behavior Therapy (I-DBT). Results suggest that the psychometric properties of the French KIMS are comparable with those of the original version in the community and the BPD samples. Moreover, fewer mindfulness skills were found in BPD patients than in control participants. It was also observed that the ability to describe and to act with awareness increased in BPD patients after I-DBT. The present work makes a French instrument measuring mindfulness in daily activities available for clinical practice and research.

Similarities between emotional dysregulation in adults suffering from ADHD and bipolar patients

BACKGROUND Emotional dysregulation in subjects with attention deficit and hyperactivity disorder (ADHD) is a topic of growing interest among clinicians and researchers. The present study aims at investigating components of emotional dysregulation in adults ADHD compared to subjects suffering from bipolar disorder (BD). METHODS A total of 150 adults ADHD, 335 adults BD subjects and 48 controls were assessed using the Affective Lability Scale (ALS) and the Affect Intensity Measure (AIM), measuring respectively emotion lability and emotion responsiveness. RESULTS ADHD and BD subjects scored significantly higher on the ALS compared to controls (p=0.0001). BD subjects scored above ADHD ones (3.07 (SD=0.66) vs. 2.30 (SD=0.68); p<0.0001). The average total scores achieved on the AIM were significantly different for the three groups (p=0.0001) with significantly higher scores for ADHD subjects compared to BD ones (3.74 (SD=0.59) vs. 3.56 (SD=0.69); p<0.0001). LIMITATIONS Suspected cases of ADHD in the BD and control groups were derived from the Wender Utah Rating Scale (WURS). This study is a retrospective one. CONCLUSION Our study thus highlights the importance of emotional dysregulation in adults suffering from ADHD, showing that they display higher emotional intensity than bipolar disorder subjects and controls. Although the current diagnostic criteria of ADHD do not contain an emotional dimension, a better recognition of the significance of emotional responsiveness in ADHD patients can improve the care afforded to these patients, beyond the inattentive and hyperactive/impulsive components.

Functions and timescale oF selF-cutting in participants suFFering From borderline personality disorder

The purpose of this study was to examine the meanings and timescale of self-cuttings in a cohort of 22 outpatients suffering from borderline personality disorder. Sixty-one events were recorded using the newly developed self-cutting-checklist (SCUC) designed to investigate the severity of self-cuttings, and intent to die, suicidal ideation, inner tension, sense of relief and anesthesia, and consequences associated with this behavior. We found that typical self-cuttings were associated with a decrease in inner tension and suicidal ideation. Moreover self-cuttings associated with a desire to die differentiated from those associated with no desire to die by significantly less reduction in inner tension. Finally, self-cuttings occurred significantly more often during evenings and nights than during daytime. In conclusion, self-cuttings can be reasonably addressed by self-report. Attention to specific issues such as intent to die and the time of the self-cuttings may improve the outcome of these particularly high-risk subjects.