Group intervention for family members of people with borderline personality disorder based on Dialectical Behavior Therapy: Implementation of the Family Connections® program in France and Switzerland.

BACKGROUND: Families and significant others of people with borderline personality disorder (BPD) show increased levels of psychological distress. Family Connections®, a 12-week group intervention based on the principles of Dialectical Behavior Therapy, was designed to provide families with both information about the disorder and emotion regulation skills. It has been progressively implemented in French-speaking European countries. METHODS: We conducted an observational, multicenter study in France and Switzerland. In total, 149 participants of the Family Connections program were included among five centers. Burden, depression, coping, and emotion regulation were assessed before and after the intervention. RESULTS: One-way repeated measures MANOVA showed that the burden, depressive symptoms, emotion regulation and coping all changed significantly after the intervention (p < 0.001, partial η2 = 0.297). T-tests showed that the burden significantly decreased after the intervention (p < 0.0001, d = -0.48), as did depressive symptoms (p < 0.0001, d = -0.36) and difficulties in emotion regulation (p < 0.0001, d =-0.32) whereas coping improved (p < 0.0001, d = 0.53). Two-way mixed ANOVA showed that burden reduction was stronger among female than male participants (p = 0.048, η2 = 0.027). Before the intervention, the burden was higher for female than male participants (p < 0.001). An initial linear regression showed the burden reduction to be associated with a decrease in the resignation of the participants (ß = 0.19, p = 0.047). A second linear regression showed the burden reduction to be associated with the intensity of the relatives' symptoms at baseline (ß = 0.22, p = 0.008) and improvement of emotional clarity of the participants (ß = 0.25, p = 0.006). CONCLUSION: This Dialectical Behavior Therapy-Based psychoeducational intervention is an appropriate way to support French-speaking European families of people with BPD.

Metabolic activity of CYP2C19 and CYP2D6 on antidepressant response from 13 clinical studies using genotype imputation: a meta-analysis.

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. CYP2D6 structural variants cannot be imputed from genotype data, limiting the determination of metabolic phenotypes, and precluding testing for association with response. The association of CYP2C19 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR = 1.46, 95% CI [1.03, 2.06], p = 0.033, heterogeneity I2 = 0%, subgroup difference p = 0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.

Sexually Transmitted Diseases and Attention-Deficit/Hyperactivity Disorder: A Systematic Literature Review.

Patients with attention-deficit/hyperactivity disorder (ADHD) suffer from inattention, hyperactivity, and impulsivity. Clinicians often assume that the specific difficulties associated with ADHD are bound to affect sexual behaviors, and favor risky sexual behaviors, thereby increasing the frequency of sexually transmitted diseases (STDs). This review provides an up-to-date synthesis of the literature concerning STDs in patients with ADHD. A systematic review of the literature was performed using the PubMed, PsychInfo, and Embase databases, with STDs as the main outcome measure. Patients with ADHD report more STDs than the general population. Results are limited by the small number of existing studies, as well as the heterogeneity of the outcome measures. Findings from this first systematic review of data on STDs in individuals with ADHD suggest that ADHD affects sexual health and sexual behaviors. Clinicians treating patients with ADHD should explore risky sexual behaviors in their patients and raise awareness about the risk of contracting STDs. Further studies are warranted to better evaluate the risk of contracting an STD in patients with ADHD.

Psychoeducation for Pathologic Narcissism and Narcissistic Personality Disorder: A Review and Proposal for a Good Psychiatric Management-based Six-week Group Program.

Pathologic narcissism (PN) and narcissistic personality disorder (NPD) are 2 common and stigmatized clinical constructs that are known to have large consequences for patients' functioning and mental health-related outcomes. To date, no treatment for these conditions has been empirically validated, but there is a relative consensus about the importance of psychoeducation. Here we present a model for a psychoeducational intervention for patients with PN or NPD. We start with a review of the current evidence on the role of psychoeducation in different treatment models for PN, and we discuss several aspects regarding the content and format of this type of intervention. Based on this review, we outline a 6-week Good Psychiatric Management-based psychoeducation group program that we developed. We also describe how such a psychoeducational intervention can be implemented individually, with fewer resources, in general care settings. Finally, we discuss the strengths and limitations of our approach and elaborate on the rationale for our proposal. We believe that this program proposal is a first step in the development of psychoeducational programs for PN and NPD that can be further corrected and enhanced.

Association between pathological narcissism and emotion regulation: The role of self-mentalizing?

Pathological narcissism (PN) is a common psychopathological issue leading to maladaptive strategies to cope with self-esteem threats, including self-enhancement and exploitation (grandiose strategies) or internalized shame, depression, and social withdrawal (vulnerable strategies). Mentalizing is a key process for regulating self and other representations and their associated emotions. Patients with PN further struggle with emotion dysregulation (ED), which during development is intertwined with the growing capacity to mentalize. We seek to contribute to emerging empirical data documenting the associations between PN and ED and between PN and mentalizing, and to provide information on the nature of their mutual relationships. In the present study, we assessed PN, ED, and three mentalizing dimensions (mentalizing self, other, and motivation to mentalize) in 183 patients consulting in our outpatient unit specialized in ED. We found that narcissistic vulnerability was negatively associated with self-mentalizing and positively associated with overall ED, both even after adjustment for borderline and attention deficit hyperactivity disorder (ADHD) symptoms. However, the association with ED was not maintained after further adjustment for self-mentalizing or overall-mentalizing, which suggests that mentalizing may play a mediating role in this relationship. On the other hand, narcissistic grandiosity was positively associated with other-mentalizing and ED and negatively associated with self-mentalizing in bivariate analyses, but these last two associations were not maintained after adjustment for comorbid borderline and/or ADHD symptomatology. This study provides new information on the link between PN and ED and on key mentalizing dimensions meaningfully relating to PN, notably through a potential role of self-mentalizing processes between PN and ED.

Adult ADHD and pathological narcissism: A retrospective-analysis.

Adult attention deficit hyperactivity disorder (ADHD) is often associated with personality pathology. However, only few studies have been conducted on the link between ADHD and pathological narcissism (PN), with or without a diagnosis of narcissistic personality disorder (NPD). In order to fill this gap, PN and NPD were assessed in 164 subjects suffering from ADHD, with several other measures including ADHD severity, quality of life, depression, anxiety, impulsivity, and emotion dysregulation (ED). We found that a significant proportion of ADHD patients suffered from NPD, and that both narcissistic grandiosity and vulnerability were associated with ADHD hyperactivity and impulsivity symptoms, but not with inattentive symptoms. These two dimensions seemed to be negatively associated with well-being and positively associated with most of the other studied psychiatric dimensions except ED, the latter being only associated with vulnerability, even after adjustment on borderline symptoms. Overall, despite important limitations that limit the generalizability of our findings to the overall ADHD population (notably linked to selection bias), we believe that this exploratory study sheds light on the potential clinical relevance of narcissistic pathology in adult ADHD patients.

[Early interventions for emotional regulation in adolescence, where are we?] / Interventions précoces pour la régulation émotionnelle à l'adolescence.

Adolescence is a vulnerable period for mental health. It is not easy to make a precise diagnosis during this period, as young people may present attenuated forms of psychiatric pathology, or on the contrary, a combination of several types of difficulties. Adopting a transdiagnostic and dimensional approach, based on clinical stages, and thus proposing interventions adapted to the severity of symptoms, is pertinent. As emotional dysregulation lies at the heart of many pathologies, it is a prime target for early intervention. Although interventions for adolescents are still underdeveloped, certain approaches derived from cognitive-behavioral therapies and the psychodynamic current have been adapted for adolescents and appear promising.

L'adolescence constitue une période vulnérable pour la santé mentale. Poser un diagnostic précis durant cette période n'est pas aisé car les jeunes peuvent présenter des formes atténuées de pathologies psychiatriques, ou, au contraire, une combinaison de plusieurs types de difficultés. Adopter une approche transdiagnostique et dimensionnelle, en fonction de stades cliniques, et ainsi proposer des interventions adaptées à la sévérité des symptômes est pertinent. La dysrégulation émotionnelle étant au cœur de nombreuses pathologies, elle est une cible de premier choix pour des interventions précoces. Bien que les interventions pour les adolescents soient encore peu développées, certaines approches issues des thérapies cognitivo-comportementales et du courant psychodynamique ont été adaptées pour les adolescents et semblent prometteuses.

Proposition of a transdiagnostic processual approach of emotion dysregulation based on core triggers and interpersonal styles.

Emotion dysregulation (ED) has primarily been described in patients suffering from borderline personality disorder (BPD) and is an integral part of this diagnosis, but it is also a transdiagnostic construct that can be found in several other psychiatric disorders. The strong relationships between ED and BPD may lead clinicians to underestimate ED associated to other clinical contexts. This can lead to difficulties in diagnostic and treatment orientation, especially in the context of comorbidities. In this article, after reviewing the literature on the development and functioning of emotion dysregulation, and on the evidence for emotion dysregulation in eight disorders (borderline personality disorder, pathological narcissism with/without narcissistic personality disorder, obsessive-compulsive personality disorder, antisocial personality disorder, bipolar disorder, autism spectrum disorder, complex post-traumatic stress disorder, and adult attention deficit hyperactivity disorder), we present a transdiagnostic processual model of emotion dysregulation based on core triggers and interpersonal styles to try to address this issue and to provide a simple but technical tool to help clinicians in their diagnostic assessment and treatment orientation. By focusing more on typical patterns and interpersonal dynamics than only on categories, we believe that this model may contribute to the actual need for improvement of our current psychiatric classifications, alongside other well-studied and under-used dimensional models of psychopathology (e.g., HiTOP, AMPD), and may be useful to build more specific treatment frameworks for patients suffering from ED.

Protocol of a monocentric, double-blind, randomized, superiority, controlled trial evaluating the effect of in-prison OROS-methylphenidate vs. placebo treatment in detained people with attention-deficit hyperactivity disorder (BATIR).

BACKGROUND: Attention-deficit hyperactivity disorder (ADHD) is characterized by difficulty paying attention, poor impulse control, and hyperactive behavior. It is associated with several adverse health and social outcomes and leads to an increased risk of criminality and recidivism. Worldwide, ADHD is thus highly prevalent in prisons. However, ADHD treatment has been neglected in such environments. Stimulant medications such as osmotic-release oral system methylphenidate (OROS-MPH) are first-line treatments in the general population, but they are under-prescribed in prisons due to concerns about abuse, even though such claims are not empirically supported. This project aims to compare the efficacy of a 3-month in-prison OROS-MPH vs. placebo treatment on the severity of core ADHD symptoms and relevant in- and post-prison outcomes. METHODS: This study is a phase III, double-blinded, randomized, superiority, controlled trial of OROS-MPH vs. placebo. After randomization, the participants will receive 3 months of treatment with OROS-MPH or placebo (1:1 ratio) while incarcerated. Upon release, all participants will be offered the treatment (OROS-MPH) for 1 year but will remain blinded to their initial study group. The study will be conducted at the Division of Prison Health, Geneva, Switzerland, among incarcerated men (n = 150). Measures will include (1) investigator-rated ADHD symptoms, (2) acute events collected by the medical and prison teams, (3) assessment of the risk of recidivism, (4) medication side effects, (5) medication adherence, (6) study retention, (7) health care/prison costs, and (8) 1-year recidivism. Analyses will include bivariable and multivariable modeling (e.g., regression models, mixed-effects models, survival analyses) and an economic evaluation (cost-benefit analysis). DISCUSSION: We expect that early identification and treatment of ADHD in prison will be an important public health opportunity and a cost-effective approach that is likely to reduce the vulnerability of incarcerated individuals and promote pathways out of criminal involvement. The study will also promote standards of care for people with ADHD in prison and provide recommendations for continuity of care after release. TRIAL REGISTRATION: ClinicalTrials.gov NCT05842330 . Registered on June 5, 2023. Kofam.ch SNCTP000005388. Registered on July 17, 2023.

Resting-State EEG Microstates and Power Spectrum in Borderline Personality Disorder: A High-Density EEG Study.

Borderline personality disorder (BPD) is a debilitating psychiatric condition characterized by emotional dysregulation, unstable sense of self, and impulsive, potentially self-harming behavior. In order to provide new neurophysiological insights on BPD, we complemented resting-state EEG frequency spectrum analysis with EEG microstates (MS) analysis to capture the spatiotemporal dynamics of large-scale neural networks. High-density EEG was recorded at rest in 16 BPD patients and 16 age-matched neurotypical controls. The relative power spectrum and broadband MS spatiotemporal parameters were compared between groups and their inter-correlations were examined. Compared to controls, BPD patients showed similar global spectral power, but exploratory univariate analyses on single channels indicated reduced relative alpha power and enhanced relative delta power at parietal electrodes. In terms of EEG MS, BPD patients displayed similar MS topographies as controls, indicating comparable neural generators. However, the MS temporal dynamics were significantly altered in BPD patients, who demonstrated opposite prevalence of MS C (lower than controls) and MS E (higher than controls). Interestingly, MS C prevalence correlated positively with global alpha power and negatively with global delta power, while MS E did not correlate with any measures of spectral power. Taken together, these observations suggest that BPD patients exhibit a state of cortical hyperactivation, represented by decreased posterior alpha power, together with an elevated presence of MS E, consistent with symptoms of elevated arousal and/or vigilance. This is the first study to investigate resting-state MS patterns in BPD, with findings of elevated MS E and the suggestion of reduced posterior alpha power indicating a disorder-specific neurophysiological signature previously unreported in a psychiatric population.

Mentalizing in Adolescents and Young Adults with Attention Deficit Hyperactivity Disorder: Associations with Age and Attention Problems.

INTRODUCTION: Growing, albeit heterogenous evidence questions whether attention deficit/hyperactivity disorder (ADHD) is associated with socio-cognitive impairments, especially beyond childhood. This study focuses on mentalizing - the socio-cognitive ability to attribute and reason in terms of mental states. We aimed to characterize mentalizing performance in terms of correct scores and types of errors in adolescents and young adults with ADHD. METHODS: Forty-nine adolescents and adults with ADHD and 49 healthy controls matched for age and gender completed a computerized naturalistic mentalizing task, the Movie for Assessment of Social Cognition (MASC). Repeated measures analyses of variance examined the effects of age group and ADHD diagnosis on MASC performance. Additionally, associations between mentalizing scores, the severity of attention problems, and the presence of comorbidity were explored in the ADHD group. RESULTS: Results showed an increased prevalence of hypomentalizing errors in adolescents with ADHD. Lower mentalizing scores in adolescents with ADHD were correlated with indices of inattentiveness, impulsivity, and vigilance problems. Hypomentalizing errors in adolescents showed to be particularly associated with inattentiveness, after controlling for age and comorbidity. In contrast, adults with ADHD performed similarly to controls and their scores on the mentalizing task were not correlated to attention problems. CONCLUSION: These findings highlight potential developmental differences in mentalizing abilities in ADHD youths and their association with attentional impairments.

Mindfulness-based interventions for patients with schizophrenia spectrum disorders: A systematic review of the literature.

BACKGROUND: Mindfulness-based interventions (MBIs) have emerged as secular practices, including elements of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT). While MBIs have been widely adopted for physical and mental illness, only a few available programs are explicitly adapted for psychosis. However, previous reviews have reported the vital heterogeneity regarding treatment program structure. Therefore, this review aims to compare the structure of different mindfulness protocols applied to patients with schizophrenia spectrum disorder (SSD). METHODS: A systematic search was conducted up to March 2023 in PubMed, Embase and PsycInfo. Following our protocol (CRD 42023253356), we followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) checklist. RESULTS: We included 22 randomized controlled trials (RCTs) involving 1500 patients SSD. All programs varied in structure, session components, duration, and instructor experience. While MBSR-like programs focused on stress reactivity, MBCT-like programs addressed primary symptoms of psychosis and relapse prevention. Despite the heterogeneity of programs, some common mechanisms emerged, including attention training, emotion and stress regulation, decentering, self-compassion, and cognitive restructuring. CONCLUSIONS: The critical heterogeneity found limits the interpretation of results. However, most recent trials present fewer risks of bias and more homogenous programs. Findings suggested potential benefits, such as reduced negative symptoms, increased well-being, and decreased hospitalization rates. For future studies, authors should align on more congruent MBIs programs for patients with SSD. Further research is needed to identify optimal mindfulness teaching approaches for patients with psychosis and investigate specific mechanisms of action, relevant processes, and optimal doses in varying settings.

Childhood maltreatment, dissociation and borderline personality disorder: Preliminary data on the mediational role of mentalizing in complex post-traumatic stress disorder.

OBJECTIVES: Treatments for borderline personality disorder (BPD) and post-traumatic stress disorder (PTSD) are less effective for patients with co-occurring symptoms of both disorders, who are considered to have complex PTSD (cPTSD), compared with patients with either condition alone. Evidence suggests that co-occurrence of symptoms indicates greater impairment in mentalizing. This study examines evidence for targeting mentalizing when treating individuals with co-occurring symptoms, irrespective of their exposure to developmental trauma and, for the first time, investigates the mediational role of mentalizing in the associations between BPD symptomatology and cPTSD. DESIGN: We identified in a routine clinical service a group of patients with BPD, with or without co-occurring symptoms of PTSD. We hypothesized that patients with co-occurring symptoms and a history of childhood maltreatment will show more severe clinical profiles and greater mentalizing problems, which in turn lead to symptoms consistent with cPTSD. METHOD: Clinical profiles of 72 patients with BPD (43 with and 29 without co-occurring symptoms of PTSD; mean age in both groups 28 years, 79% and 83% female, respectively) were identified using the Structured Clinical Interview for DSM-IV Axis II Disorders. Patients completed self-report measures of BPD and PTSD symptoms, well-being, dissociation and reflective functioning. Childhood trauma histories were evaluated. RESULTS: Compared with patients with BPD-only, those with co-occurring BPD and PTSD showed greater severity in terms of BPD and dissociative symptoms, met a broader range of BPD diagnostic criteria, had a greater sense of personal worthlessness and self-evaluated their well-being as considerably diminished. This group was also more inclined to recall increased instances of childhood sexual abuse. In a mediation analysis, mentalizing acted as a partial mediator for the relationship between BPD severity and cPTSD, as well as between dissociative symptoms and cPTSD. Interestingly, mentalizing did not mediate the relationship between childhood sexual abuse and cPTSD. CONCLUSIONS: Overall, the correlational findings are consistent with an intended focus on mentalizing to treat cPTSD symptoms in individuals who also meet criteria for a diagnosis of BPD.

Transdiagnostic risk of mental disorders in offspring of affected parents: a meta-analysis of family high-risk and registry studies.

The offspring of parents with mental disorders are at increased risk for developing mental disorders themselves. The risk to offspring may extend transdiagnostically to disorders other than those present in the parents. The literature on this topic is vast but mixed. To inform targeted prevention and genetic counseling, we performed a comprehensive, PRISMA 2020-compliant meta-analysis. We systematically searched the literature published up to September 2022 to retrieve original family high-risk and registry studies reporting on the risk of mental disorders in offspring of parents with any type of mental disorder. We performed random-effects meta-analyses of the relative risk (risk ratio, RR) and absolute risk (lifetime, up to the age at assessment) of mental disorders, defined according to the ICD or DSM. Cumulative incidence by offspring age was determined using meta-analytic Kaplan-Meier curves. We measured heterogeneity with the I2 statistic, and risk of bias with the Quality In Prognosis Studies (QUIPS) tool. Sensitivity analyses addressed the impact of study design (family high-risk vs. registry) and specific vs. transdiagnostic risks. Transdiagnosticity was appraised with the TRANSD criteria. We identified 211 independent studies that reported data on 3,172,115 offspring of parents with psychotic, bipolar, depressive, disruptive, attention-deficit/hyperactivity, anxiety, substance use, eating, obsessive-compulsive, and borderline personality disorders, and 20,428,575 control offspring. The RR and lifetime risk of developing any mental disorder were 3.0 and 55% in offspring of parents with anxiety disorders; 2.6 and 17% in offspring of those with psychosis; 2.1 and 55% in offspring of those with bipolar disorder; 1.9 and 51% in offspring of those with depressive disorders; and 1.5 and 38% in offspring of those with substance use disorders. The offspring's RR and lifetime risk of developing the same mental disorder diagnosed in their parent were 8.4 and 32% for attention-deficit/hyperactivity disorder; 5.8 and 8% for psychosis; 5.1 and 5% for bipolar disorder; 2.8 and 9% for substance use disorders; 2.3 and 14% for depressive disorders; 2.3 and 1% for eating disorders; and 2.2 and 31% for anxiety disorders. There were 37 significant transdiagnostic associations between parental mental disorders and the RR of developing a different mental disorder in the offspring. In offspring of parents with psychosis, bipolar and depressive disorder, the risk of the same disorder onset emerged at 16, 5 and 6 years, and cumulated to 3%, 19% and 24% by age 18; and to 8%, 36% and 46% by age 28. Heterogeneity ranged from 0 to 0.98, and 96% of studies were at high risk of bias. Sensitivity analyses restricted to prospective family high-risk studies confirmed the pattern of findings with similar RR, but with greater absolute risks compared to analyses of all study types. This study demonstrates at a global, meta-analytic level that offspring of affected parents have strongly elevated RR and lifetime risk of developing any mental disorder as well as the same mental disorder diagnosed in the parent. The transdiagnostic risks suggest that offspring of parents with a range of mental disorders should be considered as candidates for targeted primary prevention.

Evaluation of the level of training of French psychiatrists on borderline personality disorder: An online survey.

BACKGROUND: Borderline personality disorder is a common and treatable personality disorder that is often underdiagnosed and untreated, mainly due to a lack of training of psychiatrists and to a lack of accessibility to specialized therapies. However, no study has been conducted in France regarding this issue. Thus, we aimed to evaluate on a national scale the level of training, knowledge, and general attitude toward BPD diagnosis of French psychiatrists. METHODS: We conducted an online survey in an unselected population of residents and senior French psychiatrists between January and March 2022, the results of which are presented descriptively. RESULTS: 228 psychiatrists fully answered the questionnaire, and 21 more psychiatrists answered it partially. We found that most of the responders were unsatisfied with the residency training or the continuing medical education offered regarding BPD, a lack of training resulting in a low level of self-confidence regarding BPD management, in a low number of evidence-based therapies trained psychiatrists in issues regarding diagnostic disclosure, and in misconceptions regarding some aspects of the disorder. CONCLUSIONS: These results underlie a clear lack of training of French psychiatrists, as well as a request from the latter for more opportunities to learn. This calls for a rethinking of the teaching system to incorporate more knowledge and tools related to BPD.

Case reports: Using Good Psychiatric Management (GPM) conceptualizations in the dimensional assessment and treatment of personality disorders.

Good Psychiatric Management (GPM) is a generalist clinical management approach for borderline personality disorder that incorporates common ingredients of good standard care for any psychiatric diagnosis with what works from prevailing specialist psychotherapies. Similar to all validated therapies for BPD, it relies on a specified formulation of the disorder' symptoms as arising from interpersonal hypersensitivity, to dynamically describe typical patterns of daily self- and interpersonal issues that drive the instability that defines the general personality dysfunction characteristic of the disorder. Recent adaptations of GPM have been proposed for narcissistic personality disorder and obsessive-compulsive personality disorder, with development of similar dynamic models for both (intrapsychic coherence model and model of overcontrol). New dimensional models of personality disorder diagnosis have been developed to address limitations of categorical approach, but the incorporation of these models into usage in the delivery of clinical services (where categorical approach remains the most used) is limited. This paper describes an adaptation of GPM to two cases of personality disorder that illustrate the usefulness of GPM models for dynamic representation of complex daily fluctuations in internal psychic coherence and interpersonal functioning. Specialist psychotherapies will never meet the demands of public health needs to treat personality dysfunction, and incorporation of new dimensional models of diagnosis are needed for treatments that can provide a minimal standard of care for providers and patients.

Meta-analysis of CYP2C19 and CYP2D6 metabolic activity on antidepressant response from 13 clinical studies using genotype imputation.

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. The association of CYP2C19 and CYP2D6 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR=1.46, 95% CI [1.03, 2.06], p=0.033, heterogeneity I2=0%, subgroup difference p=0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19 and CYP2D6, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. CYP2D6 structural variants cannot be imputed from genotype data, limiting inference of pharmacogenetic effects. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.

Association of polygenic score and the involvement of cholinergic and glutamatergic pathways with lithium treatment response in patients with bipolar disorder.

Lithium is regarded as the first-line treatment for bipolar disorder (BD), a severe and disabling mental health disorder that affects about 1% of the population worldwide. Nevertheless, lithium is not consistently effective, with only 30% of patients showing a favorable response to treatment. To provide personalized treatment options for bipolar patients, it is essential to identify prediction biomarkers such as polygenic scores. In this study, we developed a polygenic score for lithium treatment response (Li+PGS) in patients with BD. To gain further insights into lithium's possible molecular mechanism of action, we performed a genome-wide gene-based analysis. Using polygenic score modeling, via methods incorporating Bayesian regression and continuous shrinkage priors, Li+PGS was developed in the International Consortium of Lithium Genetics cohort (ConLi+Gen: N = 2367) and replicated in the combined PsyCourse (N = 89) and BipoLife (N = 102) studies. The associations of Li+PGS and lithium treatment response - defined in a continuous ALDA scale and a categorical outcome (good response vs. poor response) were tested using regression models, each adjusted for the covariates: age, sex, and the first four genetic principal components. Statistical significance was determined at P < 0.05. Li+PGS was positively associated with lithium treatment response in the ConLi+Gen cohort, in both the categorical (P = 9.8 × 10-12, R2 = 1.9%) and continuous (P = 6.4 × 10-9, R2 = 2.6%) outcomes. Compared to bipolar patients in the 1st decile of the risk distribution, individuals in the 10th decile had 3.47-fold (95%CI: 2.22-5.47) higher odds of responding favorably to lithium. The results were replicated in the independent cohorts for the categorical treatment outcome (P = 3.9 × 10-4, R2 = 0.9%), but not for the continuous outcome (P = 0.13). Gene-based analyses revealed 36 candidate genes that are enriched in biological pathways controlled by glutamate and acetylcholine. Li+PGS may be useful in the development of pharmacogenomic testing strategies by enabling a classification of bipolar patients according to their response to treatment.

[Towards a pragmatic cohabitation of theoretical and clinical models: The example of "Good Psychiatric Management" in the treatment of borderline personality disorder]. / Pour une cohabitation pragmatique des modèles théoriques et cliniques : l'exemple du « Good Psychiatric Management ¼ dans le traitement du trouble de personnalité borderline.

Borderline personality disorder (BPD) is a common disorder in general and clinical populations and is related to potentially severe medical and socio-professional consequences. Treatment of BPD is based on evidence-based psychotherapies (such as Dialectical Behavioral Therapy, Mentalization-Based Therapy, Schema-Focused Therapy or Transference Focused Psychotherapy), which have been shown effective but are poorly available in France. Pharmacological treatments, which are more easily available, are not effective in treating symptoms of the disorder but can be useful in management of comorbidities. In this context, recently called "generalist" models have been developed, which every well-trained psychiatrist can implement in their daily practice, combining practical elements from evidence-based psychotherapies and elements of pharmacological management of symptoms and comorbidities. The purpose of this article is to present one of these models, the Good Psychiatric Management (GPM) and its basic principles and its applications, and to provide one of the first French-speaking resources about this model. In addition, beyond the practical elements proposed by the GPM, we discuss the deeper question that it raises, namely the question of a pragmatic integration of different theoretical and clinical models. Indeed, the treatment of BPD patients is at the junction of different conceptualizations of mental pathology (psychopathological, neurobiological) and different modalities of practice (psychotherapy, biological psychiatry). In a French context, that sometimes separates these two models, and in our opinion GPM constitutes an example of clinical collaboration which shows the interest of the combined role of psychiatrist-psychotherapist.