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.

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.

[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.

[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.

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.

[Artificial intelligence and psychiatry: questions from psychiatrists to ChatGPT]. / Intelligence artificielle et psychiatrie : questions de psychiatres à ChatGPT.

Psychiatrists and psychotherapists specialising in the fields of addiction, personality disorders, ADHD and suicidal crisis, we questioned the ChatGPT artificial intelligence program in order to form an opinion on the quality of its answers to questions on these subjects. Our aim is to satisfy our curiosity about these emerging tools. On the other hand, we want to assess the relevance of the answers in order to know whether relatives and patients can use them safely. In this article, we comment on the question-and-answer dialogue with the artificial intelligence program in the light of the literature.

Psychiatres et psychothérapeutes spécialisés dans les domaines de l'addiction, les troubles de la personnalité, le TDAH et la crise suicidaire, nous avons questionné le programme d'intelligence artificielle ChatGPT dans le but de nous faire une opinion sur la qualité de ses réponses à des questions sur ces sujets. Notre objectif est, d'une part, de satisfaire notre curiosité face à ces outils émergents. Nous voulons également évaluer la pertinence des réponses pour savoir si proches et patients peuvent les utiliser en sécurité. Dans cet article, nous commentons le dialogue de questions-réponses avec le programme d'intelligence artificielle à la lumière de la littérature spécialisée.

Quality of life and subjective sleep-related measures in bipolar disorder and major depressive disorder.

PURPOSE: Diminished quality of life (QoL) has been reported in patients with mood disorders. QoL has also been shown to be decreased by sleep disturbances. Since sleep disorders are common in mood disorders, the aim of this study was to determine whether sleep characteristics are associated to QoL among patients with Bipolar Disorder (BD) and unipolar Major Depressive Disorders (MDD). METHODS: QoL was assessed in 170 patients with mood disorders (61 BD and 109 MDD), who also completed questionnaires measuring the severity of insomnia, sleepiness, chronotype preference and obstructive sleep apnea (OSA) probability index. RESULTS: Analyses showed that BD and MDD groups had similar QoL and sleep measures but the MDD group had higher OSA scores. In BD, correlations indicated a relationship between QoL and insomnia complaints and sleepiness, whereas in MDD, correlations indicated an association between QoL and insomnia complaints and OSA score. In both groups, QoL was related to depressive symptomatology. Linear regressions showed that, in BD, QoL was related to insomnia complaints and sleepiness even in the euthymic state, whereas in MDD, QoL was related to insomnia complaints but not in euthymic patients. CONCLUSION: QoL is related to sleep differently in BD and MDD. The results suggest that insomnia and sleepiness are particularly high in BD even when patients are euthymic. These findings suggest that focusing on insomnia and sleepiness during different mood states of BD could increase QoL.

[Good Psychiatric Management for Borderline Personality Disorder - A Specialized Treatment Applicable in General Care]. / «Good Psychiatric Management¼ pour le trouble de la personnalité borderline - Un traitement spécialisé applicable aux soins généralistes.

This article presents basic notions of "Good Psychiatric Management" (GPM) for Borderline Personality Disorder (BPD). There have been several evidence-based psychotherapeutic treatments for BPD for several decades. Nevertheless, high requirements and motivation required sometimes have a discouraging effect for trainees. GPM aims at offering «good enough¼ and less difficult to implement care. This article presents the notion of Interpersonnal Hypersensitivity and its different attachment states (attached, threatened, abandoned, and desperate) describing internal coherence of BPD and founding therapeutic interventions. GPM is principle based, thus is highly adaptable, as can be seen in integration with other intervention models or implementation of stepped care.

Cet article présente les bases du «Good Psychiatric Management¼ (GPM) pour le trouble de la personnalité borderline. Il existe pour ce trouble différents traitements psychothérapeutiques fondés sur les preuves. Les exigences importantes que ceux-ci représentent en termes de formation et de motivation ont parfois comme effet de décourager les thérapeutes en formation. Le GPM décrit des soins «suffisamment bons¼, accessibles et moins difficiles à implanter. Cet article présente le concept d'hypersensibilité interpersonnelle qui décrit la cohérence interne du trouble et fonde les interventions thérapeutiques. Le GPM est basé sur l'application de principes, ce qui lui donne une adaptabilité importante, par exemple pour l'intégration avec d'autres modèles d'intervention ou des soins par paliers.

Prevalence of attention-deficit/hyperactivity disorder in people with mood disorders: A systematic review and meta-analysis.

OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) in mood disorders is associated with unfavorable outcomes, including more frequent mood episodes, and increased risk of suicide. The reported prevalence of ADHD in individuals with mood disorders varies widely. METHODS: We searched PsycInfo and PubMed for articles published before September 21st , 2020, using search terms for ADHD and mood disorders. We included original data on the prevalence of ADHD in individuals with bipolar disorder (BD) or major depressive disorder (MDD). We estimated the prevalence of ADHD, by developmental period and disorder using random-effects meta-analyses. We also compared the rate of ADHD in people with MDD and BD, and with and without mood disorders. RESULTS: Based on 92 studies including 17089 individuals, prevalence of ADHD in BD is 73% (95% CI 66-79) in childhood, 43% (95% CI 35-50) in adolescence, and 17% (95% CI 14-20) in adulthood. Data from 52 studies with 16897 individuals indicated that prevalence of ADHD in MDD is 28% (95% CI 19-39) in childhood, 17% (95% CI 12-24) in adolescence, and 7% (95% CI 4-11) in adulthood. ADHD was three times more common in people with mood disorders compared to those without and 1.7 times more common in BD compared to MDD. CONCLUSION: People with mood disorders are at a significant risk for ADHD. ADHD should be assessed and treated in individuals with BD and MDD. Comprehensive assessment strategies are needed to address challenges of diagnosing ADHD alongside mood disorders.

[Adult ADHD - recommendations for clinical management in general practice]. / Trouble du déficit d'attention/hyperactivité (TDAH) chez l'adulte - Recommandations de prise en charge par le médecin de premier recours.

Adult Attention-Deficit/Hyperactivity Disorder (ADHD) is frequently found in the general population and it negatively impacts the quality of life of those that suffer from this disorder. Although the general practitioner occupies a primordial role in the detection as well as in the management of this disorder, the lack of training as well as the stigma surrounding ADHD make it not always obvious how to approach the patient with or possibly suffering from ADHD. In this article, we propose to present a few lines of good clinical practice applicable in primary medicine for the detection, diagnosis and management of ADHD in adults.

Le trouble du déficit d'attention/hyperactivité (TDAH) chez l'adulte est fréquemment rencontré dans la population générale et impacte négativement la qualité de vie de celui qui en souffre. Bien que le médecin de premier recours occupe un rôle primordial dans la détection ainsi que dans la prise en charge de ce trouble, le manque de formations ainsi que le stigma qui entoure le TDAH font qu'il n'est pas toujours évident pour le médecin de premier recours de savoir comment aborder un patient souffrant ou possiblement souffrant d'un TDAH. Dans cet article, nous présentons quelques bonnes pratiques cliniques applicables en médecine de premiers recours pour une détection, un diagnostic et une prise en charge du TDAH chez le sujet adulte.

Sexual Function, Sexual Dysfunctions, and ADHD: A Systematic Literature Review.

BACKGROUND: The scientific literature on sexuality among mentally ill patients clearly shows a higher prevalence of sexual disorders for many mental disorders, but little is known about sexuality in individuals suffering from ADHD. Clinicians will often assume that specific difficulties of ADHD are bound to affect sexual functioning. AIM: The aim of this study was to provide a review of the literature to gain better knowledge about sexuality in subjects with ADHD and to discuss screening and management of their potential sexual problems. METHODS: A systematic review of the literature was performed in Pubmed, PsychInfo, and Embase databases. MAIN OUTCOME MEASURES: The main outcome measures were sexual function and sexual dysfunctions. RESULTS: The studies indicated that subjects with ADHD report more sexual desire, more masturbation frequency, less sexual satisfaction, and more sexual dysfunctions than the general population. CLINICAL IMPLICATIONS: Clinicians working with subjects with ADHD should explore the quality of their sexual life. STRENGTHS & LIMITATIONS: This is the first systematic review of the sexuality of individuals with ADHD. However, the results are limited by the small number of studies, by the small sample size of many studies, and the potential for bias. CONCLUSIONS: ADHD is a mental disorder affecting sexual health. Further studies are warranted to learn more about sexuality in subjects with ADHD. Soldati L, Bianchi-Demicheli F, Schockaert P, et al. Sexual Function, Sexual Dysfunctions, and ADHD: A Systematic Literature Review. J Sex Med 2020;17:1653-1664.

Assertive Community Programs for Patients with Severe Mental Disorders: Are Benefits Sustained After Discharge?

The benefits of assertive community treatment (ACT) on patients with severe mental disorders are well established over short or medium term. However, studies that investigate long term outcomes are remarkably scarce. Thus, this study aimed to evaluate patient's long term clinical and psychosocial evolution after discharge from ACT. An assessment was conducted on 29 patients characterized by inpatient facilities heavy use and refusal of care, who were included in an ACT program 8.7 (SD = 0.7) years ago and discharged 6.3 (SD = 1.8) years ago. Results of the follow up showed decreased rates of hospitalizations and symptomatology, as well as sustained improvement in adherence to care, in quality of life and in social functioning. This data suggests that ACT programs can help refractory to care patients to gain clinical and psychosocial improvement and lay foundation for better long-term adherence to care. Results also suggest that ACT didn't imply a lifetime treatment.

Roles of age, gender and psychological difficulties in adolescent mentalizing.

INTRODUCTION: Adolescence is a critical period for the development of mentalizing - the imaginative capacity to understand one's own and others' behaviour in terms of underlying mental states. Yet, factors and mechanisms underlying individual differences in adolescent mentalizing remain poorly understood. This exploratory study examined whether and how a) age and gender and b) psychological difficulties correlate with mentalizing performance in adolescents from the general population. METHODS: 89 adolescents from Geneva, Switzerland (54 females, age 12-17 years) completed a computerized task of mentalizing and a self-report measure of psychopathology. RESULTS: Mentalizing performance improved with age. Males showed lower scores on the mentalizing task and made more hypermentalizing errors than females. The main findings revealed a negative association between mentalizing performance and self-reported attention problems. Post-hoc analyses further demonstrated that self-reported attentional difficulties were particularly associated with weaker scores on items requiring mentalizing about intentions, while self-reported withdrawal/depression symptoms were particularly associated with weaker scores on items requiring mentalizing about emotions and thoughts. CONCLUSION: The present study highlights a negative association between attentional difficulties and mentalizing performance in community adolescents. Moreover, it provides preliminary evidence suggesting that age, gender and psychological difficulties can be distinctively associated with patterns of correct and incorrect mentalizing in community adolescents. Implications for future research and clinical practice are discussed.

Psychiatric disorders among offspring of patients with Bipolar and Borderline Personality Disorder.

OBJECTIVE: As part of a larger study investigating biological risk factors for bipolar disorder (BD) and borderline personality disorder (BPD), we investigated the prevalence of psychiatric diagnoses presented by young BD or BPD offspring. With respect to the scarcity of studies interested in psychiatric disorders among BPD offspring, we have chosen to report these results despite the small sample size for a prevalence study. METHOD: We recruited 21 BD and 22 BPD offspring and 23 control subjects. All subjects were assessed with a structured interview. RESULTS: Our main finding suggests that BPD offspring present a higher rate of psychiatric disorders compared to BD offspring. Attention deficit and hyperactivity disorder was the most prevalent disorder. CONCLUSION: Our results contribute to the evidence that offspring of patients with BPD, are at high risk with regard to their mental health and deserve both more research and special attention at the clinical level.

[Psychiatry : Swiss recommendations for treatment]. / Psychiatrie : recommandations thérapeutiques suisses.

The treatment of psychiatric disorders has been subject of numerous research, which are at the basis of international guidelines and recommendations. The Swiss Society for Psychiatry and Psychotherapy has decided to mandate various expert groups to develop Swiss recommendations. Such recommendations are now available for the main psychiatric disorders and this paper summarizes their main features in order to make them more visible.

La prise en charge des troubles psychiatriques a fait l'objet de nombreux travaux de recherche qui sont à la base de guidelines et recommandations internationales. La Société suisse de psychiatrie et psychothérapie a décidé de mettre à disposition des recommandations suisses et d'en confier la rédaction à des groupes d'experts. Elles existent maintenant pour les grandes pathologies psychiatriques et cet article en résume les points principaux afin de les rendre visibles.

Insomnia in adult attention-deficit/hyperactivity disorder: A comparison with borderline personality disorder population in a clinical setting and control participants.

OBJECTIVES: Many adults with attention-deficit/hyperactivity disorder (ADHD) report sleeping difficulties. The relationship between sleep and ADHD is poorly understood, and shows discrepancies between subjective and objective measures. In order to determine the specificity of sleep-associated symptoms in ADHD, subjective sleep assessments among ADHD adult patients were compared with control subjects and with individuals suffering from borderline personality disorder (BPD). METHODS: 129 outpatients with ADHD, 70 with BPD (including 17 patients with BPD and ADHD comorbidity), and 65 control participants were assessed for sleep quality, insomnia, and sleepiness, using the Pittsburgh Sleep Quality Index (PSQI), the Insomnia Severity Index (ISI), and the Epworth Sleepiness Scale (ESS). RESULTS: ADHD- and BPD-sufferers achieved higher insomnia and lower sleep quality scores than control subjects. Clinical groups did not differ in terms of sleep quality, although insomnia was more severe among BPD patients. Depression scores explained most of sleep symptoms, but even when controlling for depression, ADHD sufferers showed higher sleep latency. Inattentive symptoms were associated with somnolence, while hyperactive/impulsive symptoms were associated with insomnia and lower sleep efficiency. CONCLUSION: Sleep-related symptoms associated with ADHD were partly explained by non-specific factors, especially depression symptoms. In a dimensional perspective, hyperactive and inattentive symptoms were associated with specific sleep symptoms.

[Mentalizing in liaison psychiatry ?] / Mentaliser en psychiatrie de liaison ?

In the past few years, there has been an increased and widespread interest for Mentalization-Based Therapies (MBTs). Although originally developed by Anthony Bateman and Peter Fonagy for the treatment of Borderline Personality Disorder (BPD), the scope of MBTs has now been broadened and is relevant in liaison psychiatry, not only to cope with personality disorders or phenomena such as emotional dysregulation and suicidal behaviours, but also because being ill and expericencieng a dependency-laden relationship with health workers tend to reduce mentalization capacities, thereby increasing the probability of misunderstandings, conflicts, treatment drop-outs or medical errors. We provide clinicians with clues to identify failures and reboot the mentalization process among their patients and colleagues.

Les thérapies basées sur la mentalisation (TBM), développées pour le trouble borderline, ont connu ces dernières années un essor important. Les techniques des TBM pourraient être utiles en psychiatrie de liaison au-delà des troubles de la personnalité et de phénomènes comme la dérégulation émotionnelle ou les conduites suicidaires. En effet, le vécu de la maladie et la relation de soin, qui activent puissamment les représentations d'attachement, affaiblissent les capacités de mentalisation du patient et du soignant et, de ce fait, augmentent le risque de malentendus, de conflits, d'interruptions de traitements ou d'erreurs médicales. Nous proposons aux cliniciens quelques pistes pour déceler les failles et restaurer le processus de mentalisation dans le contexte de la psychiatrie de liaison.

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

BACKGROUND: Serotonin 3A receptor (5-HT3A R) 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-HT3A R and its association with clinical severity outcomes in relation with a functional genetic polymorphism. METHODS: Clinical severity indexes of 346 bipolar, borderline personality, and adult attention deficit hyperactivity disorders patients were tested for association with the DNA methylation status of eight 5-HT3A R gene CpGs. Relationship between the functional variant rs1062613 (C > T) and methylation status on severity of the disorders were also assessed. RESULTS: Childhood maltreatment was associated with higher severity of the disease (higher number of mood episodes, history of suicide attempts, hospitalization, and younger age at onset) across disorders and within each individual disorder. This effect was mediated by two 5-HT3A R CpGs. Compared to T allele carriers, CC carriers had higher methylation status at one CpG located 1 bp upstream of this variant. CONCLUSIONS: This study shows that epigenetic modification of the 5-HT3A R is involved in the mechanism underlying the relationship between maltreatment in childhood and the severity of several psychiatric disorders in adulthood.

Personality profiles in adults with attention deficit hyperactivity disorder (ADHD).

BACKGROUND: Previous studies suggested that the presence of ADHD in children and young adolescents may affect the development of personality. Whether or not the persistence of ADHD in adult life is associated with distinct personality patterns is still matter for debate. To address this issue, we compared the profiles of the Temperament and Character Inventory (TCI) that assesses personality dimensions in 119 adults ADHD and 403 controls. METHODS: ANCOVA were used to examine group differences (controls vs. ADHD and ADHD inattentive type vs. ADHD combined + hyperactive/impulsive types) in Temperaments and Characters. Partial correlation coefficients were used to assess correlation between TCI and expression and severity of symptoms of ADHD. RESULTS: High novelty seeking (NS), harm avoidance (HA) and self-transcendence (ST) scores as well as low self-directedness (SD) and cooperativeness (C) scores were associated with ADHD diagnosis. Low SD was the strongest personality trait associated with adult ADHD. Cases with the ADHD inattentive type showed higher HA and lower SD scores compared to the combined and hyperactive/impulsive types. High HA scores correlated with inattention symptoms whereas high NS and ST scores were related to hyperactive symptoms. Finally low SD and high NS were associated with increased ADHD severity. CONCLUSIONS: Distinct temperaments were associated with inattentive versus hyperactive/impulsive symptoms supporting the heterogeneous nature of the disorder.