[Borderline personality disorder: state of knowledge and attitudes among french-speaking mental health professionnals]. / Trouble de la personnalité borderline: état des connaissances et des représentations auprès de praticiens francophones en santé mentale.

OBJECTIVES: Patients suffering from borderline personality disorder are very prevalent in various settings (emergency rooms, psychiatric and general hospitals, ambulatory consultations). However, it remains one of the most stigmatized and neglected mental health conditions, albeit being an area that is responsible for very interesting advances in psychotherapy. Today, the prognosis of patients with borderline personality disorder is rather favorable, provided that they follow a dedicated psychotherapy. Conceptions about this condition therefore deserve to be updated as it is sufficiently described in the literature that negative attitudes towards these patients diminish the quality of care they receive as well as their prognosis, and that these attitudes change with training. We decided to study the state of knowledge and attitudes towards borderline personality disorder in a group of French-speaking caregivers interested in these patients. METHODS: Between 2019 and 2020, at the start of training sessions in psychotherapeutic approaches to borderline personality disorder, we provided two questionnaires to 126 caregivers from various professional backgrounds (psychiatrists or child psychiatrists, psychologists, mental health nurses, social workers). The first consisted of 13 questions with 3 choice answers aimed at testing knowledge about borderline personality disorder and the second of 11 questions in the form of a Likert scale aimed at evaluating attitudes towards these patients (e.g. degree of comfort, involvement, hope, avoidance with these patients) adapted frome a questionnaire of Blake and colleagues. RESULTS: The sample consisted of 126 caregivers (69 psychiatrists/pedopsychiatrists; 19 mental health nurses; 23 psychologists; 14 social workers). Fifty three of them (42.06 %) worked in an outpatient setting (either in a state facility or in private practice), 50 (39.68 %) worked in an inpatient psychiatric unit, 13 (10.32%) in both care systems, and 10 (7.94 %) worked in other facilities such as sheltered homes or workshops for persons with psychiatric disabilities. The average number of years in postgraduate training was 7.73 (SD=5.67; rank=0 to 31), and 35 (27.78%) had received at least one training course on borderline disorder in the past. The mean age of the sample was 37.89 (SD=10.08; rank=20 to 64) and there were 76 women (60.32%) and 50 men (39.68%). Concerning the first questionnaire (knowledge), the rate of correct responses among caregivers was relatively low (54%) considering that the vast majority of those assessed were caregivers already trained in mental health who were working with patients suffering from borderline personality disorder. The results showed a significant knowledge gap among professionals, in particular in the nursing profession, illustrating an ever more flagrant shortfall in formations in this sub-population. Concerning the second questionnaire (attitudes), the answers showed that attitudes of caregivers towards patients with borderline personality disorder were still tinged with fear and lack of confidence in taking charge of them. Thus, one participant out of five would have liked to avoid these patients, more than 12% of caregivers did not appreciate them, and 23% thought that they were manipulative. In addition, nearly half of the caregivers surveyed had low confidence in their ability to make a positive difference in the lives of borderline patients. However, there was a recognition of their distress as well as a demand for dedicated training. CONCLUSIONS: Stigmas and ignorance persist around patients with borderline personality disorder. Current training courses do not allow caregivers who are on the front lines (in particular nurses) and who wish to be trained to acquire sufficient knowledge and tools necessary for the care of patients suffering from this disorder. This calls for an improvement in training as well as a reflection on the most appropriate approaches possible to the various target audiences.

Drug metabolic enzyme genotype-phenotype discrepancy: High phenoconversion rate in patients treated with antidepressants.

Cytochromes from the P450 family (CYP) play a central role in the primary metabolism of frequently prescribed antidepressants, potentially affecting their efficacy and tolerance. There are however important differences in the drug metabolic capacities of each individual resulting from a combination of intrinsic and environmental factors. This variability can present an important risk for patients and increases the difficulty of drug prescription in clinical practice. Pharmacogenetic studies have uncovered a number of alleles defining the intrinsic metabolizer status, however, additional factors affecting cytochrome activity can modify this activity and result in a phenoconversion. The present study investigates the discrepancy between the genetically predicted and actually measured activities for the six most important liver cytochromes (CYP1A2, CYP2B6, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in a cohort of patients under antidepressant treatment, previously shown to have a high proportion of patients with low metabolizing activities. We now performed the genetic characterization of this cohort to determine the extent of the genetic versus environmental contribution in these decreased activities. For all enzyme tested, we observed an important rate of phenoconversion, affecting between 33 % and 65 % of the patients, as well as a significant (p < 1E-06) global reduction in the effective but not predicted activities of CYP2D6, CYP2C9 and CYP2C19 compared to the general population. Our results highlight the advantages of phenotyping versus genotyping as well as the increased risk of treatment failure or adverse effect occurrence in a polymedicated population.

Inflammation, anxiety, and stress in bipolar disorder and borderline personality disorder: A narrative review.

Bipolar disorder (BD) and borderline personality disorder (BPD) are serious and prevalent psychiatric diseases that share common phenomenological characteristics: symptoms (such as anxiety, affective lability or emotion dysregulation), neuroimaging features, risk factors and comorbidities. While several studies have focused on the link between stress and peripheral inflammation in other affective disorders such as anxiety or depression, fewer have explored this relationship in BD and BPD. This review reports on evidence showing an interplay between immune dysregulation, anxiety and stress, and how an altered acute neuroendocrine stress response may exist in these disorders. Moreover, we highlight limitations and confounding factors of these existing studies and discuss multidirectional hypotheses that either suggest inflammation or stress and anxiety as the primum movens in BD and BPD pathophysiology, or inflammation as a consequence of the pathophysiology of these diseases. Untangling these associations and implementing a transdiagnostic approach will have diagnostic, therapeutic and prognostic implications for BD and BPD patients.

[Difficult-to-engage patients: What evolution after discharge from Assertive Community Programs?] / Patients réfractaires aux soins : quelle évolution après le suivi intensif d'une équipe mobile de psychiatrie ?

OBJECTIVES: Beneficial effects of Assertive Community Treatment (ACT) programs on patients with severe mental disorders are well established over short or medium term. However, studies that investigate long term clinical and psychosocial outcomes are remarkably scarce, and it is not known whether the support and intensive care delivered by these programs maintain their benefits over time, especially after discharge. Thus, the present study sought further understanding on this issue by evaluating long term clinical and psychosocial evolution of patients who had been treated by an ACT team in 2007. We investigated the nature of treatment interventions and the level of care since discharge from ACT, especially in terms of adherence to care and number of psychiatric hospitalizations. We also examined factors, at inclusion in the ACT program and after six months of treatment, that could predict better long-term outcomes. METHODS: Twenty-nine patients with severe mental disorders, characterized by the heavy use of inpatient facilities and refusal of care, were treated by an ACT team which was implmented between 2007 and 2009. They participated at that time in an initial study on the effect of the program and were therefore assessed at inclusion and again after six months of treatment. Between 2016 and 2017, the present follow up took place and patients were assessed again on their current psychosocial functioning, quality of life and intensity of symptoms, using the same scales as those administered in the initial study. This design allowed us to compare baseline with "early" (after six months) and "late" (after a mean of 8.7 years) effects of ACT program on patients. In order to assess adherence to care since discharge from ACT, data on nature and level of psychiatric treatment was systematically reviewed, including all public and private inpatient and outpatient treatments since the end of the ACT program. RESULTS: Detailed tables on hospitalizations before, during and after ACT treatment are reported, as well as tables summarizing the level of care and nature of treatment since discharge from ACT. During the mean of 8.7 years of evolution and 6.3 years after discharge from ACT, these patients, characterized by severe mental disorders, heavy use of inpatient facilities and refusal of care, sustained a reduced rate of hospitalizations and a minor rate of disengagement from outpatient care (6.9 %). Both severity of symptoms, poorer quality of life and worst functioning in the community at inclusion (baseline) as well as early improvements (after six month of ACT treatment) of the same outcomes were significantly associated with long term improvements. Results also show other baseline predictors of long term improvement: fewer years since disorder onset was associated with improvement of functioning in the community; further advancement in the recovery process predicted better enhancement in quality of life, and a better initial functioning in the community was associated with a better improvement of symptomatology. CONCLUSIONS: This study provides insight on the sustainability of the benefits of ACT programs, suggesting that these interventions can help patients who are refractory to care to gain clinical and psychosocial improvement in the long term. Our results also suggest that baseline severity as well as early improvements after six months of treatment were associated with larger improvement at follow up. These clinical predictors provide some help to distinguish which patients are more likely to benefit from an ACT approach.

Emergency psychiatric management of borderline personality disorder: Towards an articulation of modalities for personalised integrative care.

Building on existing literature, the authors draw the landscape of psychiatric emergencies, and focus on borderline personality disorder, frequently encountered, and strongly linked to death by suicide. A review of knowledge in terms of diagnosis, prognosis, etiology, and treatment, as well as their own experiences, lead them to propose areas of progress that would secure the patient's care pathway. The evolution of society has led psychiatric emergency departments to play the role of a safety net and an entry point to the mental health system. Borderline personality disorder is one of the most common pathologies encountered in psychiatric emergencies. It represents a major concern, long characterized by an often dramatic evolution, and by the human and economic stress it generates. However, since the 1990s, knowledge of this disorder has been refined, and today there are various means of evaluation, good clinical practices and psychotherapeutic treatments, thanks to which significant and lasting improvement is possible. Recent studies highlight the crucial role of hospital caregivers, and the benefit of consolidating their skills by providing them with the knowledge and tools specific to this disorder. They also converge on the interest of setting up specific emergency treatment modalities, particularly highly structured, safe and empowering for the patient, in order to improve their effectiveness. The authors suggest that a case formulation model for persons with borderline personality disorder in emergency would make it possible to activate these two levers of progress, while improving collaboration between hospital and outpatient care. This would also address their main concern of optimizing the patient's therapeutic pathway and reinforcing adherence to treatment that could bring remission, and should be supported by data from empirical research.

Practical considerations for the evaluation and management of Attention Deficit Hyperactivity Disorder (ADHD) in adults.

Attention deficit with or without hyperactivity disorder (ADHD) is one of the most frequent neuropsychiatric disorders, and affects 2-4% of adults. In contrast with many European countries, the identification and management of adult ADHD remains underdeveloped in France, and a subject of controversy. This review provides a practical update on current knowledge about ADHD in adults for French-speaking professionals who have to detect or manage adult patients with ADHD. ADHD is classified as a neurodevelopmental disorder in the recent update of the international diagnostic classification. While symptoms and impairment due to ADHD are frequently severe during childhood, they often evolve as children grow older, with frequent persistent disabilities in adulthood. In adulthood, the clinical presentation, as in childhood, involves the symptom triad of inattention, hyperactivity and impulsivity. However, differences are noted: hyperactivity is more often internalized, symptoms of inattention may be masked by anxiety symptoms or obsessive-like compensation strategies. ADHD is often diagnosed during childhood, but it is not rare for the diagnosis to be made later. Failure to recognise symptoms resulting in misdiagnosis, or alternatively well-developed compensation factors could be two underlying reasons for the long delay until diagnosis. Other symptoms, such as emotional deregulation or executive function-related symptoms are also usually observed in adults. In addition, in adults, ADHD is often associated with other psychiatric disorders (in 80% of cases); this makes the diagnosis even more difficult. These disorders encompass a broad spectrum, from mood disorders (unipolar or bipolar), to anxiety disorders, and other neurodevelopmental disorders and personality disorders, especially borderline and antisocial personality disorder. Substance-use disorders are very common, either as a consequence of impulsivity and emotional dysregulation or as an attempt at self-treatment. Sleep disorders, especially restless leg syndrome and hypersomnolence, could share common pathophysiological mechanisms with ADHD. ADHD and comorbidity-related symptoms are responsible for serious functional impairment, in various domains, leading to academic, social, vocational, and familial consequences. The impact on other psychiatric disorders as an aggravating factor should also be considered. The considerable disability and the poorer quality of life among adults with ADHD warrant optimal evaluation and management. The diagnostic procedure for ADHD among adults should be systematic. Once the positive diagnosis is made, the evaluation enables characterisation of the levels of severity and impairment at individual level. A full examination should also assess medical conditions associated with ADHD, to provide personalized care. In recent years, a growing number of assessment tools have been translated and validated in French providing a wide range of structured interviews and standardized self-report questionnaires for the evaluation of core and associated ADHD symptoms, comorbidities and functional impairment. The treatment of ADHD in adults is multimodal, and aims to relieve the symptoms, limit the burden of the disease, and manage comorbidities. The most relevant and validated psychological approaches are psycho-education, cognitive-behavioural therapy and "third wave therapies" with a specific focus on emotional regulation. Cognitive remediation and neurofeedback are promising strategies still under evaluation. Medications, especially psychostimulants, are effective for alleviating ADHD symptoms with a large effect size. Their safety and tolerance are satisfactory, although their long-term clinical benefit is still under discussion. In France, methylphenidate is the only stimulant available for the treatment of ADHD. Unfortunately, there is no authorization for its use among adults except in continuation after adolescence. Hence the prescription, which is subject to the regulations on narcotics, is off-label in France. This article aims to provide practical considerations for the management of ADHD and associated disorders in adults, in this particular French context.

[Mentalization based treatment (MBT) for borderline personality disorder among a population of French-speaking patients]. / Implémentation francophone de la thérapie basée sur la mentalisation (TBM) pour le trouble de personnalité limite.

INTRODUCTION: Borderline Personality Disorder is a frequent disorder that is challenging for therapists to treat due to the prevalence of self-damaging and suicidal behaviours and interruptions of the therapeutic alliance, as well as a poor response to psychotropic treatments. In recent years, several empirically-validated psychotherapeutic treatments have been developed, including Mentalisation-Based Therapy, which is an integrative psychodynamic approach created in Britain. Although numerous studies have showed Mentalisation-Based Therapy to be an efficient treatment of Borderline Personality Disorder, its specific components have yet to be assessed. Furthermore, there have been no empirical studies conducted among groups of French-speaking patients. The purpose of this study is twofold: To provide an initial assessment of the efficacy of the mentalisation-based psycho-educational component, which is the first component of any mentalisation-based therapy, and to provide the first assessment of this approach among a population of French-speaking patients. METHOD: Over a three-month period, 14 Borderline Personality Disorder sufferers followed a psycho-educational Mentalisation-Based Therapy programme consisting of group sessions to introduce patients to mentalisation and weekly individual interviews. Patients filled in various question forms assessing, among others, the intensity of their depression, their degree of hopelessness, their emotional regulation strategies, and their reflective abilities. RESULTS: The psycho-educational component of Mentalisation-Based Therapy is significantly associated with improved cognitive emotional regulation, empathy and reflective abilities, and with a reduced sense of hopelessness. The programme retention rate was of 71.4%. CONCLUSION: Despite the small sample size and the short treatment period, these preliminary results demonstrate the efficiency of the psycho-educational phase of Mentalisation-Based Therapy, and in particular the positive effects of the treatment on depressive symptomatology and self-regulation processes among patients with a Borderline Personality Disorder diagnosis.

New insights into the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation.

Genome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation. A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at the single-nucleotide polymorphism (SNP), gene and pathway levels. Coverage of genetic variants was increased compared with previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. Significant findings were investigated in NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) for replication. A total of 7062 950 SNPs were analyzed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (P=1.80e-08, ITGA9 (integrin α9)) and rs76191705 (P=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At the gene level, no consistent effect was found. At the pathway level, the Gene Ontology (GO) terms GO: 0005694 (chromosome) and GO: 0044427 (chromosomal part) were associated with improvement (corrected P=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (P=0.047), whereas rs76191705 was not. The two SNPs did not replicate in NEWMEDS. ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, replication was partial. Further studies may help in clarifying their role.

Inter-hemispherical asymmetry in default-mode functional connectivity and BAIAP2 gene are associated with anger expression in ADHD adults.

Attention deficit hyperactivity disorder (ADHD) is accompanied by resting-state alterations, including abnormal activity, connectivity and asymmetry of the default-mode network (DMN). Concurrently, recent studies suggested a link between ADHD and the presence of polymorphisms within the gene BAIAP2 (i.e., brain-specific angiogenesis inhibitor 1-associated protein 2), known to be differentially expressed in brain hemispheres. The clinical and neuroimaging correlates of this polymorphism are still unknown. We investigated the association between BAIAP2 polymorphisms and DMN functional connectivity (FC) asymmetry as well as behavioral measures in ADHD adults. Resting-state fMRI was acquired from 30 ADHD and 15 healthy adults. For each subject, rs7210438 and rs8079626 within the gene BAIAP2 were genotyped. ADHD severity, impulsiveness and anger were assessed for the ADHD group. Using multivariate analysis of variance, we found that genetic features do have an impact on DMN FC asymmetry. In particular, polymorphism rs8079626 affects medial frontal gyrus and inferior parietal lobule connectivity asymmetry, lower for AA than AG/GG carriers. Further, when combining FC asymmetry and the presence of the rs8079626 variant, we successfully predicted increased externalization of anger in ADHD. In conclusion, a complex interplay between genetic vulnerability and inter-hemispherical DMN FC asymmetry plays a role in emotion regulation in adult ADHD.

[Current therapies of borderline personality disorder]. / Thérapies actuelles du trouble de personnalité borderline.

Borderline personality disorder (BPD) is a highly prevalent disorder characterized by identity disturbance, emotion dysregulation, interpersonal difficulties and self-damaging behaviours. Mental health professionals most of the time encounter difficulties in the care of these hard-to-treat patients mainly due to the frequent crises often leading to drop-outs. In this perspective, technical and theoretical changes to traditional psychotherapeutic approaches were developed. We here give the major principles that should be considered when treating BPD patients in order not only to reduce the risk of being iatrogenic but also to apply the current psychotherapeutic and psychiatric modalities internationally recognized to be efficient.

[An exploration of sexual desire and sexual activities of women with psychosis]. / Désir et pratiques sexueues chez les femm-es souffrant de psychose.

Most clinicians avoid discussing sexuality with patients with severe mental disorders. Sexual disturbances can be related to medication, to psychological issues such as self-stigma and anhedonia, and to the social context. We studied desire and sexual practices in women suffering from schizophrenia, in comparison with healthy women. Contrary to previous research, women with schizophrenia featured dyadic and individual desire similar to women of comparable age. Yet, only half of women with psychosis had sexual practice, either alone or with a partner. They were less satisfied with their activity, both in terms of function and psychological issues such as sexual self-esteem. This finding underscores the stigmatization these women suffer from, which prevents the opportunity of a possible improvement in this important interpersonal domain.

DAT1 and DRD4 genes involved in key dimensions of adult ADHD.

Attention-deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder often persisting in adulthood. Genetic studies of ADHD mainly focused on the Dopamine Transporter (DAT1) and the Dopamine Receptor 4 (DRD4) genes. Nevertheless, polymorphisms of these genes explain only a small fraction of the assigned risk, suggesting that intermediate dimensions and environmental factors should also be considered. We investigated in 77 adult ADHD subjects compared to 474 controls, how polymorphisms within the genes coding for DAT1 (40-bp VNTR in 3'UTR), the Dopamine Receptor 2 (DRD2) (rs1799732) and DRD4 (48-bp VNTR in exon 3), may modulate the expression of the disorder. By genotyping DAT1, we detected a new 9.5R allele showing a deletion of 40 bp and also an insertion of 19 bp compared to the 10R allele. This novel allele was found to be significantly protective for ADHD (p < 0.0001). Another significant difference was found in the distribution of DRD4 48-bp VNTR 6R allele when comparing patients and controls (p = 0.0007). In addition significant results were also found for DAT1 9.5R allele, which was associated with impulsiveness (p = 1.98 × 10(-4)) and trait anger scores (p = 7.66 × 10(-4)). Moreover, impulsiveness scores were partly modulated by an interaction between the DRD4 48-bp VNTR 6R allele and childhood maltreatment (p = 0.01), however, this result did not resist correction for multiple comparisons. Altogether, our results show the putative involvement of DAT1 and DRD4 genes in the aetiology of ADHD with a main role in modulation of key dimensions of the disorder.

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.

Investigation of blood mRNA biomarkers for suicidality in an independent sample.

Changes in the blood expression levels of SAT1, PTEN, MAP3K3 and MARCKS genes have been reported as biomarkers of high versus low suicidality state (Le-Niculescu et al.). Here, we investigate these expression biomarkers in the Genome-Based Therapeutic Drugs for Depression (GENDEP) study, of patients with major depressive disorder on a 12-week antidepressant treatment. Blood gene expression levels were available at baseline and week 8 for patients who experienced suicidal ideation during the study (n=20) versus those who did not (n=37). The analysis is well powered to detect the effect sizes reported in the original paper. Within either group, there was no significant change in the expression of these four genes over the course of the study, despite increasing suicidal ideation or initiation of antidepressant treatment. Comparison of the groups showed that the gene expression did not differ between patients with or without treatment-related suicidality. This independent study does not support the validity of the proposed biomarkers.

Copy number variants and therapeutic response to antidepressant medication in major depressive disorder.

It would be beneficial to find genetic predictors of antidepressant response to help personalise treatment of major depressive disorder (MDD). Rare copy number variants (CNVs) have been implicated in several psychiatric disorders, including MDD, but their role in antidepressant response has yet to be investigated. CNV data were available for 1565 individuals with MDD from the NEWMEDS (Novel Methods leading to New Medications in Depression and Schizophrenia) consortium with prospective data on treatment outcome with either a serotonergic or noradrenergic antidepressant. No association was seen between the presence of CNV (rare or common), the overall number of CNVs or genomic CNV 'burden' and antidepressant response. Specific CNVs were nominally associated with antidepressant response, including 15q13.3 duplications and exonic NRXN1 deletions. These were associated with poor response to antidepressants. Overall burden of CNVs is unlikely to contribute to personalising antidepressant treatment. Specific CNVs associated with antidepressant treatment require replication and further study to confirm their role in the therapeutic action of antidepressant.

Increased CPA6 promoter methylation in focal epilepsy and in febrile seizures.

Focal epilepsy (FE) is one of the most common forms of adult epilepsy and is usually regarded as a multifactorial disorder. Febrile seizures (FS) often appear during childhood in a subtype of FE patients, i.e. with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS). FS are the most common human convulsive event associated with fever. Genetic evidences for FS have suggested a complex mode of inheritance. Until now, to investigate genes at the genomic level, linkage analysis of familial forms and association studies have been performed, but nothing conclusive has been clearly related to FE and FS. As complex disorders, environmental factors might play a crucial role through epigenetic modification of key candidate genes such as CPA6, which encodes Carboxypeptidase A6, an extracellular protein. Therefore, we assessed DNA methylation in promoter of CPA6. In 186 FE patients and 92 FS patients compared to 93 healthy controls and 42 treated controls with antiepileptic drugs (AEDs), we found significant higher levels of methylation for epileptic patients. Methylation status were 3.4% (±3.2%) for FE cases and 4.3% (±3.5%) for FS cases, whereas healthy individuals and treated controls with AEDs showed a level of 0.8% (±2.9%) and 1.5% (±3.9%), respectively (p≤0.001 for all comparisons). These results let growing evidence for DNA methylation involvment in FE and FS.

EEG anomalies in adult ADHD subjects performing a working memory task.

Functional imaging studies have revealed differential brain activation patterns in attention deficit hyperactivity disorder (ADHD) adult patients performing working memory (WM) tasks. The existence of alterations in WM-related cortical circuits during childhood may precede executive dysfunctions in this disorder in adults. To date, there is no study exploring the electrophysiological activation of WM-related neural networks in ADHD. To address this issue, we carried out an electroencephalographic (EEG) activation study associated with time-frequency (TF) analysis in 15 adults with ADHD and 15 controls performing two visual N-back WM tasks, as well as oddball detection and passive fixation tasks. Frontal transient (phasic) theta event-related synchronization (ERS, 0-500 msec) was significantly reduced in ADHD as compared to control subjects. Such reduction was equally present in a task-independent manner. In contrast, the power of the later sustained (∼500-1200 msec) theta ERS for all tasks was comparable in ADHD and control groups. In active WM tasks, ADHD patients displayed lower alpha event-related desynchronization (ERD, ∼200-900 msec) and higher subsequent alpha ERS (∼900-2400 msec) compared to controls. The time course of alpha ERD/ERS cycle was modified in ADHD patients compared to controls, suggesting that they are able to use late compensatory mechanisms in order to perform this WM task. These findings support the idea of an ADHD-related dysfunction of neural generators sub-serving attention directed to the incoming visual information. ADHD cases may successfully face WM needs depending on the preservation of sustained theta ERS and prolonged increase of alpha ERS at later post-stimulus time points.

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.

[Adult Attention Deficit/Hyperactivity Disorder (ADHD): current issues]. / Trouble du déficit d'attention- hyperactivité de l'enfant, de l'adolescent et de l'adulte: état des lieux.

Attention Deficit/Hyperactivity Disorder (ADHD) has prevalence between 3 and 7% in childhood and adolescence. As high as 60% of childhood cases continue to have clinically significant symptoms of ADHD as adults. Psychiatric comorbidities are often found in ADHD subjects including, in childhood, emotional, behavior and learning disorders. Psychiatric comorbidities in adolescents and adults suffering from ADHD include mood and substance use disorders. Although may one fear giving psychostimulants to ADHD patients with comorbidities, recent studies have shown the benefits of such treatment not only in the clinical but also in the educational and socioprofessional point of views. Psychotherapeutic approaches should ideally accompany pharmacological treatments.

[Study of the impact of an assertive community program on the families of patients with severe mental disorders]. / Patients souffrant de troubles psychiatriques sévères suivis par une équipe mobile : impact sur leurs familles.

OBJECTIVES: Assertive Community Treatment (ACT) is known to have a positive impact on the number and length of inpatient stays. Yet, research is needed in order to help understand how ACT programs may ease off families' burden, e.g. in terms of economic expenditures. Indeed, many families with siblings suffering from chronic mental illness, who disengaged from psychiatric services, report needs related to ACT. This paper aims to describe the impact of a new ACT program in Geneva on patients and their families' burden. METHODS: Out of 91 patients consecutively treated by the ACT program for at least 3 months, 55 consented to participate in the research. Twenty-one allowed us to contact their families (out of 37 who had relatives in the area). Data were gathered on patients and families before and after a 6-month-follow-up. RESULTS: For the patients, after adjustment for the time spent during follow-up, most of the studied variables evolved favorably, particularly for their symptoms. At baseline, most of the family members felt overburdened by the financial cost (59.1%) related to their relatives with severe mental disorder and experienced inconvenience at having to give them assistance in daily life (68.2%) and to supervise them in daily activities (54.5%). Several variables evolved favorably during follow-up. Notably the best changes were observed for the inconvenience relating to assistance in daily life and relatives' emotional distress. Families of patients with delusional disorder featured less or no improvement during the ACT follow-up. The best correlate of improvement in familial burdens was improvement in patient's positives symptoms. Among those patients, being a female and suffering from a schizo-affective disorder was known to have had a higher impact on the number of interventions provided by families. DISCUSSION: ACT should be recommended for patients who feature a poor outcome when treated in other settings. In addition, our results suggest that their families can also improve considerably, particularly those confronted with patients with persistent and enduring disturbing behaviors related to positive symptoms which do not, however, warrant hospitalization. Clinicians should pay particular attention to patients suffering from delusional disorder and their families, as this disorder does not appear to be associated with improvement in family burdens. These data do not allow definitely disentangling whether the improvement of families' burden is directly related to ACT interventions with them, to the implementation of support by other structures (such as peer support groups) or to an indirect effect related to patients' improvement. To our knowledge no similar study on the effect of ACT on family burden exists. Hence, such research needs to be replicated in other areas with different clinical and cultural backgrounds.