Pharmacogenetics of suicidal events during antidepressant treatment

Background and methods Suicidal events during antidepressant treatment are a major factor affecting antidepressant prescribing. In this perspective, regulatory bodies in the US as well as in Europe issued a “black box warning” regarding the risk of suicidal events related to the use of antidepressants, not only in children and adolescents but also in adults. Although the clinical risk factors for such events are well known, unfortunately they do not help to predict who will have a suicidal event during antidepressant treatment and who will not. Recently, pharmacogenomic studies have attempted to use genetic variants to predict individual susceptibility to treatment-related suicidal ideation. This thesis reviews the literature about genetic predictors of antidepressantrelated suicidal events. In this perspective, I will describe more in details two studies I had the chance to be involved in: the Genome-Based Therapeutic Drugs for Depression (GENDEP) and the Geneva Outpatient Depression Study (GODS). Results: Several genetic predictors have been highlighted, the majority of which is relate to common mechanisms of antidepressant action, some of them overlaping with genetic predictors of antidepressant response: genes involved in the neurotrophic and synaptic plasticity systems(CREB1, BDNF and its receptor NTRK2), in noradrenergic and serotoninergic systems,(ADRA2A and 5-HTR1B), in glutamatergic system (GRIA3, GRIK2 and GDA), in the inflammatory and HPA-axis systems (IL28RA and FKBP5), in the control of the blood–brain barrier (ABCB1) and in other brain functions (PAPLN, APOO, KCNIP4 and ELP3). Discussion: These results underscore the importance of multiple genetic factors in the prediction of antidepressant induced suicidal events, which certainly underscores the multifactorial nature of this trait as well as its overlap with other phenotype such as treatment response. Although some of these genes may be of interest in predicting antidepressant-induced suicidal ideation they still need to be validated in better phenotypically designed samples. Several methodological factors are indeed responsible for the problems involved in implicating these findings in the causation of a clinically relevant phenotype. These include: discrepancies between studies in defining phenotypes with several different thresholds used to establish significant suicidal ideation, the use of scales not truly designed to measure suicidal ideation and the paucity of true suicidal events (suicide attempts and/or completion) in 6 pharmacogenomic studies. In conclusion, pharmacogenomic studies are far from fulfilling their promise. There is a need for future pharmacogenetic studies targeting events that are clinically significant in order to find associated variants that will help clinicians to improve their treatment strategies. While awaiting these genetic predictors, clinicians need to bear in mind that all studies in this field including GENDEP and GODS support a beneficial effect of antidepressants on suicidal ideation. This should therefore encourage them to prescribe antidepressant medication even in patients with suicidal ideation

Neurodevelopmental Disorders: From Pathophysiology to Novel Therapeutic Approaches

This special issue of Biomedicines on Neurodevelopmental Disorders (NDD): “From Pathophysiology to Novel Therapeutic Approaches”, is a precursor of what we hope will develop into a thriving and inspiring transdisciplinary field, including genetics, psychiatry, neurology, as well as basic and applied neurosciences and molecular biology in the research area [...

Attention Deficit Hyperactivity Disorder And Borderline Personality Disorder In Adults: A Review Of Their Links And Risks

Attention deficit hyperactivity disorder (ADHD) and borderline personality disorder (BPD) are particularly common disorders, that are highly comorbid in adult populations. The symptomatic overlap between adult ADHD and BPD includes impulsivity, emotional dysregulation and interpersonal impairment, which makes the differential diagnosis difficult. Our review aims at focusing on recent data on the comorbid ADHD+BPD form, as well as the risk factors involved in the emergence of the two disorders. While adult ADHD and BPD share some genetic and temperamental risk factors, adult ADHD is characterized by more severe trait-impulsivity compared to non-comorbid BPD; BPD patients display more severe trait-emotion regulation symptoms compared to non-comorbid ADHD. Patients with the comorbid ADHD+BPD form have severe symptoms in both dimensions. Early-life exposure to adverse events is a shared risk factor for the development of ADHD and BPD, but type and timing of adversity seem to play a differential role in the development of BPD and ADHD symptoms. Age of onset used to be a discriminative diagnostic criterion between ADHD, an early-onset neurodevelopmental disorder, and BPD, a late-onset psychological disorder. However, this distinction has been recently called into question, increasing the need for more research aiming at delineating the disorders from a developmental and clinical standpoint. Clinicians should carefully consider the comorbidity, and consider ADHD and BPD dimensionally, in order to provide more effective patient management. This might improve early preventive interventions, and treatment for comorbid conditions in adulthood

Dépression: analyse décisionnelle pour la prise en charge par le médecin de premier recours

Unipolar depression is among the leading causes of invalidity and disability-adjusted life-years. General practitioners frequently encounter patients suffering from depressive syndromes and very often, it's they, who make the initial diagnosis, take care of these patients, eventually prescribe an antidepressant treatment, identify difficult cases and address them to the specialists of mental health. In this article, we present concepts of diagnosis and differential diagnoses of depression, its therapy and the collaboration between the general practitioner and the psychiatrist/psychotherapist

Trouble déficit d'attention-hyperactivité et trouble bipolaire chez l'adulte: diagnostic différentiel ou comorbidité?

Attention deficit/hyperactivity disorder (ADHD) can sometimes coexist with bipolar disorder (BD). Despite controversies about the coexistence of the two disorders, recent clinical as well as biological studies support the concept of comorbid adult ADHD and BD. Although there is some overlapping symptomatology between both disorders, ADHD can be diagnosed in patients suffering from with BD after a detailed clinical evaluation. Clinicians should be particularly attentive to specific symptoms in order to treat adequately both disorders since untreated ADHD comorbidity with BD is associated with poor clinical and socio-professional outcome

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

One of the components of dialectical behavior therapy (DBT) is the use of mindfulness skills as a core component of treatment for subjects with borderline personality disorder (BPD). In this study, we investigated changes in and correlates of mindfulness skills over a 1-year follow-up including a 4-week session of intensive DBT followed by 10 months of standard DBT

Mentalization-based treatment for adults with attention-deficit/hyperactivity disorder: a pilot study

Recent literature suggests that, in addition to its core cognitive and behavioural symptoms, socioemotional difficulties represent key characteristics of adult attention-deficit/hyperactivity disorder (ADHD). Importantly, these deficits not only contribute negatively to the low social functioning and poorer professional achievements of ADHD patients relative to healthy individuals, they also respond poorly to medication and are not specifically addressed by current evidence-based psychological treatments. Mentalization-based treatment (MBT) is a psychological intervention focused on promoting the imaginative capacity to understand human behaviour as being driven by mental states. MBT has been shown to be effective in patients with chronic emotional dysregulation; it may therefore represent a valuable approach to address sociocognitive deficits and shape adaptive functioning in ADHD. In this study, we tailored the timelimited MBT program developed for borderline personality disorder to the specific clinical needs of individuals with ADHD. We report on the first eight patients with ADHD included in our programme at the Geneva University Hospitals. Preliminary results support the feasibility and relevance of the MBT model for ADHD. We discuss conceptual and clinical implications of the current data

Characteristics of Spirituality and Religion Among Suicide Attempters

Spirituality and religiousness are associated with a lower risk of suicide. A detailed assessment of spirituality among 88 suicide attempters hospitalized after a suicide attempt was performed. Factors associated with the recurrence of suicide attempts over 18 months were looked into. Spirituality was low among most suicide attempters in comparison with the general population. Two groups were identified: those with a high score of depression who featured "low" in spirituality and those with a more heterogeneous profile, for example, involving personality disorders, characterized by a "high" spirituality. At the follow-up, the "meaning in life" score appeared to correlate with recurrence of suicide. Clinical implications are discussed herein