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Bipolar Disorder: HELP
Articles by Frank Bellivier
Based on 169 articles published since 2010
(Why 169 articles?)
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Between 2010 and 2020, F. Bellivier wrote the following 169 articles about Bipolar Disorder.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6 · 7
1 Editorial Teasing apart Bipolar III: The causes and consequences of a Treatment-Emergent Affective Switch (TEAS) into mania. 2015

Malhi, Gin S / Masson, Marc / Bellivier, Frank. ·Academic Department of Psychiatry, Kolling Institute, Northern Sydney Local Health District, St Leonards, NSW, Australia Sydney Medical School - Northern, The University of Sydney, St Leonards, NSW, Australia CADE Clinic, Department of Psychiatry, Royal North Shore Hospital, Northern Sydney Local Health District, St Leonards, NSW, Australia Gin.malhi@sydney.edu.au. · Clinique du château de Garches, Garches, France Centre Hospitalier Sainte-Anne, Paris, France. · Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris, France AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Département de Psychiatrie et de Médecine Addictologique, Paris, France Fondation FondaMental, Créteil, France. ·Aust N Z J Psychiatry · Pubmed #26416915.

ABSTRACT: -- No abstract --

2 Review Response to Lithium in Patients with Bipolar Disorder: What are Psychiatrists' Experiences and Practices Compared to Literature Review? 2019

Montlahuc, Claire / Curis, Emmanuel / Grillault Laroche, Diane / Bagoe, Gérald / Etain, Bruno / Bellivier, Frank / Chevret, Sylvie. ·Service de Biostatistique et Information médicale, Hôpital Saint Louis, AP-HP, Paris, France. · ECSTRA Team (Épidémiologie Clinique et Statistiques pour la Recherche en Santé), UMR 1153 INSERM, Université Paris Diderot, Sorbonne Paris Cité, Paris, France. · UMR-S 1144, INSERM, Université Paris Descartes, Université Paris Diderot, Sorbonne Paris Cité, Paris, F-75013, France. · Laboratoire de Biomathématiques, Plateau iB², Faculté de Pharmacie de Paris, Université Paris Descartes, Sorbonne Paris Cité, Paris, France. · AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Département de Psychiatrie et de Médecine Addictologique, 75475 Paris Cedex 10, France. · Fondation FondaMental, CHU de Créteil, Créteil, France. ·Pharmacopsychiatry · Pubmed #29486511.

ABSTRACT: BACKGROUND: This study aims at characterizing French psychiatrists' opinions regarding definition criteria and factors associated with lithium prophylactic response in patients with bipolar disorders. METHODS: After a literature review, an online survey targeted French psychiatrists in 2016. RESULTS: Literature review showed inconsistencies in reported definition criteria and clinical predictors of lithium prophylactic response. A total of 104 psychiatrists, mostly working in hospitals, completed the survey. The inconsistencies regarding definition criteria and predictors of lithium response were confirmed. Five factors were commonly reported by psychiatrists as positively associated with successful response (family history of lithium response and of bipolar I disorder, and lithium efficacy in acute mood phases treatment) or with an unsuccessful response (rapid cycling and alcohol misuse). DISCUSSION: The divergence in psychiatrists' opinions surely plays a major role in the variability of lithium prescriptions among psychiatrists. Currently, the large variations in response definitions, and in study designs used to quantify each factor's effect, preclude synthesizing the findings. A standardization of response measures is needed to explore factors that influence the prophylactic lithium efficacy.

3 Review Can an Integrated Science Approach to Precision Medicine Research Improve Lithium Treatment in Bipolar Disorders? 2018

Scott, Jan / Etain, Bruno / Bellivier, Frank. ·Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, United Kingdom. · Centre for Affective Disorders, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom. · Faculté de Médecine, Université Paris Diderot, Paris, France. · AP-HP, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand Widal, Paris, France. · INSERM, Unité UMR-S 1144, Variabilité de Réponse aux Psychotropes, Université Paris Descartes-Paris Diderot, Paris, France. · AP-HP, Groupe Henri Mondor-Albert Chenevier, Pôle de Psychiatrie, Créteil, France. · INSERM, Unité 955, IMRB, Equipe de Psychiatrie Translationnelle, Créteil, France. ·Front Psychiatry · Pubmed #30186186.

ABSTRACT: Clinical practice guidelines identify lithium as a first line treatment for mood stabilization and reduction of suicidality in bipolar disorders (BD); however, most individuals show sub-optimal response. Identifying biomarkers for lithium response could enable personalization of treatment and refine criteria for stratification of BD cases into treatment-relevant subgroups. Existing systematic reviews identify potential biomarkers of lithium response, but none directly address the conceptual issues that need to be addressed to enhance translation of research into precision prescribing of lithium. For example, although clinical syndrome subtyping of BD has not led to customized individual treatments, we emphasize the importance of assessing clinical response phenotypes in biomarker research. Also, we highlight the need to give greater consideration to the quality of prospective longitudinal monitoring of illness activity and the differentiation of non-response from partial or non-adherence with medication. It is unlikely that there is a single biomarker for lithium response or tolerability, so this review argues that more research should be directed toward the exploration of biosignatures. Importantly, we emphasize that an integrative science approach may improve the likelihood of discovering the optimal combination of clinical factors and multimodal biomarkers (e.g., blood omics, neuroimaging, and actigraphy derived-markers). This strategy could uncover a valid lithium response phenotype and facilitate development of a composite prediction algorithm. Lastly, this narrative review discusses how these strategies could improve eligibility criteria for lithium treatment in BD, and highlights barriers to translation to clinical practice including the often-overlooked issue of the cost-effectiveness of introducing biomarker tests in psychiatry.

4 Review Molecular Signatures of Lithium Treatment: Current Knowledge. 2018

Bellivier, Frank / Marie-Claire, Cynthia. ·Variabilite de reponse aux psychotropes, INSERM U1144/Faculte de Pharmacie de Paris/Universite Paris Descartes/Universite Paris Diderot/Universite Sorbonne Paris Cite, Paris, France. · AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pole de Psychiatrie et de Medecine Addictologique, 75475 Paris cedex 10, France. · Fondation Fondamental, Creteil, France. ·Pharmacopsychiatry · Pubmed #30060262.

ABSTRACT: Lithium (Li) is the key mood stabilizer in the prevention of mood recurrences and suicide in bipolar disorders. However, only one-third of patients become asymptomatic with Li treatment, and to date, no clinical markers can predict this response variability. Li is a multitargeting drug, complicating an understanding of its mechanisms of action. The present article reviews Li's various biological effects, including those obtained in transcriptomic and epigenetic studies, in both humans and animal models. A molecular signature of the therapeutic response to Li is urgently required, including possibly from the circulation. This would better clarify the therapeutic mechanism of Li's action as well as the development of clinical biomarkers. As such, the biological underpinnings of Li's beneficial effects should provide clearer understanding of the varying pathophysiological processes in bipolar disorder presentations, with implications for classification and clinical management, possibly leading to a personalized prescription.

5 Review Transcranial direct-current stimulation (tDCS) for bipolar depression: A systematic review and meta-analysis. 2017

Dondé, Clément / Amad, Ali / Nieto, Isabel / Brunoni, André Russowsky / Neufeld, Nicholas H / Bellivier, Frank / Poulet, Emmanuel / Geoffroy, Pierre-Alexis. ·INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Center, Psychiatric Disorders: From Resistance to Response ΨR2 Team, Centre Hospitalier Le Vinatier, F-69678, France; Lyon Neuroscience Research Center, Psychiatric Disorders: From Resistance to Response ΨR2 Team, Centre Hospitalier Le Vinatier, F-69678, France. Electronic address: clement.donde-coquelet@ch-le-vinatier.fr. · University Claude Bernard Lyon 1, Villeurbanne F-69000, France. · AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, Cedex 10, France; Fondation FondaMental, Créteil 94000, France. · Service of Interdisciplinary Neuromodulation, Department and Institute of Psychiatry, Laboratory of Neurosciences (LIM-27), University of São Paulo, São Paulo, Brazil. · University of Toronto, Centre for Addiction and Mental Health, Canada. · AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, Cedex 10, France; Fondation FondaMental, Créteil 94000, France; Inserm, U1144, Paris F-75006, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris F-75013, France. · INSERM U1028, CNRS UMR5292, Lyon Neuroscience Research Center, Psychiatric Disorders: From Resistance to Response ΨR2 Team, Centre Hospitalier Le Vinatier, F-69678, France; CHU Lyon, Hôpital Edouard Herriot, Department of Psychiatry Emergencies, France; Lyon Neuroscience Research Center, Psychiatric Disorders: From Resistance to Response ΨR2 Team, Centre Hospitalier Le Vinatier, F-69678, France. · AP-HP, GH Saint-Louis - Lariboisière - F. Widal, Pôle de Psychiatrie et de Médecine Addictologique, 75475 Paris, Cedex 10, France; Fondation FondaMental, Créteil 94000, France; Inserm, U1144, Paris F-75006, France; Université Paris Diderot, Sorbonne Paris Cité, UMR-S 1144, Paris F-75013, France. Electronic address: pierre.a.geoffroy@gmail.com. ·Prog Neuropsychopharmacol Biol Psychiatry · Pubmed #28552295.

ABSTRACT: OBJECTIVE: Bipolar disorder (BD) is a severe and recurrent brain disorder that can manifest in manic or depressive episodes. Transcranial Direct Current Stimulation (tDCS) has been proposed as a novel therapeutic modality for patients experiencing bipolar depression, for which standard treatments are often inefficient. While several studies have been conducted in this patient group, there has been no systematic review or meta-analysis that specifically examines bipolar depression. We aimed to address this gap in the literature and evaluated the efficacy and tolerability of tDCS in patients fulfilling DSM-IV-TR criteria for BD I, II, or BD not otherwise specified (NOS). METHODS: We systematically searched the literature from April 2002 to November 2016 to identify relevant publications for inclusion in our systematic review and meta-analysis. Effect sizes for depression rating-scale scores were expressed as the standardized mean difference (SMD) before and after tDCS. RESULTS: Thirteen of 382 identified studies met eligibility criteria for our systematic review. The meta-analysis included 46 patients from 7 studies with depression rating-scale scores pre- and post-tDCS. Parameters of tDCS procedures were heterogeneous. Depression scores decreased significantly with a medium effect size after acute-phase of treatment (SMD 0.71 [0.25-1.18], z=3.00, p=0.003) and at the furthest endpoint (SMD 1.27 [0.57-1.97], z=3.57, p=0.0004). Six cases of affective switching under tDCS treatment protocols were observed. CONCLUSIONS: Depressive symptoms respond to tDCS in patients with BD. Additional studies, and particularly randomized controlled trials, are needed to clarify the effectiveness of tDCS in bipolar depression, the frequency of tDCS-emergent hypomania/mania, and which tDCS modalities are most efficient.

6 Review Similarities between emotional dysregulation in adults suffering from ADHD and bipolar patients. 2016

Richard-Lepouriel, Hélène / Etain, Bruno / Hasler, Roland / Bellivier, Frank / Gard, Sébastien / Kahn, Jean-Pierre / Prada, Paco / Nicastro, Rosetta / Ardu, Stefano / Dayer, Alexandre / Leboyer, Marion / Aubry, Jean-Michel / Perroud, Nader / Henry, Chantal. ·Service of psychiatric specialties, Department of mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. Electronic address: helene.richard-lepouriel@hcuge.ch. · Inserm, U955, Equipe Psychiatrie Translationnelle, Créteil 94000, France; Université Paris Est, Faculté de Médecine, Créteil 94000, France; AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie et d'Addictologie, Créteil 94000, France; Fondation Fondamental, Créteil 94000, France. · Service of psychiatric specialties, Department of mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. · Fondation Fondamental, Créteil 94000, France; AP-HP, GH Saint-Louis - Lariboisière - Fernand Widal, Pôle Neurosciences, 75010 Paris, France; Université Paris Diderot, UMR-S 1144, 75006 Paris, France. · Fondation Fondamental, Créteil 94000, France; Hôpital Charles Perrens, Service de psychiatrie adulte, Pôle 3-4-7, 33000 Bordeaux, France. · Fondation Fondamental, Créteil 94000, France; Service de Psychiatrie et Psychologie Clinique, CHU de Nancy, Hôpitaux de Brabois, Vandoeuvre Les Nancy 54500, France. · Department of Cardiology and Endodontology, Treatment Plan Unit and Division of Operative Dentistry, Dental School, University of Geneva, Geneva, Switzerland. · Service of psychiatric specialties, Department of mental Health and Psychiatry, University Hospitals of Geneva, Geneva, Switzerland; Department of Psychiatry, University of Geneva, Geneva, Switzerland. · Inserm, U955, Equipe Psychiatrie Translationnelle, Créteil 94000, France; Université Paris Est, Faculté de Médecine, Créteil 94000, France; AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie et d'Addictologie, Créteil 94000, France; Institut Pasteur, Unité Perception et Mémoire, 75015 Paris, France. ·J Affect Disord · Pubmed #27031290.

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

7 Review [Potentiation strategies]. 2016

Doumy, Olivier / Bennabi, Djamila / El-Hage, Wissam / Allaïli, Najib / Bation, Rémy / Bellivier, Frank / Holtzmann, Jérôme / Bubrovszky, Maxime / Camus, Vincent / Charpeaud, Thomas / Courvoisier, Pierre / d'Amato, Thierry / Garnier, Marion / Haesebaert, Frédéric / Bougerol, Thierry / Lançon, Christophe / Moliere, Fanny / Nieto, Isabel / Richieri, Raphaëlle / Saba, Ghassen / Courtet, Philippe / Vaiva, Guillaume / Leboyer, Marion / Llorca, Pierre-Michel / Aouizerate, Bruno / Haffen, Emmanuel. ·Centre expert Dépression résistante FondaMental, CH Charles-Perrens, Pôle de Psychiatrie générale et universitaire, 33076 Bordeaux cedex, France. Electronic address: odoumy@ch-perrens.fr. · Centre expert Dépression résistante FondaMental, CHU de Besançon, Service de Psychiatrie de l'Adulte, 25030 Besançon cedex, France. · Centre expert Dépression résistante FondaMental, CHU de Tours, Clinique Psychiatrique Universitaire, 37044 Tours cedex 9, France. · Centre expert Dépression résistante FondaMental, hôpital Fernand-Widal, Service de Psychiatrie Adulte, 75010 Paris, France. · Centre expert Dépression résistante FondaMental, Centre Hospitalier Le Vinatier, Service Universitaire de Psychiatrie Adulte, BP 300 39, 69678 Bron cedex, France. · Centre expert Dépression résistante FondaMental, Hôpital Nord, CHU de Grenoble, Service de Psychiatrie de l'adulte, CS 10217, 38043 Grenoble cedex 9, France. · Centre expert Dépression résistante FondaMental, hôpital Fontan 1, CHRU de Lille, Service de Psychiatrie Adulte, 59037 Lille cedex, France. · Centre expert Dépression résistante FondaMental, CHU de Clermont-Ferrand, Service de Psychiatrie de l'adulte B, 63003 Clermont-Ferrand, France. · Centre expert Dépression résistante FondaMental, CHU La Conception, Pôle Psychiatrie Centre, 13005 Marseille, France. · Centre expert Dépression résistante FondaMental, Département des urgences et post-urgences psychiatrique, CHRU Lapeyronie, 34295 Montpellier cedex 5, France. · Centre expert Dépression résistante FondaMental, Pôle de Psychiatrie des hôpitaux universitaires, Henri-Mondor, Hôpital Chenevier, 94000 Créteil, France. · Centre expert Dépression résistante FondaMental, CH Charles-Perrens, Pôle de Psychiatrie générale et universitaire, 33076 Bordeaux cedex, France. ·Presse Med · Pubmed #26970936.

ABSTRACT: Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 μUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects.

8 Review Bipolar Disorder: The Role of the Kynurenine and Melatonergic Pathways. 2016

Anderson, George / Jacob, Aude / Bellivier, Frank / Geoffroy, Pierre Alexis. ·Head of Research, CRC Scotland & London, UK. anderson.george@rocketmail.com. ·Curr Pharm Des · Pubmed #26654772.

ABSTRACT: Bipolar disorder (BD) is a long-recognized severe and common psychiatric disorder, with a complex and often diverse range of presentations. BD is a heterogenous disorder that has traditionally, if rather simply, been defined by the recurrences of manic and depressive episodes, and presents with numerous immune-inflammatory and circadian/sleep abnormalities. A number of different lines of research have investigated the biological underpinnings of BD and demonstrate a heritability of about 80-90%. This genetic contribution is thought to be mediated by a wide array of genetic factors, rather than being strongly influenced by a couple of genes. In this context, a clearer formulation of the biological underpinnings of BD is needed in order to encompass the diverse effects of multiple susceptibility genes. The biological underpinnings of BD includes work that has focussed on the role played by increased immune inflammatory activity, particularly changes in pro-inflammatory cytokines, as measured both centrally and systemically. Changes in immune- inflammatory activity are intimately associated with alterations in levels of oxidative and nitrosative stress (O&NS), which are increased in BD. Many of the neuroregulatory changes driven by O&NS and immune-inflammatory activity are mediated by the tryptophan catabolite (TRYCAT) pathways, with changes in TRYCATs being evident both centrally and peripherally. A consequence of increased pro-inflammatory cytokines, is their induction of indoleamine 2,3-dioxygenase (IDO), which takes tryptophan away from serotonin, Nacetylserotonin and melatonin synthesis, driving it to the synthesis of neuroregulatory TRYCATs. Most work exploring such changes has emphasized the role of TRYCATs in enhancing or decreasing neuronal activity. However, a relatively overlooked consequence of cytokine induced IDO and TRYCAT pathway activation is the impact that this has on aryl hydrocarbon receptor (AhR) activation and in decreasing melatonergic pathway activity. Melatonin is classically associated with night-time synthesis by the pineal gland, in turn regulating circadian rhythms. However, melatonin is produced by many, if not all mitochondria containing cells, with consequences for gut regulation, as well as glia and immune cell reactivity. The melatonergic pathways are genetic susceptibility factors for BD. Interactive changes in O&NS, immune-inflammatory activity, TRYCATs and the melatonergic pathways form an emerging biological perspective on the etiology, course and management of BD. Here, we review such changes in BD, and how this better integrates the diverse array of BD presentations and comorbidities, including addiction and cardiovascular disorders as well as decreased life-expectancy. We then look at the future directions such research may take.

9 Review Melatonin and Melatonin Agonists as Adjunctive Treatments in Bipolar Disorders. 2015

Geoffroy, Pierre Alexis / Etain, Bruno / Franchi, Jean-Arthur Micoulaud / Bellivier, Frank / Ritter, Philipp. ·Service de Psychiatrie Adulte (Pr. Frank BELLIVIER), Groupe Hospitalier Saint-Louis-Lariboisière- Fernand Widal, 200 rue du Faubourg Saint Denis, 75475 Paris Cedex 10 France. pierre.a.geoffroy@gmail.com. ·Curr Pharm Des · Pubmed #26088111.

ABSTRACT: Bipolar disorders (BD) present with abnormalities of circadian rhythmicity and sleep homeostasis, even during phases of remission. These abnormalities are linked to the underlying neurobiology of genetic susceptibility to BD. Melatonin is a pineal gland secreted neurohormone that induces circadian-related and sleep-related responses. Exogenous melatonin has demonstrated efficacy in treating primary insomnia, delayed sleep phase disorder, improving sleep parameters and overall sleep quality, and some psychiatric disorders like autistic spectrum disorders. In order to evaluate the efficacy of melatonin among patients with BD, this comprehensive review emphasizes the abnormal melatonin function in BD, the rationale of melatonin action in BD, the available data about the exogenous administration of melatonin, and melatonin agonists (ramelteon and tasimelteon), and recommendations of use in patients with BD. There is a scientific rationale to propose melatonin-agonists as an adjunctive treatment of mood stabilizers in treating sleep disorders in BD and thus to possibly prevent relapses when administered during remission phases. We emphasized the need to treat insomnia, sleep delayed latencies and sleep abnormalities in BD that are prodromal markers of an emerging mood episode and possible targets to prevent future relapses. An additional interesting adjunctive therapeutic effect might be on preventing metabolic syndrome, particularly in patients treated with antipsychotics. Finally, melatonin is well tolerated and has little dependence potential in contrast to most available sleep medications. Further studies are expected to be able to produce stronger evidence-based therapeutic guidelines to confirm and delineate the routine use of melatonin-agonists in the treatment of BD.

10 Review Influence of light exposure during early life on the age of onset of bipolar disorder. 2015

Bauer, Michael / Glenn, Tasha / Alda, Martin / Andreassen, Ole A / Angelopoulos, Elias / Ardau, Raffaella / Baethge, Christopher / Bauer, Rita / Baune, Bernhard T / Bellivier, Frank / Belmaker, Robert H / Berk, Michael / Bjella, Thomas D / Bossini, Letizia / Bersudsky, Yuly / Wo Cheung, Eric Yat / Conell, Jörn / Del Zompo, Maria / Dodd, Seetal / Etain, Bruno / Fagiolini, Andrea / Frye, Mark A / Fountoulakis, Kostas N / Garneau-Fournier, Jade / Gonzalez-Pinto, Ana / Gottlieb, John F / Harima, Hirohiko / Hassel, Stefanie / Henry, Chantal / Iacovides, Apostolos / Isometsä, Erkki T / Kapczinski, Flávio / Kliwicki, Sebastian / König, Barbara / Krogh, Rikke / Kunz, Mauricio / Lafer, Beny / Larsen, Erik R / Lewitzka, Ute / Lopez-Jaramillo, Carlos / MacQueen, Glenda / Manchia, Mirko / Marsh, Wendy / Martinez-Cengotitabengoa, Mónica / Melle, Ingrid / Monteith, Scott / Morken, Gunnar / Munoz, Rodrigo / Nery, Fabiano G / O'Donovan, Claire / Osher, Yamima / Pfennig, Andrea / Quiroz, Danilo / Ramesar, Raj / Rasgon, Natalie / Reif, Andreas / Ritter, Philipp / Rybakowski, Janusz K / Sagduyu, Kemal / Miranda-Scippa, Ângela / Severus, Emanuel / Simhandl, Christian / Stein, Dan J / Strejilevich, Sergio / Sulaiman, Ahmad Hatim / Suominen, Kirsi / Tagata, Hiromi / Tatebayashi, Yoshitaka / Torrent, Carla / Vieta, Eduard / Viswanath, Biju / Wanchoo, Mihir J / Zetin, Mark / Whybrow, Peter C. ·Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany. Electronic address: michael.bauer@uniklinikum-dresden.de. · ChronoRecord Association, Fullerton, CA, USA. · Department of Psychiatry, Dalhousie University, Halifax, NS, Canada. · NORMENT - K.G. Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, Oslo, Norway. · Department of Psychiatry, University of Athens Medical School, Eginition Hospital, Athens, Greece. · Unit of Clinical Pharmacology, University-Hospital of Cagliari, Italy. · Department of Psychiatry and Psychotherapy, University of Cologne Medical School, Cologne, Germany. · Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Technische Universität, Dresden, Germany. · Discipline of Psychiatry, School of Medicine, University of Adelaide, Adelaide, SA 5005, Australia. · Psychiatrie, GH Saint-Louis - Lariboisière - F. Widal, AP-HP, INSERM UMR-S1144, Faculté de Médecine, Université D. Diderot, Paris, France; Fondation FondaMental, Créteil, France. · Department of Psychiatry, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva Mental Health Center, Beer Sheva, Israel. · IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria 3220, Australia; Department of Psychiatry, ORYGEN Youth Health Research Centre, Centre for Youth Mental Health and the Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria 3052, Australia. · Department of Molecular Medicine and Department of Mental Health (DAI), University of Siena and University of Siena Medical Center (AOUS), Siena, Italy. · Department of General Adult Psychiatry, Castle Peak Hospital, Hong Kong. · Section of Neurosciences and Clinical Pharmacology, Department of Biomedical Sciences, University of Cagliari, Sardinia, Italy. · IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria 3220, Australia; Department of Psychiatry, University of Melbourne, Parkville, Victoria 3052, Australia. · AP-HP, Hôpitaux Universitaires Henri-Mondor, INSERM U955 (IMRB), Université Paris Est, Créteil, France; Fondation FondaMental, Créteil, France. · Department of Psychiatry & Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA. · 3rd Department of Psychiatry, Division of Neurosciences, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece. · Department of Psychiatry and Behavioral Sciences, Stanford School of Medicine, Palo Alto, CA, USA. · Department of Psychiatry, University Hospital of Alava, University of the Basque Country, CIBERSAM, Vitoria, Spain. · Feinberg School of Medicine, Northwestern University, Chicago, IL, USA. · Department of Psychiatry, Tokyo Metropolitan Matsuzawa Hospital, Setagaya, Tokyo, Japan. · Department of Psychiatry, Faculty of Medicine, University of Calgary, Calgary, AB, Canada. · Department of Psychiatry, Institute of Clinical Medicine, University of Helsinki, Finland; National Institute for Health and Welfare, Helsinki, Finland. · Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Federal University of Rio Grande do Sul, Porto Alegre, Brazil. · Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland. · BIPOLAR Zentrum Wiener Neustadt, Wiener Neustadt, Austria. · Department of Affective Disorders, Q, Mood Disorders Research Unit, Aarhus University Hospital, Denmark. · Bipolar Disorder Research Program, Department of Psychiatry, University of São Paulo Medical School, São Paulo, Brazil. · Mood Disorders Program, Fundacion San Vicente de Paul, Department of Psychiatry, Universidad de Antioquia, Medellín, Colombia. · Department of Psychiatry, University of Massachusetts, Worcester, MA, USA. · Michigan State University College of Human Medicine, Traverse City Campus, Traverse City, MI, USA. · Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway; Department of Research and Development, Psychiatry, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. · Department of Psychiatry, University of California San Diego, San Diego, CA, USA. · Deparment of Psychiatry, Diego Portales University, Santiago, Chile. · UCT/MRC Human Genetics Research Unit, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa. · Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe-University Frankfurt am Main, Germany. · Department of Psychiatry, University of Missouri Kansas City School of Medicine, Kansas City, MO, USA. · Department of Neuroscience and Mental Health, Federal University of Bahia, Salvador, Brazil. · Department of Psychiatry, University of Cape Town, Cape Town, South Africa. · Bipolar Disorder Program, Neuroscience Institute, Favaloro University, Buenos Aires, Argentina. · Department of Psychological Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · City of Helsinki, Department of Social Services and Health Care, Psychiatry, Helsinki, Finland. · Schizophrenia & Affective Disorders Research Project, Tokyo Metropolitan Institute of Medical Science, Seatagaya, Tokyo, Japan. · Bipolar Disorders Program, Hospital Clinic, University of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Catalonia, Spain. · Department of Psychiatry, NIMHANS, Bangalore 560029, India. · Department of Psychology, Chapman University, Orange, CA, USA. · Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior University of California Los Angeles (UCLA), Los Angeles, CA, USA. ·J Psychiatr Res · Pubmed #25862378.

ABSTRACT: BACKGROUND: Environmental conditions early in life may imprint the circadian system and influence response to environmental signals later in life. We previously determined that a large springtime increase in solar insolation at the onset location was associated with a younger age of onset of bipolar disorder, especially with a family history of mood disorders. This study investigated whether the hours of daylight at the birth location affected this association. METHODS: Data collected previously at 36 collection sites from 23 countries were available for 3896 patients with bipolar I disorder, born between latitudes of 1.4 N and 70.7 N, and 1.2 S and 41.3 S. Hours of daylight variables for the birth location were added to a base model to assess the relation between the age of onset and solar insolation. RESULTS: More hours of daylight at the birth location during early life was associated with an older age of onset, suggesting reduced vulnerability to the future circadian challenge of the springtime increase in solar insolation at the onset location. Addition of the minimum of the average monthly hours of daylight during the first 3 months of life improved the base model, with a significant positive relationship to age of onset. Coefficients for all other variables remained stable, significant and consistent with the base model. CONCLUSIONS: Light exposure during early life may have important consequences for those who are susceptible to bipolar disorder, especially at latitudes with little natural light in winter. This study indirectly supports the concept that early life exposure to light may affect the long term adaptability to respond to a circadian challenge later in life.

11 Review Sleep- and circadian rhythm-associated pathways as therapeutic targets in bipolar disorder. 2015

Bellivier, Frank / Geoffroy, Pierre-Alexis / Etain, Bruno / Scott, Jan. ·Inserm, U1144 , Paris, F-75006 , France. ·Expert Opin Ther Targets · Pubmed #25726988.

ABSTRACT: INTRODUCTION: Disruptions in sleep and circadian rhythms are observed in individuals with bipolar disorders (BD), both during acute mood episodes and remission. Such abnormalities may relate to dysfunction of the molecular circadian clock and could offer a target for new drugs. AREAS COVERED: This review focuses on clinical, actigraphic, biochemical and genetic biomarkers of BDs, as well as animal and cellular models, and highlights that sleep and circadian rhythm disturbances are closely linked to the susceptibility to BDs and vulnerability to mood relapses. As lithium is likely to act as a synchronizer and stabilizer of circadian rhythms, we will review pharmacogenetic studies testing circadian gene polymorphisms and prophylactic response to lithium. Interventions such as sleep deprivation, light therapy and psychological therapies may also target sleep and circadian disruptions in BDs efficiently for treatment and prevention of bipolar depression. EXPERT OPINION: We suggest that future research should clarify the associations between sleep and circadian rhythm disturbances and alterations of the molecular clock in order to identify critical targets within the circadian pathway. The investigation of such targets using human cellular models or animal models combined with 'omics' approaches are crucial steps for new drug development.

12 Review Sleep in patients with remitted bipolar disorders: a meta-analysis of actigraphy studies. 2015

Geoffroy, P A / Scott, J / Boudebesse, C / Lajnef, M / Henry, C / Leboyer, M / Bellivier, F / Etain, B. ·Inserm, UMR-S 1144, Paris, France; AP-HP, GH Saint-Louis - Lariboisière - Fernand Widal, Pôle Neurosciences, Paris Cedex 10, France; Université Paris Descartes, UMR-S 1144, Paris, France; Université Paris Diderot, UMR-S 1144, Paris, France; Fondation FondaMental, Créteil, France. ·Acta Psychiatr Scand · Pubmed #25430914.

ABSTRACT: OBJECTIVE: Sleep dysregulation is highly prevalent in bipolar disorders (BDs), with previous actigraphic studies demonstrating sleep abnormalities during depressive, manic, and interepisode periods. We undertook a meta-analysis of published actigraphy studies to identify whether any abnormalities in the reported sleep profiles of remitted BD cases differ from controls. METHOD: A systematic review identified independent studies that were eligible for inclusion in a random effects meta-analysis. Effect sizes for actigraphy parameters were expressed as standardized mean differences (SMD) with 95% confidence intervals (95% CI). RESULTS: Nine of 248 identified studies met eligibility criteria. Compared with controls (N=210), remitted BD cases (N=202) showed significant differences in SMD for sleep latency (0.51 [0.28-0.73]), sleep duration (0.57 [0.30-0.84]), wake after sleep onset (WASO) (0.28 [0.06-0.50]) and sleep efficiency (-0.38 [-0.70-0.07]). Moderate heterogeneity was identified for sleep duration (I2=44%) and sleep efficiency (I2=44%). Post hoc meta-regression analyses demonstrated that larger SMD for sleep duration were identified for studies with a greater age difference between BD cases and controls (β=0.22; P=0.03) and non-significantly lower levels of residual depressive symptoms in BD cases (β=-0.13; P=0.07). CONCLUSION: This meta-analysis of sleep in remitted bipolar disorder highlights disturbances in several sleep parameters. Future actigraphy studies should pay attention to age matching and levels of residual depressive symptoms.

13 Review [Treatment of bipolar disorder]. 2014

Barde, Michael / Bellivier, Frank. · ·Rev Prat · Pubmed #25638852.

ABSTRACT: Bipolar disorder is a chronic pathology whose management must lead to limit the social, professional and family impacts as well as suicidal risk. The treatment of acute episodes and prophylaxis is based on mood stabilizer treatments whose lithium is a leader. They will be chosen according to the background and history of the disease. Anti-depressants must be used with care to minimize the risk of manic episode and the induction of rapid cycles. The prognosis is not solving major episodes but avoiding major mood episodes. The management of residual symptoms (especially neuro-cognitive) is also a major challenge prognosis and justifies the implementation of adjuvant psychotherapeutic strategies.

14 Review Seasonality and bipolar disorder: a systematic review, from admission rates to seasonality of symptoms. 2014

Geoffroy, Pierre Alexis / Bellivier, Frank / Scott, Jan / Etain, Bruno. ·Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - Fernand Widal, Pôle Neurosciences, 75475 Paris Cedex 10, France; Université Paris Descartes, UMR-S 1144, Paris, F-75006, France; Université Paris Diderot, UMR-S 1144, Paris, F-75013, France; Fondation FondaMental, Créteil, 94000, France. Electronic address: pierre.a.geoffroy@gmail.com. · Inserm, U1144, Paris F-75006, France; AP-HP, GH Saint-Louis - Lariboisière - Fernand Widal, Pôle Neurosciences, 75475 Paris Cedex 10, France; Université Paris Descartes, UMR-S 1144, Paris, F-75006, France; Université Paris Diderot, UMR-S 1144, Paris, F-75013, France; Fondation FondaMental, Créteil, 94000, France. · Academic Psychiatry, Institute of Neuroscience, Newcastle University, UK; Centre for Affective Disorders, Institute of Psychiatry, London, UK. · Fondation FondaMental, Créteil, 94000, France; AP-HP, Hôpital H. Mondor - A. Chenevier, Pôle de Psychiatrie, Créteil, 94000, France; Inserm, U955, Psychiatrie génétique, Créteil, 94000, France. ·J Affect Disord · Pubmed #25063960.

ABSTRACT: INTRODUCTION: Bipolar disorder (BD) is a severe mental disorder affecting 1-4% of the population worldwide. It is characterized by periods of (hypo)manic and depressive episodes. Seasonal patterns (SP) may be observed in admission rates, mood relapses and symptom fluctuations. METHODS: We conducted a systematic review of seasonality in BD, classifying studies based on seasonal admission rates to seasonality of symptoms assessments. RESULTS: Fifty-one papers were identified of which 32 addressed hospitalization rates by season, 6 addressed categorical diagnoses, and 13 explored symptom dimensions. Seasonal peaks for different BD mood episodes are observed worldwide and widely replicated. Manic episodes peak during spring/summer and, to a lesser extent, in autumn, depressive episodes peak in early winter and, to a lesser extent, summer, and mixed episodes peak in early spring or mid/late summer. There was a high frequency of SP for manic episodes (15%) and depressive episodes (25%), the latter being associated with a more complex clinical profile (BD II subtype, comorbid eating disorders, more relapses and rapid cycling). Finally, there was evidence for greater seasonal fluctuations in mood and behavior in individuals with BD than in those with unipolar depression or 'healthy' controls. LIMITATIONS: Sample size, gender distribution, methodological quality and sophistication of the analytical approaches employed varied considerably. CONCLUSIONS: There is evidence of seasonality in BD, with emerging evidence that climatic conditions may trigger BD symptoms or episodes. A better understanding of the underlying mechanisms would facilitate the development of personalized chronobiological therapeutic and preventive strategies.

15 Review Risk of myocardial infarction and stroke in bipolar disorder: a systematic review and exploratory meta-analysis. 2014

Prieto, M L / Cuéllar-Barboza, A B / Bobo, W V / Roger, V L / Bellivier, F / Leboyer, M / West, C P / Frye, M A. ·Department of Psychiatry and Psychology, Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN, USA; Universidad de los Andes, Facultad de Medicina, Departamento de Psiquiatría, Santiago, Chile. ·Acta Psychiatr Scand · Pubmed #24850482.

ABSTRACT: OBJECTIVE: To review the evidence on and estimate the risk of myocardial infarction and stroke in bipolar disorder. METHOD: A systematic search using MEDLINE, EMBASE, PsycINFO, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and bibliographies (1946 - May, 2013) was conducted. Case-control and cohort studies of bipolar disorder patients age 15 or older with myocardial infarction or stroke as outcomes were included. Two independent reviewers extracted data and assessed quality. Estimates of effect were summarized using random-effects meta-analysis. RESULTS: Five cohort studies including 13 115 911 participants (27 092 bipolar) were included. Due to the use of registers, different statistical methods, and inconsistent adjustment for confounders, there was significant methodological heterogeneity among studies. The exploratory meta-analysis yielded no evidence for a significant increase in the risk of myocardial infarction: [relative risk (RR): 1.09, 95% CI 0.96-1.24, P = 0.20; I(2)  = 6%]. While there was evidence of significant study heterogeneity, the risk of stroke in bipolar disorder was significantly increased (RR 1.74, 95% CI 1.29-2.35; P = 0.0003; I(2)  = 83%). CONCLUSION: There may be a differential risk of myocardial infarction and stroke in patients with bipolar disorder. Confidence in these pooled estimates was limited by the small number of studies, significant heterogeneity and dissimilar methodological features.

16 Review White matter alterations in bipolar disorder: potential for drug discovery and development. 2014

Marlinge, Emeline / Bellivier, Frank / Houenou, Josselin. ·AP-HP, Groupe Henri Mondor-Albert Chenevier, Pôle de Psychiatrie, Paris, France; Inserm, U955, Equipe 15 (Psychiatrie Génétique), Paris, France; Fondation Fondamental, Créteil, France; Neurospin, I2BM, CEA, Gif-Sur-Yvette, France. ·Bipolar Disord · Pubmed #24571279.

ABSTRACT: OBJECTIVES: Brain white matter (WM) alterations have recently emerged as potentially relevant in bipolar disorder. New techniques such as diffusion tensor imaging allow precise exploration of these WM microstructural alterations in bipolar disorder. Our objective was to critically review WM alterations in bipolar disorder, using neuroimaging and neuropathological studies, in the context of neural models and the potential for drug discovery and development. METHODS: We conducted a systematic PubMed and Google Scholar search of the WM and bipolar disorder literature up to and including January 2013. RESULTS: Findings relating to WM alterations are consistent in neuroimaging and neuropathology studies of bipolar disorder, especially in regions involved in emotional processing such as the anterior frontal lobe, corpus callosum, cingulate cortex, and in fronto-limbic connections. Some of the structural alterations are related to genetic risk factors for bipolar disorder and may underlie the dysfunctional emotional processing described in recent neurobiological models of bipolar disorder. Medication effects in bipolar disorder, from lithium and other mood stabilizers, might impact myelinating processes, particularly by inhibition of glycogen synthase kinase-3 beta. CONCLUSIONS: Pathways leading to WM alterations in bipolar disorder represent potential targets for the development and discovery of new drugs. Myelin damage in bipolar disorder suggests that the effects of existing pro-myelinating drugs should also be evaluated to improve our understanding and treatment of this disease.

17 Review [Treatment of manic phases of bipolar disorder: critical synthesis of international guidelines]. 2014

Geoffroy, P A / Bellivier, F / Henry, C. ·Inserm, UMR-S1144, VariaPsy, équipe 1, Paris, France; Pôle neurosciences, AP-HP, groupe hospitalier Saint-Louis - Lariboisière - Fernand Widal, Paris, France; Université Paris-7 Paris-Diderot, UFR de médecine, Paris, France; Fondation FondaMental, 94000 Créteil, France. Electronic address: pierre.a.geoffroy@gmail.com. · Inserm, UMR-S1144, VariaPsy, équipe 1, Paris, France; Pôle neurosciences, AP-HP, groupe hospitalier Saint-Louis - Lariboisière - Fernand Widal, Paris, France; Université Paris-7 Paris-Diderot, UFR de médecine, Paris, France; Fondation FondaMental, 94000 Créteil, France. · Université Paris-Est, UFR de médecine, Créteil, France; Pôle de psychiatrie, hôpital H. Mondor - A. Chenevier, AP-HP, 94000 Créteil, France; Inserm, U955, psychiatrie génétique, 94000 Créteil, France; Fondation FondaMental, 94000 Créteil, France. ·Encephale · Pubmed #24513018.

ABSTRACT: INTRODUCTION: Bipolar disorder (BD) is the seventh leading cause of disability per year of life among all diseases in the population aged 15 to 44. It is a group of heterogeneous diseases, with frequent comorbid psychiatric or somatic disorders, variable treatment response and frequent residual symptoms between episodes. The major impairment associated with this disorder is related to the high relapse and recurrence rates, the functional impact of comorbidities and cognitive impairment between episodes. The prognosis of the disease relies on the efficacy of relapse and recurrence prevention interventions. Given the heterogeneity of the disorder, relapse and recurrence prevention needs to develop a personalized care plan from the start of the acute phase. In such a complex situation, guideline-driven algorithms of decision are known to improve overall care of patients with bipolar disorder, compared to standard treatment decisions. Although guidelines do not account for all the situations encountered with patients, this systematic approach contributes to the development of personalized medicine. METHODS: We present a critical review of recent international recommendations for the management of manic phases. We summarize treatment options that reach consensus (monotherapy and combination therapy) and comment on options that differ across guidelines. RESULTS: The synthesis of recent international guidelines shows a consensus for the initial treatment for manic phases. For acute and long-term management, the anti-manic drugs proposed are traditional mood stabilizers (lithium or valproate) and atypical antipsychotics (APA - olanzapine, risperidone, aripiprazole and quetiapine). All guidelines indicate stopping antidepressant drugs during manic phases. International guidelines also present with some differences. First, as monotherapy is often non sufficient in clinical practice, combination therapy with a traditional mood stabilizer and an APA are disputed either in first line treatment for severe cases or in second line. Second, mixed episodes treatment is not consensual either and some guidelines propose in first line valproate, carbamazepine and some APA, and advice not to use lithium. On the other hand, some guidelines do not propose specific treatment for mixed episodes and group them with manic episodes management. Duration of treatment is unclear. CONCLUSION: Guidelines utilization has shown that the systemic use by clinicians of decision algorithms in comparison to "treatment as usual" modality improves the overall care of patients with BD. Future data from cohorts of patients seem necessary to complement the existing data from clinical trials. These cohort studies will help to take into account the different individual profiles of BD and thus may help to propose a more personalized medicine.

18 Review Circadian abnormalities as markers of susceptibility in bipolar disorders. 2014

Milhiet, Vanessa / Boudebesse, Carole / Bellivier, Frank / Drouot, Xavier / Henry, Chantal / Leboyer, Marion / Etain, Bruno. ·AP-HP,Centre Expert Troubles Bipolaires, Pole de Psychiatrie, Hoapital Hopital, Albert Chenevier, 40 rue de Mesly, 94000 Creteil, France. · AP-HP, Groupe Saint-Louis -Lariboisiere - Fernand Widal, Pole Neurosciences, Paris, France. · AP-HP, Groupe Henri Mondor-Albert Chenevier, Service de Physiologie, Creteil, 94000, France. · AP-HP, Groupe Hospitalier Henri Mondor-Albert Chenevier, Pole de Psychiatrie, Creteil, 94000, France. ·Front Biosci (Schol Ed) · Pubmed #24389266.

ABSTRACT: Chronobiological models have contributed to a better understanding of the pathophysiology of bipolar disorders. Circadian functions dysregulations are associated with bipolar disorders, including biochemical (melatonin and cortisol profiles), actigraphic (sleep/wake patterns), and dimensional (chronotypes) circadian markers. These associations are observed not only during acute episodes but also during euthymic periods. Most markers that are associated with bipolar disorders are also found in the healthy relatives of patients, suggesting a strong degree of heritability. As such, they may serve as trait markers of the disorder. Several circadian genes have been found to be associated with bipolar disorders: at least three studies have reported positive associations for each of CLOCK, NPAS2, ARNTL1, NR1D1, PER3, RORB and CSNK1epsilon. Thus the clock machinery may contribute to the genetic susceptibility to bipolar disorders. The circadian model theory has also led to the development of novel therapeutic strategies such as InterPersonal and Social Rhythms Therapy and chronotherapeutics. Additionally, the circadian model theory may help explain how mood stabilizers (in particular lithium carbonate) bring about their therapeutic effects.

19 Review Can the response to mood stabilizers be predicted in bipolar disorder? 2014

Geoffroy, Pierre Alexis / Bellivier, Frank / Leboyer, Marion / Etain, Bruno. ·Pole de Psychiatrie, Centre Expert Bipolaire, Hopital Albert Chenevier, pavillon Hartman, 40, rue de Mesly, 94000 Creteil Cedex, France. · FondaMental Foundation, Creteil, 94000, France. ·Front Biosci (Elite Ed) · Pubmed #24389147.

ABSTRACT: Bipolar disorder (BD) is a severe chronic multifactorial disease that requires maintenance therapy with mood stabilizers (MS). Even with medications, the rate of response among patients with BD is low and the risk of relapse is high. Therefore, in this context of the urgent need for reliable and reproducible predictors of individual responses to MS, pharmacogenetics research is expected to provide helpful progress. Most pharmacogenetic studies of MS have focused on the response to lithium with several good putative candidate genes but informative results are sparse. There have been few studies on valproate, lamotrigine or atypical antipsychotics. Overall, the results of pharmacogenomics studies have not provided sufficient data to change daily practices in BD significantly and further investigation is warranted to identify highly relevant genetic predictors of response their roles. Although progress still remains to be made, the clinical assessment of a subject including the identification of specific individual phenotypic and pharmacogenetic characteristics is likely to become a powerful instrument for the development of personalized therapies.

20 Review Neurocognitive performance as an endophenotype for bipolar disorder. 2014

Raust, Aurelie / Daban, Claire / Cochet, Barbara / Henry, Chantal / Bellivier, Frank / Scott, Jan. ·Assistance Publique-Hopitaux de Paris (AP-HP), Groupe Henri Mondor-Albert Chenevier, Creteil, France, 2INSERM, Unit 955, Creteil, France. · INSERM, Unit 955, Creteil, France. · Assistance Publique-Hopitaux de Paris (AP-HP), Groupe Henri Mondor-Albert Chenevier, Creteil, France, INSERM, Unit 955, Creteil, France. · INSERM, Unit 955, Creteil, France, Bipolar Expert Centres, Fondation Fondamental, Creteil, France, and AP-HP, Groupe Hospitalier Lariboisiere Widal, Paris, France. · Academic Psychiatry, Institute of Neuroscience, Newcastle, UK, and Centre for Affective Disorders, Institute of Psychiatry, London, UK. ·Front Biosci (Elite Ed) · Pubmed #24389145.

ABSTRACT: Identification of the underlying liability to develop bipolar disorders (BD) is hindered by the genetic complexity and phenotypic heterogeneity of the disease. The use of endophenotypes has been acknowledged as a promising approach that may detect the hidden manifestations of a genetic liability for an illness. One of the most commonly proposed endophenotypes in BD is neurocognitive performance. We identified and examined previously published review articles that had any data pertaining to endophenotypes in BD and combined this with an extensive review of studies of cognitive deficits in BD from 2000 onwards. Using criteria for a valid endophenotype, we identifed that the domains of executive functioning and verbal memory are the most promising candidate endophenotypes for BD. However, they do not meet the criteria for specificity as similar deficits present in schizophrenia and/or severe or psychotic major depressions. Further research is needed as the findings regarding endophenotypes show between-study heterogeneity. In the future, examination of quantitative traits may offer a more promising approach to the study of endophenotypes rather than solely focusing on diagnostic categories.

21 Review Biomarkers of bipolar disorder: specific or shared with schizophrenia? 2013

Bellivier, Frank / Geoffroy, Pierre Alexis / Scott, Jan / Schurhoff, Franck / Leboyer, Marion / Etain, Bruno. ·Inserm, U955, Psychiatrie genetique, Creteil, France. frank.bellivier@inserm.fr ·Front Biosci (Elite Ed) · Pubmed #23747901.

ABSTRACT: Kraepelin's observations of the differences in the course and outcome of dementia praecox and manic depression fundamentally influenced thinking about bipolar disorder (BP) and schizophrenia (SZ) for over a century. In modern times, there is increasing awareness that a greater understanding of the similarities between these two highly prevalent and disabling conditions can teach us as many lessons about the pathophysiology of severe mental disorders as does the pursuit of differentiating factors. We review publications on developmental, genetic, epidemiological, and outcome research that challenges the Kraepelian dichotomy. We highlight the increasing evidence of the overlap in genetic susceptibility. Neuro-developmental studies provide evidence of shared early pathological processes, whilst neurophysiological investigations also suggest that different genes may have a role in the development of both phenotypes. There is also evidence of overlapping neurocognitive phenotypes. It has become increasingly clear that a simple binary classification of these disorders represents an oversimplification. It may be more apposite to think in terms of genetic influences on six continuous symptom dimensions: neurobiological, cognitive, positive, negative, depressive and manic symptoms.

22 Review [Early onset bipolar disorder: validation from admixture analyses and biomarkers]. 2013

Geoffroy, Pierre Alexis / Etain, Bruno / Jamain, Stéphane / Bellivier, Frank / Leboyer, Marion. ·Hôpital H. Mondor-A. Chenevier, Pôle de psychiatrie, et Fondation Fonda Mental, Créteil, France. ·Can J Psychiatry · Pubmed #23547648.

ABSTRACT: OBJECTIVES: Bipolar affective disorder (BD) is a multifactorial disorder with heterogeneous clinical presentations, in particular according to age at onset (AAO). The relevance of such an indicator has been discussed as a potential specifier in future nosographical classification. METHOD: We summarize available evidence of admixture analyses and biomarkers in early onset BD. RESULTS: Numerous clinical arguments have led us to conclude that the early onset BD subgroup is clinically homogeneous, with particular, recurrent, and severe characteristics.Eight admixture studies have demonstrated the existence of 3 subgroups of patients with BD according to AAO (early, intermediate, and late AAO), with 2 cut-off points of 21 (21.33) [SD 1.41]) and 35 years (34.67 [SD 5.52]). Differential clinical features and outcome measures characterize the early onset subgroup: higher rate of suicide attempts, rapid cycling, alcohol and drugs misuse, psychotic symptoms, and comorbid anxiety disorders. This may partially explain the delayed diagnosis and late initiation of mood stabilizers. Genetic, biological, imaging, and cognitive arguments may be considered as potential markers in providing external validity of the existence of this early onset subgroup. Implementation of AAO in the algorithms of treatment may be discussed, although the level of proof for focused medication strategies remains to be consolidated. CONCLUSION: Given the high frequency (44.80%) of early onset BD, awareness of clinicians should be stimulated to provide an early and accurate detection, preventive strategies, and possibly specific treatments.The forthcoming DSM-5 should include AAO as a specifier, given its relevance for course and outcome.

23 Review Reconsideration of bipolar disorder as a developmental disorder: importance of the time of onset. 2013

Geoffroy, Pierre Alexis / Etain, Bruno / Scott, Jan / Henry, Chantal / Jamain, Stéphane / Leboyer, Marion / Bellivier, Frank. ·Inserm U955, Créteil 94000, France. pierre.a.geoffroy@gmail.com ·J Physiol Paris · Pubmed #23542544.

ABSTRACT: Bipolar disorder is a multifactorial psychiatric disorder with developmental and progressive neurophysiological alterations. This disorder is typically characterized by cyclical and recurrent episodes of mania and depression but is heterogeneous in its clinical presentation and outcome. Although the DSM-IV-TR criteria identify several features that are of phenomenological relevance, these are of less utility for defining homogeneous subgroups, for analyses of correlations with biomarkers or for directing focused medication strategies. We provide a comprehensive review of existing evidence regarding to age at onset in bipolar disorder. Eight admixture studies demonstrate three homogeneous subgroups of patients with bipolar disorder identified according to age at onset (early, intermediate and late age at onset), with two cutoff points, at 21 and 34 years. It is suggested that the early-onset subgroup has specific clinical features and outcomes different from those of the other subgroups. Early-onset subgroup may be considered a more suitable clinical phenotype for the identification of susceptibility genes with recent data demonstrating associations with genetic variants specifically in this subgroup. The use of age at onset as a specifier may also facilitate the identification of other biological markers for use in brain imaging, circadian, inflammatory and cognitive research. A key challenge is posed by the use of age at onset in treatment decision algorithms, although further research is required to increase the evidence-base. We discuss three potential benefits of specifying age at onset, namely: focused medication strategies, the targeted prevention of specific comorbid conditions and decreasing the duration of untreated illness. We argue that age at onset should be included as a specifier for bipolar disorders.

24 Review [Cognitions and functioning in euthymic bipolar patients: screening and treatment]. 2012

Bellivier, Frank. ·Service de Psychiatrie d'Adultes, Groupe Hospitalier Saint-Louis-Lariboisière-Fernand Widal, 200 rue du Faubourg Saint Denis, Paris cedex 10, France. frank.bellivier@inserm.fr ·Encephale · Pubmed #23395229.

ABSTRACT: Persistent cognitive deficits in euthymic bipolar patients are now well documented. Indeed, several studies and meta-analyzes clearly establish the existence of cognitive deficits in specific domains: attention (in particular sustained attention), Memory (in particular verbal memory) and executive functions. The impact of cognitive deficits on patient's functioning is also well documented and their role appear to be more important than expected by comparison with the impairment related to thymic residual symptoms. The development of specific cognitive remediation strategies is therefore a major hope for improving the quality of remission and functional outcome. The aetiology of these deficits remains poorly understood. However, the implication of factors related to the biological/genetic vulnerability to bipolar disorder is likely well as a "neurotoxic" effects of major mood episodes, in particular acute manic episodes that seems to play a important role in the worsening of these deficits over time. This further stresses the importance maintenance strategies for long-term functional outcome.

25 Review Combination therapy for manic phases: a critical review of a common practice. 2012

Geoffroy, Pierre Alexis / Etain, Bruno / Henry, Chantal / Bellivier, Frank. ·Inserm, Créteil, France. pierre.a.geoffroy@gmail.com ·CNS Neurosci Ther · Pubmed #23095277.

ABSTRACT: All relevant guidelines recommend monotherapy as the initial treatment for manic phases of bipolar disorder (BD), with combination therapy reserved for severe cases or as a subsequent choice. However, in routine practice, monotherapy is often not sufficiently effective for acute and/or maintenance therapy. As a consequence, most patients are given combination therapies. An extensive search concerning combination treatment for manic episodes was conducted for relevant international randomized controlled studies, treatment guidelines and comprehensive reviews published since 1980. The scientific literature is sufficiently rich to validate the superiority of combination therapy over monotherapy in the manic phase in terms of efficacy and prevention of relapse; its safety profile is acceptable. Side effects are more frequent with combination therapy as a whole than with monotherapy, and discontinuation rates due to adverse events are higher. Continued administration of antipsychotics after a manic phase is controversial: drug classification, the course of the disease and the predominant polarity should all be considered before treatment is continued. Combinations including olanzapine and asenapine and to a lesser extent risperidone are associated with weight gain, those including quetiapine, haloperidol and asenapine with sedation, and those including aripiprazole with akathisia. This review of literature leads us to suggest that combination therapy including an atypical antipsychotic with lithium or valproate may be considered as a first-line approach. An appropriate algorithm for making decisions about combination treatment needs to be developed and included in future guidelines.

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