title: The role of childhood trauma in bipolar disorders.
abstract: This review will discuss the role of childhood trauma in bipolar disorders. Relevant studies were identified via Medline (PubMed) and PsycINFO databases published up to and including July 2015. This review contributes to a new understanding of the negative consequences of early life stress, as well as setting childhood trauma in a biological context of susceptibility and discussing novel long-term pathophysiological consequences in bipolar disorders. Childhood traumatic events are risk factors for developing bipolar disorders, in addition to a more severe clinical presentation over time (primarily an earlier age at onset and an increased risk of suicide attempt and substance misuse). Childhood trauma leads to alterations of affect regulation, impulse control, and cognitive functioning that might decrease the ability to cope with later stressors. Childhood trauma interacts with several genes belonging to several different biological pathways [Hypothalamic-pituitary-adrenal (HPA) axis, serotonergic transmission, neuroplasticity, immunity, calcium signaling, and circadian rhythms] to decrease the age at the onset of the disorder or increase the risk of suicide. Epigenetic factors may also be involved in the neurobiological consequences of childhood trauma in bipolar disorder. Biological sequelae such as chronic inflammation, sleep disturbance, or telomere shortening are potential mediators of the negative effects of childhood trauma in bipolar disorders, in particular with regard to physical health. The main clinical implication is to systematically assess childhood trauma in patients with bipolar disorders, or at least in those with a severe or instable course. The challenge for the next years will be to fill the gap between clinical and fundamental research and routine practice, since recommendations for managing this specific population are lacking. In particular, little is known on which psychotherapies should be provided or which targets therapists should focus on, as well as how childhood trauma could explain the resistance to mood stabilizers.
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, TOP Study Group, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Bygg 49, Ullevål Sykehus, Nydalen, PO Box 4956, 0424, Oslo, Norway. monica.aas@medisin.uio.no.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. monica.aas@medisin.uio.no.|ENBREC, European Network of Bipolar Research Expert Centres (ENBREC), Paris, France. monica.aas@medisin.uio.no.
authors.forename: Monica
authors.initials: M
authors.lastname: Aas
authors.affiliation: AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, 94000, Créteil, France. chantal.henry@inserm.fr.|Université Paris Est, Faculté de Médecine, 94000, Créteil, France. chantal.henry@inserm.fr.|Inserm, U955, 94000, Créteil, France. chantal.henry@inserm.fr.|Fondation Fondamental, Créteil, France. chantal.henry@inserm.fr.|ENBREC, European Network of Bipolar Research Expert Centres (ENBREC), Paris, France. chantal.henry@inserm.fr.
authors.forename: Chantal
authors.initials: C
authors.lastname: Henry
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, TOP Study Group, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Bygg 49, Ullevål Sykehus, Nydalen, PO Box 4956, 0424, Oslo, Norway. o.a.andreassen@medisin.uio.no.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. o.a.andreassen@medisin.uio.no.|ENBREC, European Network of Bipolar Research Expert Centres (ENBREC), Paris, France. o.a.andreassen@medisin.uio.no.
authors.forename: Ole A
authors.initials: OA
authors.lastname: Andreassen
authors.affiliation: Fondation Fondamental, Créteil, France. frank.bellivier@inserm.fr.|AP-HP, Hôpital Fernand Widal, Pôle Addictologie-Toxicologie-Psychiatrie and Université Paris-7, Paris, France. frank.bellivier@inserm.fr.|ENBREC, European Network of Bipolar Research Expert Centres (ENBREC), Paris, France. frank.bellivier@inserm.fr.
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
authors.affiliation: NORMENT, KG Jebsen Centre for Psychosis Research, TOP Study Group, Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Bygg 49, Ullevål Sykehus, Nydalen, PO Box 4956, 0424, Oslo, Norway. ingrid.melle@medisin.uio.no.|Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway. ingrid.melle@medisin.uio.no.|ENBREC, European Network of Bipolar Research Expert Centres (ENBREC), Paris, France. ingrid.melle@medisin.uio.no.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Melle
authors.affiliation: AP-HP, Hôpitaux Universitaires Henri Mondor, DHU Pepsy, Pôle de Psychiatrie, 94000, Créteil, France. Bruno.Etain@inserm.fr.|Inserm, U955, 94000, Créteil, France. Bruno.Etain@inserm.fr.|Fondation Fondamental, Créteil, France. Bruno.Etain@inserm.fr.|ENBREC, European Network of Bipolar Research Expert Centres (ENBREC), Paris, France. Bruno.Etain@inserm.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: Etain