title: Emotional reactivity, functioning, and C-reactive protein alterations in remitted bipolar patients: Clinical relevance of a dimensional approach.
abstract: OBJECTIVE
  Inter-episode mood instability has increasingly been considered in bipolar disorder. This study aimed to investigate emotional reactivity as a major dimension for better characterizing remitted bipolar patients with subthreshold mood symptoms and functional status. This study also aimed to investigate whether high-sensitivity C-reactive protein, a marker of low-grade inflammation, could be a biological marker of emotional dysregulation in bipolar disorder (BD).
  
  
  METHODS
  Cross-sectional study of 613 subjects who met Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria for BD recruited from the FondaMental Advanced Centers of Expertise in Bipolar Disorders cohort from 2009 to 2014. All patients had been in remission for at least 3 months before assessment. Patients were classified into three groups according to levels of emotional reactivity. Emotional reactivity was assessed by using the Multidimensional Assessment of Thymic States, and functional status was assessed by the Functioning Assessment Short Test. Clinical characteristics and blood sample were collected from all patients.
  
  
  RESULTS
  In total, 415 (68%) patients had abnormal emotional reactivity. Independent of potential confounders, including age, gender and subthreshold mood symptoms, serum levels of high-sensitivity C-reactive protein were significantly higher in patients with emotional hyper-reactivity (median = 4.0 mg/L, interquartile range = 2.7-5.6), and with emotional hypo-reactivity (median = 3.0 mg/L, interquartile range = 1-4) compared with patients with normal emotional reactivity (median = 0.95 mg/L, interquartile range = 0.4-1.9, p < 0.001). Patients with emotional hyper-reactivity showed significant cognitive functioning impairment ( p < 0.001).
  
  
  CONCLUSIONS
  Emotional reactivity appears to be a relevant dimension for better characterizing remitted bipolar patients with subthreshold mood symptoms. Levels of high-sensitivity C-reactive protein may be an objective marker of emotional dysregulation in BD. Further studies are needed to confirm our findings.
authors.affiliation: 1 Unité Perception et Mémoire, Institut Pasteur, Paris, France.|2 Unité Mixte de Recherche, Centre National de la Recherche Scientifique, Paris, France.
authors.forename: Aroldo A
authors.initials: AA
authors.lastname: Dargél
authors.affiliation: 3 INSERM UMRS 943, UPMC Université, Paris, France.|4 Fondation FondaMental, Fondation de cooperation scientifique, Créteil, France.
authors.forename: Ophelia
authors.initials: O
authors.lastname: Godin
authors.affiliation: 4 Fondation FondaMental, Fondation de cooperation scientifique, Créteil, France.|5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|6 Université Paris-Est, UMR_S955, UPEC, Créteil, France.|7 Pôle de Psychiatrie, Hôpital H. Mondor-A. Chenevier, AP-HP, Créteil, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Etain
authors.affiliation: 8 Grupo de Pós-Graduação e Pesquisa, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Vânia
authors.initials: V
authors.lastname: Hirakata
authors.affiliation: 5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|9 Service de psychiatrie adulte, Centre Expert Trouble Bipolaire, Hôpital Charles Perrens, Bordeaux, France.
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Azorin
authors.affiliation: 5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|9 Service de psychiatrie adulte, Centre Expert Trouble Bipolaire, Hôpital Charles Perrens, Bordeaux, France.|10 Laboratory of Psychology 'Health and Quality of Life' EA 4139, Université Bordeaux Segalen, Bordeaux, France.
authors.forename: Katia
authors.initials: K
authors.lastname: M'Bailara
authors.affiliation: 5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|11 AP-HP, GH Saint-Louis-Lariboisière-Fernand Widal, Pôle Neurosciences, Paris, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
authors.affiliation: 5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|12 University Joseph Fourier, Grenoble, France.|13 Centre Hospitalier Universitaire de Grenoble, Grenoble, France.|14 Grenoble Institut des Neurosciences (GIN), Inserm U 836, Chemin Fortuné Ferrini, La Tronche, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Bougerol
authors.affiliation: 5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|15 Centre Hospitalier Universitaire de Nancy, Hôpitaux de Brabois, Université de Lorraine, Vandoeuvre les Nancy, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Kahn
authors.affiliation: 5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|16 Centre Hospitalier de Versailles, Le Chesnay, France.|17 Université de Versailles Saint-Quentin-en-Yvelines, Versailles, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Passerieux
authors.affiliation: 5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|18 Pôle de Psychiatrie, Centre Hospitalier Princesse Grace, Monaco, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Aubin
authors.affiliation: 5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|19 Psychiatric Emergency Department, CHRU Montpellier, France.|20 INSERM U1061, Montpellier University, Montpellier, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Courtet
authors.affiliation: 4 Fondation FondaMental, Fondation de cooperation scientifique, Créteil, France.|5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|6 Université Paris-Est, UMR_S955, UPEC, Créteil, France.|7 Pôle de Psychiatrie, Hôpital H. Mondor-A. Chenevier, AP-HP, Créteil, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.affiliation: 1 Unité Perception et Mémoire, Institut Pasteur, Paris, France.|5 INSERM, U955, Equipe 15 Genetic Psychiatry, Créteil, France.|6 Université Paris-Est, UMR_S955, UPEC, Créteil, France.|7 Pôle de Psychiatrie, Hôpital H. Mondor-A. Chenevier, AP-HP, Créteil, France.
authors.forename: Chantal
authors.initials: C
authors.lastname: Henry
mesh_terms: D000328:Adult; D000342:Affective Symptoms / Q000503:physiopathology*; D001714:Bipolar Disorder / Q000097:blood* / Q000503:physiopathology*; D002097:C-Reactive Protein; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D002097:C-Reactive Protein
keywords: Bipolar disorder; C-reactive protein; dimensional approach; emotional reactivity; psychosocial functioning