title: Differential neuroendocrine and immune responses to acute psychosocial stress in women with type 1 bipolar disorder.
abstract: Bipolar disorder (BD) has been associated with immune imbalance, including lymphocyte activation and increased pro-inflammatory cytokines. Immune activation is part of stress response, and psychosocial stress has been implicated in the pathogenesis of psychiatric disorders. Here, we investigated the neuroendocrine and immune responses to acute psychosocial stress challenge in BD. Thirteen euthymic participants with type 1 BD and 15 healthy controls underwent the Trier Social Stress Test protocol (TSST). Blood samples were collected before and after TSST. Lymphocytes were isolated and stimulated in vitro to assess lymphocyte activation profile, lymphocyte sensitivity to dexamethasone, mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling by flow cytometry. Heart rate and salivary cortisol levels were monitored across the task. BD participants exhibited blunted stress responses as shown by reduced heart rate and salivary cortisol levels in comparison to healthy controls. BD was also associated with reduction in the percentage of regulatory T cells, but with expansion of activated T cells. When compared to controls, patients showed increased lymphocyte MAPK p-ERK and p-NF-κB signaling after the stress challenge, but exhibited a relative lymphocyte resistance to dexamethasone. In conclusion, stress-related neuroendocrine responses are blunted, associated with increased immune activation and lower sensitivity to glucocorticoids in BD. An inability in reducing NF-κB and MAPK signaling following TSST could be underlying the immune imbalance observed in BD.
authors.affiliation: Laboratory of Immunosenescence, Institute of Biomedical Research, Pontifical Catholic University of the Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
authors.forename: Andrea
authors.initials: A
authors.lastname: Wieck
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Grassi-Oliveira
authors.forename: Carine Hartmann
authors.initials: CH
authors.lastname: do Prado
authors.forename: Lucas Bortolotto
authors.initials: LB
authors.lastname: Rizzo
authors.forename: Agatha Schommer
authors.initials: AS
authors.lastname: de Oliveira
authors.forename: Júlia
authors.initials: J
authors.lastname: Kommers-Molina
authors.forename: Thiago Wendt
authors.initials: TW
authors.lastname: Viola
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
authors.forename: Moisés Evandro
authors.initials: ME
authors.lastname: Bauer
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000097:blood / Q000276:immunology* / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D008213:Lymphocyte Activation; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000503:physiopathology*; D013315:Stress, Psychological / Q000276:immunology* / Q000503:physiopathology*
chemical_list: D006854:Hydrocortisone
keywords: Bipolar disorder; Inflammation; Lymphocyte subsets; MAPK; NF-kappa B; Psychosocial stress