TY - JOUR
T1 - The HPA axis in bipolar disorder
T2 - Systematic review and meta-analysis
AU - Belvederi Murri, Martino
AU - Prestia, Davide
AU - Mondelli, Valeria
AU - Pariante, Carmine
AU - Patti, Sara
AU - Olivieri, Benedetta
AU - Arzani, Costanza
AU - Masotti, Mattia
AU - Respino, Matteo
AU - Antonioli, Marco
AU - Vassallo, Linda
AU - Serafini, Gianluca
AU - Perna, Giampaolo
AU - Pompili, Maurizio
AU - Amore, Mario
PY - 2016/1/1
Y1 - 2016/1/1
N2 - Objectives: To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic-Pituitary-Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD). Methods: Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD. Results: Forty-one studies were included in the meta-analyses. BD was associated with significantly increased levels of cortisol (basal and post-dexamethasone) and ACTH, but not of CRH. In the meta-regression, case-control differences in cortisol levels were positively associated with the manic phase (p = 0.005) and participants' age (p = 0.08), and negatively with antipsychotics use (p = 0.001). Reviewed studies suggest that BD is associated with abnormalities of stress-related molecular pathways in several brain areas. Variants of HPA axis-related genes seem not associated with a direct risk of developing BD, but with different clinical presentations. Also, studies on unaffected relatives suggest that HPA axis dysregulation is not an endophenotype of BD, but seems related to environmental risk factors, such as childhood trauma. Progressive HPA axis dysfunction is a putative mechanism that might underlie the clinical and cognitive deterioration of patients with BD. Conclusions: BD is associated with dysfunction of HPA axis activity, with important pathophysiological implications. Targeting HPA axis dysfunctions might be a novel strategy to improve the outcomes of BD.
AB - Objectives: To provide a quantitative and qualitative synthesis of the available evidence on the role of Hypothalamic-Pituitary-Adrenal (HPA) axis in the pathophysiology of Bipolar Disorder (BD). Methods: Meta-analysis and meta-regression of case-control studies examining the levels of cortisol, ACTH, CRH levels. Systematic review of stress reactivity, genetic, molecular and neuroimaging studies related to HPA axis activity in BD. Results: Forty-one studies were included in the meta-analyses. BD was associated with significantly increased levels of cortisol (basal and post-dexamethasone) and ACTH, but not of CRH. In the meta-regression, case-control differences in cortisol levels were positively associated with the manic phase (p = 0.005) and participants' age (p = 0.08), and negatively with antipsychotics use (p = 0.001). Reviewed studies suggest that BD is associated with abnormalities of stress-related molecular pathways in several brain areas. Variants of HPA axis-related genes seem not associated with a direct risk of developing BD, but with different clinical presentations. Also, studies on unaffected relatives suggest that HPA axis dysregulation is not an endophenotype of BD, but seems related to environmental risk factors, such as childhood trauma. Progressive HPA axis dysfunction is a putative mechanism that might underlie the clinical and cognitive deterioration of patients with BD. Conclusions: BD is associated with dysfunction of HPA axis activity, with important pathophysiological implications. Targeting HPA axis dysfunctions might be a novel strategy to improve the outcomes of BD.
KW - Bipolar disorder
KW - Cortisol
KW - Depression
KW - Glucocorticoid receptor
KW - HPA Axis
KW - Mania
UR - http://www.scopus.com/inward/record.url?scp=84949818997&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2015.10.014
DO - 10.1016/j.psyneuen.2015.10.014
M3 - Article
AN - SCOPUS:84949818997
SN - 0306-4530
VL - 63
SP - 327
EP - 342
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
ER -