Belvederi Murri Martino, Prestia Davide, Mondelli Valeria, Pariante Carmine, Patti Sara, Olivieri Benedetta, Arzani Costanza, Masotti Mattia, Respino Matteo, Antonioli Marco, Vassallo Linda, Serafini Gianluca, Perna Giampaolo, Pompili Maurizio, Amore Mario
Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy; Institute of Psychiatry, Psychology and Neuroscience, Department of Psychological Medicine, King's College London, London, UK.
Section of Psychiatry, Department of Neuroscience, Ophthalmology, Genetics and Infant-Maternal Science, University of Genoa, Italy.
Psychoneuroendocrinology. 2016 Jan;63:327-42. doi: 10.1016/j.psyneuen.2015.10.014. Epub 2015 Oct 21.
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).
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.
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.
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.
对下丘脑-垂体-肾上腺（HPA）轴在双相情感障碍（BD）病理生理学中的作用的现有证据进行定量和定性综合分析。
对检测皮质醇、促肾上腺皮质激素（ACTH）、促肾上腺皮质激素释放激素（CRH）水平的病例对照研究进行荟萃分析和荟萃回归。对与BD中HPA轴活性相关的应激反应性、遗传学、分子和神经影像学研究进行系统评价。
荟萃分析纳入了41项研究。BD与皮质醇（基础和地塞米松后）和ACTH水平显著升高相关，但与CRH无关。在荟萃回归中，皮质醇水平的病例对照差异与躁狂期呈正相关（p = 0.005），与参与者年龄呈正相关（p = 0.08），与使用抗精神病药物呈负相关（p = 0.001）。综述研究表明，BD与多个脑区应激相关分子途径的异常有关。HPA轴相关基因的变异似乎与BD的直接发病风险无关，但与不同的临床表现有关。此外，对未患病亲属的研究表明，HPA轴失调不是BD的内表型，但似乎与环境风险因素有关，如童年创伤。进行性HPA轴功能障碍是一种可能是BD患者临床和认知恶化基础的潜在机制。
BD与HPA轴活性功能障碍有关，具有重要的病理生理学意义。针对HPA轴功能障碍可能是改善BD结局的一种新策略。
