Becking Karlijn, Spijker Annet T, Hoencamp Erik, Penninx Brenda W J H, Schoevers Robert A, Boschloo Lynn
University of Groningen, University Medical Center Groningen, Interdisciplinary Center Psychopathology and Emotion regulation (ICPE) and University Center Psychiatry (UCP), Groningen, The Netherlands.
PsyQ Rijnmond, Department of Mood Disorders, Rotterdam, The Netherlands.
PLoS One. 2015 Jul 21;10(7):e0133898. doi: 10.1371/journal.pone.0133898. eCollection 2015.
Differentiating bipolar depression (BD) from unipolar depression (UD) is difficult in clinical practice and, consequently, accurate recognition of BD can take as long as nine years. Research has therefore focused on the discriminatory capacities of biomarkers, such as markers of the hypothalamic-pituitary-adrenal (HPA) axis or immunological activity. However, no previous study included assessments of both systems, which is problematic as they may influence each other. Therefore, this study aimed to explore whether cortisol indicators and inflammatory markers were a) independently associated with and/or b) showed effect modification in relation to a lifetime (hypo)manic episode in a large sample of depressed patients.
Data were derived from the Netherlands Study of Depression and Anxiety and comprised 764 patients with a DSM-IV depressive disorder at baseline, of which 124 (16.2%) had a lifetime (hypo)manic episode at the 2-year assessment, or a more recent episode at the 4-year or 6-year assessment. Baseline cortisol awakening response, evening cortisol and diurnal cortisol slope were considered as cortisol indicators, while baseline C-reactive Protein (CRP), Interleukin-6 (IL-6), and Tumor Necrosis Factor Alpha (TNF-α) were included as inflammatory markers.
In depressed men and women, none of the cortisol indicators and inflammatory markers were (independently) associated with a (hypo)manic episode. However, effect modification was found of diurnal cortisol slope and CRP in relation to a (hypo)manic episode. Further analyses showed that depressed men with high levels of diurnal cortisol slope and CRP had an increased odds (OR=10.99, p=.001) of having a (hypo)manic episode. No significant differences were found in women.
Our findings suggest that the combination of high diurnal cortisol slope and high CRP may differentiate between UD and BD. This stresses the importance of considering HPA-axis and immunological activity simultaneously, but more research is needed to unravel their interrelatedness.
在临床实践中，区分双相抑郁症（BD）和单相抑郁症（UD）很困难，因此，准确识别BD可能需要长达九年的时间。因此，研究集中在生物标志物的鉴别能力上，如下丘脑-垂体-肾上腺（HPA）轴标志物或免疫活性标志物。然而，以前没有研究同时评估这两个系统，这存在问题，因为它们可能相互影响。因此，本研究旨在探讨皮质醇指标和炎症标志物是否a）与大量抑郁症患者的终生（轻）躁狂发作独立相关，和/或b）显示效应修正。
数据来自荷兰抑郁症和焦虑症研究，包括764名基线时患有DSM-IV抑郁症的患者，其中124名（16.2%）在2年评估时有终生（轻）躁狂发作，或在4年或6年评估时有更近的发作。基线皮质醇觉醒反应、夜间皮质醇和昼夜皮质醇斜率被视为皮质醇指标，而基线C反应蛋白（CRP）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）被作为炎症标志物。
在抑郁男性和女性中，没有皮质醇指标和炎症标志物与（轻）躁狂发作（独立）相关。然而，发现昼夜皮质醇斜率和CRP与（轻）躁狂发作存在效应修正。进一步分析表明，昼夜皮质醇斜率和CRP水平高的抑郁男性发生（轻）躁狂发作的几率增加（OR=10.99，p=.001）。女性中未发现显著差异。
我们的研究结果表明，高昼夜皮质醇斜率和高CRP的组合可能区分UD和BD。这强调了同时考虑HPA轴和免疫活性的重要性，但需要更多研究来阐明它们的相互关系。
