背景:过去对精神分裂症(SCZ)和应激敏感性神经内分泌系统的研究主要集中在单个系统上,并且传统上利用了急性生物标志物(例如,来自血液的生物标志物,尿液和唾液)在时间跨度上与精神分裂症的慢性病程不匹配。在头发中使用八种生物标志物,本研究旨在探讨SCZ患者下丘脑-垂体-肾上腺皮质(HPA)轴和下丘脑-垂体-性腺(HPG)轴的功能特征及其两者的相互作用。
方法:从137名SCZ患者和73名对照者采集头发样本。SCZ患者由主治医师根据《精神障碍诊断和统计手册IV》进行诊断,治疗后临床稳定。性别,年龄,BMI,洗头的频率,婚姻状况,教育水平,同时收集精神病家族史和氯氮平剂量作为协变量.采用10项感知压力量表(PSS-10)和社会调整评定量表评估SCZ患者的慢性应激状态。八种头发生物标志物,皮质醇,可的松,脱氢表雄酮(DHEA),睾丸激素,黄体酮,皮质醇/可的松,皮质醇/DHEA和皮质醇/睾酮,用高效液相色谱串联质谱仪测定。其中,皮质醇,可的松,DHEA和皮质醇/DHEA反映了HPA轴的功能活性,睾酮和孕酮反映了HPG轴的功能活性,皮质醇/可的松反映了11β-羟基类固醇脱氢酶2型(11β-HSD2)的活性,皮质醇/睾酮反映了HPA-HPG的相互作用。
结果:SCZ患者的可的松和皮质醇/睾丸激素明显高于对照组(p<0.001,η²p=0.180和p=0.015,η²p=0.031),较低的睾酮(p=0.009,η²p=0.034),孕酮(p<0.001,η²p=0.069)和皮质醇/可的松(p=0.001,η²p=0.054)。男性和女性孕酮(p=0.003,η²p=0.088和p=0.030,η²p=0.049)和女性睾丸激素(p=0.028,η²p=0.051)存在显着组间差异。在SCZ患者中,皮质醇,皮质醇/可的松,皮质醇/DHEA和皮质醇/睾酮与PSS-10评分呈正相关(ps<0.05,0.212结论:HPA和HPG轴的功能,SCZ患者11β-HSD2活性和HPA-HPG相互作用异常。SCZ患者神经内分泌系统异常与慢性应激状态有关。这项研究为SCZ患者的神经内分泌系统异常提供了证据。
BACKGROUND: Past studies on schizophrenia (SCZ) and the stress-sensitive neuroendocrine systems have mostly focused on a single system and traditionally utilized acute biomarkers (e.g., biomarkers from blood, urine and saliva) that poorly match the chronic course of schizophrenia in time span. Using eight biomarkers in hair, this study aimed to explore the functional characteristics of SCZ patients in the hypothalamic-pituitary-adrenocortical (HPA) and hypothalamic-pituitary-gonadal (HPG) axes and the interaction between the two axes.
METHODS: Hair samples were taken from 137 SCZ patients and 73 controls. The SCZ patients were diagnosed by their attending physician according to the Diagnostic and Statistical Manual of Mental Disorders IV and were clinically stable after treatment. Gender, age, BMI, frequency of hair washing, marital status, education level, family history of mental illness and clozapine dosage were concurrently collected as covariates. The 10-item perceived stress scale (PSS-10) and the social readjustment rating scale were used to assess chronic stress status in SCZ patients. Eight hair biomarkers, cortisol, cortisone, dehydroepiandrosterone (DHEA), testosterone, progesterone, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone, were measured by high performance liquid chromatography tandem mass spectrometer. Among them, cortisol, cortisone, DHEA and cortisol/DHEA reflected the functional activity of the HPA axis, and testosterone and progesterone reflected the functional activity of the HPG axis, and cortisol/cortisone reflected the activity of 11β-hydroxysteroid dehydrogenase types 2 (11β-HSD 2), and cortisol/testosterone reflected the HPA-HPG interaction.
RESULTS: SCZ patients showed significantly higher cortisone and cortisol/testosterone than controls (p<0.001, η²p=0.180 and p=0.015, η²p=0.031), lower testosterone (p=0.009, η²p=0.034), progesterone (p<0.001, η²p=0.069) and cortisol/cortisone (p=0.001, η²p=0.054). There were significant intergroup differences in male and female progesterone (p=0.003, η²p=0.088 and p=0.030, η²p=0.049) and female testosterone (p=0.028, η²p=0.051). In SCZ patients, cortisol, cortisol/cortisone, cortisol/DHEA and cortisol/testosterone were positively associated with PSS-10 score (ps<0.05, 0.212
CONCLUSIONS: The function of the HPA and HPG axes, the activity of 11β-HSD 2 and the HPA-HPG interaction were abnormal in SCZ patients. The abnormality of neuroendocrine systems was associated with chronic stress status in SCZ patients. This study provided evidence for abnormalities in the neuroendocrine systems in SCZ patients.