Inova Amina, Birkenæs Viktoria, Quintana Daniel S, Ormerod Monica B E G, Ueland Torill, Ueland Thor, Djurovic Srdjan, Andreassen Ole, Steen Nils Eiel, Aas Monica
Institute of Clinical Medicine, University of Oslo, Norway.
Centre for Precision Psychiatry, Division of Mental Health and Addiction, University of Oslo and Oslo University Hospital, Oslo, Norway; PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
Psychoneuroendocrinology. 2025 Feb;172:107272. doi: 10.1016/j.psyneuen.2024.107272. Epub 2024 Dec 25.
People with schizophrenia (SZ) and bipolar disorder (BD) show abnormalities in the biological stress system and low-grade inflammation. However, whether the hypothalamic-pituitary-adrenal (HPA) axis-immune regulation is disrupted in SZ and BD, is yet to be determined.
Cortisol and C-reactive protein (CRP) were measured in blood samples collected at or before 10 am in participants with SZ (N = 257), BD (N = 153), and healthy controls (N = 40). Cortisol/CRP ratio was calculated as an indicator of the balance between HPA axis activity and inflammatory activity, called HPA axis-immune regulation. Global functioning and symptom levels were obtained using the Global Assessment of Functioning (GAF) Scale and Positive and Negative Syndrome Scale (PANSS). Standardized neuropsychological tests were used to assess cognitive function. All analyses were adjusted for demographic variables (age and sex) and the time of blood sampling.
Participants with a SZ or BD diagnosis had lower cortisol/CRP ratios (F=5.93, p = 0.003) compared to healthy controls. The difference was no longer statistically significant (p > 0.1) when BMI was added as a covariate to the model. Within patients, those on psychotropic treatment (n = 337) had lower cortisol/CRP ratio than those not taking psychotropic agents (n = 59) (F=4.72, p = 0.03). Compared to HC, only patients on regular psychotropic agents had lower cortisol/CRP ratio (p = 0.02). Within the SZ group, lower cortisol/CRP ratio was associated with having poorer general functioning as measured by GAF (ß=-0.18, p = 0.01), and more severe negative and general symptomatology as measured by PANSS (ß=0.19, p = 0.007 and ß=0.18, p = 0.01, respectively). In SZ, lower cortisol/CRP ratio was also associated with poorer verbal memory, learning, and processing speed (ß=-0.20 p = 0.007, ß=-0.19 p = 0.01, ß=-0.25, p > 0.001, respectively). No associations were observed between cortisol/CRP ratio and clinical and cognitive functioning in the BD group.
These findings may indicate HPA axis-immune dysregulation in SZ. Our study further indicates that disrupted HPA axis-immune regulation in people with SZ and BD is associated with psychotropic treatment and fat mass, highlighting the clinical importance of weight control and regular psychotropic treatment follow-ups within this group.
精神分裂症（SZ）和双相情感障碍（BD）患者的生物应激系统存在异常，且有低度炎症反应。然而，SZ和BD患者的下丘脑 - 垂体 - 肾上腺（HPA）轴 - 免疫调节是否受到破坏，尚待确定。
对SZ患者（N = 257）、BD患者（N = 153）和健康对照者（N = 40）在上午10点或之前采集的血样进行皮质醇和C反应蛋白（CRP）检测。计算皮质醇/CRP比值，作为HPA轴活性与炎症活性平衡的指标，即HPA轴 - 免疫调节。使用功能总体评定量表（GAF）和阳性与阴性症状量表（PANSS）评估总体功能和症状水平。采用标准化神经心理测试评估认知功能。所有分析均针对人口统计学变量（年龄和性别）以及采血时间进行了调整。
与健康对照者相比，诊断为SZ或BD的参与者皮质醇/CRP比值较低（F = 5.93，p = 0.003）。当将体重指数（BMI）作为协变量纳入模型时，差异不再具有统计学意义（p>0.1）。在患者中，接受精神药物治疗的患者（n = 337）的皮质醇/CRP比值低于未服用精神药物的患者（n = 59）（F = 4.72，p = 0.03）。与健康对照者相比，仅规律服用精神药物的患者皮质醇/CRP比值较低（p = 0.02）。在SZ组中，较低的皮质醇/CRP比值与GAF评估的较差总体功能相关（β=-0.18，p = 0.01），以及与PANSS评估的更严重的阴性和总体症状相关（分别为β = 0.19，p = 0.007和β = 0.18，p = 0.01）。在SZ中，较低的皮质醇/CRP比值还与较差的言语记忆、学习和处理速度相关（分别为β=-0.20，p = 0.007；β=-0.19，p = 0.01；β=-0.25，p>0.001）。在BD组中，未观察到皮质醇/CRP比值与临床及认知功能之间的关联。
这些发现可能表明SZ患者存在HPA轴 - 免疫失调。我们的研究进一步表明，SZ和BD患者中HPA轴 - 免疫调节的破坏与精神药物治疗和脂肪量有关，突出了该组体重控制和定期精神药物治疗随访的临床重要性。
