Ishiwata Sayuri, Hattori Kotaro, Hidese Shinsuke, Sasayama Daimei, Miyakawa Tomoko, Matsumura Ryo, Yokota Yuuki, Yoshida Sumiko, Kunugi Hiroshi
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan; Medical Genome Center, National Center of Neurology and Psychiatry, Tokyo, 187-8502, Japan.
J Psychiatr Res. 2020 Aug;127:13-19. doi: 10.1016/j.jpsychires.2020.03.010. Epub 2020 Apr 16.
Some patients with schizophrenia have impaired hypothalamic-pituitary-adrenal axis function. However, there is a dearth of studies focusing on corticotropin-releasing hormone (CRH) levels in the brains of schizophrenia patients, which motivated us to examine whether cerebrospinal fluid (CSF) CRH concentrations are altered in these patients. We also examined the possible correlation of CSF CRH level with clinical variables such as schizophrenia symptoms and antipsychotic medication. The study population comprised 20 patients with a diagnosis of schizophrenia according to DSM-5 criteria and 25 healthy controls, who underwent lumbar puncture. Most of the patients were treated with antipsychotic drugs and their doses were converted to chlorpromazine (CP) equivalent values. CSF CRH concentrations were measured by an enzyme immunoassay. Symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS). There was a significantly lower CSF CRH concentration in the patients than in the controls (Mann-Whitney U test: p = 0.014). A significantly negative correlation of CSF CRH levels with PANSS negative scores was found in the patients (Spearman's: ρ = -0.58, p = 0.007). However, CSF CRH concentrations were not significantly correlated with the PANSS total (ρ = -0.035, p = 0.89), positive (ρ = 0.25, p = 0.30), or general psychopathology (ρ = 0.13, p = 0.59) scores. No significant correlation was found with CP equivalent values (ρ = 0.00, p = 1.00). In conclusion, we found that the patients with schizophrenia had lower CSF CRH concentrations compared to the controls and that the lower CSF CRH was associated with negative symptoms of the illness. Further studies in a larger sample and in drug-free patients are warranted.
一些精神分裂症患者存在下丘脑 - 垂体 - 肾上腺轴功能受损的情况。然而，针对精神分裂症患者大脑中促肾上腺皮质激素释放激素（CRH）水平的研究却很匮乏，这促使我们去研究这些患者脑脊液（CSF）中CRH浓度是否发生了改变。我们还研究了CSF中CRH水平与精神分裂症症状和抗精神病药物等临床变量之间可能存在的相关性。研究对象包括20名根据《精神疾病诊断与统计手册》第5版（DSM - 5）标准诊断为精神分裂症的患者以及25名健康对照者，他们均接受了腰椎穿刺。大多数患者接受了抗精神病药物治疗，其剂量被换算为氯丙嗪（CP）等效值。CSF中CRH浓度通过酶免疫测定法进行测量。使用阳性和阴性症状量表（PANSS）评估症状严重程度。患者的CSF中CRH浓度显著低于对照组（曼 - 惠特尼U检验：p = 0.014）。在患者中发现CSF中CRH水平与PANSS阴性评分呈显著负相关（斯皮尔曼相关系数：ρ = -0.58，p = 0.007）。然而，CSF中CRH浓度与PANSS总分（ρ = -0.035，p = 0.89）、阳性评分（ρ = 0.25, p = 0.30）或一般精神病理学评分（ρ = 0.13, p = 0.59）均无显著相关性。与CP等效值也未发现显著相关性（ρ = 0.00, p = 1.00）。总之，我们发现精神分裂症患者的CSF中CRH浓度低于对照组，且较低的CSF中CRH与该疾病的阴性症状相关。有必要在更大样本和未使用药物的患者中进行进一步研究。
