Abstract: Background　Inflammation is closely related to schizophrenia.Anti-inflammatory drugs have a good effect on improving schizophrenia.Folic acid has obvious anti-inflammatory effects，and the body's lack of folic acid and vitamin B12 （VitB12） are closely related to the occurrence of schizophrenia．Objective　To investigate the effect of folic acid and VitB12 in treatment of first-episode schizophrenic patients on serum inflammatory cytokines （IL-1β，IL-6 and TNF-α），nerve growth factor （NGF），brain-derived neurotrophic factor（BDNF），folic acid，VitB12，homocysteine （Hcy），scores of positive and negative syndrome scale （PANSS） and clinical effect．Methods　A total of 200 patients with first-episode schizophrenia who received routine treatment in Wuhan Second Mental Hospital from 2016 to 2017 were selected and divided into control group （100 cases） and intervention group （100 cases）．All 200 first-episode schizophrenic patients were randomized to receive 16-week treatment of risperidone with either 2 mg of folic acid and 400 μg of VitB12 capsule （intervention group，n=100） or placebo （control group，n=100）．Serum levels of IL-1β，IL-6，TNF-α，NGF，BDNF，folic acid，VitB12 and Hcy were measured by enzyme-linked immunosorbent assay （ELISA）．The PANSS was used to assess the change of clinical psychiatric symptoms，the adverse effects and the clinical effect were recorded.Results　Before treatment，no significant differences were noted in the levels of serum IL-1β，IL-6，TNF-α，NGF，BDNF，folic acid，VitB12 and Hcy between two groups（P>0.05）.After 16 weeks treatment of folic acid and VitB12，the levels of serum IL-1β，TNF-α and Hcy in intervention group reduced and were significantly lower than those in the control group，and the levels of NGF，BDNF，folic acid and VitB12 increased and were higher than those in the control group （P<0.05）．However，there was no significant difference in total PANSS score，positive symptom score，negative symptom score and general pathological score between two groups before treatment （P>0.05）．After treatment，there was no significant difference in PANSS positive symptom score between two groups （P>0.05）；total PANSS score，negative symptom score and general pathological score in intervention group were lower than those in control group （P<0.05）．The total score of PANSS，positive symptom score，negative symptom score and general pathological score after treatment in control group and intervention group were lower than those before treatment （P<0.05）．There were 10 cases of marked effect，41 cases of effective and 19 cases of ineffective in the control group，56 cases of marked effect，35 cases of effective and 9 cases of ineffective in the intervention group，and the clinical effect of the intervention group was better than that of the control group （u=2.540，P=0.011）.There was no significant difference in the incidence of adverse reactions between two groups （P>0.05）．Conclusion　Folic acid combined with VitB12 intervention can effectively reduce levels of inflammatory factors and Hcy in patients with first-episode schizophrenia，which can also increase the serum NGF and BDNF levels to improve patients' PANSS score and participate in the adjuvant treatment of first-episode schizophrenia.

Key words: Schizophrenia, Folic acid, Vitamin B12, Chemokines, Nerve growth factors

摘要： 背景　炎症与精神分裂症有着密切的关系。抗炎类药物对改善精神分裂症的病情有着较好的疗效。叶酸具有明显的抗炎作用，机体缺乏叶酸和维生素B12（VitB12）与精神分裂症的发生有着密切的联系。目的　探讨叶酸联合VitB12对首发精神分裂症患者血清炎性细胞因子、神经生长因子（NGF）、脑源性神经营养因子（BDNF）、叶酸、VitB12、同型半胱氨酸（Hcy）、阳性和阴性综合征量表（PANSS）评分及临床疗效的影响。方法　选取2016—2017年湖北省武汉市第二精神病医院接受治疗的首发精神分裂症患者200例为研究对象，采用随机数字表法分为对照组（100例）和干预组（100例），两组患者均给予利培酮治疗，对照组同时服用空白安慰剂，干预组同时每日服用1粒内含2 mg叶酸和400 μg VitB12的胶囊，共治疗16周。治疗前及治疗后采用酶联免疫吸附试验（ELISA）法测定血清白介素（IL）-1β、IL-6、肿瘤坏死因子α（TNF-α）、NGF、BDNF、叶酸、VitB12、Hcy水平，采用PANSS评估患者的精神症状变化及临床疗效，记录患者不良反应。结果　治疗前，两组患者血清IL-1β、IL-6、TNF-α、NGF、BDNF、叶酸、VitB12、Hcy水平比较，差异均无统计学意义（P>0.05）。治疗后，干预组患者血清IL-1β、TNF-α、Hcy水平较对照组降低，NGF、BDNF、叶酸、VitB12水平较对照组升高（P<0.05）。干预组治疗后血清IL-1β、TNF-α、Hcy水平较治疗前降低，NGF、BDNF、叶酸、VitB12水平较治疗前升高（P<0.05）。治疗前，两组患者PANSS总分、阳性症状评分、阴性症状评分和一般病理评分比较，差异均无统计学意义（P>0.05）。治疗后，两组患者PANSS阳性症状评分比较，差异无统计学意义（P>0.05）；治疗后，干预组患者PANSS总分、阴性症状评分和一般病理评分较对照组降低（P<0.05）。对照组和干预组患者治疗后PANSS总分、阳性症状评分、阴性症状评分和一般病理评分较治疗前降低（P<0.05）。对照组显效10例，有效41例，无效19例；干预组显效56例，有效35例，无效9例；干预组临床疗效优于对照组（u=2.540，P=0.011）。两组患者不良反应发生率比较，差异均无统计学意义（P>0.05）。结论　叶酸联合VitB12能够有效降低首发精神分裂症患者体内炎性细胞因子水平及Hcy水平，提高患者血清NGF和BDNF水平来改善患者的PANSS评分，参与首发精神分裂症的辅助治疗。

关键词: 精神分裂症, 叶酸, 维生素B12, 炎症趋化因子类, 神经生长因子类