目的：探讨氯氮平联合阿戈美拉汀增效治疗对慢性精神分裂症患者认知功能和阴性症状的疗效及对血清褪黑素表达水平的影响。

方法：纳入上海市黄浦区精神卫生中心慢性精神分裂症患者98例，按随机数字表随机分为研究组和对照组，每组各49例。对照组以氯氮平联合安慰剂治疗，研究组以氯氮平取合阿戈美拉订治疗，治疗时间持续12周。2组在入组时及治疗第4周末、第8周末和第12周末予神经心理状态评定量表评估认知功能、阴性症状和抑郁症状，同样的时间点采用质分析检血清褪黑素水平。对2组的相关指标进行统计学分析。

结果：剔除脱落患者,研究组和对照组最终各纳入 42 例患者。基线期,2组认知功能各维度阴性症状、抑郁症状、血清褪黑素水平差异比较无统计学意义:治疗12周后,2组在研究组和对照组在N3(即情感交流障碍方面)(P=0.027)、词汇回忆(P=0.016)、故事回忆(P=0.002)、图形再认(P=0.017)、重复神经心理状态测验总分(P=0.007)和卡尔加里精神分裂症抑郁量表(P=0.000)评分评分、血清褪黑素水平(P=0.002)有统计学差异。与基线比较,研究组在治疗第4周末、第8周末和第12周末的认知功能,阴性症状和抑郁症状评分、血清褪黑素水平的差异有统计学意义(P均<0.01)。血清褪黑素水平改变与故事回忆(r²=0.25,P=0.02)的改善有显著相关性。

结论：氯氮平联合阿戈美拉订增效治疗对慢性精神分裂症患者认知功能、阴性症状和抑郁症状部分维度有著疗效，且部分认知功能的改善与血清褪黑素水平的改变显著相关。

Objective: To investigate the therapeutic effect of clozapine combined with agomelatine onnegative symptoms and cognitive fiunction in patients with chronic schizophrenia, as wellas its impact on serum melatonin expression levels.

Methods: 98 patients with chronic schizophrenia from Shanghai Huangpu District MentalHealth Center were included and randomly divided into research group and control groupusing a random number table, with 49 patients in each group. The control group wastreated with clozapine combined with placebo, while the research group was treated withclozapine combined with agomelatine for 12 weeks. Two groups were evaluated forcognitive function, negative symptoms, and depressive symptoms at the time of enrollmentand at the end of the 4th, 8th, and 12th week of treatment, Serum melatonin levels weremeasured by mass spectrometry analysis at the same time point. Statistical analysis wasperformed on the relevant indicators of the two groups.

Results: Excluding dropouts, the study group and control group ultimately included 42 patients each. During the baseline period, there was no statistically significant difference incognitive function dimensions, negative symptoms, depressive symptoms, and serummelatonin levels between the two groups. After 12 weeks of treatment, there werestatistically significant differences in N3 (emotional communication disorder)(P=0.027)vocabulary recall (P=0.016), story recall (P=0.002), graphic recognition(P=0.017)Repeatable Battery for the Assessment ofNeuropsychological Status(RBANS) conversion score P=0.007), Calgary Depression Scale for Schizophrenia (CDss)(P=0.000) score, and serummelatonin levels (P=0.002) between the two groups. Within the group comparison, therewere statistically significant differences in cognitive function, negative symptom anddepression symptom scores, and serum melatonin levels between the treatment group atthe 4th, 8th, and 12th weekends and the baseline period (P<0.01 for all). There was asignificant correlation between changes in serum melatonin levels and improvements instory recall (r²=0.25,P=0.02).

Conclusion: Clozapine combined with agomelatine has significant therapeutic effects onsome dimensions of cognitive function, negative symptoms, and depressive symptoms inpatients with chronic schizophrenia, and the improvement of some cognitive functions issignificantly correlated with changes in serum melatonin levels.