摘要目的:探讨十八碳四烯酸（stearidonic acid，SDA）和脂肪酸去饱和酶2（fatty acid desaturase 2， FADS2）基因rs174570位点基因型的交互作用对精神分裂症认知功能的影响。 方法:本研究为病例对照研究，招募2017年10月至2019年10月就诊于郑州大学第一附属医院精神科的首次发病未用药精神分裂症患者98例（患者组）及同期通过广告招募和医院体检的健康人群95名（对照组）。采用液相色谱-质谱联用仪（liquid chromatograph mass spectrometer，LC-MS）检测患者组与对照组外周血SDA水平，并采用配对样本 t检验分析患者组利培酮治疗前后的变化。采用全基因组关联分析（genome-wide association study，GWAS）进行全基因组单核苷酸多态性检测，并采用方差分析评估SDA关键酶 FADS2基因位点基因型分布与SDA水平的关系。采用阳性和阴性精神症状评定量表（Positive and Negative Syndrome Scale，PANSS）和MATRICS共识认知成套测验（MATRICS consensus cognitive battery，MCCB）分别评估精神症状严重程度和认知功能，2组间差异比较采用独立样本 t检验，利培酮治疗前后的变化比较采用配对样本 t检验。采用线性回归分析，分析SDA水平和 FADS2基因位点不同基因型的交互作用和精神分裂症认知功能损害的关系。 结果:患者组SDA水平（ t=-10.67）、认知功能评分（ t=-10.30~-3.30）低于对照组，差异有统计学意义（均 P<0.05）。患者组基线期SDA水平与认知功能领域的信息处理速度（speed of processing，SOP）评分呈正相关（ r=0.406， P<0.001）。患者组利培酮治疗半年后，SDA水平由（3.6±1.9）μmol/L升高至（4.4±2.3）μmol/L，治疗前后差异有统计学意义（ t=-2.29， P=0.024）。利培酮治疗前后SDA水平的变化与认知功能SOP评分的变化正相关（ r=0.327， P=0.002）。 FADS2基因rs174570位点不同基因型的患者SDA水平（ F=3.74， P=0.027）、认知功能SOP评分（ F=4.28， P=0.017）、注意性/警觉性评分（ F=6.74， P=0.002）差异均有统计学意义。两两比较显示，rs174570基因型CC携带者较CT和TT携带者SDA水平高（ P=0.024、0.048），基因型CC携带者认知功能领域SOP、注意性/警觉性和MCCB总分高于CT携带者（ P=0.006、0.001、0.002）。SDA水平和 FADS2基因rs174570位点基因型的交互作用与精神分裂症认知功能领域SOP评分正相关（β=1.82， P=0.029）。 结论:SDA和 FADS2基因rs174570位点基因型的交互作用与精神分裂症认知功能水平有关。

abstractsObjective:To explore the role of interaction between stearidonic acid (SDA) and fatty acid desaturase 2 ( FADS2) rs174570 genotyping in the cognitive function of schizophrenia (SCH). Methods:This study is a case-control study, patients with first-episode, drug-na?ve schizophrenia were recruited from the First Affiliated Hospital of Zhengzhou University′s Department of Psychiatry from October 2017 to October 2019. Healthy controls were recruited through advertisements and medical examinations during the same period. Peripheral blood SDA levels of the SCH patient group and the control group were measured and compared using liquid chromatograph-mass spectrometer (LC-MS), and paired sample t-test was conducted to analyze the changes in the patient group before and after treatment with risperidone. Genome-wide association study (GWAS) was used for analyzing the key enzyme of SDA, and analysis of variance was performed to evaluate the relationship between FADS2 single nucleotide polymorphism (SNP) genotyping and the level of SDA. The Positive and Negative Syndrome Scale (PANSS) and the MATRICS Consensus Cognitive Battery (MCCB) were used to assess the severity of psychotic symptoms and cognitive function, the comparison between the two groups was conducted by independent sample t-test, and the changes before and after risperidone treatment were analyzed by paired sample t-test. Linear regression analysis was performed to investigate the relationship between the interaction of SDA and FADS2 rs174570 genotyping, and cognitive impairment in SCH. Results:SDA levels were significantly lower in the SCH group compared to the control group ( t=-10.67, P<0.001). Cognitive score in patients with SCH were lower than that of HCs ( t=-10.30—-3.30, P<0.05 for all). Low levels of SDA in patients with SCH were positively correlated with the score of speed of processing (SOP; r=0.406, P<0.001) at baseline. After six months of treatment with risperidone, serum levels of SDA increased from (3.6±1.9) μmol/L to (4.4±2.3) μmol/L, and paired t-tests showed significant difference ( t=-2.29, P=0.024). The change of SDA levels before and after risperidone treatment was positively correlated with the change of SOP scores ( r=0.327, P=0.002). FADS2 rs174570 genotyping were significantly associated with SDA levels ( F=3.74, P=0.027) and cognitive function scores of SOP ( F=4.28, P=0.017), and attention/vigilance (AV; F=6.74, P=0.002). Pairwise comparisons showed that CC carriers of rs174570 genotype had higher SDA levels than CT and TT carriers ( P=0.024, and 0.048, respectively), and higher total scores of SOP, AV and MCCB than CT carriers ( P=0.006, 0.001, and 0.002, respectively). The interaction of SDA and FADS2 rs174570 genotyping were associated with cognitive function SOP scores in patients with SCH (β=1.82, P=0.029). Conclusion:The interaction of SDA and FADS2 rs174570 genotyping is associated with the cognitive function in patients with SCH.