Objective:This study aims to explore the relationship between the abundance of Lachnoclostridium genus in the gut microbiome and inflammatory markers with cognitive impairment in patients with first-episode schizophrenia. Methods:A total of 87 medication-naive patients with first-episode schizophrenia (patient group) and 87 matched healthy controls (control group) who visited the Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University between January 2020 and December 2022 were selected for this study. A 24-week follow-up was conducted for the patients, and all patients received treatment with risperidone. Venous blood and fecal samples were collected from the subjects at baseline and week 24 to measure the levels of superoxide dismutase-1, erythrocyte sedimentation rate, and the abundance of Lachnoclostridium. The severity of symptoms in patients with schizophrenia was assessed using the Positive and Negative Syndrome Scale, and the cognitive function of all subjects was evaluated using MATRICS Consensus Cognitive Battery tests. The differences in the abundance of Lachnoclostridium, inflammatory markers, and cognitive scores between groups were analyzed using t-tests, and the correlations between Lachnoclostridium abundance, inflammatory markers, and cognitive scores were analyzed using Pearson correlation analysis. Results:(1) At baseline, compared with the control group, patients with first-episode schizophrenia had lower levels of superoxide dismutase-1( t=6.83, P<0.001) and total cognitive function test scores( t=6.35, P<0.001), and higher abundance of Lachnoclostridium( Z=-4.64, P<0.001). (2) At baseline, the levels of superoxide dismutase-1 in patients with first-episode schizophrenia were positively correlated with social cognition( r=0.30, P=0.005), while erythrocyte sedimentation rate was negatively correlated with information processing speed and social cognition( r=-0.23, -0.31, both P<0.050). The abundance of Lachnoclostridium genus was negatively correlated with speed of processing( r=-0.28, P=0.009), working memory( r=-0.22, P=0.040), and visual memory( r=-0.32, P=0.003). (3) After 24 weeks of risperidone treatment, the levels of superoxide dismutase-1( t=-2.07, P=0.045) and total cognitive function test scores( t=-3.47, P=0.001) increased in patients, while erythrocyte sedimentation rate( t=2.21, P=0.033) decreased. The abundance of Lachnoclostridium genus showed a decreasing trend( Z=1.52, P=0.128) and did not differ significantly from the control group( Z=1.68, P=0.094). (4) Among the 39 patients who completed the 24-week follow-up, the baseline abundance of Lachnoclostridium genus was negatively correlated with attention and vigilance( r=-0.39, P=0.014) and total cognitive function test scores( r=-0.34, P=0.032) at week 24. The baseline erythrocyte sedimentation rate was positively correlated with the differences in speed of processing, working memory, social cognition, and total cognitive function test scores between baseline and week 24( r=0.42, 0.32, 0.41, 0.36, all P<0.050). (5) At baseline, the abundance of Lachnoclostridium genus had predictive value for erythrocyte sedimentation rate( r=0.45, P=0.004), attention and vigilance( r=-0.39, P=0.014), and total cognitive function test scores( r=-0.34, P=0.032) at week 24. Conclusion:In first-episode schizophrenia patients, there is a significant correlation between the abundance of gut Lachnoclostridium and inflammation and cognitive function.

Objective: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.

Objective:This study aims to explore the relationship between the abundance of Lachnoclostridium genus in the gut microbiome and inflammatory markers with cognitive impairment in patients with first-episode schizophrenia. Methods:A total of 87 medication-naive patients with first-episode schizophrenia (patient group) and 87 matched healthy controls (control group) who visited the Department of Psychiatry, the First Affiliated Hospital of Zhengzhou University between January 2020 and December 2022 were selected for this study. A 24-week follow-up was conducted for the patients, and all patients received treatment with risperidone. Venous blood and fecal samples were collected from the subjects at baseline and week 24 to measure the levels of superoxide dismutase-1, erythrocyte sedimentation rate, and the abundance of Lachnoclostridium. The severity of symptoms in patients with schizophrenia was assessed using the Positive and Negative Syndrome Scale, and the cognitive function of all subjects was evaluated using MATRICS Consensus Cognitive Battery tests. The differences in the abundance of Lachnoclostridium, inflammatory markers, and cognitive scores between groups were analyzed using t-tests, and the correlations between Lachnoclostridium abundance, inflammatory markers, and cognitive scores were analyzed using Pearson correlation analysis. Results:(1) At baseline, compared with the control group, patients with first-episode schizophrenia had lower levels of superoxide dismutase-1( t=6.83, P<0.001) and total cognitive function test scores( t=6.35, P<0.001), and higher abundance of Lachnoclostridium( Z=-4.64, P<0.001). (2) At baseline, the levels of superoxide dismutase-1 in patients with first-episode schizophrenia were positively correlated with social cognition( r=0.30, P=0.005), while erythrocyte sedimentation rate was negatively correlated with information processing speed and social cognition( r=-0.23, -0.31, both P<0.050). The abundance of Lachnoclostridium genus was negatively correlated with speed of processing( r=-0.28, P=0.009), working memory( r=-0.22, P=0.040), and visual memory( r=-0.32, P=0.003). (3) After 24 weeks of risperidone treatment, the levels of superoxide dismutase-1( t=-2.07, P=0.045) and total cognitive function test scores( t=-3.47, P=0.001) increased in patients, while erythrocyte sedimentation rate( t=2.21, P=0.033) decreased. The abundance of Lachnoclostridium genus showed a decreasing trend( Z=1.52, P=0.128) and did not differ significantly from the control group( Z=1.68, P=0.094). (4) Among the 39 patients who completed the 24-week follow-up, the baseline abundance of Lachnoclostridium genus was negatively correlated with attention and vigilance( r=-0.39, P=0.014) and total cognitive function test scores( r=-0.34, P=0.032) at week 24. The baseline erythrocyte sedimentation rate was positively correlated with the differences in speed of processing, working memory, social cognition, and total cognitive function test scores between baseline and week 24( r=0.42, 0.32, 0.41, 0.36, all P<0.050). (5) At baseline, the abundance of Lachnoclostridium genus had predictive value for erythrocyte sedimentation rate( r=0.45, P=0.004), attention and vigilance( r=-0.39, P=0.014), and total cognitive function test scores( r=-0.34, P=0.032) at week 24. Conclusion:In first-episode schizophrenia patients, there is a significant correlation between the abundance of gut Lachnoclostridium and inflammation and cognitive function.

Objective: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.

Antipsychotic medication is the primary treatment for schizophrenia, which is effective on ameliorating positive symptoms and can reduce the risk of recurrence, but it has limited efficacy for negative symptoms and cognitive dysfunction. The negative symptoms and cognitive dysfunction seriously affects the life quality and social function for the patients with schizophrenia. Currently, there is plenty evidence that antipsychotic drugs combined with adjuvant therapy drugs can effectively improve the negative symptoms and cognitive dysfunction. These drugs include anti-oxidants, nicotinic acetylcholine receptors and neuro-inflammatory drugs (anti-inflammatory drugs, minocycline), which show potential clinical effects.
Anti-Inflammatory Agents/therapeutic use* ; Antipsychotic Agents/therapeutic use* ; Cognitive Dysfunction/etiology* ; Humans ; Minocycline/therapeutic use* ; Schizophrenia/drug therapy*

The negative symptoms and cognitive symptoms of schizophrenia patients are still clinical problems to be solved. Schizophrenia patients are abnormal in oxidative stress, immune regulation, and anti-histone deacetylase (HDAC), while sulforaphane plays a role in anti-oxidative stress, anti-inflammation, and anti-HDAC. Therefore, the sulforaphane could improve the negative symptoms and cognitive deficits of schizophrenia.
Cognition ; Humans ; Isothiocyanates ; therapeutic use ; Schizophrenia ; drug therapy