[The influence of interaction between polygenic risk score and intestinal fungal microbiota on the risk of schizophrenia].

Objective: To investigate the effect of interaction between polygenic risk score (PRS) and intestinal fungal microbiota on the risk of Schizophrenia (SCH). Methods: A case-control study was carried out. Drug-naïve, first-episode SCH patients were selected from the Psychiatric Department of the First Affiliated Hospital of Zhengzhou University between October 2017 and October 2019. Meanwhile, healthy controls (HCs) were recruited from local communities through online advertisement or physical examination center. Intestinal fungal microbiota was characterized by the 18S rRNA sequencing platform. The association of fungal microbial dysbiosis (F_MD) index, α-diversity indices and PRS with SCH was detected by logistic regression analysis. Results: A total of 137 SCH patients (62 males and 75 females) and 76 HCs (31 males and 45 females) were included in the study. The age of SCH patients and HCs was (22.5±7.5) years and (22.8±2.3) years, respectively. The results of logistic regression analysis revealed that PRS (OR=1.111, 95%CI: 1.036-1.178, P=0.002) and the increase of F_MD index (OR=1.200, 95%CI: 1.124-1.281, P<0.001) were risk factors for developing SCH. The increase of fungal α-diversity Shannon (OR=0.813, 95%CI: 0.755-0.874, P<0.001) index, Simpson index (OR=0.218, 95%CI: 0.091-0.523, P<0.001) and abundance of key Aspergillus (OR=0.928, 95%CI: 0.864-0.996, P=0.040) decreased the risk of SCH. Aspergillus abundance was positively correlated with cognitive domains including working memory (r=0.280, P=0.001), verbal learning (r=0.253, P=0.003), reasoning and problem solving (r=0.191, P=0.028). Conclusion: The increase of PRS may increase the risk of SCH. The increase of fungal α-diversity indices and Aspergillus abundance may decrease the risk of SCH. The interaction between PRS and intestinal fungi (Shannon index, Simpson index and Aspergillus) is a related factor for the risk of SCH.

[Establishment of diagnostic model for schizophrenia based on neurotrophic factor and other biomarkers].

Objective: To construct a diagnostic model of schizophrenia (SCZ) based on biomarkers such as serum neurotrophic factor. Methods: Patients of schizophrenia (SCZ group) and healthy controls (HC group) who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2017 to December 2019 were prospectively selected. In the SCZ group, the mental symptoms were assessed by the positive and negative symptom scale (PANSS), cognitive function was assessed by the MATRICS consensus cognitive battery (MCCB), brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), fasting glucose (FGB) and fasting insulin (FINS) levels were detected, and insulin resistance (HOMA-IR) was calculated. The same methods were used to evaluate cognitive function, measure BDNF, GDNF, FGB and FINS levels, and calculate HOMA-IR in HC group. The indexes with statistically significant differences between the two groups were selected to be included in the model. The diagnostic model was constructed by machine learning and verified by cross-validation method, the receiver operating curve (ROC) was plotted, and the area under the curve (AUC), sensitivity and specificity were calculated. Results: (1) A total of 142 patients (70 males and 72 females) with schizophrenia were finally included, and aged (25±4) years. Meanwhile, 140 healthy controls (72 males and 68 females) were also enrolled, and aged (26±4) years. In SCZ group, scores in all areas of cognitive function were lower than those in HC group (all P<0.001), the levels of serum BDNF and GDNF [(6.7±1.8) ng/ml and (405±93) pg/ml] were also lower than those in HC group [(12.3±3.2) ng/ml and (574±139) pg/ml] (both P<0.001), but the levels of FINS and HOMA-IR [(8.4±0.8) µU/ml and 1.7±0.3] were higher than those in HC group [(6.7±0.9) µU/ml and 1.4±0.3] (both P<0.001). (2) Correlation analysis showed that the level of serum BDNF had a negative correlation with negative symptom scores and total scores (r=-0.31, P<0.001; r=-0.17, P=0.040), but had a positive correlation with attention/alertness (CPT-IP) T scores, working memory (WSM-Ⅲ) T scores and visual learning (BVMT) T scores in SCZ group (r=0.39, 0.37 and 0.29, all P<0.001). The level of serum GDNF also had a positive correlation with CPT-IP T scores, WSM-Ⅲ T scores and BVMT T scores (r=0.32, P<0.001; r=0.23, P=0.007; r=0.40, P<0.001). The values of HOMA-IR had a positive correlation with social cognition (MSCEIT) T scores in SCZ group (r=0.18, P=0.033). (3) AUC of the early diagnosis model constructed by combining BDNF, GDNF and HOMA-IR was 0.890 (95%CI: 0.832-0.940), the accuracy was 0.89, the sensitivity and specificity was 0.94 and 0.82, respectively. Conclusion: The final diagnostic model based on biomarkers of serum neurotrophic factor has good diagnostic efficiency for SCZ, but large-scale independent sample verification is still needed.

[Correlations between hormone levels and psychiatric symptoms as well as cognitive function in drug-free first-episode schizophrenics].

OBJECTIVE: To explore hormone such as follicle-stimulating hormone (FSH), luteinizing (LH), prolactin (PRL), estradiol (E2), progesterone (PROG) and testosterone (TESTO) levels in first-episode drug-free schizophrenics, and the relationship between clinical symptoms and sex hormones, in order to further study the pathogenesis of schizophrenia. METHODS: Eighty-one first-episode drug-free schizophrenics including thirty-nine male and forty-two female from First Affiliated Hospital of Zhengzhou University and seventy healthy subjects (thirty male and forty female) were enrolled.Serum levels of hormone were measured using electrical chemiluminescence immunoassay, and Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate cognitive function. RESULTS: (1) The serum levels of PRL in male patients group ((24±9) ng/ml) was higher than that of control group ((10±3) ng/ml) (P<0.05), the serum levels of E2, TESTO of male patients group ((29±10) ng/ml), ((3.2±1.7) ng/ml) was lower than that of control group ((35±11) ng/ml), ((4.4±1.6) ng/ml) (P<0.05); The serum levels of PRL, TESTO of female patients group ((29±16) ng/ml), ((0.5±0.4) ng/ml) were dramatically higher than that of control group ((13±5) ng/ml), ((0.3±0.1) ng/ml) (P<0.05), the serum levels of E2 of female patients group ((51±40) ng/ml) was lower than that of control group ((63±66) ng/ml) (P=0.05). (2) The serum levels of PRL, E2, TESTO in male patients group were negatively associated with negative symptoms (r=-0.478,-0.443,-0.576, P<0.05), PRL were negatively related to positive symptoms (r=-0.542, P<0.05); In female patients group, the serum levels of PRL were negatively associated with negative symptoms (r=-0.343, P<0.05), the serum levels of E2 was negatively related to positive symptoms, general psychopathology grade, total PANSS grade (r=-0.351,-0.487,-0.405, P<0.05), TESTO had a positive correlation with positive symptoms (r=0.445, P<0.05). (3) In male patients group, PRL had an negative correlation with working memory P point, reasoning and problem solving P points (r=-0.384,-0.374, P<0.05), the serum levels of E2 was positively related to Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.379, 0.336, 0.407, P<0.05), TESTO had a positive correlation with Information processing rate P points, Visual memory P points, Reasoning and problem solving P points (r=0.564, 0.513, 0.552, P<0.05). In female patients group, PRL had an negative correlation with working memory P point, Reasoning and problem solving P points and social cognition P points (r=-0.303,-0.358,-0.368, P<0.05), the serum levels of E2 was positively related to working memory, Reasoning and problem solving P points, social cognition P points (r=0.376, 0.453, 0.355, P<0.05). CONCLUSIONS: Our study shows that first-episode drug-free schizophrenics have hormone secretion abnormal, which suggests that hypothalamus-hypophysis-gonad axis may probably involve in physiopathologic mechanism of first-episode medicine-free schizophrenics.Slightly elevated serum PRL level may be the reaction of stress response in first-episode medicine-free schizophrenics.Endogenous testosterone and estradiol may protect cognitive function against recession, and declining of testosterone and estradiol in blood is the hazards of cognitive dysfunction in first-episode drug-free male schizophrenics. PRL, E2, TESTO may be one of the measurements of the severity of clinical symptoms.