Objective To explore wbether there is an association between the single nucleotide polymorphisms (SNPs) of phosphodiestierase-4A (PDE4A) and bipolar disorder in Han population.Methods A casecontrol association study was done in this study,432 bipolar disorder patients(patients group),and 569 age and gender-matched controls(control group)were recruited.Real-time fluorescent quantitative polymerase chain reaction (PCR) was used to detect genotypes and alleles distributive frequency of rs1051738 and rs7256672 of 432 bipolar disorder patients and 569 normal people.Results The PDE4A rs1051738 genotypes and alleles frequency distribution between patients group(AA,AC,CC genotypes:12％,8％,80％,A,C alleles:16％,84％) and control group (AA,AC,CC genotypes:2％,19％,79％,A,C alleles:12％,88％) showed statistically significance (P＜ 0.01).The frequency of PDE4A rs7256672 genotypes and alleles distribution between patients group(GG,GT,TT genotypes:18％,50％,32％,G,T alleles:43％,57％) and control group (GG,GT,TT genotypes:20％,48％,32％,G,T alleles:45％,55％)showed no significant difference(P=0.620,P=0.446).Conclusion The PDE4A rs1051738 polymorphism may be responsible for an increase in susceptibility to bipolar disorder,indicating that it maybe a functional site with marked significance to bipolar disorder.

Objective To explore whether there is association between the polymorphisms of serotonin 2A receptor(5-HT2A) rs6311,rs6305 and adenylate cyclase rs2230739 with episode of bipolar disorder.Methods A case-control association study was done in this study,152 bipolar disorder patients (patients group),and 187 ageand gender-matched controls (control group) were recruited.Ligase detection reaction(LDR) was used to detect the distributive frequency of rs6311,rs6305 and rs2230739 of 152 bipolar disorder patients and 187 normal people.Results The 5-HT2A receptor rs6311 genotypes and alleles frequency distribution between patients group(11,12,22 genotypes:21％,61％,18％ ; 1,2 alleles:51％,49％) and control group(11,12,22 genotypes:44％,45％,11％ ; 1,2 alleles:66％,34％) showed statistically significance (P＜0.01).There were no differences of 5-HT2A receptor rs6305 genotypes and alleles between patients group and control group.The frequency of rs2230739 genotypes and alleles distribution between patients group (11,12,22 genotypes: 20％,43％,37％ ; 1,2 alleles: 42％,58％) and control group(11,12,22 genotypes: 17％,48％,35％ ; 1,2 alleles: 41％,59％) showed no significant difference(P=0.661,P=0.846).Conclusion The 5-HT2A receptor rs6311 polymorphism may be responsible for an increase in susceptibility to bipolar disorder,indicating that it maybe an marker to bipolar disorder.

Objective:To explore the relationship between Th17 immunoregulatory system and depression and reveal the mechanism of depression from the perspective of neuroimmunity, as well to look for biomarkers that can be used to diagnose, evaluate and predict recurrence of depression.Methods:A total of 91 patients with depression including 45 first-episode patients (FED group) and 46 recurrent episodes patients (RMDD group) were collected who were admitted to Psychiatry Department of the First Affiliated Hospital of Zhengzhou University from March 2019 to May 2020. And 40 healthy controls matched with depression patients in age, gender and education level were collected as control group (HC group). The levels of eight inflammatory cytokines in Th17 immunoregulatory system (five pro-inflammatory cytokines: IL-1β, IL-6, IL-17A, IL-21, IL-23; three anti-inflammatory cytokines: TGF-β1, IL-10, and IL-27) were measured by enzyme-linked immunosorbent assay (ELISA). Hamilton depression scale-24 (HAMD-24) was used to evaluate the severity of depressive symptoms. Data analyses were performed with SPSS 23.0.Two independent samples t-test, one-way ANOVA, Mann Whitney U test and Kruskal Wallis H test were used for comparison between groups. Results:(1) Comparison of FED group, RMDD group and HC group showed that the levels of pro-inflammatory cytokines IL-1β (5.321(1.317, 21.287)ng/L, 11.277(4.315, 26.167) ng/L, 8.126(1.179, 9.287) ng/L), IL-6(7.787(2.077, 16.778) ng/L, 5.290(2.364.14.475) ng/L, 4.389(1.453, 4.491) ng/L), IL-21 (6.777(6.293, 9.198) ng/L, 7.261(6.293, 25.058)ng/L, 5.097(3.033, 6.507) ng/L) and anti-inflammatory cytokines TGF-β1 (59.098(13.491, 125.368) ng/L, 46.230(18.852, 122.559) ng/L, 25.292(2.716, 31.874) ng/L), IL-10 (226.930(105.117, 449.444) ng/L, 193.929(109.014, 468.269) ng/L, 131.429(77.587, 157.497) ng/L) and IL-27 (0.968(0.651, 1.879)ng/L, 1.859(0.690, 6.221) ng/L, 0.865(0.679, 1.287)ng/L) in plasma were statistically different( H=7.219, 9.482, 18.989, 16.166, 11.511, 6.262, all P<0.05), while the levels of pro-inflammatory cytokines IL-17A (2.175(1.031, 7.975)ng/L, 3.576(1.896, 11.611)ng/L, 3.807(1.301, 4.710)ng/L)and IL-23 (15.708(2.898, 114.175) ng/L, 26.893(9.282, 58.592) ng/L, 17.041(5.027, 23.613)ng/L) were not statistically significant ( H=2.179, 4.305, both P>0.05). Further pairwise comparisons showed that the levels of pro-inflammatory cytokines IL-6, IL-21 and anti-inflammatory cytokines TGF-β1 and IL-10 in plasma of FED group were higher than those of HC group, and the differences were statistically significant (all P<0.05). The levels of pro-inflammatory cytokines IL-1β, IL-6, IL-21 and anti-inflammatory cytokines TGF-β1, IL-10, IL-27 in RMDD group were higher than those in HC group, and the differences were statistically significant (all P<0.05). There were no significant differences in the eight inflammatory cytokines between FED group and RMDD group (all P>0.05). (2) Spearman correlation analysis showed that IL-1β was positively correlated with total score of HAMD-24 ( r=0.286, P<0.05). IL-6 was positively correlated with total score of HAMD-24 and factor score of anxiety or somatization ( r=0.390, 0.291, both P<0.05). TGF-β1 was negatively correlated with total score of HAMD-24 and factor scores of anxiety or somatization and cognitive impairment ( r=-4.200, -0.321, - 0.361, all P<0.05). IL-21 was positively correlated with factor score of sleep ( r=0.319, P<0.05); IL-10 was negatively correlated with total score of HAMD-24 and factor score of cognitive impairment ( r=-0.306, - 0.270, both P<0.05). There was no significant correlation between other inflammatory cytokines and total score of HAMD-24 and seven factor scores (all P>0.05). Conclusion:There is an imbalance in pro-and anti-inflammatory cytokines of Th17 immunoregulatory system in patients with depression, which is more obvious in recurrent episodes patients.The level of immune activation of Th17 immunoregulatory system may be associated with the severity of clinical symptoms, in which the inflammatory cytokine IL-6 may be a biomarker of major depressive disorder; TGF-β1 and IL-21 may be associated with depressive cognitive impairment and sleep.

Objective To investigate the interactions between cAMP-response element-binding protein 1 (CREB 1) gene polymorphisms (rs889895,rs3770704,rs2551645,rs4675690) and brain derived neurotrophic factor (BDNF) gene polymorphisms (rs7124442,rs 10835210) and the association with recurrent major depressive disorder.Methods The blood samples were taken from 768 recurrent major depressive disorder patients and 511 healthy controls.The DNA was isolated from blood samples and was detected by SNP Sequenom Mass Array analysis.Chi-square test was used to compare differences in the frequency distribution of alleles and genotype between depression and controls.The generalized multifactor dimensionality reduction (GMDR) method was used to analyze the gene-gene interaction.Binary logistic regression was used to verify the optimal model.Results After adjusting the factors of sex and age,the GMDR analysis showed rs10835210 was the optimal model.In this model,the testing balanced accuracy was 0.5319 and cross-validation consistency value was 10/10.And rs10835210 had a statistically significant effect on the risk of recurrent major depressive disorder(P=0.0107).There was no significant gene-gene interaction of five tag SNPs on recurrent major depressive disorder(P＞0.05).Binary logistic regression analysis showed the AC contributed to a significantly lower risk of recurrent major depressive disorder than did the CC (OR =0.772,95％ CI=0.608-0.980,P=0.033).It was failed to find the genetic polymorphism of CREB1 rs889895.Conclusion BDNF rs10835210 may be one of the biological markers of recurrent major depressive disorder.

Objective To explore whether the norepinephrine transporter(NET) gene T-182C and G1287A polymorphisms are involved in the etiology of schizophrenics among the Chinese Han population.Methods 249 schizophrenics(case group) and 309 healthy physical examiners(control group) of the Chinese Han population were collected.Ligase detection reaction was used to detect the genotype distributions and allele frequencies of NET rs2242446 and rs5569 polymorphisms in the two groups.The genotype distributions and allele frequencies of these two single nucleotide polymorphisms (SNPs) were also compared in the case and control groups.Results In the case group,the TF genotype of the NET gene loci rs2242446 was the most,48.6％,and the CC genotype of which was the least,8.4％.In the control group,the CT genotype was the most,47.9％,and the C C genotype was the least,11.3％,the minimum allele frequency was 29.9％.In the case group,the GG genotype of the NET gene loci rs5569 was the most,46.2％,and the CC genotype was the least,9.6％.In the control group,GG genotype was the most,51.5％,and the AA genotype was the least,10.3％,and the minimum allele frequency was 29.4％.No significant differences in the genotype and allele distribution of NET rs2242446 and rs5569 were found in Chinese-Han patients with schizophrenia and control participants (all P＞ 0.05).In gender-specific analyses,similarly,no significant differences were found for rs2242446 and rs5569 genotype and allele distributions in either the male or the female case-control comparisons (all P＞ 0.05).Conclusion The NET rs2242446 and rs5569 polymorphisms are not associated with schizophrenia in Chinese Han population.

Objective:To explore the relationship between somatic symptoms of major depressive disorder(MDD)and cortisol(COR) rhythm, C-reactive protein(CRP) and other immune-metabolism-related indicators, and understand its mechanism from the perspective of endocrine and immune regulation.Methods:A case-control study was conducted in hospitalized patients with MDD who met DSM-5 diagnostic criteria.According to the Patient Health Questionnaire (PHQ-15), PHQ-15 ≥10 were classified as the somatic major depressive disorder group(S-MDD group) and 73 patients were enrolled.PHQ-15 <5 was classified as the non-somatic depressive disorder group (NS-MDD group) and 70 patients were enrolled.Plasma cortisol (COR8, COR16 and COR24) levels were measured at 8∶00, 16∶00 and 24∶00 on the same day, plasma CRP and interleukin-6 (IL-6) level, serum uric acid (UA), blood glucose (GLU), blood lipid (TC, TG, HDL, LDL) level were detected at 8∶00.Independent sample t test, non-parametric test, chi-square test, repeated ANOVA, covariance analysis, and multivariate Logistic regression were used for statistical analysis. Results:①Time effect, grouping effect and the interaction effect of the time and grouping in the level of COR were statistically significant ( P<0.05). Covariance analysis excluded age as an influential factor, COR16, AUC(total cortisol output/area under the curve, AUC) and COR8-16 in S-MDD group ((90.50±40.57)μg/L, (1 425.12±564.78), (-6.43±5.76))were higher than those in NS-MDD group((68.74±31.51)μg/L, (1 251.57±456.61), (-8.77±5.48)), and the difference was statistically significant ( F=8.971, 4.320, 8.731, P<0.05). ②CRP in S-MDD group ((1.41±1.06)mg/L) were higher than that in NS-MDD group((0.61±0.53)mg/L), and the difference was statistically significant ( F=25.436, P<0.05). The proportion of patients with higher CRP level(CRP≥1 mg/L) in S-MDD group(58%) was higher than that in NS-MDD group(23%), and the difference was statistically significant(χ 2=17.824, P<0.01). ③Multivariate logistic regression analysis found that CRP ( OR=4.953, 95% CI: 2.407-10.193), COR8-16 ( OR=3.451, 95% CI: 1.380-8.633) were main risk factors of somatic symptoms of MDD ( P<0.05). Conclusion:Cortisol rhythm disturbance and high CRP level may be the biological basis of somatic symptoms in patients with MDD.

Objective To explore the relationship between anxious depression and cortisol rhythm disorder and influencing factors of immune metabolism. And to look for biological markers that can be used for clinical diagnosis and treatment of anxious depression. Methods Totally 43 patients with anxious depres-sion(A-MDD group) and 44 patients with non-anxious depression matched by sex,age and years of education (NA-MDD group)were recruited. Electrochemiluminescence was used to detect the plasma levels of adreno-corticotropic hormone(ACTH),cortisol(COR),c-reactive protein(CRP) and IL-6. Automatic biochemical a-nalysis was used to detect plasma total TC,TG,HDL and LDL. Using logistic regression analysis to discuss the influencing factors of anxiety depression. Results The comparison between the two group showed that the age of first onset,BMI and SBP in the A-MDD group((35. 15±11. 56),(24. 11±3. 03)kg/m2,(130. 09 ±13. 33)mmHg) were significantly higher than those in the NA-MDD group((31. 34± 14. 08),( 22. 70± 3. 19)kg/m2,( 121. 89±12. 49)mmHg)(t=2. 631,2. 009,2. 964,all P<0. 05). The HAMD score and the factor scores of cognitive impairment,change of day and night,delay,sleep disorder and feeling of despair in the A-MDD group((31. 81±5. 39),(8. 03±3. 00),(1. 17±0. 70),(6. 88±1. 93),(4. 44±1. 44),(4. 67± 2. 37)) were significantly higher than those in the NA-MDD group((25. 25±5. 017),(3. 87±3. 12),(0. 79 ±0. 78),(4. 64±2. 22),(3. 34±1. 54),(3. 61±2. 02))(t=2. 297,6. 524,2. 505,5. 210,3. 452,2. 421,all P<0. 05). The plasma TG,CRP and IL-6 levels in the A-MDD group((1. 63±1. 11)mmol/L,(1. 20±0. 77) mg/L,(3. 54±1. 90) pg/L) were significantly higher than those in the NA-MDD group (( 1. 19 ± 0. 66) mmol/L,(0. 933±0. 89)mg/L,(2. 65±1. 34)pg/L) (t=2. 254,2. 250,2. 352,all P<0. 05). The incidence of cortisol disturbance was 72% in the A-MDD group,and 48% in the NA-MDD group,and the difference was statistically significant (χ2=5. 369 P=0. 020). Multivariate Logistic regression found that sleep disorder (β=0. 729,OR=2. 072,95%CI=1. 018-3. 119),IL-6(β=0. 583,OR=1. 792,95%CI=1. 168-2. 748),cog-nitive impairment (β=0. 099,OR=1. 104,95% CI=1. 022-1. 193),cortisol rhythm disorders(β=0. 075, OR=1. 078,95%CI=1. 014-1. 146) were the risk factors for anxious depression. Conclusion Anxious de-pression has a high incidence of cortisol rhythm disorder. The COR and IL-6 may be mediators of cortisol rhythm disorder. IL-6 and cortisol rhythm disorder together with sleep disorder and negative cognition consti-tute maybe high risk factors for anxious depression.

Objective To explore the psychological process of cognitive impairment in patients with recurrent major depression disorder (MDD). Methods Patients with first-episode (n=30) and recurrent MDD (n=68) in the outpatient department of the First Affiliated Hospital of Zhengzhou University from Sep-tember 2016 to December 2017 were collected and healthy controls(n=30) were collected at the same time. According to HAMD-24 score,the group with recurrent attacks was further divided into recurrent attacks-on-set period (n=35) and recurrent attacks-remission period (n=33). All subjects were tested for cognitive function by MATRICS Consensus Cognitive Battery( MCCB). Results (1) In terms of cognitive function assessment,the scores of information processing speed ( 41. 27 ± 8. 44, 37. 00 ± 11. 68), working memory (40. 53±10. 33,41. 26±9. 37),attention/alertness ( 40. 50± 7. 25,39. 58± 8. 23),word learning ( 38. 83± 8. 39,38. 84±9. 57),visual memory(39. 30±14. 03,37. 57±10. 42),reasoning and problem solving(37. 80± 9. 55,38. 78±8. 66),and social cognition (34. 63± 9. 66) in the first-episode group and the recurrent group were lower than those in the control group ( information processing speed ( 48. 23±7. 63),working memory (50. 57±7. 84),attention/alertness (51. 63±7. 41),word learning (45. 57±9. 55),visual memory (50. 57± 8. 42),reasoning and problem solving (50. 03±9. 87) and social cognition (47. 90±19. 01)) (F=12. 818, 12. 173,26. 166,6. 004,15. 085,18. 331,10. 218,P<0. 05); (2) In working memory and social cognition, the difference was statistically significant in the first-episode group,repeated attacks-episodes(working mem-ory:37. 89±9. 15,social cognition:28. 48± 8. 35) and recurrent group-remission( working memory:44. 85± 8. 32,social cognition:40. 44 ± 11. 36, P=0. 010,0. 001). Further comparisons revealed that the score of working memory in repeated attacks-episodes was lower than that in recurrent group-remission (P=0. 003). the score of social cognition in the first-episode group was higher than that in the recurrent-attack period group (P=0. 038). The score of social cognition in the recurrent group-remission was higher than that in re-current-attack period group (P<0. 01). Conclusion There is cognitive impairment in the first episode and the recurrence MDD. The impairment in the recurrent episode is more serious than that in the first episode of depression. The impairment of social cognitive in the recurrent attacks-episodes is more serious than that in the first-episode of depression.

Objective: To investigate the possible role of tag single nucleotide polymorphisms in cAMP signaling pathway in patients with recurrent major depressive disorder in Chinese Han population. Methods: 1 030 patients with recurrent major depressive disorder according to the DSM-Ⅳ criteria were recruited as case group and 851 age- and gender- matched healthy volunteers were recruited as control group.The sequenom mass spectrometry method was adopted to explore the genotype and allele frequency distributions of tag single nucleotide polymorphisms of cAMP signaling pathway in the two groups. Results: The differences of genotype and allele frequencies of the ADCY7 gene loci rs1064448 and HTR2A gene loci rs17068986 were significant between case group and control group(P<0.05). The difference of the genotype frequencies(492∶423∶112, 356∶401∶91; 538∶392∶94, 414∶371∶61; 24∶165∶838, 3∶150∶694; 219∶468∶337, 139∶418∶237; 153∶481∶393, 115∶446∶286; 53∶286∶688, 25∶296∶524)of the ADCY9 gene loci rs2531995, BDNF gene loci rs10835210, rs7124442, CREB1 gene loci 4675690, rs2551645 and the HTR2A gene loci rs3125 were significant in case-control group(P<0.05); while the rest tagSNPs had no statistical difference in genotype and allele distribution frequencies in case-control group(P>0.05). In gender-specific analyses, the differences of the genotype and allele frequencies of the ADCY7 gene loci rs106448 and CREB1 gene loci rs2551645 were significant in male case-control group(P<0.05); the differences of the genotype(195∶177∶49, 193∶423∶41; 221∶158∶42, 237∶201∶28; 83∶188∶148, 85∶237∶122; 24∶113∶284, 10∶176∶281)of the ADCY9 gene loci rs2531995, BDNF gene loci rs10835210, CREB1 gene loci rs4675690, and HTR2A gene loci rs3125 were significant in male case-control group(P<0.05); while the rest tagSNPs had no statistical difference in genotype and allele distribution frequencies in male case-control group(P>0.05). The differences of the genotype and allele frequencies of the ADCY7 gene loci rs1064448 and HTR2A gene loci rs17068986 were significant in female case-control group(P<0.05). The differences of the genotype(16∶94∶497, 1∶73∶308; 136∶280∶189, 54∶181∶115)of the BDNF gene loci rs7124442 and CREB1 gene loci rs4675690 were significant in female case-control group(P<0.05). The differences of the allele frequencies(840: 372, 493: 267) of the ADCY9 gene loci rs2531995 were significant in female case-control group(P<0.05), while the rest tagSNPs had no statistical difference in genotype and allele distribution frequencies in female case-control group(P>0.05). Conclusion The ADCY7 gene loci rs1064448 and CREB1 gene loci rs4675690 are associated with recurrent major depressive disorder in Chinese Han population.