Objective Based on a clinical cohort study of repeated ketamine infusions for treatment-resistant depression(TRD),this study aimed to examine differences in brain-derived neurotrophic factor(BDNF)methylation among patients with varying therapeutic responses and explore its potential role in predicting treatment efficacy.Methods A retrospective analysis was conducted on peripheral plasma BDNF levels in 83 patients with TRD before and after a 2-week course of ketamine treatment(6 injections total).The Montgomery-Asberg depression rating scale(MADRS)was used to assess treatment efficacy.BDNF methylation levels were compared between responder group and non-responder group.The effect of methylation of the target CpG site on transcriptional activity was verified by using the dual luciferase reporter gene system.Results In patients with TRD who completed six repeated ketamine infusions,the responder group showed significant improvements compared to baseline levels in both MADRS scores(25.20±7.54 vs.8.10±5.32,P<0.01)and plasma BDNF concentrations[8.74(5.26,13.46)ng/mL vs.16.59(7.41,24.46)ng/mL,P<0.01].At baseline,35 CpG sites within the BDNF gene displayed significant methylation differences between response groups(P<0.05).Two CpG sites(rs1240718851 and cg06260077)located in the BDNF promoter region demonstrated a hypermethylation-low expression correlation,and dual-luciferase reporter assays confirmed that one of these sites functionally modulates BDNF expression.Conclusions The plasma BDNF concentration in TRD patients increases with the remission of depressive symptoms.The regulation of BDNF gene expression by methylation can predict the antidepressant efficacy of repeated intravenous ketamine.

Objective Based on a clinical cohort study of repeated ketamine infusions for treatment-resistant depression(TRD),this study aimed to examine differences in brain-derived neurotrophic factor(BDNF)methylation among patients with varying therapeutic responses and explore its potential role in predicting treatment efficacy.Methods A retrospective analysis was conducted on peripheral plasma BDNF levels in 83 patients with TRD before and after a 2-week course of ketamine treatment(6 injections total).The Montgomery-Asberg depression rating scale(MADRS)was used to assess treatment efficacy.BDNF methylation levels were compared between responder group and non-responder group.The effect of methylation of the target CpG site on transcriptional activity was verified by using the dual luciferase reporter gene system.Results In patients with TRD who completed six repeated ketamine infusions,the responder group showed significant improvements compared to baseline levels in both MADRS scores(25.20±7.54 vs.8.10±5.32,P<0.01)and plasma BDNF concentrations[8.74(5.26,13.46)ng/mL vs.16.59(7.41,24.46)ng/mL,P<0.01].At baseline,35 CpG sites within the BDNF gene displayed significant methylation differences between response groups(P<0.05).Two CpG sites(rs1240718851 and cg06260077)located in the BDNF promoter region demonstrated a hypermethylation-low expression correlation,and dual-luciferase reporter assays confirmed that one of these sites functionally modulates BDNF expression.Conclusions The plasma BDNF concentration in TRD patients increases with the remission of depressive symptoms.The regulation of BDNF gene expression by methylation can predict the antidepressant efficacy of repeated intravenous ketamine.

Objective To explore the correlation between the methylation level of 5-hydroxytryptamine receptor 1A(HTR1A) gene promoter region and severity of symptom in the manic epi-sode patients with bipolar disorder type Ⅰ(BD-Ⅰ). Methods Fifty six manic episode patients with BD-Ⅰand fifty nine healthy controls were randomly included in the study. The level of HTR1A gene promoter meth-ylation was measured with pyrosequencing technique in both manic episode patients with BD-Ⅰ and the healthy controls. The severity of symptoms was assessed with score of Bech-Rafaelsen Mania Rating Scale (BRMS) in patients with BD-Ⅰ. Pearson correlation analysis was employed to explore the correlation be-tween the serum level of HTR1A promoter methylation and score of BRMS in BD-Ⅰgroup. Results In-creased serum level of HTR1A gene promoter methylation was found in manic episode patients with BD-Ⅰ((66. 55±10. 55)%) compared with that in healthy controls((54. 03±8. 85)%)(P<0. 01). Positive corre-lation was found between the serum level of HTR1A gene promoter methylation and total score of BRMS in manic patient with BD-Ⅰ(r=0. 534,P<0. 01). Conclusion The current findings suggest that the serum level of HTR1A gene promoter methylation can be an epigenetic indicator for severity of manic symptom in BD-Ⅰ.

[ ABSTRACT] AIM:To compare the differences of the genome-wide methylation levels and methylated regions be-tween nasopharyngeal carcinoma ( NPC) cells in the same genetic background but different radiation resistance ( CNE-2 cells and CNE-2R cells).METHODS:Using the method which was developed by Doctor Zhao Cun-you, based on using methyl-sensitive restriction enzyme to measure the genome-wide methylation levels.In addition, MeDIP-Seq was used to analyze the methylated regions in 6 gene functional elements, including the upstream 2k sequence, 5’ UTR, coding se-quence, intron, 3’UTR and downstream 2k sequence, between CNE-2 cells and CNE-2R cells.RESULTS:The genome-wide methylation level was approximately 30%lower in CNE-2R cells than that in CNE-2 cells.No obvious difference on the amount of genes and the coverage of the peak in the 6 gene functional elements was observed.However, the methylation pattern of plentiful genes had altered in the gene function elements.CONCLUSION:The genome-wide methylation levels and methylated regions between NPC cells in the same genetic background but different radiation resistance were quite dif-ferent, indicating that the DNA methylation may be associated with NPC radioresistance.

Objective To explore the influence factors of hyperarousal,personality characteristics and coping strategies on the vulnerability to stress-related sleep disturbance.Methods A total of 345 sleep good healthy volunteers were recruited bypurposive sampling technique.Every participant completed an extensive survey that included the general condition questionnaire,Ford Insomnia Response to Stress Test (FIRST),PreSleep Arousal Scale (PSAS),NEO Personality Inventory-Revised (NEOPI-R),Coping Inventory for Stressful Situations (CISS) and Heart Rate Variability(HRV).All participants were classified as High risk group andLow risk group by using the FIRST criterion.Results The high risk group was younger than the low risk group (27.91±8.22 vs 24.82±7.73,P＜0.01),and had a higher percentage of females (34.7％ vs 53.4％,P＜0.05).The high risk group showed significantly higher scores in PSAS total (30.11±6.22),pesleep cognitive arousal (17.73± 4.51),presleep somatic arousal (12.78 ± 3.23),neuroticism (3.13 ± 0.51),emotion oriented (48.98 ± 10.54),but lower score in extraversion (2.96±0.54),then those indicators of the low risk group (28.52±5.82,16.32±4.32,11.41±2.75; 3.11±0.56,2.87±0.47,46.23±11.21,3.11±0.56,P＜0.01 or 0.05).There were significant difference between the two group in LF/HF (1.51 ±0.19 vs 1.17±0.11,P＜0.01),HF((311.21 ±72.32) ms2/Hz vs (490.43 ± 91.74)ms2/Hz,P＜0.01),LF((469.49±85.67)ms2/Hzvs (573.21±98.75) ms2/Hz,P＜0.01) in HRV.Results of linear regression analysis showed that gender,and scores of PSAS total,cognitive arousal,presleep cognitive arousal,presleep somatic arousal,neuroticism,emotion oriented and LF/HF were significant correlation with FIRST score (P＜0.01 or 0.05).Conclusion Presleep cognitive and somatic arousal,neurotic character may be the premorbid characteristics of stress-related sleep disturbance,and bad stress coping strategies are easy to promote the development of insomnia.

OBJECTIVETo investigate the genetic association between schizophrenia and the polymorphism of GABA(A) receptor β2 subunit (GABRB2) gene.

METHODSA population association analysis was performed of 5 single nucleotide polymorphisms (SNPs) in the proximal promoter of GABRB2 gene by PCR and sequencing of the genomic DNA in a cohort of 172 schizophrenics and 167 controls of Chinese Han nationality.

RESULTSOne out of the 5 SNPs, namely rs3811996, was found to be significantly associated with schizophrenia especially in the male cohorts, where the heterozygous genotypes (A/G) and minor allele G displayed lower frequencies in case group than in the controls.

CONCLUSIONWe found a new risk, SNP rs3811996, for paranoia schizophrenia, which further supports the importance of genetic variations of GABRB2 in the etiology of schizophrenia.

Alleles ; Case-Control Studies ; Ethnic Groups ; Heterozygote ; Humans ; Male ; Polymorphism, Single Nucleotide ; Promoter Regions, Genetic ; Receptors, GABA-A ; genetics ; Schizophrenia ; genetics

Objective To investigate the genetic association between schizophrenia and the polymorphism of GABAA receptorβ2 subunit (GABRB2) gene. Methods A population association analysis was performed of 5 single nucleotide polymorphisms (SNPs) in the proximal promoter of GABRB2 gene by PCR and sequencing of the genomic DNA in a cohort of 172 schizophrenics and 167 controls of Chinese Han nationality. Results One out of the 5 SNPs, namely rs3811996, was found to be significantly associated with schizophrenia especially in the male cohorts, where the heterozygous genotypes (A/G) and minor allele G displayed lower frequencies in case group than in the controls. Conclusion We found a new risk, SNP rs3811996, for paranoia schizophrenia, which further supports the importance of genetic variations of GABRB2 in the etiology of schizophrenia.

Objective To investigate the genetic association between schizophrenia and the polymorphism of GABAA receptorβ2 subunit (GABRB2) gene. Methods A population association analysis was performed of 5 single nucleotide polymorphisms (SNPs) in the proximal promoter of GABRB2 gene by PCR and sequencing of the genomic DNA in a cohort of 172 schizophrenics and 167 controls of Chinese Han nationality. Results One out of the 5 SNPs, namely rs3811996, was found to be significantly associated with schizophrenia especially in the male cohorts, where the heterozygous genotypes (A/G) and minor allele G displayed lower frequencies in case group than in the controls. Conclusion We found a new risk, SNP rs3811996, for paranoia schizophrenia, which further supports the importance of genetic variations of GABRB2 in the etiology of schizophrenia.

Objective To compare with the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) between the left and the right prefrontal on refractory negative symptoms and serum brain-derived neurotrophic factor (BDNF). Methods 80 hospitalized schizophrenics with refractory negative symptoms were divided into study group (n=40) and control group (n=40) randomly. Both groups were received 4-week treatment of 10 Hz rTMS. The stimulus lo?cation of the study group was the left prefrontal, and the control group was the right prefrontal. The type and dose of anti?psychotics remained unchanged during the treatment. The evaluation of positive and negative symptom scale (PANSS) and the measurement of BDNF concentration before treatment and after 4 weeks treatment was analyzed. Results Com?pared with before treatment, the total score of PANSS after treatment significantly decreased (P<0.05) both in the study group [(71.2±13.8) vs. (63.3±11.4)] and the control group [(70.3±13.4) vs. (63.7±12.2)]. The score of negative symptoms in the study group decreased [(22.8±6.6) vs. (18.4±5.9), P<0.01]. The BDNF concentration increased in the study group ](6.78±2.16) vs. (8.74±2.76)] and the control group [(6.83±2.32) vs. (8.66±2.70)]. Conclusion 10Hz rTMS on the left pre?frontal combined with drugs are helpful to improve the refractory negative symptom of the patients with schizophrenia. Stimulation on both left and right prefrontal lobe could increase serum BDNF concentration.

ObjectiveTo explore the metabolite status on prefrontal lobe and thalamus by proton magnetic resonance spectroscopy (1H-MRS) and affecting factors in patients of schizophrenia.Methods 159 schizophrenics met with CCMD-3 and 45 normal controls were examined at prefrontal lobe and thalamus by multi-voxel 1H-MRS.The N-acetylaspartate ( NAA),Choline-congtaining compounds ( Cho),and Creatine compounds (Cr)were measured and the ratios of NAA/Cr,Cho/Cr were determined. Positive and Negative Syndrome Scale (PANSS),Social Disability Screening Schedule (SDSS),and Wisconsin Card Sorting Test (WCST) were also assessed.ResultsOn left prefrontal lobe of patients,the NAA/Cr ratio demonstrated lower than that in normal controls (1.42 ±0.34 vs.1.64 ±0.39,t =3.70,P＜0.01 ).The same phenomenon were appeared on left thalamus (1.46±0.35 vs.1.66±0.38,t=3.32,P＜0.01) and on right thalamus (1.49±0.34 vs.1.62±0.37,t=2.04,P ＜ 0.05 ).Contributing to the NAA/Cr ratio,main influencing factors on left prefrontal lobe were age of onset,duration of illness,score of negative symptoms,antipsychotic treatment,total score of PANSS,Categories completed of WCST,total score of SDSS,year of education.Main influencing factors on left thalamus were age of onset,duration of illness,antipsychotic treatment.Main influencing factors on right thalamus were duration of illness,age of onset,score of negative symptoms,antipsychotic treatment,and family history.ConclusionsAbnormalities in neuronal function and/or integrity presented on prefrontal lobe and thalamus in schizophrenics are related to many respects,especially age of onset,duration of illness and antipsychotic treatment.