Risk factors and clinical characteristics of autism spectrum disorder with regression in China.

Autism spectrum disorder with regression (ASD-R) is characterized by the loss of previously acquired skills during the initial year of life. This study aimed to investigate the clinical characteristics, patterns of regression, and potential risk factors associated with ASD-R in the Chinese Han population. A case-control study was conducted between September 2020 and March 2022. A total of 186 children were enrolled, including 58 children with ASD-R, 70 with ASD without regression (ASD-NR), and 58 typically developing children. Demographic information, clinical characteristics, and potential risk factors related to ASD-R were assessed using a combination of questionnaires, interviews, and physician assessments. The results revealed that children with ASD-R exhibited more severe impairments in social communication and stereotyped behaviors compared with those with ASD-NR. Language regression, constituting 40% of cases within the ASD-R group, was found to be the most common type of regression. Furthermore, our analysis revealed that fever (OR = 4.01, 95% CI: 1.26-12.76) and diarrhea (OR = 6.32, 95% CI: 1.38-29.03) were identified as significant risk factors for ASD-R. These findings contribute to our understanding of the heterogeneity of ASD and highlight the importance of considering immune responses and gastrointestinal factors in the etiology of ASD-R.

Halobacterium wangiae sp. nov. and Halobacterium zhouii sp. nov., two extremely halophilic archaea isolated from sediment of a salt lake and saline soil of an inland saltern.

Two novel halophilic archaeal strains, Gai3-17T and XZYJT26T, were isolated from the sediment of Gaize salt lake and the saline soil of Mangkang ancient solar saltern in Tibet, PR China, respectively. Strains Gai3-17T and XZYJT26T were related to each other (96.5 and 89.7% similarity, respectively) and showed 97.5-95.4 and 91.5-87.7% similarities to the current members of Halobacterium based on 16S rRNA and rpoB' genes. The phylogenomic analysis indicated that strains Gai3-17T and XZYJT26T formed two distinct clades and clustered with the Halobacterium species. The two strains can be differentiated from the type strains of the six species with validly published names based on several phenotypic characteristics. The phospholipids of the two strains were phosphatidic acid, phosphatidylglycerol and phosphatidylglycerol phosphate methyl ester. One major glycolipid, sulphated galactosyl mannosyl glucosyl diether, was detected in strain Gai3-17T, while four glycolipids, mannosyl glucosyl diether, sulphated mannosyl glucosyl diether, disulphated mannosyl glucosyl diether and sulphated galactosyl mannosyl glucosyl diether were observed in strain XZYJT26T. The average nucleotide identity, digital DNA-DNA hybridization and amino acid identity values among the two strains and the members of Halobacterium were no more than 81, 25 and 77 %, respectively. These overall genome-related indices were below the threshold values for species boundary, indicating that strains Gai3-17T and XZYJT26T represent two novel species of Halobacterium. Thus, two novel species, Halobacterium wangiae sp. nov. and Halobacterium zhouii sp. nov., are proposed to accommodate strains Gai3-17T (=CGMCC 1.16101T=JCM 33551T) and XZYJT26T (=CGMCC 1.16682T=JCM 33556T), respectively.

Haladaptatus halobius sp. nov. and Haladaptatus salinisoli sp. nov., two extremely halophilic archaea isolated from Gobi saline soil.

Two extremely halophilic archaeal strains, PSR5T and PSR8T, were isolated from a saline soil sample collected from the Tarim Basin, Xinjiang, PR China. Both strains had two copies of the 16S rRNA genes rrn1 and rrn2, showing 2.6 and 3.9% divergence, respectively. The rrn1 gene of PSR5T showed 98.4 and 95.3% similarity to the rrn1 and rrn2 genes of strain PSR8T; the rrn2 gene of PSR5T displayed 97.4 and 96.7% similarity to those of strain PSR8T, respectively. Phylogenetic analyses based on the 16S rRNA and rpoB' genes revealed that strains PSR5T and PSR8T formed a single cluster, and then tightly clustered with the current four Haladaptatus species (93.5-97.1% similarities for the 16S rRNA gene and 89.3-90.9% similarities for the rpoB' gene, respectively). Several phenotypic characteristics differentiate strains PSR5T and PSR8T from current Haladaptatus members. The polar lipids of the two strains are phosphatidic acid, phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester phosphatidylglycerol sulphate and three glycolipids. One of the glycolipids is sulphated mannosyl glucosyl diether, and the remaining two glycolipids are unidentified. The average nucleotide identity, in silico DNA-DNA hybridization, amino acid identity and percentage of conserved proteins values between the two strains were 88.5, 39.1, 89.3 and 72.8 %, respectively, much lower than the threshold values proposed as a species boundary. These values among the two strains and Haladaptatus members were 77.9-79.2, 22.0-23.5, 75.1-78.2 and 56.8-69.9 %, respectively, much lower than the recommended threshold values for species delimitation. These results suggested that strains PSR5T and PSR8T represent two novel species of Haladaptatus. Based on phenotypic, chemotaxonomic, genomic and phylogenetic properties, strains PSR5T (=CGMCC 1.16851T=JCM 34141T) and PSR8T (=CGMCC 1.17025T=JCM 34142T) represent two novel species of the genus Haladaptatus, for which the names Haladaptatus halobius sp. nov. and Haladaptatus salinisoli sp. nov. are proposed.

Natrinema halophilum sp. nov., Natrinema salinisoli sp. nov., Natrinema amylolyticum sp. nov. and Haloterrigena alkaliphila sp. nov., four extremely halophilic archaea isolated from salt mine, saline soil and salt lake.

Four halophilic archaeal strains, YPL8T, SLN56T, LT61T and KZCA68T, were isolated from a salt mine, saline soil and a salt lake located in different regions of China. Sequence similarities of 16S rRNA and rpoB' genes among strains YPL8T, SLN56T, LT61T and the current members of Natrinema were 94.1-98.2 % and 89.3-95.1 %, respectively, while these values among strain KZCA68T and the current members of Haloterrigena were 97.2-97.4 % and 91.7-91.9 %, respectively. The average nucleotide identity, in silico DNA-DNA hybridization and average amino acid identity values among these four strains and their closely related species were all lower than the threshold values for species boundary. All four strains were unable to hydrolyse casein, gelatin, or Tween 80. Strain YPL8T contained phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), sulfated mannosyl glucosyl diether (S-DGD-1), disulfated mannosyl glucosyl diether (S2-DGD) and sulfated mannosyl glucosyl diether-phosphatidic acid (S-DGD-PA). Strain SLN56T contained PA, PG, phosphatidylglycerol sulphate (PGS), PGP-Me, S-DGD-1, S2-DGD and S-DGD-PA. Strain LT61T contained PA, PG, PGS, PGP-Me, S-DGD-1 and S2-DGD. The phospholipids of strain KZCA68T were PA, PG and PGP-Me. These results showed that strains YPL8T (=CGMCC 1.13883T=JCM 31181T), SLN56T (=CGMCC 1.14945T=JCM 30832T) and LT61T (=CGMCC 1.14942T=JCM 30668T) represent novel species of the genus Natrinema, for which the names, Natrinema halophilum sp. nov., Natrinema salinisoli sp. nov. and Natrinema amylolyticum sp. nov. are proposed. Strain KZCA68T (=CGMCC 1.17211T=JCM 34158T) represents a novel species of Haloterrigena, for which the name Haloterrigena alkaliphila sp. nov. is proposed.

Genome-based taxonomy of genera Halomicrobium and Halosiccatus, and description of Halomicrobium salinisoli sp. nov.

The genera Halosiccatus and Halomicrobium are the most closely related genera within the family Haloarculaceae (class Halobacteria). All species of these two genera are closely related to each other in phylogenetic analyses based on their 16S rRNA gene sequences, and also using the sequences of four housekeeping genes. The genus Halosiccatus was proposed based on inferred phylogeny using only one of the three distinct 16S rRNA genes detected in strain DC8T, while Halomicrobium zhouii, one of three species of Halomicrobium, was omitted from the reference species used in these analyses. The related 16S rRNA gene sequence similarities of type strains of Halomicrobium katesii and Halomicrobium mukohataei were as high as 99.5%-99.7%, much higher than the threshold values proposed as species boundaries. These issues could have resulted in taxonomic inaccuracies in the genera Halosiccatus and Halomicrobium, and a thorough study was undertaken to clarify the status of all species in both genera. Based on phylogenetic and phylogenomic analyses, the current four species of the two genera form a single clade with high bootstrap confidence, indicating that the genus Halosiccatus should be merged with Halomicrobium. Halomicrobium katesii Kharroub et al. 2008 is proposed as a later heterotypic synonym of Halomicrobium mukohataei (Ihara et al. 1997) Oren et al. 2002. An additional species is also described (strains LT50T and TH30), and was isolated from different Gobi saline soil samples of Tarim Basin, Xinjiang, China. Phenotypic, chemotaxonomic, genomic and phylogenetic properties indicated that strains LT50T (=CGMCC 1.15187T = JCM 30837T) and TH30 (=CGMCC 1.15189 = JCM 30839) represent a novel species of the genus Halomicrobium, for which the name Halomicrobium salinisoli sp. nov. is proposed.

Haloprofundus salilacus sp. nov., Haloprofundus halobius sp. nov. and Haloprofundus salinisoli sp. nov.: three extremely halophilic archaea isolated from salt lake and saline soil.

Three halophilic archaeal strains, Gai1-5T, SEDH52T and SQT7-1T were isolated from Gaize salt lake and Xiadi salt lake in Tibet, and saline soil from Xinjiang, respectively. Phylogenetic analysis based on 16S rRNA gene and rpoB' gene sequences showed that these three strains formed different branches separating them from Haloprofundus halophilus NK23T (97.7-98.3% similarities for 16S rRNA gene and 94.7-94.8% similarities for rpoB' gene, respectively) and Haloprofundus marisrubri SB9T (94.7-96.4% similarities for 16S rRNA gene and 92.3-93.2% similarities for rpoB' gene, respectively). Several phenotypic characteristics distinguish the strains Gai1-5 T, SEDH52T and SQT7-1T from Haloprofundus halophilus NK23T and Haloprofundus marisrubri SB9T. The average nucleotide identity (ANI) and in silico DNA-DNA hybridization (isDDH) values among the three strains and current Haloprofundus members were in the range of 83.3-88.3% and 27.2-35.7%, respectively, far below the species boundary threshold values. The major polar lipids of three strains were phosphatidic acid (PA), phosphatidylglycerol (PG), phosphatidylglycerol sulphate (PGS), phosphatidylglycerol phosphate methyl ester (PGP-Me), sulfated mannosyl glucosyl diether (S-DGD-1), mannosyl glucosyl diether-phosphatidic acid (DGD-PA) and sulfated mannosyl glucosyl diether-phosphatidic acid (S-DGD-PA). These results showed that strains Gai1-5T (= CGMCC 1.16079T = JCM 33561T), SQT7-1T (= CGMCC 1.16063T = JCM 33553 T) and SEDH52T (= CGMCC 1.17434T) represented three novel species in the genus Haloprofundus, for which the names Haloprofundus salilacus sp. nov., Haloprofundus salinisoli sp. nov., and Haloprofundus halobius sp. nov. are proposed.

Abnormal regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuations (fALFF) in first-episode drug-naïve schizophrenia patients comorbid with depression.

The current study aimed to characterize the regional homogeneity (ReHo) or fractional amplitude of low frequency fluctuations (fALFF) alterations in first-episode drug-naïve schizophrenia comorbid with depression. Sixty-nine first-episode drug-naïve schizophrenia patients and 34 healthy controls (HC) were included in the final analysis. Schizophrenia patients were divided into depressive patients (DP) and non-depressive patients (NDP), with 35 and 34 patients respectively, using the Hamilton Rating Scale for Depression -17(HRSD-17). All participants underwent resting-state fMRI (rs-fMRI), the fALFF (slow-4 and slow-5 bands) and ReHo were used to process the data. The results revealed eleven brain regions with altered slow-5 fALFF, eleven brain regions with altered slow-4 fALFF and ten brain regions with altered ReHo among DP, NDP and HC groups. Compared to NDP, the DP group had increased slow-5 fALFF in the Right Inferior Temporal Gyrus, increased ReHo in the Right Superior and Inferior Frontal Gyrus. The altered slow-5 fALFF in the Right Inferior Temporal Gyrus, altered ReHo in the Right Inferior Frontal Gyrus and Superior Frontal Gyrus were all positively correlated with the depressive symptoms in patients. However, there were no significant differences in slow-4 fALFF between DP and NDP groups. Our results indicate that the increased slow-5 fALFF in the Right Inferior Temporal Gyrus, increased ReHo in the Right Superior and Inferior Frontal Gyrus were associated with depressive symptoms in schizophrenia, which may provide preliminary evidence in better understanding the neural mechanisms underlying depressive symptoms in schizophrenia.

MicroRNA-195 predicts olanzapine response in drug-free patients with schizophrenia: A prospective cohort study.

BACKGROUND: Disturbances of microRNA-195 have been implicated in the pathogenesis of schizophrenia. However, microRNA-195 levels in schizophrenia are controversial. AIMS: To the best of our knowledge, this is the first study to examine microRNA-195 levels in untreated schizophrenia patients and their relationship to olanzapine response. METHODS: We recruited 81 untreated schizophrenia patients and 96 healthy controls. The patients received 2 months olanzapine treatment. MicroRNA-195 levels in peripheral blood mononuclear cells were measured using quantitative real-time polymerase chain reaction testing. Psychiatric symptoms were assessed using the Positive and Negative Syndrome Scale. RESULTS: No significant differences in microRNA-195 levels were found between patients and healthy controls (p > 0.05). Olanzapine significantly reduced microRNA-195 levels after 2 months treatment (p = 0.003). Interestingly, microRNA-195 levels decreased significantly in responders (p = 0.010), but not in non-responders (p > 0.05). Both baseline microRNA-195 levels (p = 0.027, p = 0.030) and the reduction rate of microRNA-195 levels (p = 0.034, p = 0.044) were positively associated with the reduction rate of Positive and Negative Syndrome Scale total score and general psychopathological subscale score. Multiple stepwise regression analysis revealed that baseline microRNA-195 level was an independent contributor to the reduction in Positive and Negative Syndrome Scale total score and the general psychopathological subscale score (p = 0.018, p = 0.030). Finally, logistic regression analysis suggested that baseline microRNA-195 level can serve as a biomarker for response to olanzapine (p = 0.037). CONCLUSIONS: Our data indicate that microRNA-195 level may predict symptomatic improvement and olanzapine response in schizophrenia patients, suggesting that microRNA-195 should be considered as a potential therapeutic target for antipsychotics.

Sex difference in cognitive impairment in drug-free schizophrenia: Association with miR-195 levels.

OBJECTIVE: There is evidence that microRNA-195 (miR-195) is associated with schizophrenia (SZ) and cognition, but the relationship between miR-195 and cognitive impairment in SZ is still unknown. Sex differences in both microRNA (miRNA) expression and cognition were found in SZ. We aim to investigate whether sex moderates the relationship between miR-195 levels and cognition in SZ. METHODS: We recruited 121 drug-free SZ patients and 129 healthy controls. miR-195 expression levels in peripheral blood mononuclear cells (PBMCs) were measured using qRT-PCR. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess cognitive function. MANCOVA, ANCOVA, correlation analysis and hierarchical linear regression analysis were used to test the effect of sex on the aforementioned variables. RESULTS: All RBANS scores significantly decreased in patients compared to healthy controls (all p < 0.001); ANCOVA analysis demonstrated female SZ patients had lower delayed memory score (F = 15.36, p < 0.001) and total score (F = 5.26, p = 0.024) than male patients. There was no diagnosis, sex or sex by diagnosis interaction effect on miR-195 levels (all p > 0.05). Interestingly, correlation analysis showed significant negative association between miR-195 and attention score (r = -0.389, p = 0.019), delayed memory score (r= -0.351, p = 0.036), and total score (r = -0.386, p = 0.020) only in female patients. Hierarchical regression analysis showed sex by miR-195 interaction was a significant predictor of the RBANS total score (ΔR2 = 0.042, F(1, 67) = 4.71, p = 0.033). CONCLUSION: Our data indicate that miR-195 is associated with cognitive impairment in female SZ patients, and it may be involved in the underlying mechanism of sex differences in cognitive impairment in SZ.

Disturbance of Oxidative Stress Parameters in Treatment-Resistant Bipolar Disorder and Their Association With Electroconvulsive Therapy Response.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective option for treatment-resistant bipolar disorder (trBD). However, the mechanisms of its effect are unknown. Oxidative stress is thought to be involved in the underpinnings of BD. Our study is the first, to our knowledge, to report the association between notable oxidative stress parameters (superoxide dismutase [SOD], glutathione peroxidase [GSH-Px], catalase [CAT], and malondialdehyde [MDA]) levels and ECT response in trBD patients. METHODS: A total 28 trBD patients and 49 controls were recruited. Six-week ECT and naturalistic follow-up were conducted. SOD, GSH-Px, CAT, and MDA levels were measured by enzyme-linked immunosorbent assay, and the 17-item Hamilton Depression Rating Scale and Young Mania Rating Scale were administered at baseline and the end of the 6th week. MANCOVA, ANCOVA, 2 × 2 ANCOVA, and a multiple regression model were conducted. RESULTS: SOD levels were lower in both trBD mania and depression (P = .001; P = .001), while GSH-Px (P = .01; P = .001) and MDA (P = .001; P = .001) were higher in both trBD mania and depression compared with controls. CAT levels were positively associated with 17-item Hamilton Depression Rating Scale scores in trBD depression (radjusted = 0.83, P = .005). MDA levels in trBD decreased after 6 weeks of ECT (P = .001). Interestingly, MDA levels decreased in responders (P = .001) but not in nonresponders (P > .05). CONCLUSIONS: Our study indicates that decreased SOD could be a trait rather than a state in trBD. Oxidative stress levels are associated with illness severity and ECT response. This suggests that the mechanism of oxidative stress plays a crucial role in the pathophysiology of trBD.

Predicting individual responses to lithium with oxidative stress markers in drug-free bipolar disorder.

Objectives: This is the first study to investigate the oxidative stress (OxS) levels in drug-free bipolar disorder (BD) patients and their association with lithium response.Methods: A total of 61 drug-free BD patients and 49 controls were included. Patients treated with lithium were followed-up for 6 weeks. The levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and malondialdehyde (MDA) were measured at baseline and at the end of the sixth week.Results: Compared to controls, the SOD levels were lower, whereas the MDA were higher in the BD-depression (BD-D) group (both P < 0.001). GSH-Px levels were higher in both the BD-D and the BD-mania (BD-M) group (both P < 0.001). Both GSH-Px and MDA levels in the BD (P = 0.009, P < 0.001) and the BD-D subgroup (P = 0.006, P = 0.001) decreased significantly after the 6-week treatment with lithium. Interestingly, both GSH-Px and MDA levels decreased in responders (P = 0.03, P = 0.002) but not in the non-responders of BD-D (both p > 0.05). Moreover, the reduction in the MDA levels were associated with lithium response (B = 1.47, Wald statistic = 5.94, P = 0.015, odds ratio = 4.35, 95% confidence interval 1.33-14.20).Conclusions: Our study demonstrates an imbalance of OxS in drug-free BD, especially BD-D. Lithium reduces the GSH-Px and MDA levels in BD patients. The reduction in MDA levels may predict individual responsiveness to lithium.

Association of DNA methylation in BDNF with escitalopram treatment response in depressed Chinese Han patients.

PURPOSE: The neurotrophin brain-derived neurotrophic factor (BDNF) has been found to be associated with both the pathophysiology of depression and antidepressants response. Gene expression differences were partly mediated by SNP, which might be identified as a predictor of antidepressant response. In the present study, we attempt to identify whether DNA methylation, another factor known to affect gene transcription, might also predict antidepressant response. METHODS: A total of 85 depressed Chinese Han patients were followed-up 8 weeks after initiating escitalopram treatment. Treatment response was assessed by changes in the Hamilton Depression Rating Scale-17 (HAMD-17) score. The Life Events Scale (LES) and the Childhood Trauma Questionnaire (CTQ) were utilized as the assessment of previous life stress. The bisulfate sequencing was used to assess DNA methylation. Four single nucleotide polymorphisms (SNPs) in the BDNF gene were genotyped using PCR-RFLP or PCR sequencing. RESULTS: We identified a DNA methylation predictor (P = 0.006-0.036) and a DNA methylation by LES interaction predictor (OR = 1.442 [1.057-1.968], P = 0.021) of general antidepressant treatment response. Lower mean BDNF DNA methylation was associated with impaired antidepressant response. Furthermore, the present data indicated that age, life stress, and SNPs genotype might be likely related to DNA methylation status. Average DNA methylation of BDNF at baseline was significantly lower than that at endpoint after 8 weeks of escitalopram treatment, which was based only on a subset of cases (n = 44). CONCLUSIONS: Our results suggest that BDNF DNA hypomethylation and its interaction with lower LES score might result in impaired antidepressant treatment response. The pharmacoepigenetic study could eventually help in finding epigenetic biomarkers of antidepressant response.

The interaction of NOS1AP, DISC1, DAOA, and GSK3B confers susceptibility of early-onset schizophrenia in Chinese Han population.

Although many major breakthrough had identificated potential susceptibility genes for schizophrenia, the aetiology of schizophrenia is still unknown. In the present study, we focused on the N-methyl-Daspartate receptors related genes nitric oxide synthase 1 adaptor gene (NOS1AP), disrupted in schizophrenia 1 gene (DISC1), d-amino acid oxidase activator gene (DAOA), and glycogen synthase kinase 3-beta gene (GSK3B). A family-based genetic association study (459 Han Chinese subjects in 153 nuclear families) using 3 single nucleotide polymorphisms in NOS1AP, 2 in DISC1, 1 in DAOA and 1 in GSK3B was conducted. We found rs12742393 have just positive trend with schizophrenia (SCZ) (p=0.07) after FDR correction. NOS1AP mRNA and serum levels were significantly elevated in SCZ patients (p<0.001; p<0.001) compared with healthy control. However, expression Quantitative Trait Loci (eQTL) analysis have demonstrated that rs12742393 genotype were not significantly associated with the NOS1AP mRNA expression. GMDR identified a significant seven-locus interaction model involving (NOS1AP-rs348624, rs12742393, rs1415263, DISC1-rs821633, rs1000731, DAOA-rs2391191and GSK3B- rs6438552) with a good testing accuracy (0.72). Our finding suggested statistically significant role of interaction of NOS1AP, DISC1, DAOA, and GSK3B polymorphisms (NOS1AP-rs348624, rs12742393, rs1415263, DISC1-rs821633, rs1000731, DAOA-rs2391191and GSK3B-rs6438552) in EOS susceptibility.

HTR1A/1B DNA methylation may predict escitalopram treatment response in depressed Chinese Han patients.

BACKGROUND: The serotonin receptor 1A and 1B (HTR1A/1B) gene have been suggested to be involved in the pathogenesis of major depressive disorder (MDD) and the antidepressant treatment response. Gene expression differences were partly mediated by genetic polymorphism and DNA methylation which might be affected by environmental factors. In the present study, we attempt to identify whether HTR1A/1B DNA methylation and genetic polymorphism could predict antidepressant treatment response. METHODS: 85 Chinese Han MDD patients were clinically assessed 8 weeks after of initiating escitalopram treatment for the first time. Antidepressant treatment response was assessed by changes in the Hamilton Depression Rating Scale-17 items (HAMD-17) score. The Life Events Scale (LES) and the Childhood Trauma Questionnaire (CTQ) were utilized as the assessment of previous life stress. The Illumina HiSeq platform was used to assess DNA methylation at 96 CpG sites located in HTR1A and HTR1B gene promoter regions. Six single nucleotide polymorphisms (SNPs) (HTR1A rs6294, rs116985176; HTR1B rs6296, rs6298, rs1228814, rs1778258) were genotype by using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) or PCR sequencing. Regression analyses were used to explore the relationship between DNA methylation and SNP and antidepressant response. RESULTS: We identified two CpG sites predictor of antidepressant treatment response (CpG 668, amplicon HTR1A_1, NC_000005.10, P = 0.025; CpG 1401, amplicon HTR1B_4, NC_000006.12, P = 0.033). The interaction of four CpG sites hypomethylation of HTR1A/1B with high recent stress might result in impaired antidepressant treatment response. What's more, the present data indicated that age, environments and antidepressant treatment might affect DNA methylation status. It was found that DNA methylation status could be influenced by antidepressant treatment in turn. However, HTR1A and HTR1B genotypes did not influence antidepressant response and DNA methylation status. CONCLUSIONS: The results suggest that HTR1A/1B DNA hypomethylation and its interaction with recent life stress might drive impaired antidepressant treatment response. Meanwhile, DNA methylation, in turn, was modified by antidepressant treatment and environments. Our results offer new evidence for the role of epigenetic and genetic polymorphism in pharmacological response to antidepressants.

Association of schizophrenia with the rs821633 polymorphism in the DISC1 gene among Han Chinese.

BACKGROUND: Previous studies report that various single nucleotide polymorphisms (SNP) in the Disrupted-in Schizophrenia 1 (DISC1) gene are closely associated with schizophrenia, but there are no studies that assess the relationship of age of onset of schizophrenia with these SNPs. OBJECTIVE: Investigate the relationship between the rs821633 SNP in the DISC1 gene and the occurrence and age of onset of schizophrenia in Han Chinese. METHODS: We used the TaqMan genotyping technology to examine the rs821633 SNP in the DISC1 gene among 315 individuals who developed schizophrenia prior to 19 years of age ('early-onset'), 407 individuals who developed schizophrenia when 19 years of age or older ('late-onset'), and 482 healthy controls. We used survival analyses to investigate the relationship between the rs821633(C) risk allele and the age of onset of schizophrenia. RESULTS: Compared to the prevalence in healthy controls, the prevalence of the C/C genotype of rs821633 and of the C allele in rs821633 were significantly greater in individuals with early-onset schizophrenia (X (2)=7.17, df=1, p=0.007; X (2)=7.20, df=2, p=0.032) and significantly greater in individuals with late-onset schizophrenia (X (2)=5.36, df=1, p=0.022; X (2)=6.58, df=2, p=0.041). However, there were no significant differences in the prevalence of the C/C genotype or the C allele between individuals with early-onset and late-onset schizophrenia. Kaplan-Meier survival analyses found no significant association between the rs821633(C) risk allele and age of onset in schizophrenia. CONCLUSION: We confirm the association of polymorphism in the rs821633 SNP in the DISC1 gene with schizophrenia among Han Chinese, but we found no association between the rs821633(C) risk allele and the age of onset in individuals with schizophrenia.