New Late Pleistocene age for the Homo sapiens skeleton from Liujiang southern China.

The emergence of Homo sapiens in Eastern Asia is a topic of significant research interest. However, well-preserved human fossils in secure, dateable contexts in this region are extremely rare, and often the subject of intense debate owing to stratigraphic and geochronological problems. Tongtianyan cave, in Liujiang District of Liuzhou City, southern China is one of the most important fossils finds of H. sapiens, though its age has been debated, with chronometric dates ranging from the late Middle Pleistocene to the early Late Pleistocene. Here we provide new age estimates and revised provenience information for the Liujiang human fossils, which represent one of the most complete fossil skeletons of H. sapiens in China. U-series dating on the human fossils and radiocarbon and optically stimulated luminescence dating on the fossil-bearing sediments provided ages ranging from ~33,000 to 23,000 years ago (ka). The revised age estimates correspond with the dates of other human fossils in northern China, at Tianyuan Cave (~40.8-38.1 ka) and Zhoukoudian Upper Cave (39.0-36.3 ka), indicating the geographically widespread presence of H. sapiens across Eastern Asia in the Late Pleistocene, which is significant for better understanding human dispersals and adaptations in the region.

The interaction of RELN-DNMT genes involving in neurotrophin signaling pathway contributes to schizophrenia susceptibility.

OBJECTIVE: Schizophrenia belongs to a severe mental illness with complicated clinical presentations, an ill-defined pathogenesis, and no known cause. Many genetic studies imply that polygenic interaction is important in the development of schizophrenia. The main mechanism of the RELN-BDNF-CREB-DNMT signaling pathway in neurodevelopment involves RELN, brain-derived neurotrophic factor (BDNF), transcription factor cyclic adenosine monophosphate response element binding protein (CREB), DNA methyltransferase 1 (DNMT1), as well as DNA methyltransferase 3B (DNMT3B). An early case-control research on 15 polymorphisms in the RELN, CREB, BDNF, DNMT1, and DNMT3B genes was done. A single gene variation has little effect on the pathogenesis of schizophrenia, but the combination of intergenic variation loci has a bigger impact because schizophrenia is a complex polygenic disorder. The objective of the current study sought to explore the impact of genetic interactions between RELN, BDNF, CREB, DNMT1, and DNMT3B on schizophrenia in order to further highlight the genetic factors influencing the risk of schizophrenia. METHODS: Taking the case-control study design, with the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) to be the evaluation norm, 134 individuals suffering from schizophrenia hospitalized in the Third People's Hospital of Zhongshan City within January 2018 to April 2020 (case group) were selected, and 64 healthy individuals (control group) from the same geographical area had been chosen as well. MassArray identified DNMT1 gene single nucleotide polymorphisms (rs2114724 and rs2228611) and DNMT3B gene SNPs (rs2424932, rs1569686, rs6119954, and rs2424908). Using the generalized multifactor dimensionality reduction (GMDR), the RELN-BDNF-CREB-DNMT pathway's gene interactions were examined for their impact on schizophrenia. RESULTS: GMDR analysis showed that the three-order interaction model RELN (rs2073559, rs2229864)-DNMT3B (rs2424908) was the optimal model (p = 0.001), with the consistency of cross-validation of 10/10 and the test accuracy of 0.8711. CONCLUSION: The interaction between the RELN (rs2073559, rs2229864)-DNMT3B (rs2424908) may be related to schizophrenia, and large sample sizes should be verified in different population.

Transition of allele-specific DNA hydroxymethylation at regulatory loci is associated with phenotypic variation in monozygotic twins discordant for psychiatric disorders.

BACKGROUND: Major psychiatric disorders such as schizophrenia (SCZ) and bipolar disorder (BPD) are complex genetic mental illnesses. Their non-Mendelian features, such as those observed in monozygotic twins discordant for SCZ or BPD, are likely complicated by environmental modifiers of genetic effects. 5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark in gene regulation, and whether it is linked to genetic variants that contribute to non-Mendelian features remains largely unexplored. METHODS: We combined the 5hmC-selective chemical labeling method (5hmC-seq) and whole-genome sequencing (WGS) analysis of peripheral blood DNA obtained from monozygotic (MZ) twins discordant for SCZ or BPD to identify allelic imbalances in hydroxymethylome maps, and examined association of allele-specific hydroxymethylation (AShM) transition with disease susceptibility based on Bayes factors (BF) derived from the Bayesian generalized additive linear mixed model. We then performed multi-omics integrative analysis to determine the molecular pathogenic basis of those AShM sites. We finally employed luciferase reporter, CRISPR/Cas9 technology, electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), PCR, FM4-64 imaging analysis, and RNA sequencing to validate the function of interested AShM sites in the human neuroblastoma SK-N-SH cells and human embryonic kidney 293T (HEK293T) cells. RESULTS: We identified thousands of genetic variants associated with AShM imbalances that exhibited phenotypic variation-associated AShM changes at regulatory loci. These AShM marks showed plausible associations with SCZ or BPD based on their effects on interactions among transcription factors (TFs), DNA methylation levels, or other epigenomic marks and thus contributed to dysregulated gene expression, which ultimately increased disease susceptibility. We then validated that competitive binding of POU3F2 on the alternative allele at the AShM site rs4558409 (G/T) in PLLP-enhanced PLLP expression, while the hydroxymethylated alternative allele, which alleviated the POU3F2 binding activity at the rs4558409 site, might be associated with the downregulated PLLP expression observed in BPD or SCZ. Moreover, disruption of rs4558409 promoted neural development and vesicle trafficking. CONCLUSION: Our study provides a powerful strategy for prioritizing regulatory risk variants and contributes to our understanding of the interplay between genetic and epigenetic factors in mediating SCZ or BPD susceptibility.

DNMT1 SNPs (rs2114724 and rs2228611) associated with positive symptoms in Chinese patients with schizophrenia.

OBJECTIVE: Schizophrenia is a serious mental disorder with complex clinical manifestations, while its pathophysiological mechanism is not fully understood. Accumulated evidence suggested the alteration in epigenetic pathway was associated with clinical features and brain dysfunctions in schizophrenia. DNA methyltransferases (DNMTs), a key enzyme for DNA methylation, are related to the development of schizophrenia, whereas the current research evidence is not sufficient. The aim of study was to explore the effects of gene polymorphisms of DNMTs on the susceptibility and symptoms of schizophrenia. METHODS: The study was case-control study that designed and employed the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) as the diagnostic standard. 134 hospitalized patients with schizophrenia in the Third People's Hospital of Zhongshan City from January 2018 to April 2020 (Case group) as well as 64 healthy controls (Control group) from the same region were involved. Single nucleotide polymorphisms (SNPs) of DNMT1 genes (r s2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) were determined with massARRAY. Linkage disequilibrium analysis and haplotype analysis were performed, and genotype and allele frequencies were compared. The Hardy-Weinberg equilibrium was tested by the Chi-square test in SPSS software (version 20.0, SPSS Inc., USA). The severity of clinical symptoms was assessed by the Positive and Negative Syndrome Scale (PANSS). The correlation between DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs2424932, rs1569686, rs6119954 and rs2424908) and clinical features was analyzed. RESULTS: There were no significant differences in genotype, allele frequency and haplotype of DNMT1 genes (rs 2114724 and rs 2228611) and DNMT3B genes (rs 2424932, rs 1569686, rs 6119954 and rs 2424908) between the case and healthy control group. There were significant differences in the PANSS total positive symptom scores, P3 (hallucinatory behavior), P6 (suspicious/persecution), G7 (motor retardation), and G15 (preoccupation) in patients with different DNMT1 gene rs 2114724 and rs 2228611 genotypes. The linkage disequilibrium analysis of gene polymorphic loci revealed that rs 2114724-rs 2228611 was complete linkage disequilibrium, and rs 1569686-rs 2424908, rs 2424932-rs 1569696 and rs 2424932-rs 2424908 were strongly linkage disequilibrium. CONCLUSION: The polymorphisms alteration in genetic pathway may be associated with development of specific clinical features in schizophrenia.

Association between DRD2/ANKK1 rs1800497 C > T polymorphism and post-traumatic stress disorder susceptibility: a multivariate meta-analysis.

Background: Previous studies have suggested that the DRD2/ANKK1 rs1800497 C > T polymorphism plays a critical role in the risk of post-traumatic stress disorder (PTSD). However, published data are inconsistent or even contradictory. Therefore, we conducted a meta-analysis to explore the underlying correlation between the rs1800497 C > T polymorphism and PTSD risk. Materials and methods: A total of five online databases were searched, and all related studies were reviewed up to 1 October 2022. Critical information was extracted, and quality assessment was conducted for all included studies. Multivariate meta-analyses were performed for the genetic model choice, and the odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were calculated to examine the statistical power of the genetic models. In addition, heterogeneity, sensitivity, cumulative analysis, and publication bias were analyzed to guarantee statistical power. Result: Overall, 12 observational studies involving 5,515 subjects were included and analyzed in this meta-analysis. Multivariate analysis indicated that a co-dominant genetic model was most likely the best choice. Pooled results revealed an elevated PTSD risk in mutated homozygote TT carriers in the general population (TT vs. CC: OR = 1.73, 95% CI = 1.14-2.62, P = 0.01, I2 = 58.9%) and other specific subgroups. Moreover, similar results were observed in other genetic models using univariate analysis. Conclusion: Current evidence suggests that the DRD2/ANKK1 rs1800497 C > T polymorphism may contribute to PTSD susceptibility.

The effect of social exclusion on intertemporal choice in suicide attempters: A preliminary experimental study.

BACKGROUND: Suicide-related theories and a growing body of evidence suggest that suicidal patients may have a tendency toward "short-sightedness"-the preference for immediate gratification when making intertemporal choice-and that social exclusion may exacerbate this tendency in suicidal patients. The present study examined the intertemporal choice performance of suicide attempters under conditions of social exclusion in a sample of affective disorder patients. METHODS: A total of 64 affective disorder patients (22 non-suicidal patients, 24 single-suicide attempters and 18 multiple-suicide attempters) completed an intertemporal choice task in an exclusion or a non-exclusion condition. Social exclusion was manipulated using the Cyberball paradigm. RESULTS: Non-suicidal patients and single-suicide attempters both exhibited an exaggerated preference for immediate rewards in the exclusion condition compared with the non-exclusion condition; in contrast, the multiple-suicide attempters appeared relatively indifferent to the social exclusion, exhibiting virtually identical preferences for immediate rewards in both the exclusion and non-exclusion conditions. In addition, the multiple-suicide attempters exhibited an exaggerated preference for immediate rewards compared with non-suicidal patients and single-suicide attempters in the non-exclusion condition, while the three groups did not differ in the exclusion condition. CONCLUSIONS: Affective disorder patients with a single or no suicide attempts are more short-sighted after being excluded, while those with multiple suicide attempts appeared consistent short-sightedness in both exclusion and non-exclusion conditions. The study provides preliminary evidence of the role of disadvantageous intertemporal choice in the suicidal process. Future research replicate and extend these findings could have implications for suicide prevention and intervention.

Loss of schizophrenia-related miR-501-3p in mice impairs sociability and memory by enhancing mGluR5-mediated glutamatergic transmission.

Schizophrenia is a polygenetic disease, the heterogeneity of which is likely complicated by epigenetic modifications yet to be elucidated. Here, we performed transcriptomic analysis of peripheral blood RNA from monozygotic twins discordant for schizophrenia and identified a schizophrenia-associated down-regulated microRNA, miR-501-3p. We showed that the loss of miR-501-3p in germline knockout (KO) male mice resulted in dendritic structure defects, glutamatergic transmission enhancement, and sociability, memory, and sensorimotor gating disruptions, which were attenuated when miR-501 expression was conditionally restored in the nervous system. Combining the results of proteomic analyses with the known genes linked to schizophrenia revealed that metabotropic glutamate receptor 5 (mGluR5) was one of the miR-501-3p targets and was elevated in vivo upon loss of miR-501. Treatment with the mGluR5 negative allosteric modulator 3-2((-methyl-4-thiazolyl) ethynyl) pyridine or the N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonopentanoic acid ameliorated the deficits observed in Mir501-KO mice. The epigenetic and pathophysiological mechanism that links miR-501-3p to the modulation of glutamatergic transmission provides etiological implications for schizophrenia.

A Polymorphism in the BDNF Gene (rs11030101) is Associated With Negative Symptoms in Chinese Han Patients With Schizophrenia.

Objective: This study aimed to investigate the association between brain-derived neurotrophic factor (BDNF) and cyclic adenosine monophosphate response element binding protein (CREB) gene polymorphisms and schizophrenia. Methods: This study used a case-control design, and diagnoses were made based on the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition criteria. One hundred and thirty-four patients with schizophrenia were recruited from the Third People's Hospital of Zhongshan City from January 2018 to April 2020. Sixty-four healthy controls were recruited from the same region. Genotypes at the BDNF gene single nucleotide polymorphisms rs11030101, rs2030324, and rs6265 and the CREB gene single nucleotide polymorphisms rs6740584 and rs2551640 were determined using a MassARRAY mass spectrometer. Linkage disequilibrium and haplotype analyses were performed, and genotype and allele frequencies were compared between groups. The positive and negative symptom scale (PANSS) was used to evaluate the association between the BDNF and CREB gene polymorphisms and schizophrenic symptoms. Results: There was no significant difference in genotype or allele frequencies for rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 between schizophrenic patients and controls (p > 0.05). In addition, there were no significant differences in rs11030101, rs2030324, rs6265, rs6740584, or rs2551640 genotype frequencies between the two groups in the dominant, recessive, or over-dominant models (p > 0.05). Three loci in the BDNF gene and two loci in the CREB gene were in a state of strong linkage disequilibrium. The frequency of haplotype AAC (rs11030101/rs2030324/rs626), composed of three loci in the BDNF gene, was significantly increased in schizophrenic patients compared with control subjects. There were significant differences in the subscores of PANSSS for negative symptoms, in patients with different rs11030101 genotypes of the BDNF gene (p < 0.05). There was also significant differences in the PANSS scores for the general symptom G12 (judgment and lack of insight) in patients with different rs6265 genotypes of the BDNF gene (p < 0.05). Conclusion: The BDNF gene rs11030101/rs2030324/rs6265 AAC haplotype was potentially associated with an increased risk of schizophrenia. In addition, genotypes at the rs11030101 and rs6265 loci may affect the negative symptoms and general symptoms of schizophrenic patients, respectively.

LncRNA RP5-998N21.4 promotes immune defense through upregulation of IFIT2 and IFIT3 in schizophrenia.

Schizophrenia is a complex polygenic disease that is affected by genetic, developmental, and environmental factors. Accumulating evidence indicates that environmental factors such as maternal infection and excessive prenatal neuroinflammation may contribute to the onset of schizophrenia by affecting epigenetic modification. We recently identified a schizophrenia-associated upregulated long noncoding RNA (lncRNA) RP5-998N21.4 by transcriptomic analysis of monozygotic twins discordant for schizophrenia. Importantly, we found that genes coexpressed with RP5-998N21.4 were enriched in immune defense-related biological processes in twin subjects and in RP5-998N21.4-overexpressing (OE) SK-N-SH cell lines. We then identified two genes encoding an interferon-induced protein with tetratricopeptide repeat (IFIT) 2 and 3, which play an important role in immune defense, as potential targets of RP5-998N21.4 by integrative analysis of RP5-998N21.4OE-induced differentially expressed genes (DEGs) in SK-N-SH cells and RP5-998N21.4-coexpressed schizophrenia-associated DEGs from twin subjects. We further demonstrated that RP5-998N21.4 positively regulates the transcription of IFIT2 and IFIT3 by binding to their promoter regions and affecting their histone modifications. In addition, as a general nuclear coactivator, RMB14 (encoding RNA binding motif protein 14) was identified to facilitate the regulatory role of RP5-998N21.4 in IFIT2 and IFIT3 transcription. Finally, we observed that RP5-998N21.4OE can enhance IFIT2- and IFIT3-mediated immune defense responses through activation of signal transducer and activator of transcription 1 (STAT1) signaling pathway in U251 astrocytoma cells under treatment with the viral mimetic polyinosinic: polycytidylic acid (poly I:C). Taken together, our findings suggest that lncRNA RP5-998N21.4 is a critical regulator of immune defense, providing etiological and therapeutic implications for schizophrenia.

Naloxone Alleviate the Severity of Delirium in Hospitalized Patients With Parkinsonism: Three Case Reports.

Purpose: Delirium is common in geriatric with Parkinson's disease (PD). Treatments for delirium have generally been neuroleptics; however, antipsychotics have potential effect to block striatal dopamine D2 receptors and worsen symptom of parkinsonism. We explored whether naloxone can alleviate delirium in PD and other forms of parkinsonism. Patients and Methods: Patients with parkinsonism who met the delirium criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) received naloxone infusions once or twice daily. Treatment effects were evaluated by the delirium rating scale-revised 98 (DRS-R98), including non-cognitive and cognitive subscales; the Richmond agitation-sedation scale (RASS); and the mini mental status examination (MMSE). Results: Two patients with primary parkinsonism, one with vascular PD were observed. The daily dose of naloxone was 2.08 ± 0.64 mg (range: 1-4 mg). Medication time last from 1 h to 7 days without side effects observed. Following with naloxone infusions, DRS-R98 scores decreased within 12 h and MMSE scores increased. The psychotic symptoms, disorientation, and attention deficits were alleviated significantly, while RASS scores decreased with naloxone treatment. Conclusion: Naloxone alleviated psychotic symptoms, improved cognitive dysfunction, and irritability in patients with delirium in the context of PD. The preliminary findings point out that the opioid system may be involved in the pathophysiology of delirium, which may be one of potential treat targets for delirium of PD.

Allele-specific DNA methylation maps in monozygotic twins discordant for psychiatric disorders reveal that disease-associated switching at the EIPR1 regulatory loci modulates neural function.

The non-Mendelian features of phenotypic variations within monozygotic twins are likely complicated by environmental modifiers of genetic effects that have yet to be elucidated. Here, we performed methylome and genome analyses of blood DNA from psychiatric disorder-discordant monozygotic twins to study how allele-specific methylation (ASM) mediates phenotypic variations. We identified that thousands of genetic variants with ASM imbalances exhibit phenotypic variation-associated switching at regulatory loci. These ASMs have plausible causal associations with psychiatric disorders through effects on interactions between transcription factors, DNA methylations, and other epigenomic markers and then contribute to dysregulated gene expression, which eventually increases disease susceptibility. Moreover, we also experimentally validated the model that the rs4854158 alternative C allele at an ASM switching regulatory locus of EIPR1 encoding endosome-associated recycling protein-interacting protein 1, is associated with demethylation and higher RNA expression and shows lower TF binding affinities in unaffected controls. An epigenetic ASM switching induces C allele hypermethylation and then recruits repressive Polycomb repressive complex 2 (PRC2), reinforces trimethylation of lysine 27 on histone 3 and inhibits its transcriptional activity, thus leading to downregulation of EIPR1 in schizophrenia. Moreover, disruption of rs4854158 induces gain of EIPR1 function and promotes neural development and vesicle trafficking. Our study provides a powerful framework for identifying regulatory risk variants and contributes to our understanding of the interplay between genetic and epigenetic variants in mediating psychiatric disorder susceptibility.

LncRNA-AC006129.1 reactivates a SOCS3-mediated anti-inflammatory response through DNA methylation-mediated CIC downregulation in schizophrenia.

Schizophrenia is a complex genetic disorder, the non-Mendelian features of which are likely complicated by epigenetic factors yet to be elucidated. Here, we performed RNA sequencing of peripheral blood RNA from monozygotic twins discordant for schizophrenia, and identified a schizophrenia-associated upregulated long noncoding RNA (lncRNA, AC006129.1) that participates in the inflammatory response by enhancing SOCS3 and CASP1 expression in schizophrenia patients and further validated this finding in AC006129.1-overexpressing mice showing schizophrenia-related abnormal behaviors. We find that AC006129.1 binds to the promoter region of the transcriptional repressor Capicua (CIC), facilitates the interactions of DNA methyltransferases with the CIC promoter, and promotes DNA methylation-mediated CIC downregulation, thereby ameliorating CIC-induced SOCS3 and CASP1 repression. Derepression of SOCS3 enhances the anti-inflammatory response by inhibiting JAK/STAT-signaling activation. Our findings reveal an epigenetic mechanism with etiological and therapeutic implications for schizophrenia.

Hypomethylation of LINE-1 elements in schizophrenia and bipolar disorder.

Schizophrenia (SCZ) and bipolar disorder (BPD) are severe mental illnesses with evidence of significant genetic and environmental etiological elements in their complex etiologies. 5'-Methylcytosine is the main epigenetic DNA modification that mediates the interplay between genetic and environmental components. In humans, most 5'-methylcytosine modifications are observed in CpG-rich regions within the long interspersed nuclear element (LINE-1). LINE-1 is a mobile retrotransposon that comprises ∼17% of the human genome, and its methylation levels are highly correlated with global DNA methylation levels. LINE-1 insertions are also reported to be mental illnesses-associated genomic risk factors. To examine the LINE-1 methylation levels in SCZ and BPD, this study employed a bisulfite conversion-specific one-label extension (BS-OLE) method to detect the methylation levels at three CpG sites (S1, S2 and S3) of LINE-1 in peripheral blood DNA from a Han Chinese cohort composed of 92 SCZ patients, 99 BPD patients and 92 controls (CON). The results showed a decreased S1 methylation level in SCZ, decreased S2 methylation level in BPD and decreased S3 methylation levels in both SCZ and BPD relative to those of the CON. A female-dependent positive correlation of the S3 methylation level with age in CON became non-significant in both SCZ and BPD. These findings demonstrated that LINE-1 methylation varied with development and disease status. The roles of LINE-1 methylation in the pathogenesis of SCZ and BPD remain to be elucidated.

Variation in global DNA hydroxymethylation with age associated with schizophrenia.

To improve understanding of DNA hydroxymethylation (5hmC) and methylation (5mC) in the development of schizophrenia, this study examined global 5hmC and 5mC levels in peripheral blood DNA of 264 patients with schizophrenia and 221 controls and observed increased 5mC levels in the patients and increased 5hmC levels in male patients but decreased levels in female patients as compared with the controls. The 5mC level displayed a gender-dependent positive correlation with age and the 5hmC level displayed a correlation with age positively in controls but negatively in patients, and their role in the pathogenesis of schizophrenia remains to be elucidated.

[An association study of COMT gene polymorphisms with schizophrenia].

OBJECTIVE: To investigate the association between 8 polymorphisms in the catechol-O-methyl transferase gene (COMT) and schizophrenia in Yuedong-Chaoshan region of China. METHODS: Eight single nucleotide polymorphism (SNPs), namely rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267, rs6269 and rs4633, in the COMT gene were genotyped in 279 schizophrenia patients and 100 healthy controls. RESULTS: There was no significant difference between any single SNP and schizophrenia. However, association might exist between haplotypes (G)-G-A-A [(rs4680)-rs165599-rs2075507-rs6269] and A-A-C-(G) [rs2075507-rs6269-rs4633-(rs6267)] and schizophrenia. CONCLUSION: In the population of Yuedong region of China, the eight SNPs (rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267, rs6269 and rs4633) in the COMT gene are unlikely to play a major role in the susceptibility to schizophrenia. There might be protective haplotypes in the COMT gene against schizophrenia.

Neuroleptic effects on P50 sensory gating in patients with first-episode never-medicated schizophrenia.

Sensory gating deficit, as reflected by P50 suppression, has been demonstrated in schizophrenia. Despite extensive evidence of the irreversible effects of typical neuroleptics on this deficit, recent studies of atypical neuroleptics have produced inconsistent findings on the reversibility of P50 suppression in schizophrenia. As the majority of these studies were limited by either their cross-sectional design or the recruitment of patients on multiple medications, the current study was designed to examine the effects of different neuroleptic medications on the P50 sensory gating index in patients with first-episode, never-medicated schizophrenia. P50-evoked potential recordings were obtained from 62 normal controls when they entered the study and from 65 patients with first-episode, never-medicated schizophrenia at baseline and after six weeks of different neuroleptic treatments (sulpiride [n=24], risperidone [n=24] and clozapine [n=17]). The first-episode, never-medicated schizophrenia patients had impaired sensory gating relative to the normal controls (mean=94.19% [SD=61.31%] versus mean=41.22% [SD=33.82%]). The test amplitude S2 was significantly higher in the schizophrenia patients than in the normal controls. The conditioning amplitude S1 and the positive symptom scores were related to the P50 gating ratios in schizophrenia at baseline. There was no change in P50 sensory gating (P>0.10) and a significant improvement in the clinical ratings (P>0.10) after six-week neuroleptic treatment for schizophrenia. P50 sensory gating was not significant for the patients who received sulpiride, risperidone or clozapine at baseline (F=1.074, df=2, 62, P=0.348) or at endpoint (F=0.441, df=2, 62, p=0.646). Our findings indicate that there is P50 sensory gating impairment in first-episode, never-medicated schizophrenia and that treatment with typical and atypical antipsychotics has no significant impact on such gating in this illness.

[The transmission disequilibrium analysis between neuronal nicotinic acetylcholine receptor alpha 7 subunit gene polymorphisms and schizophrenia].

OBJECTIVE: To investigate the association between neuronal nicotinic acetylcholine receptor alpha 7 subunit (CHRNA7) gene and schizophrenia. METHODS: The three polymorphisms rs2337980, rs1909884, rs883473 in CHRNA7 gene were detected based on PCR and polyacrylamide gel microarray in 129 schizophrenic trios. The results of genotyping were analyzed by haplotype relative risk analysis based on haplotype(HHRR), transmission disequilibrium test(TDT) and hyplotype analysis. RESULTS: (1)The HHRR analysis suggested that there was significant differences in rs2337980 allele frequencies between schizophrenia group and dummy control group(P= 0.017); (2)In TDT test, there may be transmission disequilibrium between rs2337980 and schizophrenia, the heterozygous parents excessively transferred the C allele to patients (P= 0.021); (3)The haplotype between rs2337980 and rs1909884 as well as the hyplotype among rs2337980, rs1909884 and rs883473 may have significant association with schizophrenia (global P= 0.034; global P= 0.027), the T-C and T-C-T hyplotype may have transmission disequilibrium with schizophrenia. CONCLUSION: There may be association between CHRNA7 gene polymorphisms and schizophrenia, the variant allele T in rs2337980 may have a protective effect to schizophrenia.