Comparative mitochondrial genomics of Terniopsis yongtaiensis in Malpighiales: structural, sequential, and phylogenetic perspectives.

BACKGROUND: Terniopsis yongtaiensis, a member of the Podostemaceae family, is an aquatic flowering plant displaying remarkable adaptive traits that enable survival in submerged, turbulent habitats. Despite the progressive expansion of chloroplast genomic information within this family, mitochondrial genome sequences have yet to be reported. RESULTS: In current study, the mitochondrial genome of the T. yongtaiensis was characterized by a circular genome of 426,928 bp encoding 31 protein-coding genes (PCGs), 18 tRNAs, and 3 rRNA genes. Our comprehensive analysis focused on gene content, repeat sequences, RNA editing processes, intracellular gene transfer, phylogeny, and codon usage bias. Numerous repeat sequences were identified, including 130 simple sequence repeats, 22 tandem repeats, and 220 dispersed repeats. Phylogenetic analysis positioned T. yongtaiensis (Podostemaceae) within the Malpighiales order, showing a close relationship with the Calophyllaceae family, which was consistent with the APG IV classification. A comparative analysis with nine other Malpighiales species revealed both variable and conserved regions, providing insights into the genomic evolution within this order. Notably, the GC content of T. yongtaiensis was distinctively lower compared to other Malpighilales, primarily due to variations in non-coding regions and specific protein-coding genes, particularly the nad genes. Remarkably, the number of RNA editing sites was low (276), distributed unevenly across 27 PCGs. The dN/dS analysis showed only the ccmB gene of T. yongtaiensis was positively selected, which plays a crucial role in cytochrome c biosynthesis. Additionally, there were 13 gene-containing homologous regions between the mitochondrial and chloroplast genomes of T. yongtaiensis, suggesting the gene transfer events between these organellar genomes. CONCLUSIONS: This study assembled and annotated the first mitochondrial genome of the Podostemaceae family. The comparison results of mitochondrial gene composition, GC content, and RNA editing sites provided novel insights into the adaptive traits and genetic reprogramming of this aquatic eudicot group and offered a foundation for future research on the genomic evolution and adaptive mechanisms of Podostemaceae and related plant families in the Malpighiales order.

Expression of AhATL1, an ABA Transport Factor Gene from Peanut, Is Affected by Altered Memory Gene Expression Patterns and Increased Tolerance to Drought Stress in Arabidopsis.

Arachis hypogaea abscisic acid transporter like-1 (AhATL1) modulates abscisic acid (ABA) sensitivity by specifically influencing the importing of ABA into cells, and is a key player in plant stress responses. However, there is limited information on ABA transporters in crops. In this study, we found that the level of AhATL1 expression and AhATL1 distribution increased more rapidly in the second drought (D2) compared with in the first drought (D1). Compared with the first recovery (R1), the AhATL1 expression level and ABA content remained at a higher level during the second recovery (R2). The heterologous overexpression of AhATL1 in Arabidopsis changed the expression pattern of certain memory genes and changed the post response gene type into the memory gene type. Regarding the proline and water content of Col (Arabidopsis thaliana L. Heynh., Col-0), atabcg22, and AhATL1-OX during drought training, the second drought (D2) was more severe than the first drought (D1), which was more conducive to maintaining the cell osmotic balance and resisting drought. In summary, drought stress memory resulted in a rapid increase in the AhATL1 expression and AhATL1 distribution level, and then raised the endogenous ABA content and changed the post response gene type into the memory gene type, which enhanced the drought resistance and recovery ability.

Neurotensin receptor 1 gene polymorphisms are associated with personality traits in healthy Chinese individuals.

AIMS: Neurotensin receptor 1 (NTR1) is a neurotensin (NT) receptor subtype with a high affinity for NT. NT and NTR1 signaling are involved in modulating the dopamine system. Individual variations in the dopamine system have been demonstrated to determine certain dimensions of personality, but no studies have thus far investigated the involvement of the NTR1 in the biological determination of personality. We therefore examined this link in a Chinese Han population. METHODS: We genotyped 3 single nucleotide polymorphisms (SNPs) (rs6090453C/G, rs6011914C/G, and rs2427422A/G) of the NTR1 gene and collected the data about the personality traits of novelty seeking (NS), harm avoidance (HA), and reward dependence (RD), as well as their subscales (measured by the Tridimensional Personality Questionnaire), in 575 healthy Chinese Han subjects. Then we examined the association between the 3 NTR1 gene polymorphisms and each personality trait. RESULTS: There were significant differences in the HA2, HA3 and RD1 scores between rs6090453C/G genotypes (F = 3.425, 5.651, 4.054, p = 0.033, 0.004, 0.018, respectively), in the HA2 and total RD scores between rs6011914C/G genotypes (F = 4.080, 3.712, p = 0.017, 0.025, respectively), and in the total RD (χ(2) = 7.301, p = 0.026) and RD3 (F = 4.119, p = 0.017) scores between the rs2427422A/G genotypes. There were significant male-specific differences in the RD1 scores between the rs6090453C/G genotypes (F = 3.334, p = 0.037), in the total HA (F = 3.043, p = 0.049), HA2 (F = 4.472, p = 0.012) and RD3 (χ(2) = 6.997, p = 0.030) scores between the rs6011914C/G genotypes, and in the HA2 (F = 3.177, p = 0.043), total RD (χ(2) = 7.032, p = 0.030), and RD3 (F = 4.563, p = 0.011) scores between the rs2427422A/G genotypes. We also demonstrated a significant female-specific difference in the total RD scores between the rs6011914C/G genotypes (F = 3.677, p = 0.026). There was no significant difference in the total NS and subscale scores between the genotypes of all 3 SNPs (all p > 0.05). CONCLUSIONS: The variations in the NTR1 gene were involved in the biological mechanisms of HA and RD personality traits; however, the effect is influenced by gender.

Preventive and therapeutic effect of vitamin D on depression-like behavior in a mouse adolescent depression model and its association with BDNF protein expression.

Introduction: Previous studies in different populations have shown that vitamin D supplementation may reduce depression levels. In adolescents, vitamin D deficiency has been identified as a factor contributing to the onset of depression. This study aimed to establish a model of adolescent depression in mice by using the scientific unpredictable chronic mild stress (UCMS) model and to preliminarily evaluate the effect of vitamin D on the occurrence and development of depression and whether it is related to the protein expression of the BDNF pathway. Methods: The UCMS method was used to establish a model of adolescent depression in 4-week-old C57BL/6 male mice, randomly divided into five groups: Control group, Stress group, Stress+ low-dose group, Stress+ medium-dose group, Stress+ high-dose group. At the same time as chronic stress, the administration groups were given intramuscular injections of different doses of vitamin D. After 8 weeks, behavioral tests, including the forced swimming test (FST) and open field test (OFT), were performed on each group of mice, along with recording of indicators, blood vitamin D level detection, and brain tissue western blot analysis. Results: The results showed a significant difference in vitamin D levels among mice in different groups after 8 weeks (P=0.012). The results of behavioral testing showed a significant difference in the static time of forced swimming among the groups (P<0.001). Compared with the UCMS group, the static time of mice with vitamin D injection was significantly reduced (P<0.001). The total number of times mice entered the central area, the total distance of movement, and the time spent in the central area significantly increased after vitamin D injection compared with the UCMS-only group (all P<0.001). There was no significant difference in the expression of BDNF in the brain tissues of experimental mice (P>0.05). Discussion: In conclusion, in the mouse adolescent depression model, appropriate vitamin D supplementation can reduce the occurrence of stress-induced depression. Furthermore, vitamin D deficiency may also serve as a potential risk factor for depression.

Finite element analysis of the use of two new types of internal fixation for acetabular fractures.

BACKGROUND: Both-column fracture is a common type of acetabular fracture and is sometimes accompanied by a comminuted fracture of the quadrilateral area. Such fractures are difficult to anatomically reduce and securely fix. In this study, the authors compared the application value and mechanical properties of the Bespoke 3D-printed titanium alloy plates and Union Plate in acetabular both-column fractures. METHODS: A both-column fracture model of the acetabulum was established, and the Bespoke 3D-printed titanium alloy plates, Union Plate and a common reconstruction plate were used for fixation. External loads were applied to the model at different angles, and the effects on the plates and the stress and displacement of the screws were determined. RESULTS: Under different states of hip joint activity, the maximum stress experienced by the Bespoke 3D-printed titanium alloy plates and Union Plate was significantly smaller than the maximum stress experienced by the common reconstruction plate. The Bespoke 3D-printed titanium alloy plates experienced the lowest maximum stress under different hip joint motions. There was no statistically significant difference between the maximum displacement of the Bespoke 3D-printed titanium alloy plates and Union Plate and that of the common reconstructed plate. CONCLUSIONS: The design of the Bespoke 3D-printed titanium alloy plates imparts a smaller maximum stress and better mechanical properties when repairing acetabular both-column fractures.

Efficacy and Safety of Five Broad-Spectrum Antiseizure Medications for Adjunctive Treatment of Refractory Epilepsy: A Systematic Review and Network Meta-analysis.

BACKGROUND: Overall, up to one-third of epilepsy patients have drug-resistant epilepsy. However, there was previously no meta-analysis to support the guidelines for broad-spectrum antiseizure medication selection for the adjunctive treatment of refractory epilepsy. In the present meta-analysis, we assessed the efficacy and safety of three second-generation broad-spectrum antiseizure medications, lamotrigine (LTG), levetiracetam (LEV), and topiramate (TPM), and two third-generation broad-spectrum antiseizure medications, perampanel (PER) and lacosamide (LCM), for the adjunctive treatment of refractory epilepsy. METHODS: We systematically searched PubMed, Embase, and CENTRAL from inception to July 15, 2022. The studies included in the meta-analysis were required to meet the following criteria: (1) be randomized, double-blind clinical trials; (2) include patients aged >2 years with a clinical diagnosis of drug-resistant epilepsy; (3) have at least 8 weeks for the treatment period excluding the titration phase; and (4) report the outcomes of seizure response, seizure freedom and the withdrawal rate due to treatment-emergent adverse effects. Data were extracted, and the risk of bias for each study was assessed by two authors independently using RoB2 tools. We performed the network meta-analysis for each outcome through a group of programs in the mvmeta and network packages in Stata. Relative odds ratios with 95% confidence intervals were calculated as the result of the analyses. The surface under the cumulative ranking curve (SUCRA) and mean ranks were used to rank these treatments. RESULTS: Forty-two randomized controlled trials (RCTs) (LTG-placebo: n = 6, LEV-placebo: n = 13, TPM-placebo: n = 9, PER-placebo: n = 6, LCM-placebo: n = 7, LEV-TPM: n = 1) with 10257 participants (LTG = 569, LEV = 1626, TPM = 701, PER = 1734, LCM = 1908, placebo = 3719) were included. Levetiracetam had subequal efficacy in 50 % seizure frequency reduction to TPM [odds ratio (OR) 1.00, 95% confidence interval (CI) 0.73-1.38], and LEV had a higher rate of ≥ 50% seizure frequency reduction than LCM (OR 1.49, 95% CI 1.11-2.01) and PER (OR 1.68, 95% CI 1.24-2.29). Levetiracetam was also related to a higher proportion of seizure freedom participants than TPM (OR 1.87, 95% CI 1.20-2.89), PER (OR 2.23, 95% CI 1.12-4.43), and LCM (OR 2.97, 95% CI 1.46-6.05). In addition, LEV was associated with a lower risk of experiencing at least one treatment-emergent adverse event (TEAE) than PER (OR 0.63, 95% CI 0.46-0.85) and TPM (OR 0.51, 95 % CI 0.36-0.72) and a lower proportion of patients experiencing TEAEs leading to discontinuation than PER (OR 0.51, 95% CI 0.27-0.97) and TPM (OR 0.50, 95 % CI 0.27-0.93). CONCLUSIONS: Third-generation drugs (PER and LCM) had no advantages in terms of efficacy and safety for adjunctive treatment of refractory epilepsy compared with several second-generation drugs (LEV and LTG). Levetiracetam was the priority choice for adjunctive treatment of refractory epilepsy. Perampanel and LCM had no advantages in terms of efficacy and safety among the five drugs. REGISTRATION: PROSPERO registration number, CRD42022344153; last edited on December 23, 2022.

Topiramate in the treatment of antipsychotic-induced hyperprolactinemia.

Hyperprolactinemia is a common but neglected adverse effect of antipsychotic agents. Current treatments for antipsychotic-induced hyperprolactinemia exert their action mainly through the mechanism of enhancing the inhibitory effect of dopamine on prolactin secretion; however, patients have to endure the risk of psychotic relapse or exacerbation. Topiramate, a new anticonvulsant, is widely used in the treatment of numerous psychiatric conditions. It can antagonize α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate (KA) glutamate receptors and enhance the inhibitory activity of γ-amino butyric acid (GABA). Inhibition of AMPA and KA receptors and increased GABA activity has been proved to have an inhibitory effect on prolactin release. Thus, topiramate may be an effective agent in the treatment of antipsychotic-induced hyperprolactinemia.

An investigation of mental health status of children and adolescents in china during the outbreak of COVID-19.

OBJECTIVE: The sudden outbreak of Coronavirus Disease 2019 (COVID-19) has had a dramatic effect on the mental health of the public. In the present study, we demonstrated the psychological effects on children and adolescents associated with the epidemic . METHODS: By using convenience sampling method, questionnaires, such as Spence Child Anxiety Scale, Child Depression Inventory and Coping style Scale, were distributed to participating 359 children and 3254 adolescents online. RESULTS: The anxiety levels of children and adolescents were (23.87 ± 15.79) and (29.27 ± 19.79), respectively. 22.28% respondents were suffering from depressive symptoms. Seven significant factors associated with increased levels of anxiety, including female, resident in urban regions, emotion-focused coping style. Nine factors associated with increased levels of depression, such as smartphone addiction (OR 1.411, 95% CI 1.099-1.180), Internet addiction (OR 1.844, 95% CI 1.209-2.811), and resident in Hubei province (OR 3.107, 95% CI 1.252-7.708). Two additional factors associated with decreased levels of depressive symptoms: hours spend on Internet per day before the epidemic (OR 0.652, 95% CI 0.609-0.697) and tendency to apply problem-focused coping style (OR 0.937, 95% CI 0.923-0.951). CONCLUSION: Our findings indicate that the COVID-19 outbreak has had a significant psychosocial impact on children and adolescents. Findings of current levels of anxiety and depression not only highlight the need to address emotional distress for children and adolescents during the epidemic but also provide researchers with scientific fundamentals to formulate targeted interventions based on the significant influencing factors.

Association between ADORA2A gene polymorphisms and schizophrenia in the North Chinese Han population.

BACKGROUND: A large number of studies have shown a close relationship between ADORA2A and the pathological mechanism of schizophrenia. However, to our knowledge, there has been no studies examining the association between the ADORA2A gene and schizophrenia in Chinese Han population. PURPOSE: The objective of this study was to examine the relationship between adenosine A2A receptor (ADORA2A) single nucleotide polymorphisms and schizophrenia in the North Chinese Han population. PATIENTS AND METHODS: We detected ADORA2A single nucleotide polymorphisms (SNPs) using polymerase chain reaction-restriction fragment length polymorphism analyses and summarized our results using SPSS statistical software and Haploview in schizophrenia case group (n=398) and healthy control group (n=535). RESULTS: The frequency of the CC homozygote genotype of SNP rs2298383T/C were significantly higher in the case than the control group (p=0.005, OR=1.712, 95% CI=1.172-2.502). After linkage disequilibrium analysis, SNPs rs5996696A/C and rs2298383T/C displayed strong linkage disequilibrium. We found that the frequencies of haplotypes TA (χ2=6.268, p=0.0123) and CA (χ2=7.012, p=0.0081) were significantly higher in the case group than in the control group. CONCLUSION: In conclusion, SNPs in the ADORA2A gene may be associated with schizophrenia in the northern Chinese Han population.

Topiramate add-on treatment associated with normalization of prolactin levels in a patient with schizophrenia.

Topiramate has been used increasingly in the management of psychiatric conditions. Clinical trials demonstrated that topiramate augmentation was effective in controlling negative symptoms in schizophrenia. This case report presents a case of a 38-year-old man with schizophrenia who achieved full negative symptom remission upon the adjunctive use of topiramate. However, the remarkable finding of this case is the concomitant decrease in the level of prolactin when topiramate (50 mg/day) was started and the rebound after discontinuation of topiramate. Previous studies stated that topiramate could prevent antipsychotic-induced weight gain and adverse metabolic effects. To the authors' knowledge, no study has reported that topiramate augmentation could be a treatment strategy for antipsychotic-induced hyperprolactinemia. This finding could be verified by well-designed clinical trials.

-141C insertion/deletion polymorphism of the dopamine D2 receptor gene is associated with schizophrenia in Chinese Han population: Evidence from an ethnic group-specific meta-analysis.

Accumulate evidence has implicated dopamine D2 receptor gene polymorphisms in the etiology of schizophrenia. A single nucleotide polymorphism, -141C insertion/deletion (Ins/Del) (rs1799732), in the promoter region of the dopamine D2 receptor gene has been linked to schizophrenia; however, the data are inconclusive. This study investigated whether the -141C polymorphism is associated with the risk of schizophrenia in different ethnic groups by performing a meta-analysis. A total of 24 case-control studies examining the association between -141C Ins/Del polymorphism and schizophrenia were identified according to established inclusion criteria. Significant association was revealed between -141C Ins/Del polymorphism and schizophrenia risk in dominant genetic model (Ins/Ins + Ins/Del versus Del/Del) (odds ratio = 0.33, 95% confidence interval = 0.14-0.81, z = 2.41, P = 0.02) in Chinese Han but not in Caucasian, Japanese or India populations. Our results indicate that -141C Ins/Del polymorphism might be a susceptibility factor for schizophrenia in Chinese Han population.

Association between the TPH1 A218C polymorphism and antidepressant response: evidence from an updated ethnicity, antidepressant-specific, and ethnicity-antidepressant interaction meta-analysis.

BACKGROUND: Several studies have investigated the potential association between genetic polymorphisms of tryptophan hydroxylase 1 (TPH1) and antidepressant response. However, the results are inconsistent and inconclusive. Our aim was to assess the association of the TPH1 A218C polymorphism (rs1800532) with antidepressant response using ethnicity, antidepressant-specific, and ethnicity-antidepressant interactions in an updated meta-analysis. PATIENTS AND METHODS: Data were collected from the related literature published before December 2013 from MEDLINE and EMBASE databases. The meta-analysis was stratified by ethnicity, antidepressants, and ethnicity-antidepressant interaction, and was carried out using a random-effects model as appropriate using the Stata Statistical Package (version 11.0). RESULTS: A total of 12 individual studies and the STAR*D study were identified in the current study, among which six studies and the STAR*D study (White part) reported on the TPH1 A218C polymorphism and antidepressant response in a White population, with 2035 cases, and six studies and the STAR*D study (Asian part) were carried out in an Asian population, with 707 cases. In terms of the classes of antidepressants, eight studies and the STAR*D study explored this relationship using selective serotonin reuptake inhibitors (SSRIs) and four studies used other/mixed antidepressants. We found that the TPH1 A218C genotype was not significantly associated with antidepressant response either in all populations or in White and Asian populations. Moreover, the results did not change according to an ethnicity-antidepressant interaction model either in White populations using SSRIs or other/mixed antidepressants or in Asian populations. CONCLUSION: The TPH1 A218C polymorphism may not be associated with antidepressant response either in an ethnicity, antidepressant-specific population or in an ethnicity-antidepressant interaction model.

The efficacy and safety of atypical antipsychotics for the treatment of dementia: a meta-analysis of randomized placebo-controlled trials.

BACKGROUND: The application of atypical antipsychotics (SGAs) for treatment of psychiatric and behavioral symptoms of dementia is controversial since their efficacy might be offset by their adverse events (AEs). OBJECTIVE: To assess the efficacy, safety, and tolerability of SGAs for treatment of psychological and behavioral symptoms of dementia. METHODS: Two researchers searched MEDLINE, PsychINFO, and the Cochrane Central Register of Controlled Trials independently for double-blind, placebo-controlled, randomized controlled trials (DB-PC-RCTs) as of June 2013, written in English. Efficacy was measured using the Brief Psychiatric Rating Scale (BPRS), Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory (NPI), Clinical Global Impression of Change (CGI-C), and (or) Clinical Global Impression of Severity (CGI-S). Safety and tolerability were measured by frequencies of drop-outs, AEs, and death. In total, 19 treatment comparisons drawn from 16 DB-PC-RCTs were included, and 3,343 patients randomized to the antipsychotic group and 1,707 to the placebo group were assessed. RESULTS: This meta-analysis demonstrated a significant efficacy of atypical antipsychotics on BPRS (MD = -1.58, 95% CI = -2.52 - -0.65), CMAI (-1.84, -3.01 - -0.61), NPI (-2.81, -4.35 - -1.28), CGI-C (-0.32, -0.44 - -0.20), and CGI-S (-0.19, -0.30 - -0.09), compared to placebo (p < 0.01 for all). Patients receiving atypical antipsychotics showed no difference in risk for discontinuation (p > 0.05), significantly higher risks (p < 0.05 for all) for somnolence (OR = 2.95), extrapyramidal symptoms (1.74), cerebrovascular AEs (2.50), urinary tract infection (1.35), edema (1.80), gait abnormality (3.35), and death (1.52), and a lower risk for agitation (OR = 0.80, p = 0.03). CONCLUSIONS: The higher risks for AEs and mortality may offset the efficacy of atypical antipsychotics for treatment of dementia. Efficacy, safety, and tolerability thus should be carefully considered against clinical need.

Association of Neurotensin receptor 1 gene polymorphisms with processing speed in healthy Chinese-Han subjects.

Neurotensin modulates dopamine and serotonin transmission in the brain. The study investigated whether genetic polymorphisms in the Neurotensin receptor 1 gene were associated with performance on processing speed and executive function. A total of 129 healthy Chinese-Han volunteers were recruited. Genotyping for three SNPs, including rs6090453, rs6011914, and rs2427422, was analyzed by using a PCR and a restriction fragment length polymorphism analysis. Performances of processing speed and executive function were assessed by using Trail Making Test-A (TMT-A), Wisconsin Card Sorting Test, and Stroop Color-Word Test. We found significant differences in the outcomes of TMT-A score among rs6090453C/G (F(2,126)=4.405, P=0.014) and rs2427422A/G (F(2,126)=7.498, P=0.001) genotypes. Neurotensin receptor 1 SNP polymorphisms were significantly associated with the variance in processing speed performance in a sample of Chinese college students.

Association between major depressive disorder and the norepinephrine transporter polymorphisms T-182C and G1287A: a meta-analysis.

BACKGROUND: Previous studies have implicated norepinephrine transporter (NET) gene polymorphisms in the etiology of major depressive disorder (MDD). Recently, two single nucleotide NET polymorphisms, T-182C (rs2242446) in the promoter region and G1287A (rs5569) in exon 9, were found to be associated with MDD in different populations. However, inconsistent and inconclusive results have also been obtained. METHODS: In this study, we examined whether rs2242446 and rs5569 genetic variants are related to the etiology of MDD using a meta-analysis. Relevant case-control studies were retrieved by database searching and selected according to established inclusion criteria. RESULTS: Eight articles were identified that tested the relationship between the NET T-182C and/or G1287A polymorphism and MDD. Statistical analyses revealed no significant association between these polymorphisms and MDD (OR=1.23, 95% CI=0.77-1.97, P=0.38 for T-182C; OR=1.00, 95% CI=0.78-1.29, P=0.99 for G1287A). LIMITATIONS: The results must be treated with caution because of the small sample sizes of several included studies. CONCLUSIONS: Our findings suggest that the NET T-182C and G1287A polymorphisms are not susceptibility factors for MDD.

Genetic variation of FYN contributes to the molecular mechanisms of coping styles in healthy Chinese-Han participants.

Genetic factors can influence specific human coping styles. Polymorphisms in the Src family tyrosine kinase FYN gene have been associated with several personality traits, but no studies have examined the possible relationship between FYN alleles and coping styles. To this end, we examined the association between three single nucleotide polymorphisms of FYN (rs706895, rs3730353, and rs6916861) and coping styles as measured by the Simplified Coping Style Questionnaire in 488 healthy Chinese-Han individuals. In the total sample population, there were no significant differences in the scores for active coping and passive coping among the genotypes of these three polymorphisms. In sex-specific analyses, however, both rs3730353 and rs6916861 polymorphisms showed a significant relationship with passive coping scores in female participants (rs3730353: χ(2)=8.08, P=0.018; rs6916861: χ(2)=7.78, P=0.020). Our results provided suggestive evidence that the FYN gene contributes toward the variance in human coping styles.

Association between neurotensin receptor 1 (NTR1) gene polymorphisms and schizophrenia in a Han Chinese population.

Neurotensin (NT) is a multifunctional gut hormone, neurotransmitter, and neuromodulator that triggers many physiological responses by binding to the high-affinity neurotensin receptor 1 (NTR1). Previous studies have implicated the roles of NT and NTR1 in the etiology or expression of schizophrenia. This case-control study examined the associations between schizophrenia and three NTR1 gene polymorphisms (rs6090453C/G, rs6011914C/G, and rs2427422A/G) previously linked to working memory performance in a Han Chinese population. These three polymorphisms were genotyped in 390 schizophrenic patients and 565 healthy subjects. Compared with those of the controls, the frequencies for C allele in the rs6090453C/G polymorphism were higher in the schizophrenic patients (p = 0.049) and their female subgroup (p = 0.014). The frequencies for the rs6090453C/rs6011914G/rs2427422G (CGG) haplotype were also higher in the patients (p = 0.016) and their female subgroup (p = 0.005). Moreover, in the female subgroup, the frequencies for the rs6090453G/rs6011914C/rs2427422G (GCG) haplotype were higher in the controls (p = 0.028). Our results suggest that the C allele (CC or CG genotype) in the rs6090453C/G polymorphism and the CGG haplotype may enhance schizophrenia susceptibility in the Han Chinese population, while the GCG haplotype may be a protective factor, particularly in females.

Association between PPP1R1B polymorphisms and defense mechanisms in healthy Chinese-Han subjects.

Defense mechanisms resulting from the interaction between biological factors and the environment have been established. In genetic studies, dopamine genes have been recognized to play an important role in the determination of defense mechanisms. DARPP-32 (dopamine- and cAMP-regulated phosphoprotein) plays a central role in the biology of dopamine-receptive neurons; its coding gene (PPP1R1B) has been linked to psychological and psychopathological traits. Here, we aimed to explore the association between PPP1R1B polymorphisms and defense mechanisms measured using the 88-item Defense Style Questionnaire in 400 healthy Chinese-Han subjects. Of the three polymorphisms examined, rs12601930 was associated with projection (P = 0.028) and splitting (P = 0.032), while rs3764352 was associated with splitting (P = 0.042). No significant association was found between rs879606 and defenses. When analyzed separately by gender, no significant association between defense mechanisms and PPP1R1B polymorphisms in males was observed. In females, however, rs12601930 was significantly associated with splitting (P = 0.018), and rs879606, with projection (P = 0.015), help-rejecting complaining (P = 0.030), and immature defense style (P = 0.031), while rs3764352 was not associated with any defense. The distribution of genotypes between the low- and high-scoring subgroups for each defense style showed no significant differences. Our results suggest that PPP1R1B polymorphisms are, at least partially, responsible for immature defenses.

Association between neurotensin receptor 1 gene polymorphisms and alcohol dependence in a male Han Chinese population.

Neurotensin (NT) is a 13-amino acid multifunctional neuropeptide. Previous studies have demonstrated the roles of NT and its high-affinity receptor 1 (NTR1) in genetically mediated differential sensitivities to alcohol. However, no studies have investigated the association between NTR1 gene single-nucleotide polymorphisms (SNPs) and alcohol dependence (AD). We therefore examined this link. We genotyped three SNPs (rs6090453C/G, rs6011914C/G, and rs2427422A/G) of NTR1 gene in 127 AD patients and 131 healthy controls drawn from Han Chinese males. Allele and genotype frequencies were compared, and linkage disequilibrium and haplotype analysis were performed. For rs6011914C/G, the frequencies of GG genotypes in AD patients showed an increased trend compared with controls (p = 0.057), and the ratio of GG/(CG + CC) for dominant model in AD patients was significantly higher (p = 0.024). For rs2427422A/G, both the frequencies of G alleles and GG genotypes and the ratio of GG/(AG + AA) for dominant model in AD patients were significantly higher compared with controls (p = 0.003, 0.006, 0.002, respectively). There was no significant difference in the frequencies of alleles, genotypes, and dominant or recessive model for rs6090453C/G (all p > 0.05). There were three pairs of SNP linkage disequilibriums, and the haplotype frequencies differed significantly between patients and controls for the CCA (p = 0.005, less frequent in the patients) and CCG (p = 0.002, more frequent in the patients) haplotypes. The current study supported an association between NTR1 gene variants and AD in the Han Chinese population.

Association between a casein kinase 1 ε gene polymorphism and schizophrenia in a Chinese Han population.

The casein kinase 1 (Csnk1) family of serine/threonine kinases regulates dopamine receptor (DR) signaling by phosphorylating the 32-kDa dopamine- and cAMP-regulated phosphoprotein DARPP-32, leading to inhibition of protein phosphatase 1 and a shift in the phosphorylation state of many downstream proteins. By modulating DR-activated phosphorylation cascades, Csnk1 plays a central role in neuropsychiatric disorders and modulates the stimulant response to amphetamine. No published study, however, has established a correlation between Csnk1 gene polymorphisms and schizophrenia. We genotyped the rs135745C/G polymorphism of the Csnk1ε gene in 384 schizophrenic patients and 502 healthy controls drawn from the Chinese Han population. There were significantly higher CG and CC genotype frequencies in schizophrenic patients compared to control subjects (CG, p = 0.0086, odds ratio (OR) = 1.477, 95% confidence interval (CI), 1.103-1.978; CC, p = 0.0431, OR = 2.571; 95% CI, 0.998-6.624). The C allele frequency was also higher in the schizophrenics (p = 0.0022; OR = 1.474; 95% CI, 1.149-1.891). In the dominant model, subjects with genotypes CC or CG were at greater risk for schizophrenia (p = 0.0032; OR = 1.532; 95% CI, 1.153-2.037), suggesting that a genetic variant in the Csnk1ε gene significantly enhances the probability of schizophrenia in the Chinese Han population.