Based on the “oxidative stress hypothesis” of major depressive disorder (MDD), cells regulate their structure through the Wnt pathway. Little is known regarding the interactions of dishevelled 3 (DVL3) and glycogen synthase kinase 3 beta (GSK3β) polymorphisms with MDD. The aim of the current study was to verify the relationship between DVL3 and GSK3β genetic variants in a Chinese Han population and further to evaluate whether these interactions exhibit gender-specificity. A total of 1136 participants, consisting of 541 MDD patients and 595 healthy subjects, were recruited. Five single-nucleotide polymorphisms (SNPs) of DVL3/GSK3β were selected to assess their interaction by use of a generalized multifactor dimensionality reduction method. The genotype and haplotype frequencies of DVL3/GSK3β polymorphisms were significantly different between patients and controls for DVL3 rs1709642 ( P < 0.01 ) and GSK3β rs334558, rs6438552, and rs2199503 ( P < 0.01 ). In addition, our results also showed that there were significant interaction effects between DVL3 and GSK3β polymorphisms and the risk of developing MDD, particularly in women. The interaction between DVL3 (rs1709642) and GSK3β (rs334558, rs6438552) showed a cross-validation (CV) consistency of 10/10, a P value of 0.001, and a testing accuracy of 59.22%, which was considered as the best generalized multifactor dimensionality reduction (GMDR) model. This study reveals the interaction between DVL3 and GSK3β polymorphisms on MDD susceptibility in a female Chinese Han population. The effect of gender should be taken into account in future studies that seek to explore the genetic predisposition to MDD relative to the DVL3 and GSK3β genes.
Introduction Investigations of gene-environment (G×E) interactions in major depressive disorder (MDD) have been limited to hypothesis testing of candidate genes while poly-gene-environmental causation has not been adequately address. To this end, the present study analyzed the association between three candidate genes, two environmental factors, and MDD using a hypothesis-free testing approach. Methods A logistic regression model was used to analyze interaction effects; a hierarchical regression model was used to evaluate the effects of different genotypes and the dose-response effects of the environment; genetic risk score (GRS) was used to estimate the cumulative contribution of genetic factors to MDD; and protein-protein interaction (PPI) analyses were carried out to evaluate the relationship between candidate genes and top MDD susceptibility genes. Results Allelic association analyses revealed significant effects of the interaction between the candidate genes Forkhead box ( Fox ) O1, α2-macroglobulin ( A2M ), and transforming growth factor ( TGF ) -β1 genes and the environment on MDD. Gene-gene (G×G) and gene-gene-environment (G×G×E) interactions in MDD were also included in the model. Hierarchical regression analysis showed that the effect of environmental factors on MDD was greater in homozygous than in heterozygous mutant genotypes of the FoxO1 and TGF-β1 genes; a dose-response effect between environment and MDD on genotypes was also included in this model. Haplotype analyses revealed significant global and individual effects of haplotypes on MDD in the whole sample as well as in subgroups. There was a significant association between GRS and MDD (P = 0.029) and a GRS and environment interaction effect on MDD (P = 0.009). Candidate and top susceptibility genes were connected in PPI networks. Conclusions FoxO1 , A2M , and TGF-β1 interact with environmental factors and with each other in MDD. Multi-factorial G×E interactions may be responsible for a higher explained variance and may be associated with causal factors and mechanisms that could inform new diagnosis and therapeutic strategies, which can contribute to the personalized medicine of MDD.
OverviewThe mental health problems of adolescents with human immunodeficiency virus (HIV) are important. It is of great significance to explore which factors can affect the self-evaluation and understanding of adolescents with HIV.ObjectiveWe found that adolescents with HIV have a lower level of self-concept than healthy adolescents. This study aimed to determine the factors influencing self-concept among adolescents with HIV in China.SettingA questionnaire was distributed among a total of 290 adolescents in Henan Province, China. One hundred and forty questionnaires were distributed in the case group (adolescents with HIV) and the control group (healthy adolescents) was issued 150 questionnaires.The Piers-Harris Children’s Self-concept Scale, the Perceived Stress Scale, the Perceived Social Support Scale and the Simplified Coping Style Questionnaire were adapted for a Chinese population. Differences between the groups were tested for significance using Student’s t-test, and analysis of variance was used to test continuous variables. The relationship between environmental personality factors and adolescent self-concept was examined by Pearson correlation analysis. Hierarchical linear regression analysis was used to model the effects of environmental personality factors on self-concept.ResultsThe self-concept total score among adolescents with HIV was significantly lower than healthy adolescents (p<0.05). Hierarchical regression analysis indicated that age (β=−0.19, t=−2.16, p=0.03), perceived stress (β=−0.19, t=−2.22, p=0.03), perceived social support (β=0.26, t=3.25, p=0.00), positive coping style (β=0.50, t=5.75, p=0.00) and negative coping style (β=−0.45, t=−5.33, p=0.00) were significantly associated with self-concept total scores.ConclusionsThe self-concept of adolescents with HIV is related to perceived stress, perceived social support and coping style. These findings underline the significance of self-concept among adolescents infected with HIV.
Background: Recent studies suggest that glycogen synthase kinase (GSK)-3β is involved in the development of major depressive disorder (MDD). The aim of this study was to investigate the interaction between GSK-3β polymorphism (rs6438552, rs334558, and rs2199503) and negative life events in the pathogenesis of major depressive disorder (MDD).Methods: DNA genotyping was performed on peripheral blood leukocytes in 550 patients with MDD and 552 age- and gender-matched controls. The frequency and severity of negative life events were assessed by the Life Events Scale (LES). A chi-square method was employed to assess the gene-environment interaction (G × E).Results: Differences in rs6438552, rs334558, and rs2199503 genotype distributions were observed between MDD patients and controls. Significant G × E interactions between allelic variation of rs6438552, rs334558, and rs2199503 and negative life events were observed. Individuals with negative life events and carrying genotypes of rs6438552 A+, rs334558 A+, and rs2199503G+ have increased the risk of depression.Conclusions: These results indicate that interactions between the GSK-3β rs6438552, rs334558, and rs2199503 polymorphisms and environment increases the risk of developing MDD.
To investigate the prevalence of post-traumatic stress symptoms (PTSSs) and analyze the influencing factors of PTSS among adolescents in a large sample study during the COVID-19 pandemic, we did a cross-sectional study by collecting demographic data and mental health measurements from a large group of 175,318 adolescents in 32 Chinese provinces and autonomous regions, using the Impact of Event Scale-Revised (IES-R) that was used to measure the PTSS of the participants. The results showed that the prevalence of PTSS was 35.7% in Chinese adolescents during the COVID-19 pandemic. Binary logistic regression analysis showed that, for the personal risk factors, the older age, female gender, the personality domains of extroversion, the irregular sleep schedule, the lack of aerobic exercise, and the lack of peer support were associated with the higher levels of PTSS. The family subjective and objective factors were associated with higher levels of PTSS. Our findings suggested that family factors are the most important factors that affect Chinese adolescents' PTSS due to the longtime home quarantine.
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