Gene-Environment Interactions in Schizophrenia: A Literature Review

Wahbeh, Marah H.; Avramopoulos, Dimitrios

doi:10.3390/genes12121850

Cited by 77 publications

(49 citation statements)

References 106 publications

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“…COMT might, however, confer a small risk for schizophrenia that is difficult to detect or it may not directly act on the risk for the disease, but modulate the impact of other risk factors such as environmental ones. In fact, despite the high heritability of schizophrenia, it is well-recognized that genetic factors not only coexist with nongenetic risk factors, but also interact with them [ 9 ]. Thus, the influence of COMT Val105/158Met on behaviour may be better understood in terms of gene–environment interactions, as both type of factors seem to converge on common networks implicated in brain function [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

“…Despite the high heritability of schizophrenia, it is well-recognized that nongenetic factors such as certain neurotropic infections and other early life stressors can also play a role [ 6 , 7 , 8 , 9 ]. Maternal exposure to the influenza virus during pregnancy could increase the risk for schizophrenia in offspring, and other neurotropic viruses have been assessed as infectious agents increasing the risk for schizophrenia [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

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Toxoplasma gondii Seropositivity Interacts with Catechol-O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia

Rovira

Gutiérrez

Sorlózano-Puerto

et al. 2022

Genes

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Schizophrenia is a heterogeneous and severe psychotic disorder. Epidemiological findings have suggested that the exposure to infectious agents such as Toxoplasma gondii (T. gondii) is associated with an increased risk for schizophrenia. On the other hand, there is evidence involving the catechol-O-methyltransferase (COMT) Val105/158Met polymorphism in the aetiology of schizophrenia since it alters the dopamine metabolism. A case–control study of 141 patients and 142 controls was conducted to analyse the polymorphism, the prevalence of anti-T. gondii IgG, and their interaction on the risk for schizophrenia. IgG were detected by ELISA, and genotyping was performed with TaqMan Real-Time PCR. Although no association was found between any COMT genotype and schizophrenia, we found a significant association between T. gondii seropositivity and the disorder (χ2 = 11.71; p-value < 0.001). Furthermore, the risk for schizophrenia conferred by T. gondii was modified by the COMT genotype, with those who had been exposed to the infection showing a different risk compared to that of nonexposed ones depending on the COMT genotype (χ2 for the interaction = 7.28, p-value = 0.007). This study provides evidence that the COMT genotype modifies the risk for schizophrenia conferred by T. gondii infection, with it being higher in those individuals with the Met/Met phenotype, intermediate in heterozygous, and lower in those with the Val/Val phenotype.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Toxoplasma gondii Seropositivity Interacts with Catechol-O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia

Rovira

Gutiérrez

Sorlózano-Puerto

et al. 2022

Genes

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“…SCZ is related with an approximately 15-year reduction in life expectancy in comparison to the gross population and a 5-10 percent lifetime risk of suicide. The low quality of life caused by cognitive impairment and mortality risks make SCZ a severe public health burden (Cloutier et al, 2016;Avramopoulos, 2018;Wahbeh and Avramopoulos, 2021). Despite the abundance of literature of SCZ manifestations, its exact etiology and pathogenesis are poorly known.…”

Section: Introductionmentioning

confidence: 99%

Identification of hub genes and construction of diagnostic nomogram model in schizophrenia

Zhang

Dong

et al. 2022

Front. Aging Neurosci.

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Schizophrenia (SCZ), which is characterized by debilitating neuropsychiatric disorders with significant cognitive impairment, remains an etiological and therapeutic challenge. Using transcriptomic profile analysis, disease-related biomarkers linked with SCZ have been identified, and clinical outcomes can also be predicted. This study aimed to discover diagnostic hub genes and investigate their possible involvement in SCZ immunopathology. The Gene Expression Omnibus (GEO) database was utilized to get SCZ Gene expression data. Differentially expressed genes (DEGs) were identified and enriched by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and disease ontology (DO) analysis. The related gene modules were then examined using integrated weighted gene co-expression network analysis. Single-sample gene set enrichment (GSEA) was exploited to detect immune infiltration. SVM-REF, random forest, and least absolute shrinkage and selection operator (LASSO) algorithms were used to identify hub genes. A diagnostic model of nomogram was constructed for SCZ prediction based on the hub genes. The clinical utility of nomogram prediction was evaluated, and the diagnostic utility of hub genes was validated. mRNA levels of the candidate genes in SCZ rat model were determined. Finally, 24 DEGs were discovered, the majority of which were enriched in biological pathways and activities. Four hub genes (NEUROD6, NMU, PVALB, and NECAB1) were identified. A difference in immune infiltration was identified between SCZ and normal groups, and immune cells were shown to potentially interact with hub genes. The hub gene model for the two datasets was verified, showing good discrimination of the nomogram. Calibration curves demonstrated valid concordance between predicted and practical probabilities, and the nomogram was verified to be clinically useful. According to our research, NEUROD6, NMU, PVALB, and NECAB1 are prospective biomarkers in SCZ and that a reliable nomogram based on hub genes could be helpful for SCZ risk prediction.

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“…Evidence have shown that relatives of patients with schizophrenia have a 5–10 times higher risk of developing schizophrenia ( 3 ), and those with a positive family history of mental illness are more likely to develop the problem at a younger age ( 4 ). Moreover, many environmental factors have been identified to contribute to the risk of developing schizophrenia at various times, especially during development stages (prenatal life, perinatal life, adolescence, and adulthood) ( 5 ). Such environmental factors have additive or cumulative effects, which may be linked and/or share causal factors ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

Profiles and factors associated with schizophrenia in eastern Ethiopia: A matched case-control study

Mohammed

Geda²,

Yadeta³

et al. 2022

Front. Psychiatry

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BackgroundDespite its strong hereditary and genetic connections, there are other factors reported to be linked to schizophrenia, but not well studied in eastern Ethiopia.ObjectiveThis study was aimed to investigating the potential profiles and factors associated with schizophrenia in eastern Ethiopia.Materials and methodsA matched case-control study was conducted in two public hospitals from December 1, 2021, to January 30, 2022. Cases were patients with schizophrenia who visited the hospitals, and controls were healthy individuals without any mental illness who visited the same hospitals. A questionnaire was used to collect the data. Cases and controls were matched using age and sex. STATA-14 was used for analysis. A conditional logistic regression with an adjusted odds ratio (AOR) and a 95% confidence interval (CI) was applied to identify the determinants. P-values of <0.05 were used to build the final model as a measure of statistical significance.ResultsThe mean age of the study participants group was 28.6 (±8.44) years, mean age for cases was 28.7(±8.5) ranging from 18 to 56 years and the mean age for the controls was 28.4 (±8.5), ranging from 18 to 60 years. About 181 (83.03%) of the participants were male. The odds of having schizophrenia was about 12.2 times higher among participants with family history of mental illness (AOR: 12.21; 95% CI: 4.83–30.00). The odds of having schizophrenia was 4.5 times higher among polysubstance users (AOR: 4.45; 95% CI: 1.28–5.45) and 2.8 times higher among khat consumers (AOR: 2.82; 95% CI: 1.23–6.45) compared to their counterparts.ConclusionOur findings show that genetic risk factors as well as some modifiable behaviors are associated to schizophrenia in eastern Ethiopia. At all levels, special attention should be given to those who are at risk.

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Gene-Environment Interactions in Schizophrenia: A Literature Review

Cited by 77 publications

References 106 publications

Toxoplasma gondii Seropositivity Interacts with Catechol-O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia

Toxoplasma gondii Seropositivity Interacts with Catechol-O-methyltransferase Val105/158Met Variation Increasing the Risk of Schizophrenia

Identification of hub genes and construction of diagnostic nomogram model in schizophrenia

Profiles and factors associated with schizophrenia in eastern Ethiopia: A matched case-control study

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