Background/Aim: Although individuals with substance use disorder (SUD) are at high risk of committing suicide, most studies of postmortem gene expression exclude subjects with SUD due to the potential confounding effect of drugs in the transcriptome. Thus, little is known about the gene expression profile in suicides with SUD. The identification of altered biological processes in suicides with SUD is crucial in the comprehension of the interaction between both pathologies. Methods: We evaluated the gene expression profile in the dorsolateral prefrontal area of suicides and nonsuicides with and without SUD by microarrays. Results: We identified 222 differentially expressed genes, predominately enriched in cell proliferation in the comparison between suicides with and without SUD. When comparing the transcriptome of suicides with SUD to nonsuicides with SUD, we identified 550 differentially expressed genes, mainly enriched in oxidative phosphorylation. Differentially expressed genes (1,417) between suicides and nonsuicides without SUD were detected. Most of them were related to mitochondrial function. Conclusion: Interaction between suicide and SUD seems to influence the expression of genes involved in glial proliferation and glutamatergic neurotransmission. These results highlight, for the first time, that suicides with SUD have a gene expression profile distinct from that of subjects with only one of these disorders.
Objective: To analyze sex differences in demographic and clinical characteristics of individuals who died by suicide in Mexico City.Method: Statistical analysis of residents of Mexico City whose cause of death was suicide, during two years period from January 2014 to December 2015, with a coroner's report. Suicide mortality rates were calculated by age, sex, and location within the city. The Chi-squared test was used to assess statistical differences.Results: From January 2014 to December 2015, 990 residents of Mexico City died by suicide (men: 78.28%, women: 21.72%). Among males, the highest mortality rates were among the groups of 20–24 and 75–79 years old, whereas in women, the group with the highest mortality rate was 15 to 19 years old. 74% of the sample used hanging as suicide method. However, men had higher rates of a positive result in the toxicology test (40%) (p < 0.05). There was no concordance between male and female suicide by city jurisdictions.Conclusion: Our results provide evidence that the characteristics of Mexico City's residents who committed suicide had significant sex-related differences, including where they used to live. Understanding the contributory factors associated with completed suicide is essential for the development of effective preventive strategies.
Background
Suicide represents a major health concern, especially in developing countries. While many demographic risk factors have been proposed, the underlying molecular pathology of suicide remains poorly understood. A body of evidence suggests that aberrant DNA methylation and expression is involved. In this study, we examined DNA methylation profiles and concordant gene expression changes in the prefrontal cortex of Mexicans who died by suicide.
Methods
In collaboration with the Coroner’s office in Mexico City, brain samples of males who died by suicide (n=35) and age-matched sudden death controls (n=13) were collected. DNA and RNA were extracted from prefrontal cortex tissue and analyzed with the Infinium Methylation480k and the HumanHT-12 v4 Expression Beadchips, respectively.
Results
We report evidence of altered DNA methylation profiles at 4,430 genomic regions together with 622 genes characterized by differential expression in cases versus controls. Seventy genes were found to have concordant methylation and expression changes. Metacore enriched analysis identified ten genes with biological relevance to psychiatric phenotypes and suicide (ADCY9, CRH, NFATC4, ABCC8, HMGA1, KAT2A, EPHA2, TRRAP, CD22, CBLN1) and highlighted the association that ADCY9 has with various pathways, including, signal transduction regulated by the cAMP-responsive element modulator, neurophysiological process regulated by the corticotrophin-releasing hormone and synaptic plasticity. We, therefore, went on to validate the observed hypomethylation of ADCY9 in cases versus control, through targeted bisulfite sequencing.
Conclusion
Our study represents the first analysis of DNA methylation and gene expression associated with suicide in a Mexican population using postmortem brain, providing novel insights for convergent molecular alterations associated with suicide.
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