Sex differences in brain gene expression among suicide completers

Cabrera‐Mendoza, Brenda; Fresno, Cristóbal; Monroy-Jaramillo, Nancy; Fries, Gabriel R.; Walss‐Bass, Consuelo; Glahn, David C.; Ostrosky‐Wegman, Patricia; Mendoza-Morales, Roberto Cuauhtemoc; García-Dolores, Fernando; Díaz-Otañez, Carlos Enrique; González-Sáenz, Eli Elier; Genis‐Mendoza, Alma Delia; Martínez‐Magaña, José Jaime; Romero-Pimentel, Ana Luisa; Flores, Gonzalo; Vázquez-Roque, Rubén Antonio; Nicolini, Humberto

doi:10.1016/j.jad.2020.01.167

Cited by 13 publications

(14 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Analysis of top 10 downregulated hub genes (PECAM1, ERBB2, ITGB1, EGFR, STAT3, NOTCH1, CD44, IL6, TLR4 and FN1) from PPI network revealed that these genes were strongly enriched in cell-surface receptor signaling pathway, astrocyte differentiation and regulation of MAPK cascade, suggesting that these pathways might be implicated in suicidal behavior. As previously defined, two of the top hub genes, the adhesive stress-response protein PECAM1 and the proto-oncogene ERBB2 were reported decreasing in the DLPFC in suicide victims (Cabrera-Mendoza et al 2020). Analysis of top 10 upregulated hub genes (CCK, GABRD, CRHR1, CALY, COL11A2, COL24A1, SCN3B, GRIK1, GRIK2, CACNA1G) revealed that these genes were associated with regulation of membrane potential, nervous system processes and cell-cell signaling.…”

Section: Discussionmentioning

confidence: 80%

“…Microarray studies identified a number of altered genes, regulating e.g. glial, endothelial, and mitochondrial activities (Pantazatos et al 2017) some of them showing sexual dimorphism (Labonte et al 2017) and comorbidity with substance use disorder (Cabrera et al 2019, Cabrera-Mendoza et al 2020). More recently, sequencing approaches identified additional new susceptibility genes and pathways in depression using animal models of chronic stress (Li et al 2020), and genome-wide association studies related to depression (Yang et al 2021) and suicide (Romero-Pimentel et al 2021).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Transcriptome profiling of the dorsomedial prefrontal cortex in suicide victims

Dóra

Renner

Keller

et al. 2022

Preprint

View full text Add to dashboard Cite

The default mode network (DMN) plays an outstanding role in psychiatric disorders. Still, gene expressional changes in its major component, the dorsomedial prefrontal cortex (DMPFC), have not been characterized. We used RNA-sequencing in postmortem DMPFC samples to investigate suicide victims compared to control subjects. Most of the data variance (79%) was associated with expression changes between suicide and control samples. 1400 genes differed using log2FC > ± 1 and adjusted p-value < 0.05 criteria between groups. Genes associated with depressive disorder, schizophrenia and impaired cognition were strongly overexpressed in top differentially expressed genes. Gene set enrichment and protein-protein interaction network analysis revealed that pathways related to cytokine receptor signaling were enriched in downregulated while glutamatergic synaptic signaling in upregulated genes in suicide individuals. A validated differentially expressed gene, which is known to be associated with mGluR5, was the N-terminal EF-hand calcium-binding proteins 2 (NECAB2). In situ hybridization histochemistry and immunohistochemistry proved that NECAB2 is expressed in 2 different types of inhibitory neurons located in layers II-IV and VI, respectively. Our results imply extensive gene expressional alterations in the DMPFC related to suicidal behavior. Some of these genes may contribute to the altered mental state and behavior of suicide victims.

show abstract

Section: Discussionmentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Transcriptome profiling of the dorsomedial prefrontal cortex in suicide victims

Dóra

Renner

Keller

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…In addition to the DEGs with the highest fold changes, we also focused on the individually validated DEGs. For qRT-PCR validation, we selected 14 genes whose alterations were reported in human depression and suicide or rodent depression-like behavior [52,54,[75][76][77][78][79][80]. For ITPKB, GJA1 and GLUL genes, the previously reported alteration in the DLPFC [54] was demonstrated to also occur in the DMPFC.…”

Section: Conclusion Based On Individual Degsmentioning

confidence: 99%

“…More recently, high-throughput methods were applied to establish a wider variety of genes significantly altered in suicide victims. Microarray studies identified a number of altered genes, regulating, e.g., glial, endothelial and mitochondrial activities [51] some of them showing sexual dimorphism [52] and comorbidity with substance use disorder [53,54]. More recently, sequencing approaches identified additional new susceptibility genes and pathways in depression using animal models of chronic stress [55] and also human studies related to depression [56] and suicide [57].…”

Section: Introductionmentioning

confidence: 99%

Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims

Dóra

Renner

Keller

et al. 2022

IJMS

View full text Add to dashboard Cite

The default mode network (DMN) plays an outstanding role in psychiatric disorders. Still, gene expressional changes in its major component, the dorsomedial prefrontal cortex (DMPFC), have not been characterized. We used RNA sequencing in postmortem DMPFC samples to investigate suicide victims compared to control subjects. 1400 genes differed using log2FC > ±1 and adjusted p-value < 0.05 criteria between groups. Genes associated with depressive disorder, schizophrenia and impaired cognition were strongly overexpressed in top differentially expressed genes. Protein–protein interaction and co-expressional networks coupled with gene set enrichment analysis revealed that pathways related to cytokine receptor signaling were enriched in downregulated, while glutamatergic synaptic signaling upregulated genes in suicidal individuals. A validated differentially expressed gene, which is known to be associated with mGluR5, was the N-terminal EF-hand calcium-binding protein 2 (NECAB2). In situ hybridization histochemistry and immunohistochemistry proved that NECAB2 is expressed in two different types of inhibitory neurons located in layers II-IV and VI, respectively. Our results imply extensive gene expressional alterations in the DMPFC related to suicidal behavior. Some of these genes may contribute to the altered mental state and behavior of suicide victims.

show abstract

“…The role of signal transduction and molecular systems in medicated patients with major depression or drug abuse and/or suicidal behavior is being investigated [29,30]. Given the sex differences in suicide rates, some studies hypothesize that the pattern of brain gene expression is different in male and female suicides, and changes in the expression of sex-specific genes have been identified in the prefrontal cortex of suicide bombers [31][32][33]. Carrying out toxicological analysis in cases of fatal suicide is a crucial piece to understanding consumption patterns and establishing strategies and protocols for the detection and prevention of suicide.…”

Section: Introductionmentioning

confidence: 99%

Suicidal Behavior and Its Relationship with Postmortem Forensic Toxicological Findings

Collados-Ros

Torres-Sánchez

Pérez-Cárceles

et al. 2022

Toxics

View full text Add to dashboard Cite

Suicide affects all sociodemographic levels, age groups, and populations worldwide. The factors that can increase the risk of suicidal tendencies are widely studied. The aim of this study was to analyze the types and combinations of toxics found in fatal suicide victims with different suicide mechanisms. A total of 355 autopsies were retrospectively studied, and 26 toxics were determined and related to mechanisms of suicide. Hanging (55%), drug overdose (22.7%), and jumping from a height (17.8%) were most represented suicide mechanisms with positive toxicology. Hanging was the most represented in men (50.3%; p = 0.019), while jumping from a height was more represented in women (29.7%, p = 0.028). Drugs of abuse were the most frequent toxics found in men (55.5%; p < 0.001), while medicines were the most frequent type found in women (70.3%, p < 0.001). Alcohol, nordiazepam, cocaine, and venlafaxine were the most consumed toxics. Benzodiazepines and venlafaxine were found in suicides involving drug overdose, hanging, and jumping from a height. In conclusion, most suicides were associated with drug abuse in men. Hanging was more represented in men and jumping from a height in women. Alcohol was present in combination with other toxics and medicines. The toxicological analysis is fundamental to understanding consumption patterns and establishing strategies and protocols for detecting and preventing suicide.

show abstract

Sex differences in brain gene expression among suicide completers

Cited by 13 publications

References 63 publications

Transcriptome profiling of the dorsomedial prefrontal cortex in suicide victims

Transcriptome profiling of the dorsomedial prefrontal cortex in suicide victims

Transcriptome Profiling of the Dorsomedial Prefrontal Cortex in Suicide Victims

Suicidal Behavior and Its Relationship with Postmortem Forensic Toxicological Findings

Contact Info

Product

Resources

About