Depicting the molecular features of suicidal behavior: a review from an "omics" perspective
Caibe Alves Pereira1, Guilherme Reis-de-Oliveira2, Bruna Caroline Pierone1
1Laboratory of Translational Neurosciences, Department of Biochemistry, Federal University of Santa Catarina (UFSC), Florianopolis, Santa Catarina, Brazil.
Abstract:
Background Suicide is one of the leading global causes of death. Behavior patterns from suicide ideation to completion are complex, involving multiple risk factors. Advances in technologies and large-scale bioinformatic tools are changing how we approach biomedical problems. The "omics" field may provide new knowledge about suicidal behavior to improve identification of relevant biological pathways associated with suicidal behavior. Methods We reviewed transcriptomic, proteomic, and metabolomic studies conducted in blood and post-mortem brains from individuals who experienced suicide or suicidal behavior. Omics data were combined using systems biology in silico, aiming at identifying major biological mechanisms and key molecules associated with suicide. Results Post-mortem samples of suicide completers indicate major dysregulations in pathways associated with glial cells (astrocytes and microglia), neurotransmission (GABAergic and glutamatergic systems), neuroplasticity and cell survivor, immune responses and energy homeostasis. In the periphery, studies found alterations in molecules involved in immune responses, polyamines, lipid transport, energy homeostasis, and amino and nucleic acid metabolism. Limitations We included only exploratory, non-hypothesis-driven studies; most studies only included one brain region and whole tissue analysis, and focused on suicide completers who were white males with almost none confounding factors. Conclusions We can highlight the importance of synaptic function, especially the balance between the inhibitory and excitatory synapses, and mechanisms associated with neuroplasticity, common pathways associated with psychiatric disorders. However, some of the pathways highlighted in this review, such as transcriptional factors associated with RNA splicing, formation of cortical connections, and gliogenesis, point to mechanisms that still need to be explored.
Insights
Suicide risk involves complex factors. Omics studies reveal key biological pathways in brain and blood, highlighting synaptic function, neuroplasticity, and immune responses. Further research is needed to explore novel mechanisms.
Area of Science:
- Neuroscience
- Genomics
- Proteomics
- Metabolomics
- Systems Biology
Background:
- Suicide is a leading global cause of death with complex behavioral patterns.
- Understanding biological risk factors is crucial for suicide prevention.
- Omics technologies offer novel insights into suicidal behavior.
Purpose of the Study:
- To review and synthesize findings from transcriptomic, proteomic, and metabolomic studies on suicide.
- To identify key biological mechanisms and molecules associated with suicidal behavior using systems biology.
- To explore potential biomarkers for suicide risk.
Main Methods:
- Systematic review of omics studies (transcriptomics, proteomics, metabolomics) in blood and post-mortem brain tissue.
- In silico integration of omics data using systems biology approaches.
- Analysis focused on individuals with a history of suicide or suicidal behavior.
Main Results:
- Post-mortem brain studies revealed dysregulation in glial cells, neurotransmission (GABAergic, glutamatergic), neuroplasticity, immune responses, and energy homeostasis.
- Peripheral studies identified alterations in immune molecules, polyamines, lipid transport, energy metabolism, and amino/nucleic acid metabolism.
- Synaptic function, neuroplasticity, and immune pathways emerged as critical areas.
Conclusions:
- Synaptic function balance and neuroplasticity mechanisms are vital in suicidal behavior, sharing pathways with psychiatric disorders.
- Peripheral and central omics data provide a comprehensive view of biological underpinnings.
- Further exploration of RNA splicing, cortical development, and gliogenesis pathways is warranted.
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