Projects / Programmes
Epigenetic factors and gene expression in suicidal behaviour
| Code |
Science |
Field |
Subfield |
| 3.09.00 |
Medical sciences |
Psychiatry |
|
| Code |
Science |
Field |
| B650 |
Biomedical sciences |
Psychiatry, clinical psychology, psychosomatics |
| Code |
Science |
Field |
| 3.02 |
Medical and Health Sciences |
Clinical medicine |
suicide, psychological autopsy, transcriptome, methylome, translation
Researchers (11)
Organisations (2)
Abstract
Despite a significant impact on society and increasing awareness of the latter, suicide is a major global public health problem, which is only poorly understood. According to the World Health Organization, every year one million people commit suicide. Slovenia has one of the world's highest suicide rates; in 2011 there were 30.9 suicides per 100,000 citizens, which ranked Slovenia on the 7th place. Suicide is a complex phenomenon and therefore cannot be attributed to a single causal factor, but to a combination of simultaneous effects of multiple factors, such as genetic and environmental factors. The results of previous molecular genetic studies of suicide highlight the role of the genetic code in the genes for the receptors, transporters and metabolism of neurotransmitters. Although numerous studies have been performed, we still do not have the answer on the aetiology of suicidal behaviour and its prevention. Since suicidal behaviour is complex, it is necessary for molecular-genetic studies to be addressed on several levels also. Important roles in the regulation of gene expression play epigenetic mechanisms. Epigenetics, namely, is the bond between genetic effects and environmental factors and represents good potential for deepening the understanding of suicidal behavior, which could contribute to its prevention.
The purpose of the project is to merge data on methylome and transcriptome, and associate them to suicide and certain mental state. In addition, we will try to identify specific biomarkers that would represent good targets for monitoring of patients and could contribute to timely intervention.
The epigenetic research could also help explain how the candidate genes that have been so far associated with suicidal behaviour, increase the risk for suicidal behaviour, and also explain the heredity of these changes beyond the static sequence in the DNA. This area of research is very promising from the pharmacological point of view, because the epigenetic markers, and, thus, indirectly also the gene expression, could be influenced at any stage in life. The findings of our study may contribute to improvement of prevention of suicide and more rationale psychopharmacotherapy of mental disorders that increases the risk of suicidal behaviour. Indirectly, it would also reduce the burden on the national health funds.
Significance for science
The proposed project is, in comparison with previous studies, which have been limited to exploring only the individual factors, a step forward in terms of integration and search for the interactions of various risk factors for suicide. With the juxtaposition of data on gene expression and DNA methylation the effects of the environment on the individual can be studied. Namely, the environment in combination with genetic background is crucial for the development of suicidal behaviour. Knowledge on multiple components and possible interplay between them, may allow the design of strategies for timely prevention of suicidal behaviour and also translation into clinical practice. The analysis of new biomarkers, which could be responsible for triggering suicidal behaviour, and thus better understanding of the mechanisms of the disorder, could lead to the identification of diagnostic and prognostic genomic biomarkers. On the basis of the latter preventive measures, and also pharmacotherapeutic and psychosocial interventions could be established, which would be aimed towards high risk individuals. Since Slovenia is a country with one of the highest suicide rates in the world, represents study of the phenomenon of suicidal behaviour in our population a significant advantage in terms of increased informativeness and better evaluation options of the acquired findings.
Significance for the country
Among the most important justifications of research and financing of genetic and genomic projects in medicine is their therapeutic potential. The latter is defined as the discovery of new targets for drugs for specific diseases, as well as the safe use of existing drugs and the financial sustainability of their use. Psychiatry is certainly one of the fields that is significantly less developed at this level in the sense that currently there is only one laboratory test (to determine polymorphisms in the cytochrome P450 enzymes involved in the metabolism of drugs) on the market, which can be used by psychiatrist to help determine the therapy.
With the proposed project we would like to contribute to the field of psychiatry in terms of making the conceptual guidelines that could contribute to better understanding of suicide and suicidal behaviour and to improve the level of health in Slovenia as well as elsewhere in the world. Additionally we could help towards development of more rational pharmacotherapy, which represents a greater safety for patients and also lower health funds.
The possibility that external factors influence the reversible epigenetic modifications in the genome, could in the future lead to the development of new therapeutic interventions for prevention of suicidal behaviour. A better understanding of the relationship between methylome and the expression of genes would also enable a better and more precise tailoring of treatment adopted to the patient's disease status, which is extremely dynamic and requires accurate monitoring and fast response rate.
Most important scientific results
Interim report,
final report
Most important socioeconomically and culturally relevant results
Interim report,
final report
