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Genetic and genomic analyses of suicide

English title Genetic and genomic analyses of suicide
Applicant Malafosse Alain
Number 102168
Funding scheme Project funding
Research institution Division de Neuropsychiatrie HUG Belle-Idée
Institution of higher education University of Geneva - GE
Main discipline Neurology, Psychiatry
Start/End 01.10.2003 - 30.09.2006
Approved amount 299'490.00
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Keywords (3)

Suicide; association study; gene expression

Lay Summary (English)

Lead
Lay summary
Background : The correlation between serotonergic abnormalities and suicidal behaviour are among the most robust findings in biological psychiatry. Specifically, decreased serotonin turnover, as indicated by low concentrations of its metabolite, 5-hydroxyindolacetic acid, in the cerebrospinal fluid has been associated to violent suicidal behaviour.Following the demonstration of a complex genetic contribution to suicidal behaviour, several molecular genetic studies of serotonin-related genes have been published. Unfortunately, quite all these studies concern suicide attempt, and the extension of their conclusion to suicide is impossible. Indeed, even if suicide attempt and suicide probably share a common genetic and neurobiological background, several line of evidence suggest that there may be susceptibility factors specific to suicide.
Aims of the study: The first aim is to determine whether the main serotonin-related genes (TPH, 5-HTT, MAOA, 5-HT1A, 5-HT1B/1D, 5-HT2A, CAM-KII and BDNF) are susceptibility genes to suicide by using case-control studies of in large populations of suicide completers and controls. The second aim of this study is to identify genes that are deregulated in frontal cortex of people who committed suicide, and that, in turn, may have been responsible for the disease.
Methods: First, a candidate gene case-control study design will be applied. TPH, 5HTT, MAOA, 5-HT1A, 1B/1D, 2A, CAMK-II and BDNF polymorphisms will be determined in large samples of suicide victims (500), and controls (500). Genotyping will use a high-throughput method based on pyrosequencing. Second, the expression of genes will be analysed using the microarray method in the prefrontal cortex of suicide victims, and controls. Human brains were obtained at autopsy from the Institute of Forensic Medicine, Geneva. A retrospective searching for antemortem clinical diagnosis and drug treatment through review of medical histories of psychiatric units and clinician’s information will be performed. In suicide victims, a toxicological screening (quantitative assays for antidepressant and other psychotropic drugs, and ethanol) will be performed on blood, urine, liver, and kidney samples at the Toxicology Unit, Institute of Forensic Medicine.
These studies may help understanding better the molecular mechanisms in the brain that lead to suicide and may also point towards new directions for therapeutic interventions and prevention.
Direct link to Lay Summary Last update: 21.02.2013

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