Genetic Variants Associated With Adolescent Suicide Attempts
Condition: Attempt Suicide
MeSH terms: Suicide; Suicide, Attempted
Study type: Interventional

Summary: 
      Suicidal behaviors is known to aggregate in families. The purpose of this study is to
      evaluate association between common polymorphisms in genes important for neurobiological
      pathways linked to suicidal behaviors and suicide attempt among adolescents patient.
    

Detailed description: 
      In France, suicide is the second leading cause of death among the 14-22 years population.
      Suicide behavior (SB) spans a spectrum ranging from suicidal ideation to suicide attempts and
      completed suicide. Several factors likely determine the predisposition to SB, including
      biological factors and psychosocial stressors. For biological factors, convergent evidence
      from adoption, family, and twin studies of suicide strongly suggests genetic contributions to
      liability for SB. Although genetic factors play a role in SB, identifying specific genes
      involved has proved challenging. Molecular-genetic technologies have made great advances in
      the past decade, including genome- wide searches for disease-causing genes with the linkage
      disequilibrium (LD) approach. Despite being a major public health problem in the youth
      population, genetic associations studies regarding suicidal behavior in adolescence are still
      rare. Genes that code for proteins involved in regulating serotonergic neurotransmission have
      thus been major candidate genes for association studies of SB. Among them, genes for
      serotonin metabolism (tryptophan hydroxylase, TPH), serotonin transport (5-HTT), and the
      serotonergic 2A (5-HT2A) receptor have received the most research attention.

      The identification of relevant genetic variants or SNPs in others genes which are involved in
      the neurobiological pathways (which the alteration may contribute to a suicidal behavior) can
      help not only to advance knowledge of the genetic bases of suicide but also to identify new
      therapeutic targets.

      On the basis of review of the literature, investigators will identify candidate genes that
      have been reported to be associated with suicidal events.

      The investigators will target genes related to central serotonergic and noradrenergic
      neurotransmission, and monoamine metabolism (MAOA). The investigators will also study genes
      involved in glutamatergic neurotransmission (GRIK2, GRIA3) and in the HPA axis (FKBP5) and
      genes that code for neurotrophic proteins (BDNF).

      DNA will be obtained from saliva. All genotyping will be carried out using standard
      polymerase chain reaction-based techniques that are routinely used in the Human Genetics
      Laboratory. DNA segments containing the target variable site will be amplified using unique
      sequence flanking primers.

      Tests of association between genetic variant and suicide attempt will be conducted using Chi
      squared and Armitage Trend Tests. Logistical regression analyses will be performed to
      evaluate the contribution of individual genetic variant to the prediction of suicide attempt,
      and to examine SNPs for potential gene-gene and gene-environment interactions.
    

Intervention name(s): SNP Genotyping; SNP genotyping
Intervention type(s): Genetic; Genetic
Intervention description(s): Individuals were genotyped at a total 96 SNP from 15 candidate gene
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Screening
Keywords: suicide; adolescent; genetic; SNP