Stress, Genes and the Biology of Suicidal Behavior

Abstract

Suicidal behavior is in part heritable. Studies seeking the responsible candidate genes have examined genes involved in neurotransmitter systems demonstrated to have altered function in suicide and attempted suicide. These neurotransmitter systems include the serotonergic, noradrenergic and dopaminergic systems and the HPA axis. With some exceptions, most notably the serotonin transporter promotor HTTLPR polymorphism, replication of candidate gene association studies findings has proven difficult. This chapter reviews what is known of specific gene effects and geneenvironment interactions that influence risk for suicidal behavior. Effects of childhood stress on development and how that influences adult responses to current stress will be shown to be relevant for mood disorders, aggressive/impulsive traits and suicidal behavior. KeywordsSuicide; Mood Disorders; Genetics; Stress; Serotonin; HPA axis Suicidal Behavior and GeneticsFamily, twin, and adoption studies provide evidence of the heritability of suicide and attempted suicide, in part independent of the familial transmission of major psychiatric disorders (see Brent & Mann for a review 1 ). From twin studies, based on case and register studies, estimates of heritability for suicide range between 21-50%, and 30-55% for a broader phenotype of suicidal behavior (attempts, thoughts, plans) based on general population studies. 2 Identifying the relevant genes and the neurobiological pathways through which they contribute to the etiology of suicidal behavior is important for designing and implementing preventative strategies. The first wave of genetic studies sought to identify genes involved in suicide and/ or attempted suicide by linkage studies or specific single nucleotide polymorphisms (SNPs) in association studies. Emerging approaches aim to investigate functional genomics using microarray technologies to profile expression of thousands of genes simultaneously (see Mirnics et al 3 for a review) or doing a genome wide array for hundreds of thousands of SNPs.Candidate genes for association studies have been generally selected based on evidence from neurobiological studies in suicide. Consequently, the serotonergic system has been most extensively investigated, with other target systems including the dopaminergic and

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