Suicide: a four-pathway clinical-biochemical model.

This chapter, based on a review of recent research as well as data presented in this report, proposes four hypothetical pathways leading to suicide in clinical depression: (1) an acute pathway involving severe anxiety/agitation associated with high brain corticotrophin-releasing factor (CRF or CRH) levels, (2) trait baseline and reactivity hopelessness, (3) severe anhedonia, and (4) trait impulsiveness associated with low brain serotonin turnover and low total cholesterol as a possible peripheral correlate. Clinical research showing evidence for acute versus chronic high-risk suicide factors and other studies linking severe anxiety/agitation to high CRF levels will be presented as associated with acute suicidal risk, which is potentially reversible with recognition and treatment. Evidence for anhedonia severity as a risk factor and trait, as well as evidence that baseline hopelessness and sensitivity are traits related to chronic suicide risk, will be presented. Finally, evidence relating low serum cholesterol to suicide in depressed inpatients will be presented in the context of literature suggesting a relationship between low serum cholesterol and violent death and suicide in population studies. Data suggesting a relationship between low serum cholesterol and decreased CSF 5-HIAA, suggesting reduced serotonin turnover, will be presented, in light of prior studies relating low CSF 5-HIAA and violent suicide. These data taken together suggest four pathways to suicide that are worth investigating in order to better understand the mechanisms leading to this behavior. Future possibilities and applications of these findings are discussed.