Most studies of the association of suicide and suicide attempts with """"""""depression"""""""" have suffered from methodologic limitations, e.g., retrospective diagnosis, no structured diagnostic interviews, or overly restricted to one or other domain of potential predictor variables. The investigator has implemented the first comprehensive, psychobiological, prospective study of predictors of suicidal behavior in major depression. The study utilizes a unique cohort of 400 patients hospitalized with a Major Depressive Episode (200 past attempters, 200 nonattempters) who are receiving extensive diagnostic, behavioral and biological baseline assessments as part of the NIMH-funded Mental Health Clinical Research Center for the Study of Suicidal Behavior at Columbia University. The investigator is now requesting funding to continue support of the second half of this prospective study. Patients are reassessed for clinical state, life events, treatment and suicidal behavior at 3 months, 12 months and 24 months after discharge. Since determinants of suicidal behavior are derived from multiple domains including psychopathologic, genetic, biologic, psychologic, familial and psychosocial, the development of a general explanatory or predictive model of suicide attempt behavior is dependent on simultaneous assessment of potential risk factors from multiple domains in the same patient population. The testing of such a predictive model for suicidal behavior requires a prospective follow-up study. The investigator proposes a stress-diathesis model which posits that risk factors from both the stress/ trigger domain and from the diathesis/threshold domain are required in suicide attempters. The major hypotheses of the present study are that when a major depression is present, other factors, particularly from the diathesis/ threshold domain are paramount, e.g., characterological traits (such as aggression, impulsivity), and biological measures (CSF 5-HIAA, prolactin response to fenfluramine, serotonin-related gene markers) in distinguishing attempters from nonattempters, both retrospectively and prospectively. A second series of hypotheses is that predictors of high lethality suicide attempts differ from predictors of low lethality attempts. Thus far, the investigator has studied 175 patients at baseline, have tracked approximately 90 percent at three months and 80 percent at two years. Baseline analyses have identified several factors distinguishing attempters and nonattempters including aggression/impulsivity traits, low serotonergic activity, family history of suicidal acts, tryptophan (TPH) hydroxylase genotype, but not objective severity of depression. Future suicide attempts were related to past suicide attempt history, aggression/impulsivity, low serotonergic activity, level of antidepressant treatment and otherwise similar factors to past attempts. An expanded study population will permit comprehensive hypothesis testing and comparison of predictors.
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