A positive history of suicide attempts, a history of childhood adversity, certain demographic variables, and issues related to social and medical support have been found to be stronger predictors of suicidal behaviors among psychiatric patients. The risk of suicide completion among clinical populations varies as a function of diagnosis and clinical features. For instance, among patients with major depressive disorder, the risk is conditional on the population of depressed patients, i.e., suicide risk is higher among depressed inpatients, lower among depressed patients from the general population and somewhere in between for depressed outpatients. For the latter group, the percentage of individuals who die by suicide is estimated to be between 2% and 5%. Clinical predictors ofsuicide among patients with major depression include symptom severity (as measured by a requirement of hospitalization), comorbidity with substance-related disorders, high levels of hopelessness, and a history of a past suicide attempt.
Over the last decades, it has become increasingly clear that individuals who die by suicide also have constitutional risk factors. However, the relationship between these predisposing factors, which to a certain extent are conferred by the individual's biological makeup, and suicide is not direct, but seems to be mediated and moderated by a number of different factors. Among these factors are clinical and demographic risk factors, such as those listed earlier, history of early life sexual and physical abuse, personality variants such as behavioral traits, and triggering factors such as recent life events and interpersonal stressors.
Epidemiological and clinical studies have consistently suggested that a positive family history of suicide acts as an important risk factor for suicide. As psychopathology also runs in families, a major question has been to what extent suicide aggregates in families independently of psychopa-thology. Studies have suggested that first-degree relatives of suicide probands have a 4-10 times higher risk of suicidal behavior than relatives of psychiatrically normal controls, and this is once other risk factors and psychopathology are accounted for. Genetic-epidemiological studies suggest that at least part of this familial aggregation is attributable to genetic effects (Turecki 2001).
Several lines of evidence point to the fact that familial transmission of suicidal behavior maybe mediated through the transmission of personality traits such as impulsive-aggressive behaviors. Personality traits represent emotional, behavioral, motivational, interpersonal, experiential, and cognitive styles that help us relate to and cope with the world. Clinical and community research suggest links between suicidality and extreme personality profiles. For instance, children who score high on a measure of disruptive behavior, a composite of aggressive, impulsive, and hyperactive behaviors, were found to be more likely to attempt suicide as young adults (Brezo et al. 2008). In general, most clinical and psychological autopsy studies (which use proxy-based interviews to investigate individuals who died by suicide) report elevated measures of ► impulsivity and ► aggressive behaviors among suicide attempters and completers as compared to controls, particularly among younger individuals. There is also direct and indirect evidence suggesting that relatives of suicide completers and suicide attempters have higher scores on these personality traits than controls.
Impulsivity may be conceptualized as the inability to resist impulses, which, from the strict phenomenological point of view, refer to explosive and instantaneous, automatic or semiautomatic psychomotor actions that are characterized by their sudden and incoercible nature. A more behavioral definition considers impulsivity as a drive, stimulus, or behavior that occurs without reflection or consideration for the consequences of such behavior. However, studies suggest that it is not the exclusive presence of impulsivity that appears to account for its observed association with suicide. Rather, impulsivity is frequently comorbid with other personality traits, particularly aggressive behaviors. As such, suicides tend to have high levels of aggressive-destructive impulsive traits, generally referred to as impulsive-aggressive behaviors. These have been operationally defined in suicide studies as a tendency to react with animosity or overt hostility, without consideration of possible consequences, when piqued or under stress.
The last decades have seen a growing interest in the understanding of the biological processes underlying suicide. Suicidal behavior has been associated with several neurobi-ological alterations, particularly in neurotransmission. For close to four decades, molecular studies have considered
► monoamines as prime suspects in suicidal behavior.
► Serotonin, in particular, has been the most investigated monoaminergic neurotransmitter system, and several lines of evidence suggest its involvement in the vulnerability to, and process of, suicide (Turecki and Lalovic 2005). Overall, while not always consistent, studies suggest that suicidal behavior is associated with reduced serotonergic neurotransmission. The evidence supporting serotonergic changes associated with suicide comes from studies using different and complementary approaches, including, but not limited to, investigations of cerebrospinal fluid levels of the serotonin metabolite 5-hydroxyindole acetic acid (5-HIAA), neuroendocrine challenges, postmortem receptor binding and imaging studies with receptor ligands. The serotonergic alterations seem to be more pronounced in the prefrontal cortex, where there is evidence of a decrease in presynaptic
► serotonin transporter binding and an upregulation of postsynaptic serotonin receptors. Together, these results imply reduced serotonergic input to this brain region. Among other functions, the ► prefrontal cortex is involved in the ► behavioral inhibition and expression of emotions. Reduced serotonergic input to this brain region could result in the impaired inhibition of behaviors such as impulsive aggression, which in turn could increase suicide risk.
Although the most extensively investigated neurotrans-mitter alterations associated with suicide have been those related to serotonergic changes, other neurotransmitters have also been investigated. Among these neurotrans-mitters are the noradrenergic, dopaminergic, opioid, gluta-matergic, and GABAergic neurotransmitter systems. More recently, promising and consistent results have pointed to the implication of the polyamine system, which is involved in the stress response, depression, and suicide.
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