Suicide is the third leading cause of death in adolescence in the United States. In addition, nonfatal forms of suicidal behavior are the most common reasons for the psychiatric hospitalization of adolescents in many countries (Center for Disease Control 1994). About 1600 youngsters, age 15–19, committed suicide in the United States in 2001; 3.4 million youngsters in this age group seriously considered suicide; 1.7 million made a suicide attempt; and 590,000 made a suicide attempt sufficiently serious to require medical attention (Grunbaum et al. 2004). It is of note that not all suicidal ideation or behavior in pediatric population is directly attributable to depression (Zalsman et al. 2006c). One major survey, the biennial Youth Risk Behavior Survey (YRBS) data for adolescents (Grunbaum et al. 2004), found that during the preceding 12 months, 28.6% of high school students nationwide had felt so sad or hopeless almost every day for ∼2 weeks in a row that they stopped doing some usual activities; 16.9% of students had seriously considered attempting suicide; 16.5% of students nationwide had made a plan to attempt suicide; 8.5% of students had actually attempted suicide one or more times; and 2.9% of students nationwide had made a suicide attempt that had to be treated by a doctor or nurse. Understanding the precursors of suicidal behavior in youths is important for the treatment and prevention of suicidal behavior in this population (Grunbaum et al. 2004).

Despite suicidal behavior being a major public health problem in the youth, relevant genetic studies are still sparse. Adoption studies suggest that there is a genetic susceptibility to suicide that is partially independent of the presence of a psychiatric disorder (Roy 1983). Roy et al. (1983) found suicide rates for monozygotic and dizygotic twins as 11.3% and 1.8%, respectively. When considered together with results from earlier twin studies, even greater differences were noted: 13.2% in monozygotic pairs versus 0.7% in dizygotic pairs.

These findings are supported by the study of Brent et al. (1996) who screened 58 adolescent suicide probands and concluded that suicidal behavior may be transmitted as a familial trait, regardless of the presence of Axis I or II diagnosis.

Suicidal behavior in adolescents has been found to have biochemical, genetic, and psychological correlates (Apter et al. 1990; Brent et al. 2003; Mann 2003). Suicidal behavior refers to the occurrence of suicide attempts and ranges from fatal acts (completed suicide) and high-lethality and failed suicide attempts (where serious intention and careful planning are evident, and survival is fortuitous) to low-lethality attempts.

Usually impulsive attempts that are triggered by social crisis seem to be ambivalent and contain a strong element of appeal for help (Beck et al. 1976; Stengel 1973). Intent and lethality are positively correlated and related to biological abnormalities that mostly involve the serotonergic system. The clinical and neurobiological study of failed suicides can provide information about completed suicide because the two populations are clinically and demographically similar (Mann 2003).

Among adolescents, the annual rate of suicide attempts that require medical attention is 2.6%, while suicide is much less prevalent. Among 15–19 year olds, the rates in 1998 were 14.6 per 100,000 in boys and 2.9 per 100,000 in girls (Brent 2002). There is a strong relationship between attempted suicide in adolescent psychiatric patients and eventual death from suicide (Garrison et al. 1991). Predisposition to suicidal behavior might be genetically transmitted as a trait independent of Axis I or II diagnosis (Brent et al. 1996). Suicide and suicidal behavior of adolescents are linked to a wide variety of psychiatric disorders, including affective illness, alcohol and substance abuse, conduct disorder, and schizophrenia (Shaffer 1998). Over 90% of adolescent and adult suicide victims appear to have at least one Axis I disorder (Brent 1995).

Several neurobiological systems were linked to suicide and suicidal behavior; mainly from neuroendocrine studies of the hypothalamic axes and studies of the serotonergic system (5-HT). Data were collected utilizing several methodologies such as hormonal suppression tests, sleep studies, postmortem studies, and genetic factor analysis. Currently, it is believed that the most plausible biological system related to suicidality, impulsive violence, and anxiety is the serotonergic system (Apter et al. 1990, 1993b; Mann 2003; Zalsman et al. 2006c).