Psychiatry Research 119 (2003) 199–204
0165-1781/03/$ - see front matter ᮊ 2003 Elsevier Science Ireland Ltd. All rights reserved.
Serum tryptophan ratio and suicidal behavior in adolescents:
a prospective study
Duncan B. Clark*
Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, 3811 O’Hara Street, Pittsburgh, PA 15213,
Received 22 August 2002; received in revised form 5 February 2003; accepted 26 April 2003
A lower ratio of tryptophan to other amino acids in serum (tryptophan ratio), established as an index of serotonin
precursor available to the brain, has been shown to be associated with increased suicidal behavior in cross-sectional
studies. The purpose of this study was to conduct the first prospective examination of the utility of the tryptophan
ratio along with clinical variables in predicting suicidal behavior in high-risk and reference adolescents. Adolescents
with alcohol use disorders (AUDs) and prior suicidal attempts (ns20), adolescents with AUDs without suicide
attempts (ns20), and community controls with neither of these characteristics (ns20) were matched on demographic
variables. These groups were not significantly different on the tryptophan ratio at baseline. Of 56 subjects who
completed follow-up assessments, six had suicidal behavior in the follow-up period. The tryptophan ratio, along with
demographic and clinical variables, was examined using Cox regression with a backward stepwise variable elimination
procedure. In the final model, the tryptophan ratio and major depressive disorder both significantly contributed to the
prediction of suicidal behavior. This finding suggests that the tryptophan ratio may improve the identification of
adolescents at high risk for suicidal behavior.
ᮊ 2003 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Tryptophan; Suicide; Adolescents
Risk factors for suicidal behavior in adolescents
include alcohol use disorders (AUDs), major
depressive disorder (MDD) and previous suicide
attempts (Brent et al., 1999; Kelly et al., 2001).
Despite advances in the identification of clinical
risk factors, the prediction of suicidal behavior
remains an inexact pursuit (Cornelius et al., 2001).
*Tel.: q1-412-624-2636; fax: q1-412-624-0850.
E-mail address: email@example.com (D.B. Clark).
Characteristics influencing brain serotonin are con-
sidered leading candidates for biological markers
predicting suicidal behavior (Mann et al., 2001),
with one of these characteristics being low periph-
eral tryptophan (Pfeffer et al., 1998).
Tryptophan, a large neutral amino acid found in
dietary proteins, is the precursor for serotonin.
Brain tryptophan levels are determined by the ratio
of plasma tryptophan concentration to the concen-
trations of other large neutral amino acids compet-
ing for transport across the blood-brain barrier