TY - JOUR
T1 - Tryptophan via serotonin/kynurenine pathways abnormalities in a large cohort of aggressive inmates: Markers for aggression
AU - Comai, Stefano
AU - Bertazzo, Antonella
AU - Vachon, Jeanne
AU - Daigle, Marc
AU - Toupin, Jean
AU - Côté, Gilles
AU - Turecki, Gustavo
AU - Gobbi, Gabriella
PY - 2016/10/3
Y1 - 2016/10/3
N2 - Aggressive behavior is one of the most challenging symptoms in psychiatry, and biological markers for aggression lack of large sample validations. Serotonin (5-HT) and other neuroactive compounds deriving from Tryptophan (Trp), including kynurenine (Kyn), have not yet been investigated in large cohorts of aggressive individuals to validate their potential as biomarkers of aggression.In 361 male inmates we measured serum levels of Trp, 5-hydroxytryptophan, 5-HT, Kyn, the ratios 5-HT/Trp * 1000 and Kyn/Trp * 1000, and performed Structured Clinical Interview for DSM-IV Axis-I and -II Disorders (SCID-I and -II), global assessment of functioning (GAF), and scales for aggressive behavior, impulsivity, adult attention-deficit/hyperactivity disorder (ADHD), and intelligent quotient (IQ).Aggressive compared to non-aggressive inmates exhibited lower Trp and Kyn serum levels but higher levels of 5-HT and 5-HT/Trp * 1000, higher levels of impulsivity and ADHD indices, lower IQ and GAF, higher prevalence of mood disorders, drug abuse/dependence, and borderline, conduct and antisocial behaviors. Interestingly, Kyn/Trp * 1000 was positively correlated to the number of severe aggressive acts (r = 0.593, P <0.001). After adjusting for confounding factors, logistic regression analysis indicated that 5-HT/Trp * 1000, antisocial behavior, and GAF were predictors of aggressive behavior. The model combining these three predictors had an area under the ROC curve of 0.851 (95% CI 0.806-0.895).This study indicates that while circulating Trp is reduced in aggressive individuals, the combination of biological (5-HT/Trp ratio) and psychopathological (antisocial behavior and GAF) markers discriminates between aggressive and non-aggressive behavior suggesting the potential of a multi-marker approach in psychiatry given the heterogenic nature of mental diseases.
AB - Aggressive behavior is one of the most challenging symptoms in psychiatry, and biological markers for aggression lack of large sample validations. Serotonin (5-HT) and other neuroactive compounds deriving from Tryptophan (Trp), including kynurenine (Kyn), have not yet been investigated in large cohorts of aggressive individuals to validate their potential as biomarkers of aggression.In 361 male inmates we measured serum levels of Trp, 5-hydroxytryptophan, 5-HT, Kyn, the ratios 5-HT/Trp * 1000 and Kyn/Trp * 1000, and performed Structured Clinical Interview for DSM-IV Axis-I and -II Disorders (SCID-I and -II), global assessment of functioning (GAF), and scales for aggressive behavior, impulsivity, adult attention-deficit/hyperactivity disorder (ADHD), and intelligent quotient (IQ).Aggressive compared to non-aggressive inmates exhibited lower Trp and Kyn serum levels but higher levels of 5-HT and 5-HT/Trp * 1000, higher levels of impulsivity and ADHD indices, lower IQ and GAF, higher prevalence of mood disorders, drug abuse/dependence, and borderline, conduct and antisocial behaviors. Interestingly, Kyn/Trp * 1000 was positively correlated to the number of severe aggressive acts (r = 0.593, P <0.001). After adjusting for confounding factors, logistic regression analysis indicated that 5-HT/Trp * 1000, antisocial behavior, and GAF were predictors of aggressive behavior. The model combining these three predictors had an area under the ROC curve of 0.851 (95% CI 0.806-0.895).This study indicates that while circulating Trp is reduced in aggressive individuals, the combination of biological (5-HT/Trp ratio) and psychopathological (antisocial behavior and GAF) markers discriminates between aggressive and non-aggressive behavior suggesting the potential of a multi-marker approach in psychiatry given the heterogenic nature of mental diseases.
KW - Aggressive behavior
KW - Biomarkers
KW - Kynurenine
KW - Serotonin
KW - Tryptophan
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U2 - 10.1016/j.pnpbp.2016.04.012
DO - 10.1016/j.pnpbp.2016.04.012
M3 - Article
VL - 70
SP - 8
EP - 16
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
SN - 0278-5846
ER -