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Prog Neuropsychopharmacol Biol Psychiatry. 2016 Oct 3;70:8-16. doi: 10.1016/j.pnpbp.2016.04.012. Epub 2016 Apr 23.

Tryptophan via serotonin/kynurenine pathways abnormalities in a large cohort of aggressive inmates: markers for aggression.

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Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University Health Center, McGill University, Montreal, QC, Canada; Division of Neuroscience, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.
Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Padova, Italy.
Institut Philippe-Pinel, Montreal, Qc, Canada.
Institut Philippe-Pinel, Montreal, Qc, Canada; Université du Québec à Trois-Rivières, Trois-Rivières, QC, Canada.
Institut Philippe-Pinel, Montreal, Qc, Canada; Department of Psychoeducation, Sherbrooke University, QC, Canada.
McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, Canada.
Neurobiological Psychiatry Unit, Department of Psychiatry, McGill University Health Center, McGill University, Montreal, QC, Canada. Electronic address:


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.


aggressive behavior; biomarkers; kynurenine; serotonin; tryptophan

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