Impact of Tryptophan Metabolism on the Vulnerability to Alcohol-Related Blackouts and Violent Impulsive Behaviours

Vignau, Jean; Soichot, Marion; Imbenotte, M.; Jacquemont, M. C.; Danel, Thierry; Vandamme, Michel; Lhermitte, Michel; Allorge, Delphine

doi:10.1093/alcalc/agp044

Cited by 11 publications

(7 citation statements)

References 69 publications

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“…Therefore, KYN metabolites may contribute to the aggression/impulsivity and neurocognitive deficits proposed as endophenotypes associated with suicidal behavior (Mann, 2009). A possible relationship between KYN and impulsivity is also suggested by two studies finding that KYN was strongly elevated (7-fold) in patients with a history of violent impulsive behaviors and alcohol-related blackouts (Vignau, 2010). Relationships between KYN, its metabolites, and behavioral phenotypes were not assessed in this study but should be tested in future studies.…”

Section: Discussionmentioning

confidence: 86%

“…Additionally, suicide risk is elevated among patients being treated with cytokines for medical problems, as seen in individual case histories (Baron, 1993; Janssen, 1994); in a case series of patients with multiple sclerosis who developed suicidal ideation (n=11) or made suicide attempts (n=4), and whose suicidality remitted after withdrawal of the interferon (Fragoso, 2010); and in a prospective study of patients with hepatitis C who experienced increased suicidal ideation over 8 weeks (Dieperink, 2004). KYN may be involved in other types of violent behavior apart from suicide attempts, according to two different research groups who have observed increased KYN plasma levels in antisocial violent offenders (Tiihonen, 2001) and in alcoholics with a history of blacked-out violent impulsive behaviors (Vignau, 2010). …”

Section: Discussionmentioning

confidence: 99%

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Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder

Sublette

Galfalvy

Fuchs

et al. 2011

Brain, Behavior, and Immunity

220

157

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Background Inflammation has been linked to depression and suicide risk. One inflammatory process that has been minimally investigated in this regard is cytokine-stimulated production of kynurenine (KYN) from tryptophan (TRP). Recent data suggest that KYN increases in cerebrospinal fluid (CSF) are associated with depressive symptoms secondary to immune activation. KYN may alter dopaminergic and glutamatergic tone, thereby contributing to increased arousal, agitation and impulsivity - important risk factors in suicide. We hypothesized that patients with Major Depressive Disorder (MDD) and a history of suicide attempt would have higher levels of KYN than depressed nonattempters, who in turn would have higher levels than healthy volunteers. Methods Plasma KYN, TRP, and neopterin were assayed by high performance liquid chromatography in three groups: healthy volunteers (n=31) and patients with MDD with (n=14) and without (n=16) history of suicide attempt. Analysis of variance tested for group differences in KYN levels. Results KYN levels differed across groups (F=4.03, df=(2,58), p=0.023): a priori planned contrasts showed that KYN was higher in the MDD suicide attempter subgroup compared with MDD non-attempters (t=2.105, df=58, p=0.040), who did not differ from healthy volunteers (t=0.418, df=58, p=0.677). In post-hoc testing, KYN but not TRP was associated with attempt status, and only suicide attempters exhibited a positive correlation of the cytokine activation marker neopterin with the KYN:TRP ratio, suggesting that KYN production may be influenced by inflammatory processes among suicide attempters. Conclusions These preliminary results suggest that KYN and related molecular pathways may be implicated in the pathophysiology of suicidal behavior.

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Section: Discussionmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder

Sublette

Galfalvy

Fuchs

et al. 2011

Brain, Behavior, and Immunity

220

157

View full text Add to dashboard Cite

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“…Some amino acids are correlated with violence in previous studies, especially tryptophan [67], which is the amino acid precursor of 5-HT biosynthesis [13]. A study of violent criminals found the plasma content of the amino acid tryptophan and other large neutral amino acids were increased [67][68][69]; however, much more studies have reported decreased tryptophan is correlated with aggressive behaviours [15,[70][71][72]. Instead of finding the plasma tryptophan as a differential metabolite, we found phenylalanine, tyrosine and tryptophan biosynthesis was a differential metabolic pathway between the schizophrenia patients with and without violence, which support amino acids play an important role in regulating violence.. We found vanillylmandelic acid, involved in tyrosine metabolism, was increased in V.SC, which is consistent with an earlier study reporting tyrosine supplements increased aggressive behaviours in mice [17].…”

Section: Discussionmentioning

confidence: 95%

Dysregulation of amino acids and lipids metabolism in schizophrenia with violence

Chen

Tang³

et al. 2020

BMC Psychiatry

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Background: Many studies have related biochemical characteristics to violence and have reported schizophrenia could elevated the risk of violent behaviour. However, the metabolic characteristics of schizophrenia patients with violence (V.SC) are unclear. Methods: To explore the metabolic characteristics of schizophrenia with violence and to identify potential biomarkers, untargeted metabolomics was performed by using gas chromatography time-of-flight mass spectrometry to analyse the plasma metabolites of fifty-three V.SC and twenty-four schizophrenia patients without violence (NV.SC). Multivariate and univariate analyses were performed to identify differential metabolites and biomarkers. Violence was assessed by the MacArthur Violence Assessment Study method. Psychiatric symptoms were assessed by the Positive and Negative Syndrome Scale. Results: Multivariate analysis was unable to distinguish V.SC from NV.SC. Glycerolipid metabolism and phenylalanine, tyrosine and tryptophan biosynthesis were the differential metabolic pathways between V.SC and NV.SC. We confirmed ten metabolites and five metabolites as metabolic biomarkers of V.SC by random forest and support vector machine analysis, respectively. The biomarker panel, including the ratio of L-asparagine to L-aspartic acid, vanillylmandelic acid and glutaric acid, yielded an area under the receiver operating characteristic curve of 0.808. Conclusions: This study gives a holistic view of the metabolic phenotype of schizophrenia with violence which is characterized by the dysregulation of lipids and amino acids. These results might provide information for the aetiological understanding and management of violence in schizophrenia; however, this is a preliminary metabolomics study about schizophrenia with violence, which needs to be repeated in future studies.

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“…Sublette et al (2011) is the first report of an association between KYN levels and history of suicide attempts among individuals with MDD. KYN may be involved in other types of violent behavior apart from suicide attempts, according to two different research groups who observed increased KYN plasma levels in antisocial violent offenders (Tiihonen et al, 2001) and in alcoholics with a history of blacked-out violent impulsive behaviors (Vignau et al, 2010). This study tested two a priori planned contrasts and found that mean plasma KYN levels were higher in MDD suicide attempters compared with MDD nonattempters.…”

Section: Case Controlmentioning

confidence: 89%

The influence of inflammatory cytokines in physiopathology of suicidal behavior

Miná

Lacerda-Pinheiro

Maia

et al. 2015

Journal of Affective Disorders

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Impact of Tryptophan Metabolism on the Vulnerability to Alcohol-Related Blackouts and Violent Impulsive Behaviours

Abstract: Put together, these findings support the validity of the BOVIB criterion to differentiate a sub-group of vulnerable AD subjects and suggest that OTL may help to concurrently define a specific endophenotype.

Cited by 11 publications

References 69 publications

Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder

Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder

Dysregulation of amino acids and lipids metabolism in schizophrenia with violence

The influence of inflammatory cytokines in physiopathology of suicidal behavior

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