Alcohol and Alcoholism Advance Access published online on September 16, 2009
Alcohol and Alcoholism, doi:10.1093/alcalc/agp044
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Impact of Tryptophan Metabolism on the Vulnerability to Alcohol-Related Blackouts and Violent Impulsive Behaviours
1 Centre Hospitalier Universitaire, Service d’Addictologie 57, boulevard de Metz 59037 Lille Cedex, France
2 Laboratoire de Toxicologie, Faculté des Sciences Pharmaceutiques et Biologiques de Lille 2, rue du Professeur Laguesse B.P. 83, 59006 Lille cedex, France
3 Unité Temps, émotion et cognition, Université Lille 3, Domaine du Pont de Bois 59653 Villeneuve d’Ascq Cedex, France
4 EA2679, Faculté de Médecine/Pôle Recherche, place de Verdun, 59045 Lille Cedex, France
* Corresponding author: Jean Vignau, Centre Hospitalier Universitaire, Service d’Addictologie 57, boulevard de Metz 59037 Lille Cedex, France. Tel: +33-320-44-60-98; Fax: +33-320-44-54-37; E-mail: j-vignau{at}chru-lille.fr
Received 3 October 2008; first review notified 9 December 2008; in revised form 12 June 2009, 20 July 2009; accepted 24 July 2009
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Abstract |
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Aims: We examined (1) the association of SLC6A4 genotypes and alcohol dependence (AD) in a sample of alcoholics; (2) the validity of lifetime occurrence of blacked-out violent impulsive behaviour (BOVIB) during binge drinking bouts as a criterion for subtyping AD patients and (3) a mechanistic hypothesis for BOVIB involving tryptophan-2,3-dioxygenase (TDO) activity. Methods: Three common polymorphisms of the SLC6A4 gene (5-HTTLPR, A/G SNP of LPR region and VNTR in intron 2) were genotyped. An oral tryptophan (Trp) load (OTL) was administered to a sample of patients seeking help for AD. BOVIB history and psychological status were screened by BOVIB-Q, depression (BDI), anxiety (BAI, STAI) and personality (TCI) questionnaires. During the 7 h following Trp load, serum kynurenine (Kyn) and Trp were monitored. Results: BOVIB+ patients showed significantly higher scores on depression, anxiety and character scales but no significant association was found between SLC6A4 polymorphisms and BOVIB. Patients with a history of BOVIB (BOVIB+ subgroup) differed from those exempt from such episodes (BOVIB– subgroup) for TDO activity response to OTL assessed by the Kyn:Trp ratio (P = 0.043) and the slope of concentration increase ratio (SCIR) of serum Kyn (P = 0.043). Conclusions: 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.