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

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.