Impact of tryptophan metabolism on the vulnerability to alcohol-related blackouts and violent impulsive behaviours.
OBJECTIVE
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.
Vignau
Jean
J
Centre Hospitalier Universitaire, Service d'Addictologie, 59037 Lille Cedex, France. j-vignau@chru-lille.fr
Soichot
Marion
M
Imbenotte
Michel
M
Jacquemont
Marie-Claudine
MC
Danel
Thierry
T
Vandamme
Michel
M
Lhermitte
Michel
M
Allorge
Delphine
D
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000437:Alcoholism / Q000150:complications / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D000647:Amnesia / Q000139:chemically induced / Q000378:metabolism* / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000523:psychology; D007737:Kynurenine / Q000097:blood; D008875:Middle Aged; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D014364:Tryptophan / Q000008:administration & dosage / Q000097:blood*; D014366:Tryptophan Oxygenase / Q000378:metabolism; D014754:Violence / Q000523:psychology*
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D007737:Kynurenine; D014364:Tryptophan; D014366:Tryptophan Oxygenase