Can serotonin transporter genotype predict serotonergic function, chronicity, and severity of drinking?

Bankole A. Johnson, Martin A. Javors, John D. Roache, Chamindi Seneviratne, Susan E. Bergeson, Nassima Ait-Daoud, Michael A. Dawes, Jennie Z. Ma

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

Abstract

Serotonin transporter (5-HTT) activity is greater in carriers of the long (L) vs. short (S) alleles of the 5-HTT-linked polymorphic region (5′-HTTLPR) among healthy control subjects but not alcohol-dependent adults. In 198 alcoholics, we determined the relationship between current or lifetime drinking and platelet 5-HTT function and density among allelic variants of the 5′-HTTLPR. SS subjects were younger than L-carriers (LL and LS) (p < 0.0085) and had fewer years of lifetime drinking. For L-carriers, the mean of Bmax for paroxetine binding, but not Vmax for serotonin (5-HT) uptake, was lower than that for SS subjects (p < 0.05). More L-carriers than their SS counterparts had Vmax for 5-HT uptake below 200 nmol/107 platelets-min (p < 0.05) and Bmax for paroxetine binding below 600 nmol/mg protein (p < 0.06). Current drinking (drinks per day during the past 14 days) correlated positively with Km and Vmax of platelet 5-HT uptake (p < 0.05) and negatively with Bmax, but not Kd, of paroxetine binding (p < 0.05) for L-carriers alone. Years of lifetime drinking correlated negatively with Km and Vmax of platelet 5-HT uptake (p < 0.05) and Bmax, but not Kd, of paroxetine binding (p < 0.05) for L-carriers alone. Among L-carriers alone, there were higher levels of platelet 5-HT uptake and lower levels of platelet paroxetine binding with increased drinking, and more lifetime drinking was associated with modestly lower levels of 5-HT uptake and paroxetine binding. Thus, 5-HTT expression varies with current and lifetime drinking in L-carriers alone.

Original languageEnglish (US)
Pages (from-to)209-216
Number of pages8
JournalProgress in Neuro-Psychopharmacology and Biological Psychiatry
Volume32
Issue number1
DOIs
StatePublished - Jan 1 2008

Keywords

  • Alcohol dependence
  • Genotype
  • Humans
  • Paroxetine
  • Platelet
  • Serotonin transporter

ASJC Scopus subject areas

  • Pharmacology
  • Biological Psychiatry

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