Pharmacogenetics of selective serotonin reuptake inhibitor response: a 6-month follow-up

Pharmacogenetics. 2004 Sep;14(9):607-13. doi: 10.1097/00008571-200409000-00005.

Abstract

Background: We previously reported the association between some genetic factors and short-term antidepressant outcome. In the present paper we investigated the same gene variants in a prospective 6-months naturalistic follow-up.

Methods: The sample included 185 inpatients affected by recurrent major depression consecutively admitted to the Psychiatric Inpatient Unit of San Raffaele Hospital from 1998 to 2003 and prospectively followed for 6 months after their recovery. All the patients were undertaking continuation therapy. The functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR), the tryptophan hydroxylase A218C substitution, a VNTR polymorphism located 1.2 kb upstream of the monoamine oxidase-A coding sequences, the CLOCK gene T3111C and the PER3exon15 gene T1940G substitutions were analysed, using PCR-based techniques.

Results: No association was found between clinical variables and relapses; subjects showing TT genotype at CLOCK gene tended to relapse within 6 months after recovery more than TC and CC subjects taken together. A non-significant tendency of SERTPR*s/s subjects to a minor frequency of relapse was also observed.

Conclusion: Some subjects showing remission after acute treatment relapsed within 6 months, despite undertaking a maintenance treatment; the causes could be heterogeneous, but CLOCK gene variants may influence the outcome.

MeSH terms

  • Adult
  • Alleles
  • Antidepressive Agents / pharmacology*
  • CLOCK Proteins
  • DNA / metabolism
  • Depressive Disorder, Major / genetics*
  • Exons
  • Female
  • Follow-Up Studies
  • Genotype
  • Humans
  • Imidazoles
  • Male
  • Membrane Glycoproteins / genetics*
  • Membrane Transport Proteins / genetics*
  • Middle Aged
  • Monoamine Oxidase / genetics
  • Nerve Tissue Proteins / genetics*
  • Pharmacogenetics / methods*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Selective Serotonin Reuptake Inhibitors / pharmacology*
  • Serotonin Plasma Membrane Transport Proteins
  • Time Factors
  • Trans-Activators / genetics
  • Treatment Outcome

Substances

  • Antidepressive Agents
  • Imidazoles
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Trans-Activators
  • DNA
  • clodanolene
  • Monoamine Oxidase
  • CLOCK Proteins
  • CLOCK protein, human