Platelet serotonergic predictors of clinical improvement in obsessive compulsive disorder

J Clin Psychopharmacol. 2004 Feb;24(1):18-23. doi: 10.1097/01.jcp.0000104905.75206.50.

Abstract

Objective: Serotonin reuptake inhibitors (SRIs) are the most efficient pharmacological treatment of obsessive-compulsive disorders (OCD). Previous studies have suggested that some peripheral serotonergic parameters can be used to predict the clinical outcome of the treatment of OCD patients with SRIs. We tried to identify further peripheral serotonergic parameters that could help predict the clinical outcome of SRI treatment in a sample of patients with OCD.

Methods: We compared 19 OCD patients before and after 8 weeks of SRI treatment with 19 sex-matched and age-matched controls. We assessed clinical improvement and whole-blood serotonin (5-HT) concentration, platelet 5-HT transporter (5-HTT) and 5-HT2A receptor binding characteristics and platelet IP3 content.

Results: Before treatment, OCD patients had higher platelet IP3 content and fewer 5-HTT binding sites than the controls. Treatment with SRIs further lowered the number of 5-HTT binding sites, normalized platelet IP3 contents, and lowered the number of platelet 5-HT2A binding sites and whole-blood 5-HT concentrations below control values. The patients who improved most following SRI treatment had higher whole-blood 5-HT concentrations before treatment.

Conclusion: Our results confirm that whole-blood 5-HT concentration is a predictor for clinical improvement and indicate that abnormal intracellular mechanisms may be involved in OCD patients, in particular, the overstimulation of the phosphoinositide signaling system.

Publication types

  • Clinical Trial
  • Comparative Study
  • Controlled Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Binding Sites / drug effects
  • Binding Sites / physiology
  • Biomarkers / chemistry
  • Blood Platelets / chemistry*
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Carrier Proteins / blood
  • Carrier Proteins / chemistry
  • Cell Membrane / drug effects
  • Cell Membrane / metabolism
  • Child
  • Diet
  • Female
  • France
  • Humans
  • Imipramine / metabolism
  • Imipramine / pharmacology
  • Inositol Phosphates / chemistry
  • Inositol Phosphates / metabolism
  • Iodine Isotopes / chemistry
  • Iodine Isotopes / pharmacokinetics
  • Lysergic Acid Diethylamide / metabolism
  • Lysergic Acid Diethylamide / pharmacology
  • Male
  • Membrane Glycoproteins / blood
  • Membrane Glycoproteins / chemistry
  • Membrane Transport Proteins*
  • Middle Aged
  • Nerve Tissue Proteins*
  • Obsessive-Compulsive Disorder / diagnosis*
  • Obsessive-Compulsive Disorder / drug therapy
  • Paroxetine / metabolism
  • Paroxetine / pharmacology
  • Psychiatric Status Rating Scales
  • Radiochemistry
  • Receptor, Serotonin, 5-HT2A / chemistry
  • Receptor, Serotonin, 5-HT2A / physiology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin / blood
  • Serotonin Plasma Membrane Transport Proteins
  • Treatment Outcome*
  • Tritium
  • Tryptophan / metabolism

Substances

  • Biomarkers
  • Carrier Proteins
  • Inositol Phosphates
  • Iodine Isotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Receptor, Serotonin, 5-HT2A
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Serotonin Uptake Inhibitors
  • Tritium
  • Serotonin
  • Paroxetine
  • Tryptophan
  • Lysergic Acid Diethylamide
  • Imipramine