Platelet serotonergic predictors of clinical improvement in obsessive compulsive disorder.
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.


CONCLUSIONS
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.
Delorme
Richard
R
Service de Psychopathologie de l'Enfant et de l'adolescent, AP-HP, Hôpital Robert Debré, Paris, France.
Chabane
Nadia
N
Callebert
Jacques
J
Falissard
Bruno
B
Mouren-Siméoni
Marie-Christine
MC
Rouillon
Frédéric
F
Launay
Jean-Marie
JM
Leboyer
Marion
M
D000293:Adolescent; D000328:Adult; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000737:chemistry; D001792:Blood Platelets / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D002352:Carrier Proteins / Q000097:blood / Q000737:chemistry; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002648:Child; D004032:Diet; D005260:Female; D005602:France; D006801:Humans; D007099:Imipramine / Q000378:metabolism / Q000494:pharmacology; D007295:Inositol Phosphates / Q000737:chemistry / Q000378:metabolism; D007456:Iodine Isotopes / Q000737:chemistry / Q000493:pharmacokinetics; D008238:Lysergic Acid Diethylamide / Q000378:metabolism / Q000494:pharmacology; D008297:Male; D008562:Membrane Glycoproteins / Q000097:blood / Q000737:chemistry; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins; D009771:Obsessive-Compulsive Disorder / Q000175:diagnosis* / Q000188:drug therapy; D017374:Paroxetine / Q000378:metabolism / Q000494:pharmacology; D011569:Psychiatric Status Rating Scales; D011854:Radiochemistry; D044402:Receptor, Serotonin, 5-HT2A / Q000737:chemistry / Q000502:physiology; D012701:Serotonin / Q000097:blood; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use; D016896:Treatment Outcome; D014316:Tritium; D014364:Tryptophan / Q000378:metabolism
D015415:Biomarkers; D002352:Carrier Proteins; D007099:Imipramine; D007295:Inositol Phosphates; D007456:Iodine Isotopes; D008238:Lysergic Acid Diethylamide; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017374:Paroxetine; D044402:Receptor, Serotonin, 5-HT2A; D012701:Serotonin; D050486:Serotonin Plasma Membrane Transport Proteins; D017367:Selective Serotonin Reuptake Inhibitors; D014316:Tritium; D014364:Tryptophan; C493230:SLC6A4 protein, human