Research Article| Volume 30, ISSUE 2, P131-139, July 15, 1991

Download started.


Serotonin uptake and imipramine binding in the blood platelets of obsessive-compulsive disorder patients

  • Bijan Bastani
    Address reprint requests to Bijan Bastani, M.D., Psychobiology Clinic, University Hospitals of Cleveland, 2040 Abington Road, Cleveland, OH 44106-5000.
    Department of Psychiatry, Laboratory of Biological Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
    Search for articles by this author
  • Ramesh C. Arora
    Department of Psychiatry, Laboratory of Biological Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
    Search for articles by this author
  • Herbert Y. Meltzer
    Department of Psychiatry, Laboratory of Biological Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA
    Search for articles by this author
  • Author Footnotes
    2 We are grateful to Ms. Lisa Kregel for laboratory assistance, Mr. William Daley for coordinating research activities, Ms.Jar-chi Lee for data analysis, and to Ms. Lee Mason for typing the manuscript.
    1 Herbert Y. Meltzer is the recipient of a USPHS Research Career Scientist Award MH 47808.
      This paper is only available as a PDF. To read, Please Download here.


      14C-Serotonin (5-HT) uptake and 3H-imipramine binding (IB) were studied in the blood platelets of 20 obsessive-compulsive disorder (OCD) patients, 53 normal controls (5-HT uptake) and 32 normal controls (IB binding). The maximum number of binding sites (Bmax) was significantly decreased in OCD patients compared to normal controls, but there was no difference in the affinity for 3H-imipramine (Kd). The affinity for 5-HT uptake (Km) was also decreased in the OCD patients but the maximum velocity of 5-HT uptake sites (Vmax) was not significantly different in OCD patients and normal volunteers. There were trends for the Slowness Subscale of the Maudsley Obsessional-Compulsive Inventory (MOCI) to be positively correlated with the Km of 5-HT uptake (p = 0.094), whereas the Global Scale, Checking Subscale, and Doubting Conscientiousness Subscale of MOCI were negatively correlated with the Kd of IB (p = 0.066, p = 0.08, and p = 0.062, respectively). The results provide further evidence for the dysfunction of the serotonergic system in OCD.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Ahtee L.
        • Briley M.
        • Raisman R.
        • Lebrec D.
        • Langer S.Z.
        Reduced uptake of serotonin but unchanged 3H-imipramine binding in the platelets from cirrhotic patients.
        Life Sci. 1981; 29: 2323-2329
        • American Psychiatric Association
        ed 3. Diagnostic and statistical manual of mental disorders. American Psychiatruc Association, Washington, DC1987 (revised)
        • Arora R.C.
        • Meltzer H.Y.
        A modified assay method for determining serotonin uptake in human platelets.
        Clin Chim Acta. 1981; 112: 225-233
        • Arora R.C.
        • Meltzer H.Y.
        Imipramine binding in subpopulations of normal human blood platelets.
        Biol Psychiatry. 1984; 19: 257-262
        • Arora R.C.
        • Tong C.
        • Jackman H.L.
        • Stoff D.
        • Meltzer H.Y.
        Serotonin uptake and imipramine binding in blood platelets and brain of Fawn-hooded and Sprague-Dawley rats.
        Life Sci. 1983; 33: 437-442
        • Arora R.C.
        • Wunnicke V.
        • Meltzer H.Y.
        Effect of protein concentration on kinetic constants (Kd and Bmax) of 3H-imipramine binding in blood platelets.
        Biol Psychiatry. 1985; 20: 116-119
        • Arora R.C.
        • Locascio J.J.
        • Meltzer H.Y.
        3H-imipramine binding in blood platelets of schizophrenic patients.
        Psychiatry Res. 1986; 19: 215-224
        • Barbaccia M.L.
        • Gandolfi O.
        • Chuang D.-M.
        • Costa E.
        Modulation of neuronal serotonin uptake by a putative endogenous ligand of imipramine recognition sites.
        in: Proc Natl Acad Sci. 80. 1983: 5134-5138
        • Barkai A.I.
        • Kowalik S.
        • Baron M.
        Effect of membrane protein concentration on binding of 3H-imipramine in human platelets.
        Biol Psychiatry. 1985; 20: 215-219
        • Barkai A.I.
        • Baron M.
        • Kowalik S.
        • Cooper T.B.
        Modification of ligand binding to membranes by a soluble acceptor. Alpha-1-acid geycoprotein attenuates 3H-imipramine binding to cerebral membranes.
        Biol Psychiatry. 1986; 21: 883-888
        • Bastani B.
        • Nash J.F.
        • Meltzer H.Y.
        Prolactin and cortisol responses to MK-212, a serotonin agonist, in obsessive-compulsive disorder.
        Arch Gen Psychiatry. 1990; 47: 833-839
        • Black D.W.
        • Kelly M.
        • Myers C.
        • Noyers R.
        Tritiated imipramine binding in obsessive-compulsive volunteers and psychiatrically normal controls.
        Biol Psychiatry. 1990; 27: 319-327
        • Briley M.
        • Langer S.Z.
        • Sette M.
        Allosteric interaction between the 3H-imipramine binding site and the serotonin uptake mechanism.
        in: Proc Br Pharmacol Soc. 1981: 817P-818P
        • Briley M.S.
        • Langer S.Z.
        • Raisman R.
        • Sechter D.
        • Zarifian E.
        Tritiated imipramine binding sites are decreased in platelets of untreated depressed patients.
        Science. 1980; 209: 303-305
        • Brusov O.S.
        • Fornenko A.M.
        • Katasonov A.B.
        Human plasma inhibitors of platelet serotonin uptake and imiramine receptor binding: Extraction and heterogeneity.
        Biol Psychiatry. 1985; 20: 235-244
        • Carstens M.E.
        • Engelbrecht A.H.
        • Russell V.A.
        • et al.
        Imipramine binding sites on platelets of patients with major depressive disorder.
        Psychiatry Res. 1986; 18: 333-342
        • Coppen A.
        • Swade C.
        • Wood K.
        Platelet 5-hydroxytryptamine accumulation in depressive illness.
        Clin Chim Acta. 1978; 87: 165-168
        • Dixon M.
        • Webb E.C.
        in: Academic Press, New York1958: 62-179
        • Endicott J.
        • Spitzer R.L.
        Diagnostic interview: Schedule for affective disorders and schizophrenia.
        Arch Gen Psychiatry. 1987; 35: 837-844
        • Faludi B.
        • Magyar I.
        • Tekes K.
        • Tothfalusi L.
        • Magyar K.
        Measurement of 3H-serotonin uptake in platelets of major depressive episodes.
        Biol Psychiatry. 1988; 23: 833-836
        • Flament M.F.
        • Rapport J.L.
        • Murphy D.L.
        • Berg C.J.
        • Lake R.
        Biochemical changes during clomipramine treatment of childhood obsessive-compulsive disorder.
        Arch Gen Psychiatry. 1987; 44: 219-225
        • Friedl W.
        • Propping P.
        • Weck B.
        3H-imipramine binding in platelets: Influence of varying proportions of intact platelets in membrane preparations on binding.
        Psychopharamcology. 1983; 80: 96-99
        • Gentsch C.
        • Lichsteiner M.
        • Gastpar M.
        • Gastpar G.
        • Foer H.
        3H-imipramine binding sites in platelets of hospitalized psychiatric patients.
        Psychiatry Res. 1985; 14: 177-187
        • Hamilton M.
        A rating scale for depression.
        J Neurol Neurosurg Psych. 1960; 23: 56-62
        • Healy D.
        • O'Halloran A.
        • Carney P.A.
        • Leonard B.E.
        Variations in platelet 5-hydroxy-tryptamine in control and depressed populations.
        J Psychiatr Res. 1986; 20: 345-353
        • Insel T.R.
        • Mueller E.A.
        • Alterman I.
        • Linnoila M.
        • Murphy D.L.
        Obsessive-compulsive disorder and serotonin: is there a connection?.
        Biol Psychiatry. 1985; 20: 1174-1188
        • Langer S.Z.
        • Briley M.S.
        • Raisman R.
        • Henry J.F.
        • Marselli P.L.
        Specific 3H-imipramine binding in human platelets: influence of age and sex.
        Naunyn Schmiedebergs Arch Pharmacol. 1980; 313: 189-194
        • Lowry O.H.
        • Rosebrough N.J.
        • Farr A.L.
        • Randall R.J.
        Protein measurement with the folin phenol reagent.
        J Biol Chem. 1951; 193: 265-275
        • Malmgren R.
        • Bewig H.
        • Olsson P.
        Effects of different anticoagulants on human platelet size distribution and serotonin (5-HT) induced shape change and uptake kinetics.
        Thromb Res. 1985; 39: 649-661
        • Meltzer H.Y.
        • Arora R.C.
        Platelet serotonin studies in affective disorders: evidence for a serotonergic abnormality?.
        in: Sandler M. Coppen A. Harnett S. 5-Hydroxytryptamine in Psychiatry: A Spectrum of Ideas. Oxford University Press, New York1991: 50-89
        • Meltzer H.Y.
        • Arora R.C.
        • Baber R.
        • Tricou B.J.
        Serotonin uptake in blood platelets of psychiatric patients.
        Arch Gen Psychiatry. 1981; 38: 1322-1326
        • Meltzer H.Y.
        • Arora R.C.
        • Robertson A.
        • Lowy M.
        Platelet 3H-imipramine binding and platelet 5-HT uptake in affective disorders and schizophrenia.
        Clin Neuropharmacol. 1984; 7: 320-321
        • Paul S.M.
        • Rehavi M.
        • Skolnick P.
        • Goodwin F.K.
        Demonstration of specific high affinity binding sites for [3H]imipramine on human platelets.
        Life Sci. 1980; 26: 953-959
        • Paul S.M.
        • Rehavi M.
        • Skolnick P.
        • Ballenger J.C.
        • Goodwin F.K.
        Depressed patients have decreased binding of tritiated imipramine to platelet serotonin transporter.
        Arch Gen Psychiatry. 1981; 38: 1315-1317
        • Poirer M.-F.
        • Benkelfat C.
        • Loo H.
        • et al.
        Reduced Bmax of [3H]imipramine binding to platelets of depressed patients free of previous medication with 5-HT uptake inhibitors.
        Psychopharmacology. 1986; 89: 450-461
        • Rachman S.J.
        • Hodgson R.J.
        Obsessions and compulsions.
        Prentice-Hall, Englewood Cliffs, NJ1980
        • Rasmussen S.A.
        • Tsuang M.T.
        The epidemiology of obsessive compulsive disorder.
        in: Jenike M.A. Obsessive-Compulsive Disorder: Theory and Management. PSG Publishing, Littleton, MA1986: 23-44
        • Rausch J.L.
        • Janowsky D.S.
        • Risch S.C.
        • Huey L.Y.
        A kinetic analysis and replication of decreased platelet serotonin uptake in depressed patients.
        Psychiatry Res. 1986; 19: 105-112
        • Rehavi M.
        • Ventura I.
        • Sarne Y.
        Demonstration of endogenous “imipramine-like” material in brain.
        Life Sci. 1985; 36: 687-693
        • Sahai S.
        • Arora R.C.
        • Meltzer H.Y.
        Platelet monoamine oxidase. I: Effect of temperature, anticoagulant, and centrifugation technique.
        Biol Psychiatry. 1981; 16: 1077-1083
        • Scott M.
        • Reading M.
        • Reading H.W.
        • Loudon J.B.
        Studies on human platelets in affective disorders.
        Psychopharmacology. 1979; 60: 131-135
        • Sneddon J.M.
        Blood platelets as a model for monoamine containing neurons.
        Prog Neurobiol. 1973; 1: 151-198
        • Spitzer R.L.
        • Endicott J.
        • Robins E.
        Research diagnostic criteria: rationale and reliability.
        Arch Gen Psychiatry. 1978; 35: 773-782
        • Stahl S.M.
        The human platelet: A diagnostic and research tool for the study of biogenic amines in psychiatric and neurologic disorders.
        Arch Gen Psychiatry. 1977; 34: 509-516
        • Thoren P.
        • Asberg M.
        • Asberg M.
        • Bertilsson L.
        • Mellstrom B.
        • Sjogvist F.
        • Traskman L.
        Cloripramine treatment of obsessive-compulsive disorder. II. Biochemical aspects.
        Arch Gen Psychiatry. 1980; 37: 1289-1294
        • Thoren P.
        • Asberg M.
        • Cronholm B.
        • Jornestedt L.
        • Traskman L.
        Clomipramine treatment of obsessive-compulsive disorder: 1. A controlled clinical trial.
        Arch Gen Psychiatry. 1980; 37: 1281-1285
        • Tuomisto J.
        • Tukiainen E.
        Nature. 1976; 262: 596-598
        • Tuomisto J.
        • Tukiainen E.
        • Ahlfors U.G.
        Decreased uptake of 5-hydroxytryptamine in blood platelets from patients with endogenous depression.
        Psychophamacology. 1979; 65: 141-147
        • Weizman A.
        • Carmi M.
        • Hermesh H.
        • et al.
        High-affinity imipramine binding and serotonin uptake in platelets of eight adolescent and ten adult obsessive-compulsive patients.
        Am J Psychiatry. 1986; 143: 335-339
        • Wennogle L.P.
        • Meyerson L.R.
        Serotonin modulates the dissociation of [3H]imipramine from human platelet recognition sites.
        Eur J Pharmacol. 1983; 86: 303-307
        • Wood P.L.
        • Suranyi-Cadotte B.E.
        • Nair N.P.V.
        • LaFaille F.
        • Schwartz G.
        Lack of association between [3H]imipramine binding sites and uptake of serotonin in control, depressed and schizophrenic patients.
        Neuropharmacology. 1983; 22: 1211-1214
        • Zohar J.
        • Insel R.
        Obsessive-compulsive disorder: Psychobiological approaches to diagnosis, treatment, and pathophysiology.
        Biol Psychiatry. 1987; 22: 667-687
        • Zohar J.
        • Mueller E.A.
        • Insel T.R.
        • Zohar-Kadouch R.C.
        • Murphy D.L.
        Serotonergic responsivity in obsessive-compulsive disorder. Comparisons of patients and healthy controls.
        Arch Gen Psychiatry. 1987; 44: 946-951