Platelet dense granule secretion in adolescents with conduct disorder and substance abuse: Preliminary evidence for variation in signal transduction

  • Howard B. Moss
    Address reprint requests to Howard B. Moss, M.D., Center for Education and Drug Abuse Research, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, 3811 O'Hara Street, Pittsburgh, PA 15213.
    Center for Education and Drug Abuse Research, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Search for articles by this author
  • Jeffrey K. Yao
    Center for Education and Drug Abuse Research, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.
      Platelet aggregation responses to agonists have been employed as peripheral indices of the physiological responsiveness and density of neurotransmitter receptors, and in investigations of membrane functioning in psychopathological conditions. In particular, there are mechanistic similarities between neuronal secretory and receptor dynamics, and those involved in platelet dense granule secretion. Consequently, we have explored the platelet dense granule secretory responses to various agonists in abstinent male adolescents who meet current psychiatric diagnostic criteria for Conduct Disorder and Psychoactive Substance Use Disorder (CD+/PSUD+) in contrast to controls (CD−/PSUD−). The results showed a significant hyporesponsivity among experimental subjects to collagen, thrombin, adenosine diphosphate (ADP), ADP plus 0.2 μgm of serotonin, and ADP plus 1.0 μgm of serotonin. Only dense granule responses to arachidonic acid did not differentiate the groups. Taken together, the lack of agonist specificity suggests that a variation in signal transduction mechanisms could account for the observed reduction in dense granule secretion among CD+/PSUD+ adolescents. Association between dense granule secretory responses and substance use behavior, and comorbid psychiatric conditions are also examined.

      Key Words

      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


        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders.
        4th ed. American Psychiatric Association, Cold Spring Harbor, NY1994
        • Biederman J
        • Newcorn J
        • Sprich S
        Comorbidity of attention deficit hyperactivity disorder with conduct, depressive, anxiety, and other disorders.
        Am J Psychiatry. 1991; 148: 564-577
        • Boullin DJ
        • Woods HF
        • Grimes RPJ
        • Grahame-Smith DG
        Increased platelet aggregation responses to 5-hydroxytryptamine in patients taking chlorpromazine.
        Br J Clin Pharmacol. 1975; 2: 29-35
        • Boyle MH
        • Offord DR
        • Racine YA
        • Fleming JE
        • Szatmari P
        • Links PS
        Predicting substance use in early adolescence based on parent and teacher assessments of childhood psychiatric disorder: Results from the Ontario Child Health Study Follow-up.
        J Child Psychol Psychiatry. 1993; 34: 433-535
        • Boyle MH
        • Offord DR
        • Racine YA
        • Szatmari P
        • Fleming JE
        • Links P
        Predicting substance use in late adolescence: Results the Ontario Child Health Study Follow-up.
        Am J Psychiatry. 1992; 149: 761-767
        • Brook JS
        • Whiteman M
        • Gordon AS
        • Brook DW
        • Cohen P
        The psychosocial etiology of adolescent drug use and abuse.
        Genet Psychol Monogr. 1990; 116
        • Challen A
        • Branch WJ
        • Cummings JH
        Quantitation of platelet mass during aggregation in the electronic (Wellcome) Whole Blood Aggregometer.
        J Pharmacol Methods. 1982; 8: 115-122
        • Colman RW
        Platelet receptors.
        Hematol Oncol Clin North Am. 1990; 4: 27-42
        • De Clerk F
        • David J-L
        • Janssen PAJ
        Inhibition of 5-hydroxytryptamine-induced and -amplified human platelet aggregation by ketanserin (R 41 468), a selective 5-HT2 receptor antagonist.
        Agents Actions. 1982; 12: 388-397
        • Eysenck HJ
        Crime and Personality.
        3rd ed. Routledge and Kegan, Washington, DC1977
        • Feinman R
        • Detwiler T
        • Ingerman-Wojenski C
        The lumi-aggregometer as a research tool and clinical tool.
        in: Longnecker G The Platelets: Physiology and Pharmacology. Academic Press Inc, London1985: 429-440
        • Fowles DC
        The three arousal model: Implications of Gray's two-factor learning theory for heart rate, electrodermal activity and psychopathy.
        Psychophysiology. 1980; 17: 87-104
        • Hare RD
        Psychopathy. Theory and Research.
        John Wiley & Sons, Orlando1970
        • Hefez A
        • Oppenheim B
        • Youdim MBH
        Human platelet aggregation response to serotonin as an index of efficacy of chlorpromazine.
        in: Usdin E Sourkes T Youdin MBH Enzymes and Neurotransmitters in Mental Disease. John Wiley & Sons, New York1980: 77
        • Ingerman-Wojenski CM
        • Silver MJ
        A quick method for screening platelet dysfunctions using the whole blook lumiaggregometer.
        Thromb Haemostas. 1984; 51: 154-156
        • Lidberg L
        • Levander S
        • Schalling D
        • Lidberg Y
        Urinary catecholamines, stress, and psychopathy: A study of arrested men awaiting trial.
        Psychosom Med. 1978; 40: 116-125
        • Lesch K-P
        • Wolozin DL
        • Murphy DL
        • Riederer P
        Primary structure of the human serotonin uptake site: Identity with the brain serotonin transporter.
        J Neurochem. 1993; 60: 2319-2322
        • Manji HK
        G proteins: Implications for psychiatry.
        Am J Psychiatry. 1992; 149: 746-760
        • McBride PA
        • Mann JJ
        • Polley MJ
        • Wiley AJ
        • Sweeney JA
        Assessment of binding indices and physiological responsiveness of the 5-HT2 receptor on human platelets.
        Life Sci. 1987; 40: 1799-1809
        • McBride PA
        • Anderson GM
        • Hertzig ME
        • Sweeney JA
        • Kream J
        • Cohen DJ
        • Mann JJ
        Serotonergic responsivity in male young adults with autistic disorder. Results of a pilot study.
        Arch Gen Psychiatry. 1989; 46: 213-221
        • Moss HB
        • Yao JK
        • Panzak GL
        Serotonergic responsivity and behavioral dimensions in antisocial personality disorder with substance abuse.
        Biol Psychiatry. 1990; 28: 325-338
        • Moss HB
        • Vanyukov M
        • Martin CS
        Salivary cortisol responses and the risk for substance abuse in prepubertal boys.
        Biol Psychiatry. 1995; 38: 547-555
        • Nathan DG
        Introduction: Hematologic Diseases.
        in: Wyngaarden JB Smith LH Cecil Textbook of Medicine. W.B. Saunders, New York1988: 873-878
        • Ogloff JR
        • Wong S
        Electrodermal and cardiovascular evidence of a coping response in psychopaths.
        Criminal Justice and Behavior. 1990; 17: 231-245
        • Orvaschel H
        • Puig-Antich J
        • Chambers W
        • Fabrizi M
        • Johnson R
        Retrospective assessment of prepubertal major depression with the Kiddei-SADS-E.
        J Am Acad Child Adol Psychiatry. 1982; 21: 392-397
        • Passenon MK
        Platelet 5-hydroxytryptamine as model in pharmacology.
        Annales Medicanae Experimentalis et Biologiae Fenniae. 1968; 46: 416-422
        • Paul SM
        • Rehavi M
        • Rice KC
        • Ittah Y
        • Skolnick P
        Does high-affinity 3H-impramine binding label serotonin reuptake sites in brain and platelet?.
        Life Sci. 1981; 28: 2753-2760
        • Petersen SN
        • Lapetina EG
        Platelet activation and inhibition. Novel signal transduction mechanisms.
        Ann N Y Acad Sci. 1994; 714: 53-63
        • Pletcher A
        Platelets as models for monaminergic neurons.
        in: Youdin MBH Lovenberg W Sharman DF Lagnado JR Essays in Neurochemistry and Neuropharmacology. John Wiley & Sons, Philadelphia1978: 48-101
        • Pletcher A
        Liberation of catecholamines from blood platelets.
        Br J Pharmacol. 1981; 72: 349-354
        • Riess H
        • Braun G
        • Brehm G
        • Hiller E
        Critical evaluation of platelet aggregation in whole human blood.
        Am J Clin Pathol. 1986; 85: 50-56
        • Rubin R
        Effects of ethanol on platelets.
        Lab Invest. 1990; 63: 729-732
        • Sneddon JM
        Blood platelets as a model for monoamine-containing neurons.
        Prog Neurobiol. 1973; 15: 151-198
        • Spitzer R
        • Williams B
        • Gibbons M
        Instruction Manual for the Structured Clinical Interview for DSM-III-R (SCID, 4/1/87 Revision). Biometrics Research Department, NYS Psychiatric Institute, New York1987
        • Stahl SM
        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
        • Tarter RE
        • Alterman AI
        • Edwards KL
        Vulnerability to alcoholism in men: A behavior-genetic perspective.
        J Stud Alcohol. 1985; 46: 329-356
        • Tarter RE
        Evaluation and treatment of adolescent substance abuse: A decision tree method.
        Am J Drug Alcohol Abuse. 1990; 16: 1-46
        • Vanyukov MM
        • Moss HB
        • Plail JA
        • Blackson T
        • Mezzich AC
        • Tarter RE
        Antisocial symptoms in preadolescent boys and their parents: Associations with cortisol.
        Psychiatric Res. 1993; 46: 9-17
        • Virkkunen M
        • Linnoila M
        Brain serotonin, type II alcoholism and impulsive violence.
        J Stud Alcohol Suppl. 1993; 11: 163-169
        • Wand GS
        • Waltman C
        • Martin CS
        • McCaul ME
        • Levine MA
        • Wolfgang D
        Differential expression of guanosine triphosphate binding proteins in men at high and low risk for the future development of alcoholism.
        J Clin Invest. 1994; 94: 1004-1011
        • Whalley LJ
        • Reading HW
        • Rosie R
        ADP and arachidonic acid-induced platelet aggregation in schizophrenia and atypical psychoses.
        Psychol Med. 1984; 14: 207-211
        • Yao JK
        • van Kammen DP
        • Gurkis J
        • Peters JL
        Platelet aggregation and dense granule secretion in schizophrenia.
        Psychiatry Res. 1994; 54: 13-24