Research Article| Volume 23, ISSUE 8, P797-806, April 15, 1988

Download started.


Decreased mononuclear leukocyte TSH responsiveness in patients with major depression

      This paper is only available as a PDF. To read, Please Download here.


      A subgroup of individuals with major depressive disorder have an impaired thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH). The molecular relationship between the mechanism of this “blunted” TSH response and depression is unknown. Numerous recent studies have characterized similarities and interactions between the immune and neuroendocrine systems. As the immune system both produces and responds to TSH, we utilized a peripheral blood leukocyte system to compare immunoreactive (ir)-TSH responsiveness in 10 adult patients (1 man, 9 women) with Research Diagnostic Criteria for major depressive disorder to that of 9 control subjects. All subjects had normal baseline serum TSH and T4 concentrations. Isolated mononuclear leukocytes were treated in vitro with either 0.5 μg/ml staphylococcal enterotoxin A (SEA), 50 μg/ ml TRH, or no stimulant. After incubation, the cells were monitored for ir-TSH production by indirect immunofluorescence and reverse hemolytic plaque assay using antisera to TSH-β. The culture supernates were analyzed by TSH radioimmunoassay. SEA- and TRH-treated cell cultures from depressed individuals had significantly fewer immunofluorescent positive cells, as well as significantly fewer and smaller plaques, than did similarly treated leukocytes from control subjects. The increase in supernatant ir-TSH was significantly less in TRH-treated cultures from depressed patients as compared to normals (p < 0.05). These results suggest that examination of mononuciear leukocyte TSH production may reflect an altered state of neuroendocrine function and may thus be a useful marker for major depressive disorder.
      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


      1. Ader R Psychoneuroimmunology. Academic Press, Orlando, FL1981
        • Bartrop RW
        • Lazarus LE
        • Luckhurst E
        • Kiloh LG
        • Penny R
        Depressed lymphocyte function after bereavement.
        Lancet. 1977; ii: 834-836
        • Blalock JE
        • Smith EM
        A complete regulatory loop between the immune and neuroendocrine systems.
        in: Fed Proc. 44. 1985: 108-111
        • Blalock JE
        • Bost KL
        • Smith EM
        Neuroendocrine peptide hormones and their receptors in the immune system.
        J Neuroimmunol. 1985; 10: 31-40
        • Blalock JE
        • Johnson HM
        • Smith EM
        • Torres BA
        Enhancement of the in vitro antibody response by thyrotropin.
        Biochem Biophys Res Commun. 1985; 125: 30-34
        • Blalock JE
        • Smith EM
        • Meyer WJ
        The pituitary-adrenocortical axis and the immune system.
        in: Clinics in Endocrinology and Metabolism. vol 14. W.B. Saunders, East Sussex, UK1985: 1021-1038
        • Boyum A
        Isolation of leukocytes from human blood.
        Scand J Clin Lab Invest Suppl. 1986; 21: 77-89
        • Calabrese JR
        • Skwerer RG
        • Barna B
        • Gulledge AD
        • Valenzuela R
        • Butkus A
        • Subichin S
        • Krupp NE
        Depression, immunocompetence and prostaglandins of the E series.
        Psychiatry Res. 1986; 17: 41-47
        • Descotes J
        • Tedone R
        • Evreux JC
        Different effects of psychotropic drugs on delayed hypersensitivity responses in mice.
        J Neuroimmunol. 1985; 9: 81-85
        • Guillemin R
        • Cohn M
        • Melnuchluk T
        Neural Modulation of Immunity.
        Raven Press, New York1985
        • Harbour-McMenamin D
        • Blalock JE
        Neuroendocrinology and the immune system.
        in: Zorab R Collu R Van Loon G Clinical Neuroendocrinology. Blackwell Scientific, Boston1987 (in press).
        • Hunter WM
        • Greenwood FC
        Preparation of iodine-131 labeled human growth hormone of high specific activity.
        Nature. 1962; 194: 495-496
        • Kirkegaard C
        The thyrotropin response to thyrotropin-releasing hormone in endogenous depression.
        Psychoneuroendocrinology. 1981; 6: 189-212
        • Kirkegaard C
        • Smith E
        Continuation of therapy in endogenous depression controlled by changes in the TRH stimulation test.
        Psychol Med. 1981; 8: 501-503
        • Kirkegaard C
        • Bjorum N
        • Cohn D
        • Lauridsen VB
        Thyrotropin releasing hormone (TRH) stimulation test in manic depressive disease.
        Arch Gen Psychiatry. 1978; 35: 1017-1023
        • Kruger T
        • Blalock JE
        Cellular requirements for thyrotropin enhancement of in vitro antibody production.
        J Immunol. 1986; 137: 197-200
        • Kruger TE
        • Smith EM
        • Blalock JE
        Thyrotropin releasing hormone (TRH) enhancement of antibody production.
        in: Fed Proc. 46. 1987: 3547
        • Loosen PT
        The TRH-induced TSH response in psychiatric patients: A possible neuroendocrine marker.
        Psychoneuroendocrinology. 1985; 10: 237-260
        • Loosen PT
        • Prange AJ
        The serum thyrotropin (TSH) response to thyrotropin-releasing hormone (TRH) in depression: A review.
        AM J Psychiatry. 1982; 139: 405-416
        • Naber D
        • Steinbrock H
        • Greil W
        Effects of short- and long-term neuroleptic treatment on thyroid function.
        Prog Neuropsychopharmacol. 1980; 49: 199-206
        • Neill JD
        • Frawley LS
        Detection of hormone release from individual cells in mixed populations using a reverse hemolytic plaque assay.
        Endocrinology. 1983; 112: 1135-1137
        • Smith EM
        • Phan M
        • Coppenhaver D
        • Kruger TE
        • Blalock JE
        Human lymphocyte production of immunoreactive thyrotropin.
        in: Proc Natl Acad Sci USA. 80. 1983: 6010-6013
        • Utiger R
        in: Jaffe BM Behrman HR Methods of Hormone Radioimmunoassay. Academic Press, Orlando, FL1979: 315-325
        • Weksler ME
        • Hausman PB
        • Schwab R
        Effects of aging on the immune response.
        in: Stites DP Stobo JD Fudenberg HH Wells JV Basic and Clinical Immunology. Lange Medical Publications, Los Altos1984: 302-311
        • Woloski BMRNJ
        • Smith EM
        • Meyer WJ
        • Fuller GM
        • Blalock JE
        Corticotropin-releasing activity of monokines.
        Science. 1985; 230: 1035-1037