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October 1986, Vol 43, No. 10 >
Article | October 1986

Prostaglandin Receptor Sensitivity in Psychiatric Disorders

Philip D. Kanof, MD, PhD; Celeste Johns, MD; Michael Davidson, MD; Larry J. Siever, MD; Emil F. Coccaro, MD; Kenneth L. Davis, MD
[+] Author Affiliations

Accepted for publication April 23, 1986.

Reprint requests to Veterans Administration Medical Center, Psychiatry Service (116A), 130 W Kingsbridge Rd, Bronx, NY 10468 (Dr Kanof).


Arch Gen Psychiatry. 1986;43(10):987-993. doi:10.1001/archpsyc.1986.01800100081011
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References
Comments

• The cyclic adenosine monophosphate (cAMP) responses to prostaglandin E1 (PGE,) in platelets and leukocytes from drug-free schizophrenic patients, depressive patients, and normal controls have been compared. Both schizophrenic and depressive patients had a significantly lower platelet cAMP response to PGE1 than controls. The platelet cAMP response to PGE, did not discriminate among exacerbated, remitted, and poor-prognosis schizophrenic patients, or between exacerbated and remitted depressive patients. The cAMP response to PGE1 was negatively correlated with global symptom severity in actively ill schizophrenic patients, but was not correlated with symptom severity in exacerbated depressive patients. The leukocyte cAMP response to PGE1 did not differ among normal controls, schizophrenic patients, and depressive patients. These data indicate that a diminished platelet cAMP response to PGE1 may be a marker common to both schizophrenia and depression but that this effect does not extend to a cAMP-linked PGE1 receptor on another blood cell type.

REFERENCES

1 +
Wolfe LS:  Eicosonoids: Prostaglandins, thromboxanes, and leukotrienes, and other derivatives of carbon-20 unsaturated fatty acids . J Neurochem 1982;;38:1-14.
2 +
Chiu EYK, Richardson JS:  Behavioral and neurochemical aspects of prostaglandins in brain function . Gen Pharmacol 1985;;16:163-175.
3 +
Dismukes K, Daly JW:  Accumulation of adenosine 3':5'-monophosphate in rat brain slices: Effects of prostaglandins . Life Sci 1975;;17:199-209.
4 +
Collier HOJ, Roy AC:  Morphine-like drugs inhibit the stimulation by E prostaglandins of cyclic AMP formation by rat brain homogenate . Nature 1974;;248:24-27.
5 +
Moskowitz J, Harwood JP, Reid WD, Krishna G:  The interaction of norepinephrine and prostaglandin E1 in the adenyl-cyclase system of human and rabbit blood platelets . Biochim Biophys Acta 1971;;230:279-285.
6 +
Jakobs KM, Saur W, Schultz G:  Reduction of adenylate cyclase activity in lysates of human platelets by the alpha-adrenergic component of epinephrine . J Cyclic Nucleotide Res 1976;;2:381-392.
7 +
Alvarez R, Taylor A, Fazzari JJ, Jacobs JR:  Regulation of cyclic AMP metabolism in human platelets: Sequential activation of adenylate cyclase and cyclic AMP phosphodiesterase by prostaglandins . Mol Pharmacol 1981;;20:302-309.
8 +
Pandey GN, Garver DL, Tamminga C, Ericksen S, Ali SI, Davis JM:  Postsynaptic supersensitivity in schizophrenia . Am J Psychiatry 1977;;134:518-522.
9 +
Kafka MS, van Kammen DP, Bunney WE:  Reduced cyclic AMP production in the blood platelets from schizophrenic patients . Am J Psychiatry 1979;;136:685-687.
10 +
Rotrosen J, Miller AD, Mandio D, Traficante LJ, Gershon S:  Prostaglandins, platelets, and schizophrenia . Arch Gen Psychiatry 1980;;37:1047-1054.
11 +
Kafka MS, van Kammen DP, Kleinman JE, Nurnberger JI, Siever LJ, Uhde TW, Polinsky RJ:  Alpha-adrenergic receptor function in schizophrenia, affective disorders, and some neurological diseases . Commun Psychopharmacol 1980;;4:477-486.
12 +
Garver DL, Johnson C, Kanter DR:  Schizophrenia and reduced cyclic AMP production: Evidence for the role of receptor-linked events . Life Sci 1982;;31:1987-1992.
13 +
Kafka MS, van Kammen DP:  Alpha-adrenergic receptor function in schizophrenia . Arch Gen Psychiatry 1983;;40:264-270.
14 +
Kaiya H, Imai H, Muramatsu Y, Nozaki M, Fujimara H, Adachi S, Namba M:  Platelet aggregation response in schizophrenia and prostaglandin E1 . Psychiatry Res 1983;;9:309-318.
15 +
Murphy DL, Donnelly C, Moskowitz J:  Catecholamine receptor function in depressed patients . Am J Psychiatry 1974;;131:1389-1391.
16 +
Wang YC, Pandey GN, Mendels J, Frazer A:  Platelet adenylate cyclase responses in depression: Implications for a receptor defect . Psychopharmacol 1974;;36:291-300.
17 +
Siever LJ, Kafka MS, Targum S, Lake CR:  Platelet alpha-adrenergic binding and biochemical responsiveness in depressed patients and controls . Psychiatry Res 1984;;11:287-302.
18 +
Bourne HR, Melmon KL:  Adenyl cyclase in human leukocytes: Evidence for activation by separate beta-adrenergic and prostaglandin receptors . J Pharmacol Exp Ther 1971;;178:1-7.
19 +
Pandey GN, Dysken MW, Garver DL, Davis JM:  Beta-adrenergic receptor function in affective illness . Am J Psychiatry 1979;;136:675-678.
20 +
Spitzer RL, Endicott J, Robins E:  Research diagnostic criteria: Rationale and reliability . Arch Gen Psychiatry 1978;;36:773-782.
21 +
Overall JE, Gorham DR: The brief psychiatric rating scale. Psychol Rep 1962;;10:799-812.
22 +
Hamilton MA:  A rating scale for depression . J Neurol Neurosurg Psychiatry 1960;;23:56-62.
23 +
Corash L:  Platelet heterogeneity: Relevance to the use of platelets to study psychiatric disorders . Schizophr Bull 1980;;6:254-258.
24 +
Galant SP, Duriseti L, Underwood S, Allred S, Insel PA:  Beta adrenergic receptors of polymorphonuclear particulates in bronchial asthma . J Clin Invest 1980;;65:577-585.
25 +
Boyum A:  Isolation of mononuclear cells and granulocytes from blood . Scand J Clin Lab Invest 1968;;21( (suppl 97) ):77-89.
26 +
Brown BL, Albano JM, Ekins RP, Sghersi AM:  A simple and sensitive saturation assay method for the measurement of adenosine 3':5'-cyclic monophosphate . Biochem J 1971;;121:561-562.
27 +
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ:  Protein measurement with the Folin phenol reagent . J Biol Chem 1951;;193:265-275.
28 +
Davies AO, Lefkowitz RJ:  In vitro desensitization of beta adrenergic receptors in human neutrophils: Attenuation by corticosteroids . J Clin Invest 1983;;71:565-571.
29 +
Feldberg W:  Possible association of schizophrenia with a disturbance of prostaglandin metabolism: A physiological hypothesis . Psychol Med 1976;;6:359-369.
30 +
Horrobin DF:  Schizophrenia as a prostaglandin deficiency disease . Lancet 1977;;1:936-937.
31 +
Malek-Ahmadi P, Weddle MA:  Schizophrenia and prostaglandins: Theories and therapeutic implications . Gen Pharmacol 1982;;13:467-469.
32 +
Horrobin DF, Huang YS:  Schizophrenia: The role of abnormal fatty acid and prostaglandin metabolism . Med Hypothesis 1983;;10:329-336.
33 +
Horrobin DF, Manku MS:  Possible role of prostaglandin E1 in the affective disorders and alcoholism . Br Med J 1980;;280:1363-1366.
34 +
Mathé AA, Sedvall G, Wiesel FA, Nyback H:  Increased content of immunoreactive prostaglandin E in cerebrospinal fluid of patients with schizophrenia . Lancet 1980;;1:16-18.
35 +
Abdel-Halim MS, Ekstedt J, Anggard E:  Determination of PGF2a, E2, D2 and 6-keto-F1a in human cerebrospinal fluid . Prostaglandins 1979;;17:405-409.
36 +
Romero SD, Chyatte D, Byer DE, Romero C, Yaksh JL:  Measurement of prostaglandins in the cerebrospinal fluid in cat, dog, and man . J Neurochem 1984;;43:1642-1649.
37 +
Linnoila M, Whorton R, Rubinow DR, Cowdry RW, Ninan PT, Walters RN:  CSF prostaglandin levels in depressed and schizophrenic patients . Arch Gen Psychiatry 1983;;40:405-409.
38 +
Gerner RH, Merrill JE:  Cerebrospinal fluid prostaglandin E in depression, mania, and schizophrenia as compared to normals . Biol Psychiatry 1983;;18:565-569.
39 +
Abdulla YH, Hamadah K:  Effect of ADP on PGE1 formation in blood platelets from patients with depression, mania and schizophrenia . Br J Psychiatry 1975;;127:591-595.
40 +
Hillier K, Roberts PJ, Woollard PM:  Catecholamine-stimulated prostaglandin synthesis in rat brain synaptosomes . Br J Pharmacol 1976;;58:426P-427P.
41 +
Schaefer A, Komlos M, Seregi A:  Effects of biogenic amines and psychotropic drugs on endogenous prostaglandin biosynthesis in the rat brain homogenates . Biochem Pharmacol 1978;;27:213-218.
42 +
Bergstrom S, Farnebo LO, Fuxe K:  Effect of prostaglandin E2 on central and peripheral catecholamine neurons . Eur J Pharmacol 1973;;21:362-368.
43 +
Westfall TC, Kitay D:  The effects of prostaglandins on the release of 3H-dopamine from superfused slices of rat striatum following electrical stimulation . Proc Soc Exp Biol Med 1977;;155:305-307.
44 +
Schwarz RD, Uretsky NJ, Bianchine JR:  Prostaglandin inhibition of amphetamine-induced circling in mice . Psychopharmacol 1982;;78:317-321.
45 +
Fung YK, Schwarz RD:  An in vivo method for testing drugs that influence striatal dopaminergic functions . Pharmacol Biochem Behav 1983;;19:321-324.
46 +
Schwarz RD, Uretsky NJ, Bianchine JR:  Prostaglandin inhibition of apomorphine-induced circling in mice . Pharmacol Biochem Behav 1982;;17:1233-1237.
47 +
Poddubiuk ZM, Kleinrok Z:  A comparison of the central actions of prostaglandins A1, E1, E2, F1α and F2α in the rat: II. The effect of intraventricular prostaglandins on the action of some drugs on the level of turnover of biogenic amines in the rat brain . Psychopharmacology 1976;;50:95-102.
48 +
Bloss JL, Singer GH:  Neuropharmacological and behavioral evaluation of PGE2 and 11-thiol-11-desoxy PGE2 in the mouse and rat . Psychopharmacology 1978;;52:295-302.
49 +
Meltzer HY, Stahl M:  The dopamine hypothesis of schizophrenia: A review . Schizophr Bull 1976;;2:19-76.
50 +
Schildkraut JJ:  The catecholamine hypothesis of affective disorders: A review of supporting evidence . Am J Psychiatry 1965;;122:509-522.
51 +
Baldessarini RJ:  The basis for amine hypothesis in affective disorders: A critical evaluation . Arch Gen Psychiatry 1975;;32:1087-1093.
52 +
Wendel OT, Strandhoy JW:  The effects of prostaglandins E2 and F2α on synaptosome accumulation and release of 3H-norepinephrine . Prostaglandins 1978;;16:441-449.
53 +
Hillier K, Templeton WW:  Regulation of norepinephrine overflow in rat cerebral cortex by prostaglandin E2 . Br J Pharmacol 1980;;70:469-473.
54 +
Siggins G, Hoffer B, Bloom F:  Prostaglandin-norepinephrineinteractions in brain: Microelectrophoretic and histochemical correlates . Ann NY Acad Sci 1971;;180:302-323.
55 +
Partington CR, Edwards MW, Daly JW:  Regulation of cyclic AMP formation in brain tissues by alpha-adrenergic receptors: Requisite intermediacy of prostaglandins of the E series . Proc Natl Acad Sci USA 1980;;77:3024-3028.
56 +
Siever LJ, Davis KL:  Toward a dysregulation hypothesis of depression . Am J Psychiatry 1985;;142:1017-1031.

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1 +
Wolfe LS:  Eicosonoids: Prostaglandins, thromboxanes, and leukotrienes, and other derivatives of carbon-20 unsaturated fatty acids . J Neurochem 1982;;38:1-14.
2 +
Chiu EYK, Richardson JS:  Behavioral and neurochemical aspects of prostaglandins in brain function . Gen Pharmacol 1985;;16:163-175.
3 +
Dismukes K, Daly JW:  Accumulation of adenosine 3':5'-monophosphate in rat brain slices: Effects of prostaglandins . Life Sci 1975;;17:199-209.
4 +
Collier HOJ, Roy AC:  Morphine-like drugs inhibit the stimulation by E prostaglandins of cyclic AMP formation by rat brain homogenate . Nature 1974;;248:24-27.
5 +
Moskowitz J, Harwood JP, Reid WD, Krishna G:  The interaction of norepinephrine and prostaglandin E1 in the adenyl-cyclase system of human and rabbit blood platelets . Biochim Biophys Acta 1971;;230:279-285.
6 +
Jakobs KM, Saur W, Schultz G:  Reduction of adenylate cyclase activity in lysates of human platelets by the alpha-adrenergic component of epinephrine . J Cyclic Nucleotide Res 1976;;2:381-392.
7 +
Alvarez R, Taylor A, Fazzari JJ, Jacobs JR:  Regulation of cyclic AMP metabolism in human platelets: Sequential activation of adenylate cyclase and cyclic AMP phosphodiesterase by prostaglandins . Mol Pharmacol 1981;;20:302-309.
8 +
Pandey GN, Garver DL, Tamminga C, Ericksen S, Ali SI, Davis JM:  Postsynaptic supersensitivity in schizophrenia . Am J Psychiatry 1977;;134:518-522.
9 +
Kafka MS, van Kammen DP, Bunney WE:  Reduced cyclic AMP production in the blood platelets from schizophrenic patients . Am J Psychiatry 1979;;136:685-687.
10 +
Rotrosen J, Miller AD, Mandio D, Traficante LJ, Gershon S:  Prostaglandins, platelets, and schizophrenia . Arch Gen Psychiatry 1980;;37:1047-1054.
11 +
Kafka MS, van Kammen DP, Kleinman JE, Nurnberger JI, Siever LJ, Uhde TW, Polinsky RJ:  Alpha-adrenergic receptor function in schizophrenia, affective disorders, and some neurological diseases . Commun Psychopharmacol 1980;;4:477-486.
12 +
Garver DL, Johnson C, Kanter DR:  Schizophrenia and reduced cyclic AMP production: Evidence for the role of receptor-linked events . Life Sci 1982;;31:1987-1992.
13 +
Kafka MS, van Kammen DP:  Alpha-adrenergic receptor function in schizophrenia . Arch Gen Psychiatry 1983;;40:264-270.
14 +
Kaiya H, Imai H, Muramatsu Y, Nozaki M, Fujimara H, Adachi S, Namba M:  Platelet aggregation response in schizophrenia and prostaglandin E1 . Psychiatry Res 1983;;9:309-318.
15 +
Murphy DL, Donnelly C, Moskowitz J:  Catecholamine receptor function in depressed patients . Am J Psychiatry 1974;;131:1389-1391.
16 +
Wang YC, Pandey GN, Mendels J, Frazer A:  Platelet adenylate cyclase responses in depression: Implications for a receptor defect . Psychopharmacol 1974;;36:291-300.
17 +
Siever LJ, Kafka MS, Targum S, Lake CR:  Platelet alpha-adrenergic binding and biochemical responsiveness in depressed patients and controls . Psychiatry Res 1984;;11:287-302.
18 +
Bourne HR, Melmon KL:  Adenyl cyclase in human leukocytes: Evidence for activation by separate beta-adrenergic and prostaglandin receptors . J Pharmacol Exp Ther 1971;;178:1-7.
19 +
Pandey GN, Dysken MW, Garver DL, Davis JM:  Beta-adrenergic receptor function in affective illness . Am J Psychiatry 1979;;136:675-678.
20 +
Spitzer RL, Endicott J, Robins E:  Research diagnostic criteria: Rationale and reliability . Arch Gen Psychiatry 1978;;36:773-782.
21 +
Overall JE, Gorham DR: The brief psychiatric rating scale. Psychol Rep 1962;;10:799-812.
22 +
Hamilton MA:  A rating scale for depression . J Neurol Neurosurg Psychiatry 1960;;23:56-62.
23 +
Corash L:  Platelet heterogeneity: Relevance to the use of platelets to study psychiatric disorders . Schizophr Bull 1980;;6:254-258.
24 +
Galant SP, Duriseti L, Underwood S, Allred S, Insel PA:  Beta adrenergic receptors of polymorphonuclear particulates in bronchial asthma . J Clin Invest 1980;;65:577-585.
25 +
Boyum A:  Isolation of mononuclear cells and granulocytes from blood . Scand J Clin Lab Invest 1968;;21( (suppl 97) ):77-89.
26 +
Brown BL, Albano JM, Ekins RP, Sghersi AM:  A simple and sensitive saturation assay method for the measurement of adenosine 3':5'-cyclic monophosphate . Biochem J 1971;;121:561-562.
27 +
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ:  Protein measurement with the Folin phenol reagent . J Biol Chem 1951;;193:265-275.
28 +
Davies AO, Lefkowitz RJ:  In vitro desensitization of beta adrenergic receptors in human neutrophils: Attenuation by corticosteroids . J Clin Invest 1983;;71:565-571.
29 +
Feldberg W:  Possible association of schizophrenia with a disturbance of prostaglandin metabolism: A physiological hypothesis . Psychol Med 1976;;6:359-369.
30 +
Horrobin DF:  Schizophrenia as a prostaglandin deficiency disease . Lancet 1977;;1:936-937.
31 +
Malek-Ahmadi P, Weddle MA:  Schizophrenia and prostaglandins: Theories and therapeutic implications . Gen Pharmacol 1982;;13:467-469.
32 +
Horrobin DF, Huang YS:  Schizophrenia: The role of abnormal fatty acid and prostaglandin metabolism . Med Hypothesis 1983;;10:329-336.
33 +
Horrobin DF, Manku MS:  Possible role of prostaglandin E1 in the affective disorders and alcoholism . Br Med J 1980;;280:1363-1366.
34 +
Mathé AA, Sedvall G, Wiesel FA, Nyback H:  Increased content of immunoreactive prostaglandin E in cerebrospinal fluid of patients with schizophrenia . Lancet 1980;;1:16-18.
35 +
Abdel-Halim MS, Ekstedt J, Anggard E:  Determination of PGF2a, E2, D2 and 6-keto-F1a in human cerebrospinal fluid . Prostaglandins 1979;;17:405-409.
36 +
Romero SD, Chyatte D, Byer DE, Romero C, Yaksh JL:  Measurement of prostaglandins in the cerebrospinal fluid in cat, dog, and man . J Neurochem 1984;;43:1642-1649.
37 +
Linnoila M, Whorton R, Rubinow DR, Cowdry RW, Ninan PT, Walters RN:  CSF prostaglandin levels in depressed and schizophrenic patients . Arch Gen Psychiatry 1983;;40:405-409.
38 +
Gerner RH, Merrill JE:  Cerebrospinal fluid prostaglandin E in depression, mania, and schizophrenia as compared to normals . Biol Psychiatry 1983;;18:565-569.
39 +
Abdulla YH, Hamadah K:  Effect of ADP on PGE1 formation in blood platelets from patients with depression, mania and schizophrenia . Br J Psychiatry 1975;;127:591-595.
40 +
Hillier K, Roberts PJ, Woollard PM:  Catecholamine-stimulated prostaglandin synthesis in rat brain synaptosomes . Br J Pharmacol 1976;;58:426P-427P.
41 +
Schaefer A, Komlos M, Seregi A:  Effects of biogenic amines and psychotropic drugs on endogenous prostaglandin biosynthesis in the rat brain homogenates . Biochem Pharmacol 1978;;27:213-218.
42 +
Bergstrom S, Farnebo LO, Fuxe K:  Effect of prostaglandin E2 on central and peripheral catecholamine neurons . Eur J Pharmacol 1973;;21:362-368.
43 +
Westfall TC, Kitay D:  The effects of prostaglandins on the release of 3H-dopamine from superfused slices of rat striatum following electrical stimulation . Proc Soc Exp Biol Med 1977;;155:305-307.
44 +
Schwarz RD, Uretsky NJ, Bianchine JR:  Prostaglandin inhibition of amphetamine-induced circling in mice . Psychopharmacol 1982;;78:317-321.
45 +
Fung YK, Schwarz RD:  An in vivo method for testing drugs that influence striatal dopaminergic functions . Pharmacol Biochem Behav 1983;;19:321-324.
46 +
Schwarz RD, Uretsky NJ, Bianchine JR:  Prostaglandin inhibition of apomorphine-induced circling in mice . Pharmacol Biochem Behav 1982;;17:1233-1237.
47 +
Poddubiuk ZM, Kleinrok Z:  A comparison of the central actions of prostaglandins A1, E1, E2, F1α and F2α in the rat: II. The effect of intraventricular prostaglandins on the action of some drugs on the level of turnover of biogenic amines in the rat brain . Psychopharmacology 1976;;50:95-102.
48 +
Bloss JL, Singer GH:  Neuropharmacological and behavioral evaluation of PGE2 and 11-thiol-11-desoxy PGE2 in the mouse and rat . Psychopharmacology 1978;;52:295-302.
49 +
Meltzer HY, Stahl M:  The dopamine hypothesis of schizophrenia: A review . Schizophr Bull 1976;;2:19-76.
50 +
Schildkraut JJ:  The catecholamine hypothesis of affective disorders: A review of supporting evidence . Am J Psychiatry 1965;;122:509-522.
51 +
Baldessarini RJ:  The basis for amine hypothesis in affective disorders: A critical evaluation . Arch Gen Psychiatry 1975;;32:1087-1093.
52 +
Wendel OT, Strandhoy JW:  The effects of prostaglandins E2 and F2α on synaptosome accumulation and release of 3H-norepinephrine . Prostaglandins 1978;;16:441-449.
53 +
Hillier K, Templeton WW:  Regulation of norepinephrine overflow in rat cerebral cortex by prostaglandin E2 . Br J Pharmacol 1980;;70:469-473.
54 +
Siggins G, Hoffer B, Bloom F:  Prostaglandin-norepinephrineinteractions in brain: Microelectrophoretic and histochemical correlates . Ann NY Acad Sci 1971;;180:302-323.
55 +
Partington CR, Edwards MW, Daly JW:  Regulation of cyclic AMP formation in brain tissues by alpha-adrenergic receptors: Requisite intermediacy of prostaglandins of the E series . Proc Natl Acad Sci USA 1980;;77:3024-3028.
56 +
Siever LJ, Davis KL:  Toward a dysregulation hypothesis of depression . Am J Psychiatry 1985;;142:1017-1031.

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