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Neuropeptides involved in the pathophysiology of schizophrenia and major depression

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Abstract

The present review summarizes the finding on the role of neuropeptides in the pathophysiology of schizophrenia and major depression. Several neuropeptides as vasopressin and endorphins in particular, β-endorphin and gamma-type endorphins, cholecystokinin (CCK), neurotensin, somatostatin and Neuropeptide Y have been implicated in schizophrenia. During the last decade, however, few attempts to explore the significance of most of these and other neuropeptides in the pathophysiology of the disease or their therapeutic potential are found in the literature. An exception is neurotensin, which exerts neuroleptic-like effects in animal studies, while CSF, brain and blood studies are inconclusive. Things are different in major depression. Here much attention is paid to the endocrine abnormalities found in this disorder, in particular the increased activity of the hypothalamic-pituitary-adrenal (HPA) axis. Neuropeptides as corticotropin-releasing hormone (CRH), vasopressin and corticosteroids are implicated in the symptomatology of this disorder. As a consequence much work is going on investigating the influence of CRH and corticosteroid antagonists or inhibitors of the synthesis of corticosteroids as potential therapeutic agents. This review emphasizes the role of vasopressin in the increased activity of the HPA axis in major depression and suggests exploration of the influence of the now available non-peptidergic vasopressin orally active V1 antagonists.

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References

  • Agren, H. and Lundqvist, G. (1984) “Low levels of somatostatin in human CSf mark depressive episodes”, Psychoneuroendocrinology 9, 233–248.

    Article  PubMed  CAS  Google Scholar 

  • Albus, M., Von Gellhorn, K., Munch, U., Naber, D. and Ackenheil, M. (1986) “A double-blind study with ceruletide in chronic schizophrenic patients: biochemical and clinical results”, Psychiatry Res. 19, 1–7.

    Article  PubMed  CAS  Google Scholar 

  • Arato, M., Banki, C.M., Nemeroff, C.B. and Bissette, G. (1986) “Hypothalamic-pituitary-adrenal axis and suicide”, Ann. NY Acad. Sci. 487, 263–270.

    Article  PubMed  CAS  Google Scholar 

  • Arato, M., Banki, C.M., Bissette, G. and Nemeroff, C.B. (1989) “Elevated CSF CRF in suicide victims”, Biol. Psychiatry 25, 355–359.

    Article  PubMed  CAS  Google Scholar 

  • Arborelius, L., Owens, M.J., Plotsky, P.M. and Nemeroff, C.B. (1999) “The role of corticotropin-releasing factor in depression and anxiety disorders”, J. Endocrinol. 160, 1–12.

    Article  PubMed  CAS  Google Scholar 

  • Asher, R. (1949) “Myxoedematous madness”, Br. Med. J. 22, 555–562.

    Google Scholar 

  • Austin, J., Hoogendoorn, B., Buckland, P., Speight, G., Cardno, A., Bowen, T., Williams, N., Spurlock, G., Sanders, R., Jones, L., Murphy, K., McCarthy, G., McGuffin, P., Owen, M.J. and O'Donovan, M.C. (2000a) “Comparative sequencing of the proneurotensin gene and association studies in schizophrenia”, Mol. Psychiatry 5(2), 208–212.

    Article  PubMed  CAS  Google Scholar 

  • Austin, J., Buckland, P., Cardno, A.G., Williams, N., Spurlock, G., Hoogendoorn, B., Zammit, S., Jones, G., Sanders, R., Jones, L., McCarthy, G., Jones, S., Bray, N.J., McGuffin, P., Owen, M.J. and O'Donovan, M.C. (2000b) “The high affinity neurotensin receptor gene (NTSR1): comparative sequencing and association studies in schizophrenia”, Mol. Psychiatry 5(5), 552–557.

    Article  PubMed  CAS  Google Scholar 

  • Azorin, J.M., Blum, A., Charbaut, J., Escande, M., Granier, F., Huber, J.P., Metzger, J.Y., Richou, H., Sitsen, A., Van Amerongen, P., et al. (1990) “Des-enkephalin-gamma-endorphin in the treatment of schizophrenia”, Int. Clin. Psychopharmacol. 5, 205–215.

    Article  PubMed  CAS  Google Scholar 

  • Bachus, S.E., Hyde, T.M., Herman, M.M., Egan, M.F. and Kleinman, J.E. (1997) “Abnormal cholecystokinin mRNA levels in entorhinal cortex of schizophrenics”, J. Psychiatr. Res. 31, 233–256.

    Article  PubMed  CAS  Google Scholar 

  • Banki, C.M., Bissette, G., Arato, M., O'Connor, L. and Nemeroff, C.B. (1987) “CSF corticotropin-releasing factor-like immunoreactivity in depression and schizophrenia”, Am. J. Psychiatry 144, 873–877.

    PubMed  CAS  Google Scholar 

  • Banki, C.M., Bissette, G., Arato, M. and Nemeroff, C.B. (1988) “Elevation of immunoreactive CSF TRH in depressed patients”, Am. J. Psychiatry 145, 1526–1531.

    PubMed  CAS  Google Scholar 

  • Banki, C.M., Karmacsi, L., Bissette, G. and Nemeroff, C.B. (1992a) “CSF corticotropin releasing hormone, somatostatin, and thyrotropin releasing hormone in schizophrenia”, Psychiatry Res. 43(1), 13–21.

    Article  PubMed  CAS  Google Scholar 

  • Banki, C.M., Karmacsi, L., Bissette, G. and Nemeroff, C.B. (1992b) “Cerebrospinal fluid neuropeptides in mood disorder and dementia”, J. Affect. Disord. 25, 39–45.

    Article  PubMed  CAS  Google Scholar 

  • Barberis, C. and Tribollet, E. (1996) “Vasopressin and oxytocin receptors in the central nervous system”, Crit. Rev. Neurobiol. 10, 119–154.

    PubMed  CAS  Google Scholar 

  • Beal, M.F., Svendsen, C.N., Bird, E.D. and Martin, J.B. (1987) “Somatostatin and neuropeptide Y are unaltered in the amygdala in schizophrenia”, Neurochem. Pathol. 6(3), 169–176.

    Article  PubMed  CAS  Google Scholar 

  • Bean, A.J., Dagerlind, A., Hokfelt, T. and Dobner, P.R. (1992) “Cloning of human neurotensin/neuromedin N genomic sequences and expression in the ventral mesencephalon of schizophrenics and age/sex matched controls”, Neuroscience 50(2), 259–268.

    Article  PubMed  CAS  Google Scholar 

  • Beckmann, H., Lang, R.E. and Gattaz, W.F. (1985) “Vasopressin—oxytocin in cerebrospinal fluid of schizophrenic patients and normal controls”, Psychoneuroendocrinology 10, 187–191.

    Article  PubMed  CAS  Google Scholar 

  • Beinfeld, M.C. and Garver, D.L. (1991) “Concentration of cholecystokinin in cerebrospinal fluid is decreased in psychosis: relationship to symptoms and drug response”, Prog. Neuropsychopharmacol. Biol. Psychiatry 15, 601–609.

    Article  PubMed  CAS  Google Scholar 

  • Berrettini, W.H., Rubinow, D.R., Nurnberger, Jr, J.I., Simmons-Alling, S., Post, R.M. and Gershon, E.S. (1985) “CSF substance P immunoreactivity in affective disorders”, Biol. Psychiatry 20, 965–970.

    Article  PubMed  CAS  Google Scholar 

  • Berrettini, W.H., Doran, A.R., Kelsoe, J., Roy, A. and Pickar, D. (1987) “Cerebrospinal fluid neuropeptide Y in depression and schizophrenia”, Neuropsychopharmacology 1(1), 81–83.

    Article  PubMed  CAS  Google Scholar 

  • Biggins, J.A., Perry, E.K., McDermott, J.R., Smith, A.I., Perry, R.H. and Edwardson, J.A. (1983) “Post mortem levels of thyrotropinreleasing hormone and neurotensin in the amygdala in Alzheimer's disease, schizophrenia and depression”, J. Neurol. Sci. 58(1), 117–122.

    Article  PubMed  CAS  Google Scholar 

  • Bissette, G., Widerlov, E., Walleus, H., Karlsson, I., Eklund, K., Forsman, A. and Nemeroff, C.B. (1986) “Alterations in cerebrospinal fluid concentrations of somatostatinlike immunoreactivity in neuropsychiatric disorders”, Arch. Gen. Psychiatry 43, 1148–1151.

    PubMed  CAS  Google Scholar 

  • Bloom, F., Segal, D., Ling, N. and Guillemin, R. (1976) “Endorphins: profound behavioral effects in rats suggest new etiological factors in mental illness”, Science 194, 630–632.

    Article  PubMed  CAS  Google Scholar 

  • Bourgeois, M., Laforge, E., Muyard, J., Blayac, J. and Lemoine, J. (1980) “Endorphins and schizophrenias. II. Trial treatment of schizophrenia with des-Tyr-gamma-endorphin (DT gamma E) (including a personal trial)”, Ann. Med. Psychol. (Paris) 138, 1112–1119.

    CAS  Google Scholar 

  • Brambilla, F., Aguglia, E., Massironi, R., Maggioni, M., Grillo, W., Castiglioni, R., Catalano, M. and Drago, F. (1986) “Neuropeptide therapies in chronic schizophrenia: TRH and vasopressin administration”, Neuropsychobiology 15, 114–121.

    Article  PubMed  CAS  Google Scholar 

  • Brambilla, F., Bondiolotti, G.P., Maggioni, M., Sciascia, A., Grillo, W., Sanna, F., Latina, A. and Picotti, G.B. (1989) “Vasopressin (DDAVP) therapy in chronic schizophrenia: effects on negative symptoms and memory”, Neuropsychobiology 20, 113–119.

    Article  PubMed  CAS  Google Scholar 

  • Breslin, N.A., Suddath, R.L., Bissette, G., Nemeroff, C.B., Lowrimore, P. and Weinberger, D.R. (1994) “CSF concentrations of neurotensin in schizophrenia: an investigation of clinical and biochemical correlates”, Schizophr. Res. 12(1), 35–41.

    Article  PubMed  CAS  Google Scholar 

  • Burnet, P.W. and Harrison, P.J. (2000) “Substance P (NK1) receptors in the cingulate cortex in unipolar and bipolar mood disorder and schizophrenia”, Biol. Psychiatry 47, 80–83.

    Article  PubMed  CAS  Google Scholar 

  • Caberlotto, L. and Hurd, Y.L. (1999) “Reduced neuropeptide Y mRNA expression in the prefrontal cortex of subjects with bipolar disorder”, Neuroreport 10(8), 1747–1750.

    Article  PubMed  CAS  Google Scholar 

  • Caberlotto, L. and Hurd, Y.L. (2001) “Neuropeptide YY(1) and Y(2) receptor mRNA expression in the prefrontal cortex of psychiatric subjects. Relationship of Y(2) subtype to suicidal behavior”, Neuropsychopharmacology 25(1), 91–97.

    Article  PubMed  CAS  Google Scholar 

  • Carraway, R.E. and Leeman, S.E. (1973) “The isolation of a new hypotensive peptide, neurotensin, from bovine hypothalami”, J. Biol. Chem. 248, 6854.

    PubMed  CAS  Google Scholar 

  • Carraway, R.E. and Leeman, S.E. (1976) “Characterization of radioimmunoassayable neurotensin in the rat: its differential distribution in the central nervous system, small intestine and stomach”, J. Biol. Chem. 254, 7045.

    Google Scholar 

  • Carroll, B.J. (1982) “Use of the dexamethasone suppression test in depression”, J. Clin. Psychiatry 43, 44–50.

    PubMed  CAS  Google Scholar 

  • Casey, D.E., Korsgaard, S., Gerlach, J., Jorgensen, A. and Simmelsgaard, H. (1981) “Effect of des-tyrosine-gamma-endorphin in tardive dyskinesia”, Arch. Gen. Psychiatry 38, 158–160.

    PubMed  CAS  Google Scholar 

  • Charlton, B.G., Wright, C., Leake, A., Ferrier, I.N., Cheetham, S.C., Horton, R.W., Crompton, M.R. and Katona, C.L. (1988) “Somatostatin immunoreactivity in postmortem brain from depressed suicides”, Arch. Gen. Psychiatry 45, 597–598.

    PubMed  CAS  Google Scholar 

  • Coppen, A. (1967) “The biochemistry of affective disorders”, Br. J. Psychiatry 113, 1237–1264.

    Article  PubMed  CAS  Google Scholar 

  • Crawley, J.N. (1991) “Cholecystokinin-dopamine interactions”, Trends Pharmacol. Sci. 12, 232–236.

    Article  PubMed  Google Scholar 

  • Croiset, G., Nijsen, M.J. and Kamphuis, P.J. (2000) “Role of corticotropin-releasing factor, vasopressin and the autonomic nervous system in learning and memory”, Eur. J. Pharmacol. 405, 225–234.

    Article  PubMed  CAS  Google Scholar 

  • DeBattista, C., Posener, J.A., Kalehzan, B.M. and Schatzberg, A.F. (2000) “Acute antidepressant effects of intravenous hydrocortisone and CRH in depressed patients: a double-blind, placebo-controlled study”, Am. J. Psychiatry 157, 1334–1337.

    Article  PubMed  CAS  Google Scholar 

  • De Bellis, M.D., Gold, P.W., Geracioti, Jr., T.D., Listwak, S.J. and Kling, M.A. (1993) “Association of fluoxetine treatment with reductions in CSF concentrations of corticotropin-releasing hormone and arginine vasopressin in patients with major depression”, Am. J. Psychiatry 150, 656–657.

    PubMed  Google Scholar 

  • De Souza, E.B. (1995) “Corticotropin-releasing factor receptors: physiology, pharmacology, biochemistry and role in central nervous system and immune disorders”, Psychoneuroendocrinology 20, 789–819.

    Article  PubMed  Google Scholar 

  • Detera-Wadleigh, S.D., de Miguel, C., Berrettini, W.H., DeLisi, L.E., Goldin, L.R. and Gershon, E.S. (1987) “Neuropeptide gene polymorphisms in affective disorder and schizophrenia”, J. Psychiatr. Res. 21, 581–587.

    Article  PubMed  CAS  Google Scholar 

  • De Wied, D., Kovacs, G.L., Bohus, B., Van Ree, J.M. and Greven, H.M. (1978) “Neuroleptic activity of the neuropeptide beta-LPH62-77 ([Des-Tyrl]gamma-endorphin; DT gamma E)”, Eur. J. Pharmacol. 49, 427–436.

    Article  PubMed  Google Scholar 

  • De Wied, D. and Burbach, J.P.H. (1999) “Neuropeptides and behavior”, In: Adelman, G. and Smith, B.H. eds, Encyclopedia of Neuroscience (Birkhäuser, Boston), pp 1431–1436.

    Google Scholar 

  • Dinan, T.G. (1994) “Glucocorticoids and the genesis of depressive illness. A psychobiological model”, Br. J. Psychiatry 164, 365–371.

    Article  PubMed  CAS  Google Scholar 

  • Dinan, T.G., Lavelle, E., Scott, L.V., Newell-Price, J., Medbak, S. and Grossman, A.B. (1999) “Desmopressin normalizes the blunted adrenocorticotropin response to corticotropin-releasing hormone in melancholic depression: evidence of enhanced vasopressinergic responsivity”, J. Clin. Endocrinol. Metab. 84, 2238–2240.

    Article  PubMed  CAS  Google Scholar 

  • Doran, A.R., Rubinow, D.R., Roy, A. and Pickar, D. (1986) “CSF somatostatin and abnormal response to dexamethasone administration in schizophrenic and depressed patients”, Arch. Gen. Psychiatry 43, 365–369.

    PubMed  CAS  Google Scholar 

  • Duval, F., Macher, J.P. and Mokrani, M.C. (1990) “Difference between evening and morning thyrotropin responses to protirelin in major depressive episode”, Arch. Gen. Psychiatry 47, 443–448.

    PubMed  CAS  Google Scholar 

  • Duval, E., Mokrani, M.C., Bailey, P., Correa, H., Diep, T.S., Crocq, M.A. and Macher, J.P. (1999) “Thyroid axis activity and serotonin function in major depressive episode”, Psychoneuroendocrinology 24, 695–712.

    Article  PubMed  CAS  Google Scholar 

  • Emrich, H.M., Zaudig, M., Kissling, W., Dirlich, G., von Zerssen, D. and Herz, A. (1980) “Des-tyrosyl-gamma-endorphin in schizophrenia: a double-blind trial in 13 patients”, Pharmakopsychiatr. Neuro-Psychopharmakol. 13, 290–298.

    CAS  Google Scholar 

  • Farmery, S.M., Owen, F., Poulter, M. and Crow, T.J. (1985) “Reduced high affinity cholecystokinin binding in hippocampus and frontal cortex of schizophrenic patients”, Life Sci. 36, 473–477.

    Article  PubMed  CAS  Google Scholar 

  • Ferrier, I.N., Roberts, G.W., Crow, T.J., Johnstone, E.C., Owens, D.G., Lee, Y.C., O'Shaughnessy, D., Adrian, T.E., Polak, J.M. and Bloom, S.R. (1983) “Reduced cholecystokinin-like and somato-statin-like immunoreactivity in limbic lobe is associated with negative symptoms in schizophrenia”, Life Sci. 33, 475–482.

    Article  PubMed  CAS  Google Scholar 

  • Fink, M., Papakostas, Y. and Lee, J. (1981) “Clinical trials with des-tyr-gamma-endorphin (GK-78)”, In: Perris, C., Struwe, G. and Jansson, B., eds, Biological Psychiatry (Elsevier/North-Holland Biomedical Press, Amsterdam).

    Google Scholar 

  • France, R.D., Urban, B., Krishnan, K.R., Bissett, G., Banki, C.M., Nemeroff, C. and Speilman, F.J. (1988) “CSF corticotropin-releasing factor-like immunoactivity in chronic pain patients with and without major depression”, Biol. Psychiatry 23, 86–88.

    Article  PubMed  CAS  Google Scholar 

  • Frasch, A., Zetzsche, T., Steiger, A. and Jirikowski, G.F. (1995) “Reduction of plasma oxytocin levels in patients suffering from major depression”, Adv. Exp. Med. Biol. 395, 257–258.

    PubMed  CAS  Google Scholar 

  • Frederiksen, S.O., Ekman, R., Gottfries, C.G., Widerlov, E. and Jonsson, S. (1991) “Reduced concentrations of galanin, arginine vasopressin, neuropeptide Y and peptide YY in the temporal cortex but not in the hypothalamus of brains from schizophrenics”, Acta Psychiatr. Scand. 83, 273–277.

    Article  PubMed  CAS  Google Scholar 

  • Frye, M.A., Dunn, R.T., Gary, K.A., Kimbrell, T.A., Callahan, A.M., Luckenbaugh, D.A., Cora-Locatelli, G., Vanderham, E., Winokur, A. and Post, R.M. (1999) “Lack of correlation between cerebrospinal fluid thyrotropin-releasing hormone (TRH) and TRH-stimulated thyroid-stimulating hormone in patients with depression”, Biol. Psychiatry 45, 1049–1052.

    Article  PubMed  CAS  Google Scholar 

  • Gabriel, S.M., Davidson, M., Haroutunian, V., Powchik, P., Bierer, L.M., Purohit, D.P., Perl, D.P. and Davis, K.L. (1996) “Neuropeptide deficits in schizophrenia vs. Alzheimer's disease cerebral cortex”, Biol. Psychiatry 39, 82–91.

    Article  PubMed  CAS  Google Scholar 

  • Gaffori, O., Stewart, J.M. and De Wied, D. (1984) “Influence of substance P and fragments on passive avoidance behavior”, Experientia 40, 89–91.

    Article  PubMed  CAS  Google Scholar 

  • Garver, D.L., Beinfeld, M.C. and Yao, J.K. (1990) “Cholecystokinin, dopamine and schizophrenia”, Psychopharmacol. Bull. 26. 377–380.

    PubMed  CAS  Google Scholar 

  • Garver, D.L., Bissette, G., Yao, J.K. and Nemeroff, C.B. (1991) “Relation of CSF neurotensin concentrations to symptoms and drug response of psychotic patients”, Am. J. Psychiatry 148(4), 484–488.

    PubMed  CAS  Google Scholar 

  • Geracioti, Jr, T.D., Orth, D.N., Ekhator, N.N., Blumenkopf, B. and Loosen, P.T. (1992) “Serial cerebrospinal fluid corticotropin-releasing hormone concentrations in healthy and depressed humans”, J. Clin. Endocrinol. Metab. 74, 1325–1330.

    Article  PubMed  CAS  Google Scholar 

  • Gerner, R.H. and Yamada, T. (1982) “Altered neuropeptide concentrations in cerebrospinal fluid of psychiatric patients”, Brain Res. 238, 298–302.

    Article  PubMed  CAS  Google Scholar 

  • Gerner, R.H., van Kammen, D.P. and Ninan, P.T. (1985) “Cerebrospinal fluid cholecystokinin, bombesin and somato statin in schizophrenia and normals”, Prog. Neuropsychopharmacol. Biol. Psychiatry 9, 73–82.

    Article  PubMed  CAS  Google Scholar 

  • Gispen-de Wied, C.C., Kok, F.W., Koppeschaar, H.P., Wynne, H.J., Westenberg, H.G., Thijssen, J.H. and Van Ree, J.M. (1993) “Stimulation of the pituitary-adrenal system with graded doses of CRH and low dose vasopressin infusion in depressed patients and healthy subjects: a pilot study”, Eur. Neuropsychopharmacol. 3, 533–541.

    Article  PubMed  CAS  Google Scholar 

  • Gjerris, A., Hammer, M., Vendsborg, P., Christensen, N.J. and Rafaelsen, O.J. (1985) “Cerebrospinal fluid vasopressin—changes in depression”, Br. J. Psychiatry 147, 696–701.

    Article  PubMed  CAS  Google Scholar 

  • Gjerris, A., Widerlov, E., Werdelin, L. and Ekman, R. (1992) “Cerebrospinal fluid concentrations of neuropeptide Y in depressed patients and in controls”, J. Psychiatry Neurosci. 17(1), 23–27.

    PubMed  CAS  Google Scholar 

  • Glovinsky, D., Kalogeras, K.T., Kirch, D.G., Suddath, R. and Wyatt, R.J. (1994) “Cerebrospinal fluid oxytocin concentration in schizophrenic patients does not differ from control subjects and is not changed by neuroleptic medication”, Schizophr. Res. 11, 273–276.

    Article  PubMed  CAS  Google Scholar 

  • Gold, P.W., Goodwin, F.K., Post, R.M. and Robertson, G.L. (1981) “Vasopressin function in depression and mania [proceedings]”, Psychopharmacol. Bull. 17, 7–9.

    PubMed  CAS  Google Scholar 

  • Goldstein, G., Fava, M., Culler, M., Fisher, A., Rickels, K., Lydiard, R.B. and Rosenbaum, J., (2000) “Elevated plasma thymopoietin associated with therapeutic nonresponsiveness in major depression”, Biol. Psychiatry 48, 65–69.

    Article  PubMed  CAS  Google Scholar 

  • Harrison, S. and Geppetti, P. (2001) “Substance P”, Int. J. Biochem. Cell Biol. 33, 555–576.

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto, H., Onishi, H., Koide, S., Kai, T. and Yamagami, S. (1996) “Plasma neuropeptide Y in patients with major depressive disorder”, Neurosci. Lett. 216(1), 57–60.

    Article  PubMed  CAS  Google Scholar 

  • Heikkla, L. (1993) “Somatostatin in the cerebrospinal fluid of schizophrenic patients before and after neuroleptic drug treatment”, Schizophr. Res. 8(3), 273–277.

    Article  Google Scholar 

  • Heikkila, L., Rimon, R., Terenius, L. and Dynorphin, A. (1990) “substance P in the cerebrospinal fluid of schizophrenic patients”, Psychiatry Res. 34, 229–236.

    Article  PubMed  CAS  Google Scholar 

  • Hein, M.D. and Jackson, I.M. (1990) “Review: thyroid function in psychiatric illness”, Gen. Hosp. Psychiatry 12, 232–244.

    Article  PubMed  CAS  Google Scholar 

  • Hermes, M.L. and Renaud, L.P. (1993) “Differential responses of identified rat hypothalamic paraventricular neurons to suprachiasmatic nucleus stimulation”, Neuroscience 56, 823–832.

    Article  PubMed  CAS  Google Scholar 

  • Heuser, I., Bissette, G., Dettling, M., Schweiger, U., Gotthardt, U., Schmider, J., Lammers, C.H., Nemeroff, C.B. and Holsboer, F. (1998) “Cerebrospinal fluid concentrations of corticotropinreleasing hormone, vasopressin and somatostalin in depressed patients and healthy controls: response to amitriptyline treatment”, Depress. Anxiety 8, 71–79.

    Article  PubMed  CAS  Google Scholar 

  • Holsboer, F. (2000) “The corticosteroid receptor hypothesis of depression”, Neuropsychopharmacology 23, 477–501.

    Article  PubMed  CAS  Google Scholar 

  • Holsboer, F. and Barden, N. (1996) “Antidepressants and hypothalamic-pituitary-adrenocortical regulation”, Endocr. Rev. 17, 187–205.

    PubMed  CAS  Google Scholar 

  • Holsboer, F., Lauer, C.J., Schreiber, W., and Krieg, J.C. (1995) “Altered hypothalamic-pituitary-adrenocortical regulation in healthy subjects at high familial risk for affective disorders”, Neuroendocrinology 62, 340–347.

    Article  PubMed  CAS  Google Scholar 

  • Hommer, D.W., Pickar, D., Roy, A., Ninan, P., Boronow, J. and Paul, S.M. (1984) “The effects of ceruletide in schizophrenia”, Arch. Gen. Psychiatry 41, 617–619.

    PubMed  CAS  Google Scholar 

  • Hoogendijk, W.J., Purba, J.S., Hofman, M.A., de Vos, R.A., Jansen, E.N. and Swaab, D.F. (1998) “Depression in Parkinson's disease is not accompanied by more corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus”, Biol. Psychiatry 43, 913–917.

    Article  PubMed  CAS  Google Scholar 

  • Hucks, D., Lowther, S., Crompton, M.R., Katona, C.L. and Horton, R.W. (1997) “Corticotropin-releasing factor binding sites in cortex of depressed suicides”, Psychopharmacology (Berl) 134, 174–178.

    Article  CAS  Google Scholar 

  • Iadarola, M.J., Ofri, D. and Kleinman, J.E. (1991) “Enkephalin, dynorphin and substance P in postmortem substantia nigra from normals and schizophrenic patients”, Life Sci. 48, 1919–1930.

    Article  PubMed  CAS  Google Scholar 

  • Iager, A.C., Kirch, D.G., Bigelow, L.B. and Karson, C.N. (1986) “Treatment of schizophrenia with a vasopressin analogue”, Am. J. Psychiatry 143, 375–377.

    PubMed  CAS  Google Scholar 

  • Inder, W.J., Donald, R.A., Prickett, T.C., Frampton, C.M., Sullivan, P.F., Mulder, R.T. and Joyce, P.R. (1997) “Arginine vasopressin is associated with hypercortisolemia and suicide attempts in depression”, Biol. Psychiatry 42, 744–747.

    Article  PubMed  CAS  Google Scholar 

  • Iritani, S., Kuroki, N., Niizato, K. and Ikeda, K. (2000) “Morphological changes in neuropeptide Y-positive fiber in the hippocampal formation of schizophrenics”, Prog. Neuropsychopharmacol. Biol. Psychiatry 24(2), 241–249.

    Article  PubMed  CAS  Google Scholar 

  • Irwin, M., Brown, M., Patterson, T., Hauger, R., Mascovich, A. and Grant, I. (1991) “Neuropeptide Y and natural killer cell activity: findings in depression and Alzheimer caregiver stress”, FASEB J. 5(15), 3100–3107.

    PubMed  CAS  Google Scholar 

  • Ishunina, T.A. and Swaab, D.F. (1999) “Vasopressin and oxytocin neurons of the human supraoptic and paraventricular nucleus: size changes in relation to age and sex”, J. Clin. Endocrinol. Metab 84, 4637–4644.

    Article  PubMed  CAS  Google Scholar 

  • Jackson, I.M. (1998) “The thyroid axis and depression”, Thyroid 8, 951–956.

    Article  PubMed  CAS  Google Scholar 

  • Jacquet, Y.F. and Marks, N. (1976) “The C-fragment of betalipotropin: an endogenous neuroleptic or antiosychotogen?”, Science 194, 632–634.

    Article  PubMed  CAS  Google Scholar 

  • Joja, O., Goldstein, R. and Popa, M. (1993) “Vasotocin effects in depressive patients with eating disorders”, Rom. J. Endocrinol. 31, 171–177.

    PubMed  CAS  Google Scholar 

  • Kaiya, H., Tamura, Y., Adachi, S., Moriuchi, I., Namba, M., Tanaka, M., Yoshida, H., Yanaihara, N. and Yanaihara, C. (1981) “Substance P-like immunoreactivity in plasma of psychotic patients and effects of neuroleptics and electroconvulsive therapy”, Psychiatry Res. 5, 11–21.

    Article  PubMed  CAS  Google Scholar 

  • Kasckow, J.W., Baker, D. and Geracioti, Jr., T.D. (2001) “Corticotropin-releasing hormone in depression and post-traumatic stress disorder”, Peptides 22, 845–851.

    Article  PubMed  CAS  Google Scholar 

  • Kathol, R.G., Jaeckle, R.S., Lopez, J.F. and Meller, W.H. (1989) “Consistent reduction of ACTH responses to stimulation with CRH, vasopressin and hypoglycaemia in patients with major depression”, Br. J. Psychiatry 155, 468–478.

    Article  PubMed  CAS  Google Scholar 

  • Keck, M.E. and Holsboer, F. (2001) “Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders”, Peptides 22, 835–844.

    Article  PubMed  CAS  Google Scholar 

  • Kerwin, R., Robinson, P. and Stewart, J.M. (1992) ”Distribution of CCK binding sites in the human hippocampal formation and their alteration in schizophrenia: a post-mortem autoradiographic study”, Psychol. Med. 22, 37–43.

    PubMed  CAS  Google Scholar 

  • Kirkegaard, C., Faber, J., Hummer, L. and Rogowski, P. (1979) “Increased levels of TRH in cerebrospinal fluid from patients with endogenous depression”, Psychoneuroendocrinology 4, 227–235.

    Article  PubMed  CAS  Google Scholar 

  • Kinkead, B. and Nemeroff, C.B. (2002) ”Neurotensin: an endogenous antipsychotic?”, Curr. Opin. Pharmacol. 2(1), 99–103.

    Article  PubMed  CAS  Google Scholar 

  • Kissling, W., Moller, J.H., Cootjans, J. Roy, D., Husebö, B., Christiansen, P. and Godt, H.H. (1986) “Multicenter double-blind comparison between des-enkephalin-γ-endorphin (DE-γE, Org 5878) and haloperidol concerning the efficacy and safety in the treatment of schizophrenia” In: Psychiatry, Its Related Disciplines, the Next 25 Years: World Psychiatric Association, Regional Symposium, p. 178.

  • Kleinman, J.E., Hong, J., Iadarola, M., Govoni, S. and Gillin, C.J. (1985) ”Neuropeptides in human brain-postmortem studies”, Prog. Neuropsychopharmacol. Biol. Psychiatry 9, 91–95.

    Article  PubMed  CAS  Google Scholar 

  • Kling, M.A., Roy, A., Doran, A.R., Calabrese, J.R., Rubinow, D.R., Whitfield, Jr, H.J., May, C., Post, R.M., Chrousos, C.P. and Gold, P.W. (1991) ”Cerebrospinal fluid immunoreactive corticotropin-releasing hormone and adrenocorticotropin secretion in Cushing's disease and major depression: potential clinical implications”, J. Clin. Endocrinol. Metab. 72, 260–271.

    PubMed  CAS  Google Scholar 

  • Kling, M.A., Rubinow, D.R., Doran, A.R., Roy, A., Davis, C.L., Calabrese, J.R., Nieman, L.K., Post, R.M., Chrousos, G.P. and Gold, P.W. (1993) ”Cerebrospinal fluid immunoreactive somatostatin concentrations in patients with Cushing's disease and major depression: relationship to indices of corticotropin-releasing hormone and cortisol secretion”, Neuroendocrinology 57, 79–88.

    Article  PubMed  CAS  Google Scholar 

  • Korsgaard, S., Casey, D.E., Damgaard Pedersen, N.E., Jorgensen, A. and Gerlach, J. (1981) ”Vasopressin in anergic schizophrenia. A cross-over study with lysine-8-vasopressin and placebo”, Psychopharmacology (Berl) 74, 379–382.

    Article  CAS  Google Scholar 

  • Korsgaard, S., Casey, D.E. and Gerlach, J. (1982) ”High-dose destyrosine-gamma-endorphin in tardive dyskinesia”, Psychopharmacology (Berl) 78, 285–286.

    Article  CAS  Google Scholar 

  • Kramer, M.S. (2000) ”Update on substance P (NK-1 receotir) antagonists in clinical trials for depression”, Neuropeptides 34, 255.

    Article  PubMed  CAS  Google Scholar 

  • Kramer, M.S., Cutler, N., Feighner, J., Shrivastava, R., Carman, J., Sramek, J.J., Reines, S.A., Liu, G., Snavely, D., Wyatt-Knowles, E., Hale, J.J., Mills, S.G., MacCoss, M., Swain, C.J., Harrison, T., Hill, R.G., Hefti, F., Scolnick, E.M., Cascieri, M.A., Chicchi, G.G., Sadowski, S., Williams, A.R., Hewson, L., Smith, D., Rupniak, N.M., et al. (1998) ”Distinct mechanism for antidepressant activity by blockade of central substance P receptors”, Science 281, 1640–1645.

    Article  PubMed  CAS  Google Scholar 

  • Lahti, R.A., Cochrane, E.V., Roberts, R.C., Conley, R.R. and Tamminga, C.A. (1998) ”[3H]Neurotensin receptor densities in human postmortem brain tissue obtained from normal and schizophrenic persons. An autoradiographic study”, J. Neural Transm. 105(4–5), 507–516.

    Article  PubMed  CAS  Google Scholar 

  • Laruelle, M., Seghers, A., Goffinet, S., Bouchez, S. and Legros, J.J. (1990) ”Plasmatic vasopressin neurophysin in depression: basic levels and relations with HPA axis”, Biol. Psychiatry 27, 1249–1263.

    Article  PubMed  CAS  Google Scholar 

  • Leake, A., Perry, E.K., Perry, R.H., Fairbairn, A.F. and Ferrier, I.N. (1990) ”Cortical concentrations of corticotropin-releasing hormone and its receptor in Alzheimer type dementia and major depression”, Biol. Psychiatry 28, 603–608.

    Article  PubMed  CAS  Google Scholar 

  • Legros, J.J. and Louis, F. (1973) ”Identification of a vasopressin-neurophysin and of an oxytocin-neurophysin in man”, Neuroendocrinology 13, 371–375.

    Article  CAS  Google Scholar 

  • Legros, J.J., Gazzotti, C., Carvelli, T., Franchimont, P., Timsit-Berthier, M., von Frenckell, R. and Ansseau, M. (1992) “Apomorphine stimulation of vasopressin- and oxytocin-neurophysins. Evidence for increased oxytocinergic and decreased vasopressinergic function in schizophrenics”, Psychoneuroendocrinology 17, 611–617.

    Article  PubMed  CAS  Google Scholar 

  • Leibowitz, S.F. (1994) ”Specificity of hypothalamic peptides in the control of behavioral and physiological processes”, Ann. NY Acad. Sci. 739, 12–35.

    Article  PubMed  CAS  Google Scholar 

  • Lembeck, F. (1953) ”Zur Frage der zentralen Übertragung afferenter Impulse. III. Mittelung. Den Vorkommen und die Bedeutung der Substanz P in den dorsalen Wurzeln des Rückenmarks”, Arch. Exp. Pathol. Pharmakol. 219, 197–213.

    CAS  Google Scholar 

  • Lenzinger, E., Meszaros, K., Hornik, K., Parzer, P., Hollerer, E., Langer, G., Resch, F. and Legros, J.J. (1996) ”Correlation between vasopressin baseline and TSH-blunting in depressives”, Biol. Psychiatry 39, 341–345.

    Article  PubMed  CAS  Google Scholar 

  • Lesch, K.P., Laux, G., Pfuller, H., Erb, A. and Beckmann, H. (1987) “Growth hormone (GH) response to GH-releasing hormone in depression”, J. Clin. Endocrinol. Metab. 65, 1278–1281.

    PubMed  CAS  Google Scholar 

  • Lesch, K.P., Widerlov, E., Ekman, R., Laux, G., Rupprecht, R., Schulte, H.M. and Beckmann, H. (1989) ”The influence of human corticotropin-releasing hormone on somatostatin secretion in depressed patients and controls”, J. Neural Transm. 75, 111–118.

    Article  PubMed  CAS  Google Scholar 

  • Lindstrom, L.H., Widerlov, E., Bisette, G. and Nemeroff, C. (1988) “Reduced CSF neurotensin concentration in drug-free schizophrenic patients”, Schizophr. Res. 1(1), 55–59.

    Article  PubMed  CAS  Google Scholar 

  • Linkowski, P., Geenen, V., Kerkhofs, M., Mendlewicz, J. and Legros, J.J. (1984) ”Cerebrospinal fluid neurophysins in affective illness and in schizophrenia”, Eur. Arch. Psychiatry Neurol. Sci. 234, 162–165.

    Article  PubMed  CAS  Google Scholar 

  • Liu, R.Y., Zhou, J.N., Hoogendijk, W.J., van Heerikhuize, J., Kamphorst, W., Unmehopa, U.A., Hofman, M.A. and Swaab, D.F. (2000) ”Decreased vasopressin gene expression in the biological clock of Alzheimer disease patients with and without depression”, J. Neuropathol. Exp. Neurol. 59, 314–322.

    PubMed  CAS  Google Scholar 

  • Lolait, S.J., O'Carroll, A.M., Mahan, L.C., Felder, C.C., Button, D.C., Young, III, W.S., Mezey, E. and Brownstein, M.J. (1995) “Extrapituitary expression of the rat V1b vasopressin receptor gene”, Proc. Natl. Acad. Sci. USA 92, 6783–6787.

    Article  PubMed  CAS  Google Scholar 

  • Lotstra, F., Verbanck, P., Mendlewicz, J. and Vanderhaeghen, J.J. (1984) ”No evidence of antipsychotic effect of caerulein in schizophrenic patients free of neuroleptics: a double-blind cross-over study”, Biol. Psychiatry 19, 877–882.

    PubMed  CAS  Google Scholar 

  • Mai, J.K., Berger, K. and Sofroniew, M.V. (1993) ”Morphometric evaluation of neurophysin-immunoreactivity in the human brain: pronounced inter-individual variability and evidence for altered staining patterns in schizophrenia”, J. Hirnforsch. 34, 133–154.

    PubMed  CAS  Google Scholar 

  • Manchanda, R. and Hirsch, S.R. (1981) ”(Des-Tyr)-gamma-endorphin in the treatment of schizophrenia”, Psychol. Med. 11, 401–404.

    Article  PubMed  CAS  Google Scholar 

  • Mattes, J.A., Hom, W. and Rochford, J.M. (1985a) “A high-dose, double-blind study of ceruletide in the treatment of schizophrenia”, Am. J. Psychiatry 142, 1482–1484.

    PubMed  CAS  Google Scholar 

  • Mattes, J.A., Hom, W., Rochford, J.M. and Orlosky, M. (1985b) “Ceruletide for schizophrenia: a double-blind study”, Biol. Psychiatry 20, 533–538.

    Article  PubMed  CAS  Google Scholar 

  • Mauri, M.C., Rudelli, R., Vanni, S., Panza, G., Sicaro, A., Audisio, D., Sacerdote, P. and Panerai, A.E. (1998) ”Cholecystokinin, beta-endorphin and vasoactive intestinal peptide in peripheral blood mononuclear cells of drug-naive schizophrenic patients treated with haloperidol compared to healthy controls”, Psychiatry Res. 78, 45–50.

    Article  PubMed  CAS  Google Scholar 

  • McMahon, B.M., Boules, M., Warrington, L. and Richelson, E. (2002) ”Neurotensin analogs indications for use as potential antipsychotic compounds”, Life Sci. 70(10), 1101–1109.

    Article  PubMed  CAS  Google Scholar 

  • Meltzer, H.Y., Busch, D.A., Tricou, B.J. and Robertson, A. (1982) “Effect of (Des-Tyr)-gamma-endorphin in schizophrenia”, Psychiatry Res. 6, 313–326.

    Article  PubMed  CAS  Google Scholar 

  • Miller, C., Kirchmair, R., Troger, J., Saria, A., Fleischhacker, W.W., Fischer-Colbrie, R., Benzer, A. and Winkler, H. (1996) ”CSF of neuroleptic-naive first-episode schizophrenic patients: levels of biogenic amines, substance P and peptides derived from chromogranin A (GE-25) and secretogranin II (secretoneurin)”, Biol. Psychiatry 39, 911–918.

    Article  PubMed  CAS  Google Scholar 

  • Mizuki, Y., Ushijima, I., Yamada, M., Tanaka, M. and Inanaga, K. (1986) ”A treatment trial with an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin in schizophrenia”, Int. Clin. Psychopharmacol. 1, 303–313.

    Article  PubMed  CAS  Google Scholar 

  • Modell, S., Lauer, C.J., Schreiber, W., Huber, J., Krieg, J.C. and Holsboer, F. (1998) ”Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders”, Neuropsychopharmacology 18, 253–262.

    Article  PubMed  CAS  Google Scholar 

  • Molchan, S.E., Lawlor, B.A., Hill, J.L., Martinez, R.A., Davis, C.L., Mellow, A.M., Rubinow, D.R. and Sunderland, T. (1991) ”CSF monoamine metabolites and somatostatin in Alzheimer's disease and major depression”, Biol. Psychiatry 29, 1110–1118.

    Article  PubMed  CAS  Google Scholar 

  • Molchan, S.E., Hill, J.L., Martinez, R.A., Lawlor, B.A., Mellow, A.M., Rubinow, D.R., Bissette, G., Nemeroff, C.B. and Sunderland, T. (1993) ”CSF somatostatin in Alzheimer's disease and major depression: relationship to hypothalamic-pituitaryadrenal axis and clinical measures”, Psychoneuroendocrinology 18, 509–519.

    Article  PubMed  CAS  Google Scholar 

  • Montgomery, S.A., Green, M., Rimon, R., Heikkila, L., Forsstrom, R., Hirsch, S.R., Hallstrom, C., Hippius, H., Naber, R., Khan, M.C., et al. (1992) ”Inadequate treatment response to des-enkephalin-gamma-endorphin compared with thioridazine and placebo in schizophrenia”, Acta Psychiatr. Scand. 86, 97–103.

    Article  PubMed  CAS  Google Scholar 

  • Nair, N.P., Bloom, D.M., Debonnel, G., Schwartz, G. and Mosticyan, S. (1984) ”Cholecystokinin-octapeptide in chronic schizophrenia: a double-blind placebo-controlled study”, Prog. Neuropsychopharmacol. Biol. Psychiatry 8, 711–714.

    Article  PubMed  CAS  Google Scholar 

  • Nakase, S., Kitayama, I., Soya, H., Hamanaka, K. and Nomura, J. (1998) ”Increased expression of magnocellular arginine vasopressin mRNA in paraventricular nucleus of stress-induced depression-model rats”, Life Sci. 63, 23–31.

    Article  PubMed  CAS  Google Scholar 

  • Nemeroff, C.B. (1980) ”Neurotensin: perchance an endogenous neuroleptic?”, Biol. Psychiatry 15(2), 283–302.

    PubMed  CAS  Google Scholar 

  • Nemeroff, C.B., Youngblood, W.W., Manberg, P.J., Prange, Jr., A.J. and Kizer, J.S. (1983) ”Regional brain concentrations of neuropeptides in Huntington's chorea and schizophrenia”, Science 221(4614), 972–975.

    Article  PubMed  CAS  Google Scholar 

  • Nemeroff, C.B., Widerlov, E., Bissette, G., Walleus, H., Karlsson, I., Eklund, K., Kilts, C.D., Loosen, P.T. and Vale, W. (1984) ”Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients”, Science 226, 1342–1344.

    Article  PubMed  CAS  Google Scholar 

  • Nemeroff, C.B., Owens, M.J., Bissette, G., andorn, A.C. and Stanley, M. (1988) ”Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims”, Arch. Gen. Psychiatry 45, 577–579.

    PubMed  CAS  Google Scholar 

  • Nemeroff, C.B., Bissette, G., Widerlov, E., Beckmann, H., Gerner, R., Manberg, P.J., Lindstrom, L., Prange, Jr., A.J. and Gattaz, W.F. (1989) “Neurotensin-like immunoreactivity in cerebrospinal fluid of patients with schizophrenia, depression, anorexia nervosa-bulimia, and premenstrual syndrome”, J. Neuropsychiatry Clin. Neurosci. 1(1), 16–20.

    PubMed  CAS  Google Scholar 

  • Nilsson, C., Karlsson, G., Blennow, K., Heilig, M. and Ekman, R. (1996) “Differences in the neuropeptide Y-like immunoreactivity of the plasma and platelets of human volunteers and depressed patients”, Peptides, 17(3), 359–362.

    Article  PubMed  CAS  Google Scholar 

  • Ordway, G.A., Stockmeier, C.A., Meltzer, H.Y., Overholser, J.C., Jaconetta, S. and Widdowson, P.S. (1995) “Neuropeptide Y in frontal cortex is not altered in major depression” J. Neurochem. 65(4), 1646–1650.

    Article  PubMed  CAS  Google Scholar 

  • Palacios, J.M., Rigo, M., Chinaglia, G. and Probst, A. (1990) “Reduced density of striatal somatostatin receptors in Huntington's chorea”, Brain Res. 522(2), 342–346.

    Article  PubMed  CAS  Google Scholar 

  • Palacios, J.M., Chinaglia, G., Rigo, M., Ulrich, J. and Probst, A. (1991) “Neurotensin receptor binding levels in basal ganglia are not altered in Huntington's chorea or schizophrenia”, Synapse 7(2), 114–122.

    Article  PubMed  CAS  Google Scholar 

  • Panza, G., Monzani, E., Sacerdote, P., Penati, G. and Panerai, A.E. (1992) “Beta-endorphin, vasoactive intestinal peptide and cholecystokinin in peripheral blood mononuclear cells from healthy subjects and from drug-free and haloperidoltreated schizophrenic patients”, Acta Psychiatr. Scand. 85, 207–210.

    Article  PubMed  CAS  Google Scholar 

  • Peselow, E., Angrust, B., Sudilovsky, A., Corwin, J., Siekierski, J., Trent, F. and Rotrosen, J. (1987) “Double blind controlled trials of cholecystokinin octapeptide in neuroleptic-refractory schizophrenia”, Psychopharmacology (Berl). 91, 80–84.

    Article  CAS  Google Scholar 

  • Peters, J., Van Kammen, D.P., Gelernter, J., Yao, J. and Shaw, D. (1990) “Neuropeptide Y-like immunoreactivity in schizophrenia. Relationships with clinical measures”, Schizophr. Res. 3(5,6), 287–294.

    Article  PubMed  CAS  Google Scholar 

  • Pitts, A.F., Samuelson, S.D., Meller, W.H., Bissette, G., Nemeroff, C.B. and Kathol, R.G. (1995) “Cerebrospinal fluid corticotropin-releasing hormone, vasopressin and oxytocin concentrations in treated patients with major depression and controls”, Briol. Psychiatry 38, 330–335.

    Article  CAS  Google Scholar 

  • Prange, Jr., A.J., Wilson, I.C., Breese, G.R. and Lipton, M.A. (1975) “Behavioral effects of hypothalamic releasing hormones in animals and men”, Prog. Brain Res. 42, 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Price, L.H., Cappiello, A., Malison, R.T., McDougle, C.J., Pelton, G.H., Schollnhammer, G. and Heninger, G.R. (1997) “Effects of antiglucocorticoid treatment on 5-HT1A function in depressed patients and healthy subjects”, Neuropsychopharmacology 17, 246–257.

    Article  PubMed  CAS  Google Scholar 

  • Purba, J.S., Hoogendijk, W.J., Hofman, M.A. and Swaab, D.F. (1996) “Increased number of vasopressin- and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression”, Arch. Gen. Psychiatry 53, 137–143.

    PubMed  CAS  Google Scholar 

  • Raadsheer, F.C., Hoogendijk, W.J., Stam, F.C., Tilders, F.J. and Swaab, D.F. (1994) “Increased number of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients”, Neuroendocrinology 60, 436–444.

    Article  PubMed  CAS  Google Scholar 

  • Raadsheer, F.C., van Heerikhuize, J.J., Lucassen, P.J., Hoogendijk, W.J., Tilders, F.J. and Swaab, D.F. (1995) “Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression”, Am. J. Psychiatry 152, 1372–1376.

    PubMed  CAS  Google Scholar 

  • Rafaelsen, O.J. and Gjerris, A. (1985) “Neuropeptides in the cerebrospinal fluid (CSF) in psychiatric disorders”, Prog. Neuropsychopharmacol. Biol. Psychiatry 9, 533–538.

    Article  PubMed  CAS  Google Scholar 

  • Raskind, M., Orenstein, H. and Weitzman, R.E. (1979) “Vasopressin in depression”, Lancet 1, 164.

    Article  PubMed  CAS  Google Scholar 

  • Reinikainen, K.J., Koponen, H., Jolkkonen, J. and Riekkinen, P.J. (1990) “Decreased somatostatin-like immunoreactivity in the cerebrospinal fluid of chronic schizophrenic patients with cognitive impairment”, Psychiatry Res. 33(3), 307–312.

    Article  PubMed  CAS  Google Scholar 

  • Rimon, R., Le Greves, P., Nyberg, F., Heikkila, L., Salmela, L. and Terenius, L. (1984) “Elevation of substance P-like peptides in the CSF of psychiatric patients”, Biol. Psychiatry 19, 509–516.

    PubMed  CAS  Google Scholar 

  • Rioux, L., Nissanov, J. and Joyce, J.N. (1998) “Increased number of [125I] BH-substance P in schizophrenia”, Prog. Neuropsychopharmacol. Biol. Psychiatry 22, 1295–1299.

    Article  CAS  Google Scholar 

  • Risch, S.C., Lewine, R.J., Jewart, R.D., Pollard, W.E., Caudle, J.M., Kalin, N.H., Stipetic, M., Eccard, M.B. and Risby E.D. (1991) “Relationship between cerebrospinal fluid peptides and neurotransmitters in depression”, In: Risch, S.C., ed., Central Nervous System Peptide Mechanisms in Stress and Depression (American Psychiatric Press, Washington DC).

    Google Scholar 

  • Roberts, G.W., Ferrier, I.N., Lee, Y., Crow, T.J., Johnstone, E.C., Owens, D.G., Bacarese-Hamilton, A.J., McGregor, G., O'Shaughnessey, D. and Polak, J.M. (1983) “Peptides, the limbic lobe and schizophrenia”, Brain Res. 288, 199–211.

    Article  PubMed  CAS  Google Scholar 

  • Ronken, E., Wiegant, V.M., Kaspersen, F.M., van Nispen, J.W., de Boer, T., Bruning, H.W., Rust, C.J. and Tonnaer, J.A. (1993) “Topography and characteristics of specific binding sites for non-opioid gamma-type endorphins in the rat brain as studied by autoradiography with [35S]Met-desenkephalin-gamma-endorphin”, Brain Res. 615, 63–70.

    Article  PubMed  CAS  Google Scholar 

  • Roy, A., Pickar, D., Paul, S., Doran, A., Chrousos, G.P. and Gold, P.W. (1987) “CSF corticotropin-releasing hormone in depressed patients and normal control subjects”, Am. J. Psychiatry 144, 641–645.

    PubMed  CAS  Google Scholar 

  • Roy, B.F., Benkelfat, C., Hill, J.L., Pierce, P.F., Dauphin, M.N., Kelly, T.M., Sunderland, T., Weinberger, D.R. and Breslin, N. (1994a) “Serum antibody for somatostatin-14 and prodynorphin 209–240 in patients with obsessive-compulsive disorder, schizophrenia, Alzheimer's disease, multiple sclerosis, and advanced HIV infection”, Biol. Psychiatry 35(5), 335–344.

    Article  PubMed  CAS  Google Scholar 

  • Roy, A., Wolkowitz, O.M., Bissette, G. and Nemeroff, C.B. (1994b) “Differences in CSF concentrations of thyrotropin-releasing hormone in depressed patients and normal subjects: negative findings”, Am. J. Psychiatry 151, 600–602.

    PubMed  CAS  Google Scholar 

  • Rubinow, D.R., Gold, P.W., Post, R.M., Ballenger, J.C., Cowdry, R., Bollinger, J. and Reichlin, S. (1983) “CSF somatostatin in affective illness”, Arch. Gen. Psychiatry 40, 409–412.

    PubMed  CAS  Google Scholar 

  • Rupniak, N.M. and Kramer, M.S. (1999) “Discovery of the antidepressant and anti-emetic efficacy of substance P receptor (NK1) antagonists”, Trends Pharmacol. Sci. 20, 485–490.

    Article  PubMed  CAS  Google Scholar 

  • Saiz-Ruiz, J., Carrasco, J.L., Martin, M., Manzanares, J. and Hernanz, A. (1992) “Plasmatic somatostatin as a marker of positive symptoms of schizophrenia”, Prog. Neuropsychopharmacol. Biol. Psychiatry 16(2), 203–210.

    Article  PubMed  CAS  Google Scholar 

  • Santarelli, L., Gobbi, G., Debs, P.C., Sibille, E.T., Blier, P., Hen, R. and Heath, M.J. (2001) “Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function”, Proc. Natl. Acad. Sci. USA 98, 1912–1917.

    Article  PubMed  CAS  Google Scholar 

  • Sattin, A. (1998) “A heuristic model of mental depression derived from basic and applied research on thyrotropin-releasing hormone”, Thyroid 8, 957–962.

    Article  PubMed  CAS  Google Scholar 

  • Sawchenko, P.E., Imaki, T., Potter, E., Kovacs, K., Imaki, J. and Vale, W. (1993) “The functional neuroanatomy of corticotropin-releasing factor”, Ciba Found. Symp. 172, 5–21

    PubMed  CAS  Google Scholar 

  • Scott, L.V. and Dinan, T.G. (1998) “Vasopressin and the regulation of hypothalamic-pituitary-adrenal axis function: implications for the pathophysiology of depression”, Life Sci. 62, 1985–1998.

    Article  PubMed  CAS  Google Scholar 

  • Sharma, R.P., Janicak, P.G., Bissette, G. and Nemeroff, C.B. (1997) “CSF neurotensin concentrations and antipsychotic treatment in schizophrenia and schizoaffective disorder”, Am. J. Psychiatry 154(7), 1019–1021.

    PubMed  CAS  Google Scholar 

  • Siuciak, J.A., Lewis, D.R., Wiegand, S.J. and Lindsnay, R.M. (1997) “Antidepressant-like effect of brain-derived neurotrophic factor (BDNF)”, Pharmacol. Biochem. Behav. 56, 131–137.

    Article  PubMed  CAS  Google Scholar 

  • Sorensen, P.S., Gjerris, A. and Hammer M (1985) “Cerebrospinal fluid vasopressin in neurological and psychiatric disorders”, J. Neurol. Neurosurg. Psychiatry 48, 50–57.

    Article  PubMed  CAS  Google Scholar 

  • Staner, L., Duval, F., Calvi-Gries, F., Mokrani, M.C., Bailey, P., Hode, Y., Toussaint, M., Luthringer, R., Muzet, A. and Macher, J.P. (2001) “Morning and evening TSH response to TRH and sleep EEG disturbances in major depressive disorder”, Prog. Neuropsychopharmacol. Biol. Psychiatry 25, 535–547.

    Article  PubMed  CAS  Google Scholar 

  • Steckler, T., Holsboer, F. and Reul, J.M. (1999) “Glucocorticoids and depression”, Bailliere's Best. Pract. Res. Clin. Endocrinol. Metab. 13, 597–614.

    Article  CAS  Google Scholar 

  • Tamminga, C.A., Tighe, P.J., Chase, T.N., DeFraites, E.G. and Schaffer, M.H. (1981) “Des-tyrosine-gamma-endorphin administration in chronic schizophrenics. A preliminary report”, Arch. Gen. Psychiatry 38, 167–168.

    PubMed  CAS  Google Scholar 

  • Tamminga, C.A., Littman, R.L., Alphs, L.D., Chase, T.N., Thaker, G.K. and Wagman, A.M. (1986) “Neutronal cholecystokinin and schizophrenia: pathogenic and therapeutic studies”, Psychopharmacology (Berl) 88, 387–391.

    Article  CAS  Google Scholar 

  • Tang, Q., Gandhoke, R., Burritt, A., Hruby, V.J., Porreca, F. and Lai, J. (1999) “Hign-affinity interaction of (des-Tyrosyl)dynorphin A(2–17) with NMDA receptors”, J. Pharmacol. Exp. Ther. 291, 760–765.

    PubMed  CAS  Google Scholar 

  • Tooney, P.A., Crawter, V.C. and Chahl, L.A. (2001) “Increased tachykinin NK(1) receptor immunoreactivity in the prefrontal cortex in schizophrenia”, Biol. Psychiatry 49, 523–527.

    Article  PubMed  CAS  Google Scholar 

  • Toru, M., Watanabe, S., Shibuya, H., Nishikawa, T., Noda, K., Mitsushio H., Ichikawa H., Kurumaji A., Takashima, M. and Mataga, N. (1988) “Neurotransmitters, receptors and neuropeptides in post-mortem brains of chronic schizophrenic patients”, Acta Psychiatr. Scand. 78, 121–137.

    Article  PubMed  CAS  Google Scholar 

  • Traskman-Bendz, L., Ekman, R., Regnell, G. and Ohman, R. (1992) “HPA-related CSF neuropeptides in suicide attempters”, Eur. Neuropsychopharmacol. 2, 99–106.

    Article  PubMed  CAS  Google Scholar 

  • Van Kammen, D.P., Waters, R.N., Gold, P., et al. (1981) “Spinal fluid vasopressin, angiotensin I and II, beta-endorphin and opioid activity in schizophrenia: a preliminary evaluation”, In: Perris, C., Struwe, G. and Jansson, B., eds, Biological Psychiatry (Elsevier/North-Holland Biomedical Press, Amsterdam).

    Google Scholar 

  • Van Londen, L., Goekoop, J.G., van Kempen, G.M., Frankhuijzen-Sierevogel, A.C., Wiegant, V.M., van der Velde, E.A. and De Wied, D. (1997) “Plasma levels of arginine vasopressin elevated in patients with major depression”, Neuropsychopharmacology 17, 284–292.

    Article  PubMed  Google Scholar 

  • Van Londen, L., Kerkhof, G.A., Van den, B.F., Goekoop, J.G., Zwinderman, K.H., Frankhuijzen-Sierevogel, A.C., Wiegant, V.M. and De Wied, D. (1998) “Plasma arginine vasopressin and motor activity in major depression”, Biol. Psychiatry 43, 196–204.

    Article  PubMed  Google Scholar 

  • Van Londen, L., Goekoop, J.G., Kerkhof, G.A., Zwinderman, K.H., Wiegant V.M. and De Wied, D. (2001) “Weak 24-h periodicity of body temperature and increased plasma vasopressin in melancholic depression”, Eur. Neuropsychopharmacol. 11, 7–14.

    Article  PubMed  Google Scholar 

  • Verbanck, P.M., Lotstra, F., Gilles, C., Linkowski, P., Mendlewicz, J. and Vanderhaeghen, J.J. (1984) “Reduced cholecystokinin immunoreactivity in the cerebrospinal fluid of patients with psychiatric disorders”, Life Sci. 34, 67–72.

    Article  PubMed  CAS  Google Scholar 

  • Verhoeven, W.M., van Praag, H.M., van Ree, J.M. and de Wied, D. (1979) “Improvement of schizophrenic patients treated with [des-Tyr1]-gamma-endorphin (DTgammaE)”; Arch. Gen. Psychiatry 36, 294–298.

    PubMed  CAS  Google Scholar 

  • Verhoeven, W.M., van Ree J.M., de Wied, D. and van Praag, H.M. (1981) “Gamma-Type endorphins and schizophrenia”, Arch. Gen. Psychiatry 38, 1182–1183.

    PubMed  CAS  Google Scholar 

  • Verhoeven, W.M., Westenberg, H.G. and Van Ree, J.M. (1986) “A comparative study on the antipsychotic properties of desenkephalin-gamma-endorphin and ceruletide in schizophrenic patients”, Acta Psychiatr. Scand. 73, 372–382.

    Article  PubMed  CAS  Google Scholar 

  • Verhoeven, W.M., van Ree, J.M., Westenberg, H.G., Krul, J.M., Brouwer, G.J., Thijssen, J.H., de Wied, D., van Praag, H.M., Ceulemans, D.L., Kahn, R.S. (1984) “Clinical, biochemical, and hormonal aspects of treatment with Des-tyr1-gamma-endorphin in schizophrenia”, Psychiatry Res. 11, 329–346.

    Article  PubMed  CAS  Google Scholar 

  • Virge, L., Humphries, C., Mortimer, A., Barnes, T., Hirsch, S. and de Belleroche, J. (1995) “Cholecystokinin messenger RNA deficit in frontal and temporal cerebral cortex in schizophrenia”, Biol. Psychiatry 37, 694–701.

    Article  Google Scholar 

  • Volavka, J., Hui K.S., Anderson, B., Nemes, Z., O'Donnell, J. and Lajtha, A. (1983) “Short-lived effect of (Des-Tyr)-gamma-endorphin in schizophrenia”, Psychiatry Res. 10, 243–252.

    Article  PubMed  CAS  Google Scholar 

  • Von Bardeleben, U. and Holshoer, F. (1989) “Cortisol response to a combined dexamethason-hCRH challenge in patients with depression”, J. Neuroendocrinol. 1, 485–488.

    Article  PubMed  CAS  Google Scholar 

  • Von Bardeleben, U., Holsboer, F., Stalla, G.K. and Muller, O.A. (1985) “Combined administration of human corticotropin-releasing factor and lysine vasopressin induces cortisol escape from dexamethasone suppression in healthy subjects”, Life Sci. 37, 1613–1618.

    Article  Google Scholar 

  • Wei, J. and Hemmings, G.P. (1999) “The CCK-A receptor gene possibly associated with auditory hallucinations in schizophrenia”, Eur. Psychiatry 14, 67–70.

    Article  PubMed  CAS  Google Scholar 

  • Westrin, A., Ekman, R. and Traskman-Bendz, L. (1999) “Alterations of corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) plasma levels in mood disorder patients with a recensuicide attempt”, Eur. Neuropsychopharmacol. 9(3), 205–211.

    Article  PubMed  CAS  Google Scholar 

  • Westrin, A., Ekman, R., Regnell, G. and Traskman-Benciz, L. (2001) “A follow up study of suicide attempters: increase of CSF-somatostatin but no change in CSF-CRH”, Eur. Neuropsychopharmacol. 11, 135–143.

    Article  PubMed  CAS  Google Scholar 

  • Widdowson, P.S., Ordway, G.A. and Halaris, A.E. (1992) “Reduced neuropeptide Y concentrations in suicide brain”, J. Neurochem 59, 73–80.

    Article  PubMed  CAS  Google Scholar 

  • Widerlov, E., Lindstrom, L.H., Besev, G., Manberg, P.J., Nemeroff, C.B., Breese, G.R., Kizer, J.S. and Pranger, Jr., A.J. (1982) “Subnormal CSF levels of neurotensin in a subgroup of schizophrenic patients: normalization after neuroleptic treatment”, Am. J. Psychiatry 139(9), 1122–1126.

    PubMed  CAS  Google Scholar 

  • Widerlov, E., Lindstrom, L.H., Wahlestedt, C. and Ekman, R. (1988a) “Neuropeptide Y peptide YY as possible cerebrospinal fluid markers for major depression and schizophrenia, respectively”, J. Psychiatr. Res. 22(1), 69–79.

    Article  PubMed  CAS  Google Scholar 

  • Widerlov, E., Bissette, G. and Nemeroff, C.B. (1988b) “Monoamine metabolites, corticotropin releasing factor and somatostatin as CSF markers in depressed patients”, J. Affect. Disord. 14, 99–107.

    Article  PubMed  CAS  Google Scholar 

  • Wiegant, V.M., Ronken, E., Kovacs, G. and De Wied, D. (1992) “Endorphins and schizophrenia”, Prog. Brain Res. 93, 433–453.

    Article  PubMed  CAS  Google Scholar 

  • Wolf, S.S., Hyde, T.M., Saunders, R.C., Herman, M.M., Weinberger, D.R. and Kleinman, J.E. (1995) “Autoradiographic characterization of neurotensin receptors in the entorhinal cortex of schizophrenic patients and control subjects”, J. Neural. Transm. Gen. Sect. 102(1), 55–65.

    Article  PubMed  CAS  Google Scholar 

  • Wolkowitz, O.M. and Reus, V.I. (1999) “Treatment of depression with antiglucocorticoid drugs”, Psychosom. Med. 61, 698–711.

    PubMed  CAS  Google Scholar 

  • Wong, M.L., Kling, M.A., Munson, P.J., Listwak, S., Licinio, J., Prolo, P., Karp, B., McCutcheon, I.E., Geracioti, Jr., T.D., De Bellis, M.D., Rice, K.C., Goldstein, D.S., Veldhuis, J.D., Chrousos, G.P., Oldfield, F.H., McCann, S.M. and Gold, P.W. (2000) “Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone”, Proc. Natl Acad. Sci. USA 97, 325–330.

    Article  PubMed  CAS  Google Scholar 

  • Yamamura, Y., Ogawa, H., Chihara, T., Kondo, K., Onogawa, T., Nakamura, S., Mori, T., Tominaga, M. and Yabuuchi, Y. (1991) “OPC-21268, an orally effective, nonpeptide vasopressin V1. receptor antagonist”, Science 252, 572–574.

    Article  PubMed  CAS  Google Scholar 

  • Zachrisson, O., de Belleroche, J., Wendt, K.R., Hirsch, S. and Lindefors, N. (1999) “Cholecystokinin CCK(B) receptor mRNA isoforms: expression in schizophrenic brains”, Neuroreport 10, 3265–3268.

    Article  PubMed  CAS  Google Scholar 

  • Zech, M. and Bogerts, B. (1985) Methionine-enkephalin and substance P in the basal ganglia of normals, Parkinson patients, Huntington patients and schizophrenics. A qualitative immunohistochemical study”, Acta Neuropathol. (Berl.) 68, 32–38.

    Article  CAS  Google Scholar 

  • Zech, M., Roberts, G.W., Bogerts, B., Crow, T.J. and Polak, J.M. (1986) “Neuropeptides in the amygdala of controls, schizophrenics and patients suffering from Huntington's chorea: an immunohistochemical study”, Acta Neuropathol. (Berl.) 71(3–4), 259–266.

    Article  CAS  Google Scholar 

  • Zhou, J.N., Riemersma, R.F., Unmehopa, U.A., Hoogendijk, W.J., van Heerikhuize J.J., Hofman, M.A. and Swaab, D.F. (2001) “Alterations in arginine vasopressin neurons in the suprachiasmatic nucleus in depression”, Arch. Gen. Psychiatry 58, 655–662.

    Article  PubMed  CAS  Google Scholar 

  • Zobel, A.W., Nickel, T., Kunzel, H.E., Ackl, N., Sonntag, A., Ising, M. and Holsboer, F. (2000) “Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated”, J. Psychiatry Res. 34, 171–181.

    Article  CAS  Google Scholar 

  • Zohar, J., Drummer, D., Edelstein, E.D., Kaiser, N., Belmaker, R.H. and Nir, I. (1985) “Effect of lysine vasopressin in depressed patients on mood and 24-hour rhythm of growth hormone, cortisol, melatonin and prolactin”, Psychoneuroendocrinology 10, 273–279.

    Article  PubMed  CAS  Google Scholar 

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  1. Rudolf Magnus Institute for Neurosciences, University Medical Center Utrecht, P.O. Box 80040, 3508 TA, Utrecht, The Netherlands

    David De Wied & Hein O. Sigling

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De Wied, D., Sigling, H.O. Neuropeptides involved in the pathophysiology of schizophrenia and major depression. neurotox res 4, 453–468 (2002). https://doi.org/10.1080/10298420290031432

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