Hostname: page-component-6bf8c574d5-qdpjg Total loading time: 0 Render date: 2025-02-21T17:04:14.913Z Has data issue: false hasContentIssue false
  • English
  • Français

Hyperprolactinemia in antipsychotic-naive patients with first-episode psychosis

Published online by Cambridge University Press:  18 April 2013

A. Riecher-Rössler ,
J. K. Rybakowski ,
M. O. Pflueger ,
R. Beyrau ,
R. S. Kahn ,
P. Malik  and
W. W. Fleischhacker
A. Riecher-Rössler*
Affiliation:
University of Basel Psychiatric Clinics, Basel, Switzerland
J. K. Rybakowski
Affiliation:
Department of Adult Psychiatry, Poznan University of Medical Sciences, Poznan, Poland
M. O. Pflueger
Affiliation:
University of Basel Psychiatric Clinics, Basel, Switzerland
R. Beyrau
Affiliation:
Department of Clinical Chemistry, University Hospital Basel, Switzerland
R. S. Kahn
Affiliation:
Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Centre Utrecht, The Netherlands
P. Malik
Affiliation:
Department of Biological Psychiatry, Medical University Innsbruck, Austria
W. W. Fleischhacker
Affiliation:
Department of Biological Psychiatry, Medical University Innsbruck, Austria
*
*Address for correspondence: Prof. Dr med. A. Riecher-Rössler, Center for Gender Research and Early Detection, University of Basel Psychiatric Clinics, c/o University Hospital Basel, Petersgraben 4, CH-4031 Basel, Switzerland. (Email: anita.riecher@upkbs.ch)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Hyperprolactinemia is frequent in patients with schizophrenic psychoses. It is usually regarded as an adverse effect of antipsychotics but has recently also been shown in patients without antipsychotic medication. Our objective was to test whether hyperprolactinemia occurs in antipsychotic-naive first-episode patients (FEPs).

Method

In the framework of the European First Episode Schizophrenia Trial (EUFEST), 249 out of 498 FEPs were eligible for this study, of whom 74 were antipsychotic naive. All patients were investigated regarding their serum prolactin levels with immunoassays standardized against the 3rd International Reference Standard 84/500.

Results

Twenty-nine (39%) of the 74 antipsychotic-naive patients showed hyperprolactinemia not explained by any other reason, 11 (50%) of 22 women and 18 (35%) of 52 men.

Conclusions

Hyperprolactinemia may be present in patients with schizophrenic psychoses independent of antipsychotic medication. It might be stress induced. As enhanced prolactin can increase dopamine release through a feedback mechanism, this could contribute to explaining how stress can trigger the outbreak of psychosis.

Keywords

Antipsychoticdopaminefirst-episode psychosisprolactinschizophreniastress
Type
Original Articles
Information
Psychological Medicine , Volume 43 , Issue 12 , December 2013 , pp. 2571 - 2582
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Akhondzadeh, S, Rezaei, F, Larijani, B, Nejatisafa, AA, Kashani, L, Abbasi, SH (2006). Correlation between testosterone, gonadotropins and prolactin and severity of negative symptoms in male patients with chronic schizophrenia. Schizophrenia Research 84, 405–410.CrossRefGoogle ScholarPubMed
Aston, J, Rechsteiner, E, Bull, N, Borgwardt, S, Gschwandtner, U, Riecher-Rössler, A (2010). Hyperprolactinaemia in early psychosis – not only due to antipsychotics. Progress in Neuro-Psychopharmacology and Biological Psychiatry 34, 1342–1344.CrossRefGoogle Scholar
Büschlen, J, Berger, GE, Borgwardt, SJ, Aston, J, Gschwandtner, U, Pflueger, MO, Kuster, P, Radü, EW, Stieglitz, R-D, Riecher-Rössler, A (2010). Pituitary volume increase during emerging psychosis. Schizophrenia Research 125, 41–48.CrossRefGoogle ScholarPubMed
Bushe, C, Shaw, M, Peveler, RC (2008). A review of the association between antipsychotic use and hyperprolactinaemia. Journal of Psychopharmacology 22, 46–55.CrossRefGoogle ScholarPubMed
Bushe, CJ, Bradley, AJ, Wildgust, HJ, Hodgson, RE (2009). Schizophrenia and breast cancer incidence: a systematic review of clinical studies. Schizophrenia Research 114, 6–16.CrossRefGoogle ScholarPubMed
Chong, RY, Uhart, M, McCaul, ME, Johnson, E, Wand, GS (2008). Whites have a more robust hypothalamic-pituitary-adrenal axis response to a psychological stressor than blacks. Psychoneuroendocrinology 33, 246–254.CrossRefGoogle ScholarPubMed
Dickson, RA, Seeman, MV, Corenblum, B (2000). Hormonal side effects in women: typical versus atypical antipsychotic treatment. Journal of Clinical Psychiatry 61 (Suppl. 3), 10–15.Google ScholarPubMed
El Yazaji, M, Battas, O, Agoub, M, Moussaoui, D, Gutknecht, C, Dalery, J, d'Amato, T, Saoud, M (2002). Validity of the depressive dimension extracted from principal component analysis of the PANSS in drug-free patients with schizophrenia. Schizophrenia Research 56, 121–127.CrossRefGoogle ScholarPubMed
Evans, AM, Petersen, JW, Sekhon, GS, DeMars, R (1989). Mapping of prolactin and tumor necrosis factor-beta genes on human chromosome 6p using lymphoblastoid cell deletion mutants. Somatic Cell and Molecular Genetics 15, 203–213.CrossRefGoogle ScholarPubMed
Fitzgerald, P, Dinan, TG (2008). Prolactin and dopamine: what is the connection? A review article. Journal of Psychopharmacology 22, 12–19.CrossRefGoogle ScholarPubMed
Fleischhacker, WW, Keet, IP, Kahn, RS; EUFEST Steering Committee (2005). The European First Episode Schizophrenia Trial (EUFEST): rationale and design of the trial. Schizophrenia Research 78, 147–156.CrossRefGoogle ScholarPubMed
Garcia-Rizo, C, Fernandez-Egea, E, Oliveira, C, Justicia, A, Parellada, E, Bernardo, M, Kirkpatrick, B (2012). Prolactin concentrations in newly diagnosed, antipsychotic-naive patients with nonaffective psychosis. Schizophrenia Research 134, 16–19.CrossRefGoogle ScholarPubMed
Garner, B, Pariante, CM, Wood, SJ, Velakoulis, D, Phillips, L, Soulsby, B, Brewer, WJ, Smith, DJ, Dazzan, P, Berger, GE, Yung, AR, van den Buuse, M, Murray, R, McGorry, PD, Pantelis, C (2005). Pituitary volume predicts future transition to psychosis in individuals at ultra-high risk of developing psychosis. Biological Psychiatry 58, 417–423.CrossRefGoogle ScholarPubMed
Guest, PC, Schwarz, E, Krishnamurthy, D, Harris, LW, Leweke, FM, Rothermundt, M, van Beveren, NJ, Spain, M, Barnes, A, Steiner, J, Rahmoune, H, Bahn, S (2011). Altered levels of circulating insulin and other neuroendocrine hormones associated with the onset of schizophrenia. Psychoneuroendocrinology 36, 1092–1096.CrossRefGoogle ScholarPubMed
Guy, W (1976). Clinical Global Impressions. In ECDEU Assessment Manual for Psychopharmacology – Revised, pp. 218–222 (DHEW publication number ADM 76–338). National Institute of Mental Health: Rockville, MD.Google Scholar
Haddad, PM, Wieck, A (2004). Antipsychotic-induced hyperprolactinaemia: mechanisms, clinical features and management. Drugs 64, 2291–2314.CrossRefGoogle ScholarPubMed
Häfner, H, Maurer, K, Löffler, W, Riecher-Rössler, A (1993). The influence of age and sex on the onset and early course of schizophrenia. British Journal of Psychiatry 162, 80–86.CrossRefGoogle ScholarPubMed
Howard, L, Kirkwood, G, Leese, M (2007). Risk of hip fracture in patients with a history of schizophrenia. British Journal of Psychiatry 190, 129–134.CrossRefGoogle ScholarPubMed
Howes, OD, Kapur, S (2009). The dopamine hypothesis of schizophrenia: version III: – the final common pathway. Schizophrenia Bulletin 35, 549–562.CrossRefGoogle ScholarPubMed
Hummer, M, Malik, P, Gasser, RW, Hofer, A, Kemmler, G, Moncayo Naveda, RC, Rettenbacher, MA, Fleischhacker, WW (2005). Osteoporosis in patients with schizophrenia. American Journal of Psychiatry 162, 162–167.CrossRefGoogle ScholarPubMed
Kahn, RS, Fleischhacker, WW, Boter, H, Davidson, M, Vergouwe, Y, Keet, IP, Gheorghe, MD, Rybakowski, JK, Galderisi, S, Libiger, J, Hummer, M, Dollfus, S, Lopez-Ibor, JJ, Hranov, LG, Gaebel, W, Peuskens, J, Lindefors, N, Riecher-Rössler, A, Grobbee, DE; EUFEST Study Group (2008). Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial. Lancet 371, 1085–1097.CrossRefGoogle ScholarPubMed
Kay, SR, Fiszbein, A, Opler, LA (1987). The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophrenia Bulletin 13, 261–276.CrossRefGoogle ScholarPubMed
Kirschbaum, C, Kudielka, BM, Gaab, J, Schommer, NC, Hellhammer, DH (1999). Impact of gender, menstrual cycle phase, and oral contraceptives on the activity of the hypothalamus-pituitary-adrenal axis. Psychosomatic Medicine 61, 154–162.CrossRefGoogle ScholarPubMed
Klomp, A, Koolschijn, PC, Pol, HE, Kahn, RS, van Haren, NE (2012). Hypothalamus and pituitary volume in schizophrenia: a structural MRI study. International Journal of Neuropsychopharmacology 15, 281–288.CrossRefGoogle ScholarPubMed
Kraepelin, E (1909–1915). Psychiatry, vols 1–4 [in German]. Barth: Leipzig.Google Scholar
Kretschmer, E (1921). Körperbau und Charakter. Untersuchungen zum Konstitutionsproblem und zur Lehre von den Temperamenten [Physique and Character: An Investigation of the Nature of Constitution and of the Theory of Temperament]. 25th edn, 1967. Springer: Berlin, Heidelberg, New York.Google Scholar
Low, WJ (2008). Neuroendocrinology. In Williams Textbook of Endocrinology (ed. Kronenberg, H. M., Melmed, S., Polonsky, K. S. and Larsen, P. R.), pp. 85–295. W.B. Saunders Co.: Philadelphia, PA.Google Scholar
MacMaster, FP, El-Sheikh, R, Upadhyaya, AR, Nutche, J, Rosenberg, DR, Keshavan, M (2007). Effect of antipsychotics on pituitary gland volume in treatment-naive first-episode schizophrenia: a pilot study. Schizophrenia Research 92, 207–210.CrossRefGoogle ScholarPubMed
Malik, P, Kemmler, G, Hummer, M, Riecher-Rössler, A, Kahn, RS, Fleischhacker, WW (2011). Sexual dysfunction in first-episode schizophrenia patients: results from European First Episode Schizophrenia Trial. Journal of Clinical Psychopharmacology 31, 274–280.CrossRefGoogle ScholarPubMed
Miller, KK (2004). Management of hyperprolactinemia in patients receiving antipsychotics. CNS Spectrums 9, 28–32.CrossRefGoogle ScholarPubMed
Mizrahi, R, Addington, J, Rusjan, PM, Suridjan, I, Ng, A, Boileau, I, Pruessner, JC, Remington, G, Houle, S, Wilson, AA (2012). Increased stress-induced dopamine release in psychosis. Biological Psychiatry 71, 561–567.CrossRefGoogle ScholarPubMed
O'Keane, V, Meaney, AM (2005). Antipsychotic drugs: a new risk factor for osteoporosis in young women with schizophrenia? Journal of Clinical Psychopharmacology 25, 26–31.CrossRefGoogle ScholarPubMed
Pariante, CM (2008). Pituitary volume in psychosis: the first review of the evidence. Journal of Psychopharmacology 22, 76–81.CrossRefGoogle ScholarPubMed
Phillips, LJ, McGorry, PD, Garner, B, Thompson, KN, Pantelis, C, Wood, SJ, Berger, G (2006). Stress, the hippocampus and the hypothalamic-pituitary-adrenal axis: implications for the development of psychotic disorders. Australian and New Zealand Journal of Psychiatry 40, 725–741.CrossRefGoogle ScholarPubMed
Prabhakar, VK, Davis, JR (2008). Hyperprolactinaemia. Best Practice and Research: Clinical Obstetrics and Gynaecology 22, 341–353.Google ScholarPubMed
R Development Core Team (2011). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna, Austria.Google Scholar
Riecher-Rössler, A, de Geyter, C (2007). The forthcoming role of treatment with oestrogens in mental health. Swiss Medical Weekly 137, 565–572.Google ScholarPubMed
Riecher-Rössler, A, Häfner, H (1993). Schizophrenia and oestrogens – is there an association? European Archives of Psychiatry and Clinical Neuroscience 242, 323–328.CrossRefGoogle ScholarPubMed
Riecher-Rössler, A, Häfner, H, Dütsch-Strobel, A, Stumbaum, M (1998). Gonadal function and its influence on psychopathology. Archives of Women's Mental Health 1, 15–26.CrossRefGoogle Scholar
Riecher-Rössler, A, Häfner, H, Stumbaum, M, Maurer, K, Schmidt, R (1994). Can estradiol modulate schizophrenic symptomatology? Schizophrenia Bulletin 20, 203–214.CrossRefGoogle ScholarPubMed
Riecher-Rössler, A, Kulkarni, J (2011). Estrogens and gonadal function in schizophrenia and related psychoses. In Biological Basis of Sex Differences in Psychopharmacology (ed. Neill, J. C. and Kulkarni, J.), pp. 155–171. Springer: Heidelberg.Google Scholar
Riecher-Rössler, A, Schmid, C, Bleuer, S, Birkhäuser, M (2009). Antipsychotics and hyperpolactinaemia: pathophysiology, clinical relevance, diagnosis and therapy [in German]. Neuropsychiatry 23, 71–83.Google ScholarPubMed
Roig, B, Virgos, C, Franco, N, Martorell, L, Valero, J, Costas, J, Carracedo, A, Labad, A, Vilella, E (2007). The discoidin domain receptor 1 as a novel susceptibility gene for schizophrenia. Molecular Psychiatry 12, 833–841.CrossRefGoogle ScholarPubMed
Rybakowski, JK, Dmitrzak-Weglarz, M, Kapelski, P, Hauser, J (2011). Functional -1149 G/T polymorphism of the prolactin gene in schizophrenia. Neuropsychobiology 65, 41–44.CrossRefGoogle ScholarPubMed
Schwab, SG, Mondabon, S, Knapp, M, Albus, M, Hallmayer, J, Borrmann-Hassenbach, M, Trixler, M, Gross, M, Schulze, TG, Rietschel, M, Lerer, B, Maier, W, Wildenauer, DB (2003). Association of tumor necrosis factor alpha gene -G308A polymorphism with schizophrenia. Schizophrenia Research 65, 19–25.CrossRefGoogle ScholarPubMed
Segal, M, Avital, A, Rojas, M, Hausvater, N, Sandbank, S, Liba, D, Moguillansky, L, Tal, I, Weizman, A (2004). Serum prolactin levels in unmedicated first-episode and recurrent schizophrenia patients: a possible marker for the disease's subtypes. Psychiatry Research 127, 227–235.CrossRefGoogle ScholarPubMed
Stevens, A, Ray, D, Alansari, A, Hajeer, A, Thomson, W, Donn, R, Ollier, WE, Worthington, J, Davis, JR (2001). Characterization of a prolactin gene polymorphism and its associations with systemic lupus erythematosus. Arthritis and Rheumatism 44, 2358–2366.3.0.CO;2-K>CrossRefGoogle ScholarPubMed
Tochigi, M, Zhang, X, Umekage, T, Ohashi, J, Kato, C, Marui, T, Otowa, T, Hibino, H, Otani, T, Kohda, K, Liu, S, Kato, N, Tokunaga, K, Sasaki, T (2004). Association of six polymorphisms of the NOTCH4 gene with schizophrenia in the Japanese population. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics 128B, 37–40.CrossRefGoogle ScholarPubMed
Ungless, MA, Argilli, E, Bonci, A (2010). Effects of stress and aversion on dopamine neurons: implications for addiction. Neuroscience and Biobehavioral Reviews 35, 151–156.CrossRefGoogle ScholarPubMed
van Os, J, Kenis, G, Rutten, BP (2010). The environment and schizophrenia. Nature 468, 203–212.CrossRefGoogle ScholarPubMed
van Winkel, R, Stefanis, NC, Myin-Germeys, I (2008). Psychosocial stress and psychosis. A review of the neurobiological mechanisms and the evidence for gene-stress interaction. Schizophrenia Bulletin 34, 1095–1105.CrossRefGoogle ScholarPubMed
Walter, A, Riecher-Rössler, A, Studerus, E, Smieskova, R, Tamagni, C, Rapp, C, Borgwardt, S (2012). Pituitary gland volume in individuals with an at-risk mental state: a longitudinal MRI analysis. Schizophrenia Research 136 (Suppl. 1), S300.CrossRefGoogle Scholar
Yasui-Furukori, N, Saito, M, Nakagami, T, Sugawara, N, Sato, Y, Tsuchimine, S, Furukori, H, Kaneko, S (2010). Gender-specific prolactin response to antipsychotic treatments with risperidone and olanzapine and its relationship to drug concentrations in patients with acutely exacerbated schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 34, 537–540.CrossRefGoogle ScholarPubMed