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Schizophrenia: still Kraepelin's Dementia Praecox?*

Published online by Cambridge University Press:  11 October 2011

Heinz Häfner
Heinz Häfner*
Affiliation:
Schizophrenia Research Unit, Central Institute of Mental Health, Mannheim, Germany
*
Address for correspondence: Professor H. Häfner, Central Institute of Mental Health, J5, D-68159 Mannheim (Germany). Fax: +49-621-1703.266 E-mail: hhaefner@as200.zi-mannheim.de
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Abstract

Summary

Asking whether E. Kraepelin's early dementia praecox and disease concepts (1896) are still valid today, we condensed his early theory into four theses:1) schizophrenia is a disease entity, distinguishable from affective psychosis. 2) It is caused by a specific neuropathology. 3) It usually manifests itself in adolescence or early adulthood. 4) Underlying schizo- phrenia is a progressive disease process that leads to defects and dementia.

Having tested whether Kraepelin's dementia praecox and modern schizophrenia are actually comparable, we studied 1) how schizophrenia and depression are linked or separable in terms of symptoms, risk factors and illness course from onset until five years after first treatment contact. The analyses are based on a population-based sample of 130 first admissions because of schiz- ophrenia, 130 age- and sex-matched first admissions because of unipolar depressive disorder and 130 “healthy” population con- trols from the study area. 2) Results will be presented that, though not very specific, confirm Kraepelin's farsighted hypothesis of a neuropathological basis of the disorder. In this context it will be discussed whether the brain changes are developmental or degenerative in origin. 3) The distribution of age of onset extends far into old age. In a sample of 1109 consecutive first admis- sions because of nonaffective psychosis from the total age range it was shown that age-dependent developmental factors mod- ify certain components of symptomatology linearly and significantly. The main risk factors, too, significantly change with age. 4) Long-term course was examined in three studies of epidemiologically recruited first-episode samples: Study 1 included five cross sections over 5 years, Study 2 was a prospective pre-post-comparison over 12 years supplemented by a retrospective assessment of the illness course (IRAOS) and Study 3 encompassed 10 cross sections over fifteen years. Finally, the disease concept of schizophrenia, as it presents itself in the light of current knowledge, will be outlined and compared with Kraepelin's earlier and later view of the disorder.

Declaration of Interest

the paper is based on a lecture (Lettura magistrale) presented at the SIEP Sesto Congresso Nazionale, “Gli Esiti della Schizofrenia - Trattamenti, Pratica nei Servizi, Valutazione” in Sirmione, November 6-8, 2003. Unfortunately, the illustrations shown there and some 20 % of the relevant references could not be included in this printed ver- sion for lack of space. This paper was written within the framework of the German Research Network on Schizophrenia and was funded by the German Federal Ministry for Education and Research BMBF (grant 01GI 0236). The ABC study was supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) as part of the Special Research Branch (Sonderforschungsbereich) 258 at the Central Institute of Mental Health until December 1998. From January 1999 to Sept. 2002 it was continued to be funded by the DFG.

Keywords

Age and schizophreniaage and depressionage-dependent risk factorsschizophrenia and life-cycleearly- course depression in schizophreniacourse of schizophreniadisease concept of schizophreniasymptomatology and mental developmentdevelopmental versus degenerative brain changesdepressive and psychotic symptom dimensionsdimensional concept of schizophrenia
Type
Invited Papers
Information
Epidemiology and Psychiatric Sciences , Volume 13 , Issue 2 , June 2004 , pp. 99 - 112
Copyright
Copyright © Cambridge University Press 2004

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Footnotes

*

Paper presented at the VI National Congress of the Italian Society of Psychiatric Epidemiology (SIEP), held in Sirmione (BS), 6–8 November 2003.

References

REFERENCES

Almeida, O.P., Howard, R.J., Levy, R. & David, A.S. (1995). Psychotic states arising in late life (late paraphrenia): psychopathology and nosology. British Journal of Psychiatry 166, 205–214.CrossRefGoogle ScholarPubMed
Altamura, A.C., Bassetti, R., Bignotti, S., Pioli, R. & Mundo, E. (2003). Clinical variables related to suicide attempts in schizophrenic patients: a retospective study. Schizophrenia Research 60, 47–55.CrossRefGoogle Scholar
Alzheimer, A. (1897). Beitrage zur pathologischen Anatomie der Hirnrinde und zur anatomischen Grundlage einiger Psychosen. Monatsschrift fiir Psychiatrie und Neurologie 2, 82–120.CrossRefGoogle Scholar
Bartels, S.J., Drake, R.E. & McHugo, G.J. (1992). Alcohol abuse, depres- sion, and suicidal behaviour in schizophrenia. American Journal of Psychiatry 149, 394–395.Google Scholar
Bebbington, P. & Kuipers, E (2003). Schizophrenia and psychosocial stresses. In Schizophrenia, 2nd ed. (ed. Hirsch, S.R. and Weinberger, D.R.), pp. 613–636. Blackwell Publishing: Oxford.CrossRefGoogle Scholar
Behl, C. (2002). Neuroprotective effects of estrogens in the central ner- vous system: mechanisms of action. In Risk and Protective Factors in Schizophrenia. Towards a Conceptual Model of the Disease Process (ed. Hafner, H.), pp. 263–270. Steinkopff Verlag: Darmstadt.CrossRefGoogle Scholar
Biehl, H., Maurer, K., Schubart, C., Krumm, B. & Jung, E. (1986). Prediction of outcome and utilization of medical services in a prospective study of first onset schizophrenics - results of a prospec- tive 5-year follow-up study. European Archives for Psychiatry and Neurological Science 236, 139–147.CrossRefGoogle Scholar
Birchwood, M.J., Smith, J., Macmillan, F.Hogg, B., Prasad, R., Harvey, C. & Bering, S. (1989). Predicting relapse in schizophrenia: the devel- opment and implementation of an early signs monitoring system using patients and families as observers, a preliminary investigation. Psychological Medicine 19, 649–656.CrossRefGoogle Scholar
Bleuler, E. (1911). Dementia praecox oder Gruppe der Schizophrenien. In Handbuch der Psychiatrie (ed, Aschaffenburg, G.), pp. 1–420. Deuticke: Leipzig.Google Scholar
Bogerts, B., Meertz, E. & Schonfeldt-Bausch, R. (1985). Basal ganglia and limbic system pathology in schizophrenia. Archives of General Psychiatry 42, 784–791.CrossRefGoogle ScholarPubMed
Breier, A., Schreiber, J.L., Dyer, J. & Pickar, D. (1991). National Institute of Mental Health longitudinal study of chronic schizophrenia: prog- nosis and predictors of outcome. Archives of General Psychiatry 48, 239–246.CrossRefGoogle Scholar
Cahn, W., Hulshoff, P., Hilleke, E., Lems, E.B.T.E., van Haren, N.E.M., Schnack, H.G., van der Linden, J.A., Schothorst, P.F., van Egeland, H. & Kahn, R.S. (2002). Brain volume changes in first-episode schizo- phrenia: A 1-year follow-up study. Archives of General Psychiatry 59, 1002–1010.CrossRefGoogle Scholar
Cardno, A.G., Jones, L.A., Murphy, K.C., Sanders, R.D., Asherson, P., Owen, M.J. & McGuffin, P. (1998). Sibling pairs with schizophrenia or schizoaffective disorder: associations of sub types, symptoms and demographic variables. Psychological Medicine 28, 815–823.CrossRefGoogle ScholarPubMed
Castle, D.J. & Howard, R. (1992). What do we know about the aetiolo- gy of late-onset schizophrenia? European Psychiatry 7, 99–108.CrossRefGoogle Scholar
Castle, D.J., Wessely, S., van Os, J. &. Murray, R.M. (1998). Psychosis in the Inner City. Psychology Press: East Sussex.Google Scholar
Corey-Bloom, J., Jernigan, T., Archibald, S., Harris, M.J. & Jeste, D.V. (1995). Quantitative magnetic resonance imaging of the brain in late-life schizophrenia. American Journal of Psychiatry 152, 447–449.Google ScholarPubMed
Davis, K.L., Buchsbaum, M.S., Shihabuddin, L., Spiegel-Cohen, J., Metzger, M., Frecska, E., Keefe, R.S. & Powchik, P. (1998). Ventricular enlargement in poor-outcome schizophrenia. Biological Psychiatry 43, 783–793.CrossRefGoogle ScholarPubMed
DeLisi, L.E. (1999). Regional brain volume change over the life-time course of schizophrenia. Journal of Psychiatric Research 33, 535–541.CrossRefGoogle ScholarPubMed
DeLisi, L.E. (2004). When does structural brain change appear in schiz- ophrenia and is it clinically relevant? In Search for the Causes of Schizophrenia, vol. V (ed. Gattaz, W.F. and Hafner, H.), pp. 367–377. Steinkopff-Verlag: Darmstadt.CrossRefGoogle Scholar
DeLisi, L.E., Goldin, L.R., Maxwell, M.E., Kazuba, D.M. & Gershon, E.S. (1987). Clinical features of illness in siblings with schizophrenia or schizoaffective disorder. Archives of General Psychiatry 44, 891–896.CrossRefGoogle ScholarPubMed
DeLisi, L.E., Hoff, A.L., Schwartz, J.E., Shields, G.W., Halthore, S.N., Gupta, S.M., Henn, F.A., Anand, A.K. (1991). Brain morphology in first-episode schizophrenic-like psychotic patients: a quantitative magnetic resonance imaging study. Biological Psychiatry 29, 159–175.CrossRefGoogle ScholarPubMed
Dobmeier, P., Bottlender, R., Wittmann, J., GroB, A., Wegner, U., Strau, B.A. & Moller, H.-J. (2000). Depressive Symptome bei schizophrenen Erkrankungen - Ergebnisse der Munchner 15-Jahres-Katamnese. In Methodik von Verlaufs- und Therapiestudien in Psychiatrie und Psychotherapie (ed. Maier, W.Engel, R.R. and Moller, H.-J.), pp. 179–188. Hogrefe: Gottingen.Google Scholar
Dohrenwend, B.P., Levav, I., Shrout, P.E., Link, B.G., Skodol, A.E. & Martin, J.L. (1987). Life stress and psychopathology: progress with research begun with Barbara Snell Dohrenwend. American Journal of Community Psychology 15, 677–713.CrossRefGoogle ScholarPubMed
Elkis, H., Friedman, L., Wise, A. & Meltzer, H.Y. (1995). Meta-analysis of studies of ventricular enlargement and cortical sulcal prominence in mood disorders. Comparisons with controls or patients with schizophrenia. Archives of General Psychiatry 52, 735–746.CrossRefGoogle ScholarPubMed
Fink, G., Sumner, B., McQueen, J.K., Wilson, H. & Rose, R. (1998). Sex steroid control of mood, mental state and memory. Clinical and Experimental Pharmacology and Physiology 25, 764–765.CrossRefGoogle ScholarPubMed
Goldberg, T.E., David, A. & Gold, J.M. (2003). Neurocognitive deficits in schizophrenia. In Schizophorenia, 2nd ed. (ed. Hirsch, S.R. and Weinberger, D.W.), pp. 168–184. Blackwell Publishing: Oxford.CrossRefGoogle Scholar
Gur, R.E., Cowell, P.E., Latshaw, A., Turetsky, B.I., Grossman, R.I., Arnold, S.E., Bilker, W.B. & Gur, R.C. (2000). Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia. Archives of General Psychiatry 57, 761–768.CrossRefGoogle ScholarPubMed
Häfner, H. & Maurer, K. (in press). Prodromal symptoms and early detection of schizophrenia. In Early Detection and Management of Mental Disorders (ed. Maj, M.). John Wiley: Chichester.Google Scholar
Häfner, H. & Nowotny, B. (1995). Epidemiology of early-onset schizo- phrenia. European Archives of Psychiatry and Clinical Neuroscience 245, 80–92.CrossRefGoogle Scholar
Häfner, H., Behrens, S., de Vry, J. & Gattaz, W.F. (1992) An animal model for the effects of estradiol on dopamine-mediated behavior: Implications for sex differences in schizophrenia. Psychiatry Research 38, 125–134.CrossRefGoogle Scholar
Häfner, H., Hambrecht, M., Loffler, W., Munk-JØrgensen, P. & Riecher-Rossler, A. (1998a). Is schizophrenia a disorder of all ages? A com-parison of first episodes and early course across the life-cycle. Psychological Medicine 28, 351–365.CrossRefGoogle Scholar
Häfner, H., an der Heiden, W., Behrens, S., Gattaz, W.F., Hambrecht, M., Loffler, W., Maurer, K., Munk-jØrgensen, P., Nowotny, B., Riecher-Rossler, A. & Stein, A. (1998b). Causes and consequences of the gen- der difference in age at onset of schizophrenia. Schizophrenia Bulletin 24, 99–113.CrossRefGoogle Scholar
Häfner, H., Loffler, W., Maurer, K., Hambrecht, M. & an der Heiden, W. (1999). Depression, negative symptoms, social stagnation and social decline in the early course of schizophrenia. Ada Psychiatrica Scandinavica 100, 105–118.CrossRefGoogle ScholarPubMed
Häfner, H., Loffler, W., Maurer, K., Riecher-Rossler, A. & Stein, A. (2003). 1RAOS - Interview for the Retrospective Assessment of the Onset and Course of Schizophrenia and Other Psychoses. Hogrefe & Huber: Gottingen.Google Scholar
Häfner, H., Maurer, K. & Trendler, G. (submitted for publication). Schizophrenia and depression: challenging the paradigm of separate diseases.Google Scholar
Harris, M.J. & Jeste, D.V. (1988). Late-onset schizophrenia: An overview. Schizophrenia Bulletin 14, 39–55.CrossRefGoogle ScholarPubMed
Harrison, G., Croudace, T, Mason, P., Glazebrook, C. & Medley, I. (1996). Predicting the long-term outcome of schizophrenia. Psychological Medicine 26, 697–705.CrossRefGoogle ScholarPubMed
Harvey, P.D., Howanitz, E., Parrella, M., White, L. & Davidson, M. (1998). Symptoms, cognitive functioning, and adaptive skills in geriatric patients with lifelong schizophrenia: a comparison across treatment sites. American Journal of Psychiatry 155, 1080–1086.CrossRefGoogle ScholarPubMed
Heckers, S. (2004). The hippocampus and schizophrenia. In Search for the Causes of Schizophrenia, vol. V (ed. Gattaz, W.F. and Häfner, H.), pp. 182–200. Steinkopff-Verlag: Darmstadt.CrossRefGoogle Scholar
Herz, M. & Melville, C. (1980). Relapse in schizophrenia. American Journal of Psychiatry 137, 801–805.Google ScholarPubMed
Hirayasu, Y., Shenton, M.E., Salisbury, D.F.Dickey, C.C., Fischer, I.A., Mazzoni, P., Kisler, T., Arakaki, H., Kwon, J.S., Anderson, J.E., Yurgelun-Todd, D., Tohen, M. & McCarley, R.W. (1998). Lower left temporal lobe MRI volumes in patients with first-episode schizo- phrenia compared with psychotic patients with first-episode affec- tive disorder and normal subjects. American Journal of Psychiatry 155, 1384–1391.CrossRefGoogle Scholar
Hirsch, S.R. & Jolley, A.G. (1989). The dysphoric syndrome in schizo- phrenia and its implications for relapse. British Journal of Psychiatry 155, Suppl 5, 46–50.CrossRefGoogle Scholar
Hirsch, S.R., Jolley, A.G., Barnes, T.R.E., Liddle, P.F., Curson, D.A., Patel, A., York, A., Bercu, S. & Patel, M. (1989). Dysphoric and depressive symptoms in chronic schizophrenia. Schizophrenia Research 2, 259–264.CrossRefGoogle ScholarPubMed
Hirsch, S., Bowen, J., Emami, J.Cramer, P., Jolley, A., Haw, C. & Dickinson, M. (1996). One year prospective study of the effects of life events and medication in the aetiology of schizophrenic relapse. British Journal of Psychiatry 168, 49–56.CrossRefGoogle ScholarPubMed
Hollis, C. (2003). Child and adolescent onset schizophrenia. In Schizophorenia, 2nd ed. (ed. Hirsch, S.R. and Weinberger, D.W.), pp. 34–53. Blackwell Publishing: Oxford.CrossRefGoogle Scholar
Howard, R. & Jeste, D.V. (2003). Late-onset schizophrenia. In Schizophrenia, 2nd ed. (ed. Hirsch, S.R. and Weinberger, D.R.), pp. 68–79. Blackwell Publishing: Oxford.CrossRefGoogle ScholarPubMed
Howard, R., Almeida, O. & Levy, R. (1994a). Phenomenology, demog- raphy and diagnosis in late paraphrenia. Psychological Medicine 24, 397–410.CrossRefGoogle Scholar
Howard, R.J., Almeida, O., Levy, R., Graves, P. & Graves, M. (1994b). Quantitative magnetic resonance imaging volume try distinguishes delusional disorder from late-onset schizophrenia. British Journal of Psychiatry 165, 474–480.CrossRefGoogle Scholar
Jablensky, A. (2000). Symptome schizophrener Storungen. In Psychiatrie der Gegenwart 5, Schizophrenic und affektive Storungen, 4th ed., (ed. Helmchen, H.Henn, F.Lauter, H. and Sartorius, N.), pp.3–51. Springer-Verlag: Berlin Heidelberg New York.Google Scholar
Jablensky, A. & Woodbury, M.A. (1995). Dementia praecox and manic- depressive insanity in 1908: a grade of membership analysis of the Kraepelinian dichotomy. European Archives of Psychiatry and Clinical Neuroscience 245, 202–209.CrossRefGoogle ScholarPubMed
Jablensky, A., Hugler, H., von Cranach, M. & Kalinov, K. (1993). Kraepelin revisited: reassessment and statistical analysis of demen- tia praecox and manic-depressive insanity in 1908. Psychological Medicine 23, 843–858.CrossRefGoogle Scholar
Jablensky, A., McGrath, J., Herrman, H., Castle, D., Gureje, O., Morgan, V. & Korten, A. (1999). People Living with Psychotic Illness: an Australian Study 1997–98. National Survey of Mental Health and Wellbeing Report 4., pp. 1–20. Commonwealth of Australia: Canberra.Google Scholar
James, A.C., Javaloyes, A., James, S. & Smith, D.M. (2002). Evidence for non-progressive changes in adolescent-onset schizophrenia: follow- up magnetic resonance imaging study. British Journal of Psychiatry 180, 339–344.CrossRefGoogle ScholarPubMed
Jaskiw, G.E., Juliano, D.M., Goldberg, T.E., Hertzman, M., Urow-Hamell, E. & Weinberger, D.R. (1994). Cerebral ventricular enlargement in schizophreniform disorder does not progress: a seven year follow-up study. Schizophrenia Research 14, 23–28.CrossRefGoogle Scholar
Jeste, D.V., Harris, M.J., Pearlson, G.D., Rabins, P., Lesser, I., Miller, B., Coles, C. & Yassa, R. (1988). Late-onset schizophrenia. Studying clinical validity. Psychiatric Clinics of North America 11, 1–13.CrossRefGoogle ScholarPubMed
Jones, P.B., Harvey, I., Lewis, S.W., Toone, B.K., von Os, J., Williams, M. & Murray, R.M. (1994). Cerebral ventricle dimensions as risk fac- tors for schizophrenia and affective psychosis: an epidemiological approach. Psychological Medicine 24, 995–1011.CrossRefGoogle Scholar
Jones, P.B., Rantakallio, P., Hartikainen, A.L., Isohanni, H. & Sipila, P. (1998). Schizophrenia as a long-term outcome of pregnancy, deliv- ery and perinatal complications: A 28-year follow-up of the 1966 North Finland general population birth cohort. American Journal of Psychiatry 155, 355–364.CrossRefGoogle Scholar
Johnstone, E.C., Lawrie, S.M. & Cosway R (2002). What does the Edinburgh high-risk study tell us about schizophrenia? American Journal of Medical Genetics (Neuropsychiatric Genetics) 114, 906–912.CrossRefGoogle ScholarPubMed
Kendler, K.S., McGuire, M., Gruenberg, A.M., O'Hare, A., Spellman, M. & Walsh, D. (1993). The Roscommon family study. I. Methods, diagnosis of probands and risk of schizophrenia in relatives. Archives of General Psychiatry 50, 527–540.CrossRefGoogle Scholar
Kendler, K.S., Karkowski-Shuman, L. & Walsh, D. (1996). The risk for psychiatric illness in siblings of schizophrenics: the impact of psy- chotic and non-psychotic affective illness and alcoholism in parents. Ada Psychiatrica Scandinavica 94, 49–55.CrossRefGoogle Scholar
Kendler, K.S., Karkowski-Shuman, L., O'Neill, A., Straub, R.E.; MacLean, C.J. & Walsh, D. (1997). Resemblance of psychotic symp- toms and syndromes in affected sibling pairs from the Irish study of high-density schizophrenia families. American Journal of Psychiatry 154, 191–198.Google Scholar
Knights, A. & Hirsch, S.R. (1981) ‘Revealed’ depression and drug treat- ment for schizophrenia. Archives of General Psychiatry 38, 806–811.CrossRefGoogle Scholar
Kohler, C., Swanson, C.L., Gur, R.C., Mozley, L. H. & Gur, R.E. (1998). Depression in schizophrenia. II. MRI and PET findings. Biological Psychiatry 43, 173–180.Google Scholar
Koreen, A.R., Siris, S.G., Chakos, M., Alvir, J., Mayerhoff, D. & Lieberman, J. (1993). Depression in first episode schizophrenia. American Journal of Psychiatry 150, 1643–1648.Google ScholarPubMed
Kraepelin, E. (1896). Psychiatrie, 5th ed.Barth: Leipzig.Google Scholar
Kraepelin, E. (1913). Psychiatrie. 8th ed, Vol. 3, Part 2. Barth: Leipzig.Google Scholar
Kraepelin, E. (1909–1915). Psychiatrie, 8th ed. (Bd. 1–4. Barth: Leipzig.Google Scholar
Kraepelin, E. (1920). Die Erscheinungsformen des Irreseins. Zeitschrift der gesamten Psychiatrie und Neurologie 62, 1–29.CrossRefGoogle Scholar
Kulkarni, J., De Castella, A., Downey, M., Hammond, J., Reidel, A., Ward, S., White, S., Taffe, J., Fitzgerald, P. & Burger, H. (2002) Clinical estrogen trials in schizophrenia. In Risk and Protective Factors in Schizophrenia. Towards a Conceptual Model of the Disease Process (ed. Häfner, H.), pp. 271–284. Steinkopff Verlag: Darmstadt.CrossRefGoogle Scholar
Lawrie, S.M., Whalley, H.C., Abukmeil, S.S., Kestelman, J.N.L., Miller, P., Best, J.J.K.; Owens, D.G.C. & Johnstone, E.C. (2001). Brain structure, genetic liability, and psychotic symptoms in sub- jects at high risk of developing schizophrenia. Biological Psychiatry 49, 811–823.CrossRefGoogle Scholar
Lieberman, J.A., Perkins, D., Belger, A., Chakos, M., Jarskog, F., Boteva, K. & Gilmore, J. (2001). The early stages of schizophrenia: specula- tions on pathogenesis, pathophysiology and therapeutic approaches. Biological Psychiatry 50, 884–897.CrossRefGoogle Scholar
Lieberman, J.A., Tollefson, G., Tohen, M., Green, A.I., Gur, R.E., Kahn, R., McEvoy, J., Perkins, D., Sharma, T., Zipursky, R., Wei, H., Hamer, R.M. & HGDH Study Group (2003). Comparative efficacy and safety of atypical and coventional antipsychotic drugs in first- episode psychosis: a randomized, double-blind trial of olanzapine versus haloperidol. American Journal of Psychiatry 160, 1396–1404.CrossRefGoogle Scholar
Maier, W., Lichtermann, D., Minges, J., Hallmayer, J., Heun, R., Benkert, O. & Levinson, D.F. (1993). Continuity and discontinuity of affec- tive disorders and schizophrenia: results of a controlled family study. Archives of General Psychiatry 50, 871–883.CrossRefGoogle Scholar
Malla, A.K. & Norman, R.M.G. (1994). Prodromal symptoms in schizo- phrenia. British Journal of Psychiatry 164, 287–293.CrossRefGoogle Scholar
Mandel, M.R.Severe, J.B., Schooler, N.R., Gelenberg, A.J. & Mieske, M. (1982). Development and prediction of post-psychotic depression in neuroleptic-treated schizophrenics. Archives of General Psychiatry 39, 197–203.CrossRefGoogle Scholar
McCarley, R.W., Wible, C.G., Frumin, M., Hirayasu, Y., Levitt, J.J., LA., Fischer & Shenton, M.E. (1999). MRI anatomy of schizophre- nia. Biological Psychiatry 45, 1099–1119.CrossRefGoogle Scholar
McEwen, B.S., Biegon, A., Rainbow, T.C., Paden, C., Snyder, L. & DeGroff, V. (1981). The interaction of estrogens with intracellular receptors and with putative neurotransmitter receptors: implications for the mechanisms of activation of regulation of sexual behaviour and ovulaton. In Steroid Hormone Regulation of the Brain (ed. Fuxe, K.Gustafsson, J.A. and Wetterberg, L.), pp. 15–29. Pergamon Press: New York.CrossRefGoogle Scholar
McGlashan, T.H. & Carpenter, W.T. (1976) Postpsychotic depression in schizophrenia. Archives of General Psychiatry 33, 231–239.CrossRefGoogle ScholarPubMed
Nair, T., Christensen, J.D., Kingsbury, S.J., Kumar, N.G., Terry, W.M. & Garver, D.L. (1997). Progression of cerebroventricular enlargement and the subtyping of schizophrenia. Psychiatry Research 74, 141–150.CrossRefGoogle ScholarPubMed
Olfson, M.Mechanic, D., Boyer, C.A., Hansell, S., Walkup, J. & Weiden, P.J. (1999). Assessing clinical predictions of early rehospitalization in schizophrenia. Journal of Nervous and Mental Disease 187, 721–729.CrossRefGoogle ScholarPubMed
Palmer, B.W., McClure, F. & Jeste, D.V. (2001). Schizophrenia in late- life: findings challenge traditional concepts. Harvard Review of Psychiatry 9, 51–58.CrossRefGoogle ScholarPubMed
Pantelis, C., Velakoulis, D., McGorry, P.D., Wood, S.J., Suckling, J., Phillips, L.J., Yung, A.R., Bullmore, E.T., Brewer, W., Soulsby, B., Desmond, P. & McGuire, P.K. (2003). Neuroanatomical abnormali- ties before and after onset of psychosis: a cross-sectional and longi- tudinal MRI comparison. Lancet 361, 281–288.CrossRefGoogle Scholar
Riecher-Rossler, A., Hafner, H., Stumbaum, M., Maurer, K. & Schmidt, R. (1994). Can estradiol modulate schizophrenic symptomatology? Schizophrenia Bulletin 20, 203–214.CrossRefGoogle ScholarPubMed
Riecher-Rossler, A., Hafner, H., Hafner-Ranabauer, W., Loffler, W. & Reinhard, I. (2003). Late-onset schizophrenia versus paranoid psy- choses. American Journal of Geriatric Psychiatry 11, 595–604.Google Scholar
Roth, M. & Morrissey, J. (1952). Problems in the diagnosis and classifi- cation of mental disorders in old age. Journal of Mental Science 98, 66–80.CrossRefGoogle Scholar
Seidman, L.J., Faraone, S.V., Goldstein, J.M., Kremen, W.S., Horton, N.J., Makris, N., Toomey, R., Kennedy, D., Caviness, V.S. & Tsuang, M.T. (2002). Left hippocampal volume as a vulnerability indicator for schizophrenia. Archives of General Psychiatry 59, 839–849.CrossRefGoogle ScholarPubMed
Siris, S.G. & Bench, C. (2003). Depression and schizophrenia. In Schizophrenia, 2nd ed. (ed. Hirsch, S.R. and Weinberger, D.R.), pp. 142–167. Blackwell Publishing: Oxford.CrossRefGoogle Scholar
Sponheim, S.R., Iacono, W.G. & Beiser, M. (1991). Stability of ventric- ular size after the onset of psychosis in schizophrenia. Psychiatry Research and Neuroimaging 40, 21–29.CrossRefGoogle Scholar
Sumner, B.E.H. & Fink, G. (1995). Oestradiol-176 in its positive feed- back mode significantly increases 5-HT2a receptor density in the frontal, cingulate and piriform cortex of the female rat. Journal of Physiology 483, 52.Google Scholar
Sumner, B.E.H., Grant, K.E., Rosie, R., Hegele-Hartung, C., Fritzemeier, K.-H. & Fink, G. (1999). Effects of tamoxifen on serotonin trans- porter and 5-hydroxytryptamine receptor binding sites and mRNA levels in the brain of ovariectomized rats with or without acute estra- diol replacement. Molecular Brain Research 73, 119–128.CrossRefGoogle Scholar
Tollefson, G.D., Andersen, S.W. & Tran, P.V. (1999). The course of depressive symptoms in predicting relapse in schizophrenia: a dou- ble-blind, randomized comparison of olanzapine and risperidone. Biological Psychiatry 46, 365–373.CrossRefGoogle Scholar
Tsuang, M.T. (2000). Schizophrenia: genes and environment. Biological Psychiatry 47', 210–220.CrossRefGoogle ScholarPubMed
van Os, J., Howard, R., Takei, N. & Murray, R. (1995). Increasing age is a risk factor for psychosis in the elderly. Social Psychiatry and Psychiatric Epidemiology 30, 161–164.CrossRefGoogle ScholarPubMed
van Os, J., Verdoux, H., Maurice-Tison, S., Gay, B., Liraud, F., Salamon, R. & Bourgeois, M. (1999). Self-reported psychosis-like symptoms and the continuum of psychosis. Social Psychiatry and Psychiatric Epidemiology 34, 459–463.CrossRefGoogle ScholarPubMed
Vita, A., Giobbio, G.M., Dieci, M., Garbarini, M., Moganti, C., Comazzi, M. & Invernizzi, G. (1994). Stability of cerebral ventricular size from the appearance of the first psychotic symptoms to the later diagnosis of schizophrenia. Biological Psychiatry 35, 960–962.CrossRefGoogle Scholar
Weinberger, DR (1999). Cell biology of the hippocampal formation in schizophrenia. Biological Psychiatry 45, 395–402.CrossRefGoogle ScholarPubMed
Weinberger, D.R., DeLisi, L.E., Perman, G., Targum, S. & Wyatt, R.J. (1982). Computed tomography scans in schizophreniform disorder and other acute psychiatric patients. Archives of General Psychiatry 39, 778–783.CrossRefGoogle Scholar
Wiersma, D., Wanderling, J., Dragomirecka, E., Ganev, K., Harrison, G.An Der Heiden, W., Nienhuis, F.J. & Walsh, D. (2000). Social dis- ability in schizophrenia: its development and prediction over 15 years in incidence cohorts in six European centres. Psychological Medicine 30, 1155–1167.CrossRefGoogle Scholar
Wing, J.K. & Brown, G.W. (1970). Institutionalism and Schizophrenia. A Comparative Study of three Mental Hospitals 1960–1968. Cambridge University Press: Cambridge.CrossRefGoogle Scholar
Woods, B.T. (2004). Schizophrenia as a progressive developmental dis- order: the evidence and its implications. In Search for the Causes of Schizophrenia, vol. V (ed. Gattaz, W.F. and Hafner, H.), pp. 388–393. Steinkopff-Verlag: Darmstadt.CrossRefGoogle Scholar
Woolley, C.S. & McEwen, B.S. (1994). Estradiol regulates hippocampal dendritic spine density via an N-Methyl-D-aspartate receptor- dependent mechanism. Journal of Neuroscience 14, 7680–7687.CrossRefGoogle ScholarPubMed
Wyatt, R.J. (1991). Neuroleptics and the natural course of schizophre- nia. Schizophrenia Bulletin 17, 325–351.CrossRefGoogle Scholar