Hostname: page-component-cd9895bd7-p9bg8 Total loading time: 0 Render date: 2024-12-18T18:12:47.742Z Has data issue: false hasContentIssue false
  • English
  • Français

Does active psychosis cause neurobiological pathology? A critical review of the neurotoxicity hypothesis

Published online by Cambridge University Press:  25 September 2013

B. R. Rund
B. R. Rund*
Affiliation:
Department of Psychology, University of Oslo, and Vestre Viken Hospital Trust, Drammen, Norway
*
* Address for correspondence: Dr B. R. Rund, Department of Psychology, University of Oslo, PO Box 1094, Blindern, 0317 Oslo, Norway. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Since the neurotoxicity hypothesis was launched in 1991, it has generated a great deal of interest and given rise to several studies investigating the validity of the hypothesis that being psychotic has a toxic effect on the brain. The toxicity argument is used to justify early treatment. This review attempts to assess the studies that have addressed the question: Does an active psychosis, indexed by the duration of untreated psychosis (DUP), cause neurobiological pathology?

Method

The validity of the hypothesis has been studied primarily by correlation analyses that assess whether there are significant correlations between DUP and changes in neurocognitive functioning or brain structure. In this review, relevant reports were identified by a literature survey.

Results

Of the 35 studies (33 papers) evaluated, six neurocognitive studies supported the hypothesis and 16 did not. Eight morphology studies supported the hypothesis and five did not. In general, the studies that did not support the neurotoxicity hypothesis were larger in size and had more adequate designs (longitudinal) than those that supported the hypothesis.

Conclusions

Overall, there is limited empirical evidence for the neurotoxicity hypothesis in the studies reviewed. However, it is possible that there is a threshold value for a toxic effect of psychosis, rather than a linear relationship between DUP and a neurotoxic effect, and that several of the studies evaluated did not have a long enough DUP to detect a toxic effect of active psychosis.

Keywords

Duration of untreated psychosis (DUP)morphologyneurocognitionneurotoxicityreviewschizophrenia
Type
Review Article
Information
Psychological Medicine , Volume 44 , Issue 8 , June 2014 , pp. 1577 - 1590
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

Addington, J, Van Mastrigt, S, Addington, D (2004). Duration of untreated psychosis: impact on 2-year outcome. Psychological Medicine 34, 277–284.CrossRefGoogle ScholarPubMed
Amminger, GP, Edwards, J, Brewer, WJ, Harrigan, S, McGorry, PD (2002). Duration of untreated psychosis and cognitive deterioration in first-episode schizophrenia. Schizophrenia Research 54, 223–230.CrossRefGoogle ScholarPubMed
Ayres, AM, Busatto, GF, Menezes, PR, Schaufelberger, MS, Coutinho, L, Murray, RM, McGuire, PK, Rushe, T, Scazufca, M (2007). Cognitive deficits in first-episode psychosis: a population-based study in São Paulo, Brazil. Schizophrenia Research 90, 338–343.CrossRefGoogle ScholarPubMed
Bangalore, SS, Goradia, DD, Nutche, J, Diwadkar, VA, Prasad, KMR, Keshavan, MS (2009). Untreated illness duration correlates with gray matter loss in first-episode psychoses. Neuroreport 20, 729–734.CrossRefGoogle ScholarPubMed
Barnes, TRE, Hutton, SB, Chapman, MJ, Mutsatsa, S, Puri, BK, Joyce, EM (2000). Clinical correlates of duration of untreated psychosis. British Journal of Psychiatry 177, 207–211.CrossRefGoogle ScholarPubMed
Becker, HE, Nieman, DH, Wilting, S, Dingemans, PM, van de Fliert, JR, Velthorst, E, de Haan, L, van Amelsvoort, TA, Linszen, DH (2010). Neurocognitive functioning before and after the first psychotic episode: does psychosis result in cognitive deterioration? Psychological Medicine 40, 1599–1606.CrossRefGoogle ScholarPubMed
Cahn, W, Pol, HEH, Lems, EBTE, van Haren, NEM, Schnack, HG, van der Linden, JA, Schothorst, P, van Engeland, H, Kahn, RS (2002). Brain volume changes in first-episode schizophrenia. Archives of General Psychiatry 59, 1002–1010.CrossRefGoogle ScholarPubMed
Chang, WC, Hui, CLM, Tang, JYM, Wong, GHY, Chan, SKW, Lee, EHM, Chen, EYH (2013). Impacts of duration of untreated psychosis on cognition and negative symptoms in first-episode schizophrenia: a 3-year prospective follow-up study. Psychological Medicine 43, 1883–1893.CrossRefGoogle ScholarPubMed
Craig, TJ, Bromet, EJ, Fennig, S, Tanenberg-Karant, M, Lavelle, J, Galambos, N (2000). Is there an association between duration of untreated psychosis and 24-month clinical outcome in a first-admission series? American Journal of Psychiatry 157, 60–66.CrossRefGoogle Scholar
Crespo-Facorro, B, Roiz-Santiáñez, R, Pelayo-Terán, JM, Gonzalez-Blanch, C, Perez-Iglesias, R, Gutierrez, A, de Lucas, EM, Tordesillas, D, Vázguez-Barquero, JL (2007). Caudate nucleus volume and its clinical and cognitive correlations in first episode schizophrenia. Schizophrenia Research 91, 87–96.CrossRefGoogle ScholarPubMed
Cuesta, MJ, de Jalòn, EG, Campos, MS, Ibanez, B, Sanchez-Torres, AM, Peralta, V (2012). Duration of untreated negative and positive symptoms of psychosis and cognitive impairment in first-episode psychosis. Schizophrenia Research 141, 222–227.CrossRefGoogle ScholarPubMed
Fannon, D, Chitnis, X, Doku, V, Tennakoon, L, O'Ceallaigh, S, Soni, W, Sumich, A, Lowe, J, Santamaria, M, Sharma, T (2000). Features of structural brain abnormality detected in first-episode psychosis. American Journal of Psychiatry 157, 1829–1834.CrossRefGoogle ScholarPubMed
Galderisi, S, Davidson, M, Kahn, RS, Mucci, A, Boter, H, Gheorghe, MD, Rybakowski, JK, Libiger, J, Dollfus, S, López-Ibor, JJ, Peuskens, J, Hranov, LG, Fleischhacker, WW (2009). Correlates of cognitive impairment in first-episode schizophrenia: the EUFEST study. Schizophrenia Research 115, 104–114.CrossRefGoogle ScholarPubMed
Galinska, B, Szulc, A, Czernikiewicz, A (2005). Duration of untreated psychosis in first-episode schizophrenia: clinical and cognitive correlates [in Polish]. Psychiatria Polska 39, 859–868.Google ScholarPubMed
Gaynor, K, Dooley, B, Lawlor, E, Lawoyin, LR, O'Callaghan, E (2009). Cognitive deterioration and duration of untreated psychosis. Early Intervention in Psychiatry 3, 157–160.CrossRefGoogle ScholarPubMed
Goldberg, TE, Burdick, KE, McCormack, J, Napolitano, B, Patel, RC, Sevy, SM, Goldman, R, Lencz, T, Malhotra, AK, Kane, JM, Robinson, DG (2009). Lack of an inverse relationship between duration of untreated psychosis and cognitive function in first-episode schizophrenia. Schizophrenia Research 107, 262–266.CrossRefGoogle ScholarPubMed
Hawkins, KA, Keefe, RSE, Christensen, BK, Addington, J, Woods, SW, Callahan, J, Zipursky, RB, Perkins, DO, Tohen, M, Breier, A, McGlashan, TH (2008). Neuropsychological course in the prodrome and first episode of psychosis: findings from the PRIME North America Double Blind Treatment Study. Schizophrenia Research 105, 1–9.CrossRefGoogle ScholarPubMed
Heydebrand, G, Weiser, M, Rabinowitz, J, Hoff, AL, DeLisi, LE, Csernansky, JG (2004). Correlates of cognitive deficits in first-episode schizophrenia. Schizophrenia Research 68, 1–9.CrossRefGoogle ScholarPubMed
Hietala, J, Cannon, TD, Sylvalathi, E, Vilkman, H, Laakso, A, Vahlberg, T, Alakare, B, Räkköläinen, V, Salokangas, RKR (2003). Regional brain morphology and duration of illness in never-medicated first-episode patients with schizophrenia. Schizophrenia Research 64, 79–81.CrossRefGoogle ScholarPubMed
Ho, B-C, Alicata, D, Ward, J, Moser, DJ, O'Leary, DS, Arndt, S, Andreasen, NC (2003). Untreated initial psychosis: relation to cognitive deficits and brain morphology in first-episode schizophrenia. American Journal of Psychiatry 160, 142–148.CrossRefGoogle ScholarPubMed
Hoff, AL, Sakuma, M, Razi, K, Heydebrand, G, Csernansky, JG, DeLisi, LE (2000). Lack of association between duration of untreated illness and severity of cognitive and structural brain deficits at the first episode of schizophrenia. American Journal of Psychiatry 157, 1824–1828.CrossRefGoogle ScholarPubMed
Joyce, E, Hutton, S, Mutsatsa, S, Gibbins, H, Webb, E, Paul, S, Robbins, T, Barnes, T (2002). Executive dysfunction in first-episode schizophrenia and relationship to duration of untreated psychosis: the West London Study. British Journal of Psychiatry 181, 38–44.CrossRefGoogle Scholar
Keshavan, MS, Haas, GL, Kahn, CE, Aguilar, E, Dick, EL, Schooler, NR, Sweeney, JA, Pettegrew, JW (1998). Superior temporal gyrus and the course of early schizophrenia: progressive, static, or reversible? Journal of Psychiatric Research 32, 161–167.CrossRefGoogle ScholarPubMed
Lappin, JM, Morgan, K, Morgan, C, Hutchinson, G, Chitnis, X, Suckling, J, Fearon, P, McGuire, PK, Jones, PB, Leff, J, Murray, RM, Dazzan, P (2006). Gray matter abnormalities associated with duration of untreated psychosis. Schizophrenia Research 83, 145–153.CrossRefGoogle ScholarPubMed
Lappin, JM, Morgan, KD, Morgan, C, Dazzan, P, Reichenberg, A, Zanelli, JW, Fearon, P, Jones, PB, Lloyd, T, Tarrant, J, Farrant, A, Leff, J, Murray, RM (2007). Duration of untreated psychosis and neuropsychological function in first-episode psychosis. Schizophrenia Research 95, 103–110.CrossRefGoogle ScholarPubMed
Lawoyin, R, Gaynor, K, Dooley, B, Lawelor, E, Clarke, M, O'Callaghan, E (2007). Toxic psychosis? Duration of untreated psychosis, symptomatology and cognitive deterioration in first episode psychosis. Irish Journal of Psychological Medicine 24, 145–148.CrossRefGoogle ScholarPubMed
Leeson, VC, Barnes, TRE, Harrison, M, Matheson, E, Harrison, I, Mutsatsa, SH, Ron, MA, Joyce, EM (2010). The relationship between IQ, memory, executive function, and processing speed in recent-onset psychosis: 1-year stability and clinical outcome. Schizophrenia Bulletin 36, 400–409.CrossRefGoogle ScholarPubMed
Madsen, AL, Karle, A, Rubin, P, Cortsen, M, Andersen, HS, Hemmingsen, R (1999). Progressive atrophy of the frontal lobes in first-episode schizophrenia: interaction with clinical course and neuroleptic treatment. Acta Psychiatrica Scandinavica 100, 367–374.CrossRefGoogle ScholarPubMed
Malla, AK, Bodnar, M, Joober, R, Lepage, M (2011). Duration of untreated psychosis is associated with orbital-frontal grey matter volume reductions in first-episode psychosis. Schizophrenia Research 125, 13–20.CrossRefGoogle ScholarPubMed
Malla, AK, Mittal, C, Lee, M, Scholten, DJ, Assis, L, Norman, RMG (2002). Computed tomography of the brain morphology of patients with first-episode schizophrenic psychosis. Journal of Psychiatry and Neuroscience 27, 350–358.Google ScholarPubMed
Marshall, M, Rathbone, J (2011). Early intervention for psychosis. Cochrane Database of Systematic Reviews. Issue 6, Art No. CD004718.CrossRefGoogle ScholarPubMed
McGlashan, TH (2006). Is active psychosis neurotoxic? Schizophrenia Bulletin 32, 609–613.CrossRefGoogle ScholarPubMed
Norman, RMG, Townsend, L, Malla, AK (2001). Duration of untreated psychosis and cognitive functioning in first-episode patients. British Journal of Psychiatry 179, 340–345.CrossRefGoogle ScholarPubMed
Olabi, B, Ellison-Wright, I, McIntosh, AM, Wood, SJ, Bullmore, E, Lawrie, SM (2011). Are there progressive brain changes in schizophrenia? A meta-analysis of structural magnetic resonance imaging studies. Biological Psychiatry 70, 88–96.CrossRefGoogle ScholarPubMed
Penttilä, M, Jääskeläinen, E, Haapea, M, Tanskanen, P, Veijola, J, Ridler, K, Murray, GK, Barnes, A, Jones, PB, Isohanni, M, Koponen, H, Miettunen, J (2010). Association between duration of untreated psychosis and brain morphology in schizophrenia within the Northern Finland 1966 Birth Cohort. Schizophrenia Research 123, 145–152.CrossRefGoogle ScholarPubMed
Rapp, C, Studerus, E, Bugra, H, Aston, J, Tamagni, C, Walter, A, Pflueger, M, Borgwardt, S, Riecher-Rössler, A (2013). Duration of untreated psychosis and cognitive functioning. Schizophrenia Research 145, 443–449.CrossRefGoogle ScholarPubMed
Rund, BR (2009). Is schizophrenia a neurodegenerative disorder? Nordic Journal of Psychiatry 63, 196–201.CrossRefGoogle ScholarPubMed
Rund, BR, Melle, I, Friis, S, Johannessen, JO, Larsen, TK, Midbøe, LJ, Opjordsmoen, S, Simonsen, E, Vaglum, P, McGlashan, T (2007). The course of neurocognitive functioning in first-episode psychosis and its relation to premorbid adjustment, duration of untreated psychosis, and relapse. Schizophrenia Research 91, 132–140.CrossRefGoogle ScholarPubMed
Rund, BR, Melle, I, Friis, S, Larsen, TK, Midbøe, LJ, Opjordsmoen, S, Simonsen, E, Vaglum, P, McGlashan, T (2004). Neurocognitive dysfunction in first-episode psychosis: correlates with symptoms, premorbid adjustment, and duration of untreated psychosis. American Journal of Psychiatry 161, 466–472.CrossRefGoogle ScholarPubMed
Scully, PJ, Coakley, G, Kinsella, A, Waddington, JL (1997). Psychopathology, executive (frontal) and general cognitive impairment in relation to duration of initially untreated versus subsequently treated psychosis in chronic schizophrenia. Psychological Medicine 27, 1303–1310.CrossRefGoogle ScholarPubMed
Sheitman, BB, Lieberman, JA (1998). The natural history and pathophysiology of treatment resistant schizophrenia. Journal of Psychiatric Research 32, 143–150.CrossRefGoogle ScholarPubMed
Takahashi, T, Suzuki, M, Tanino, R, Zhou, S-Y, Hagino, H, Niu, L, Kawasaki, Y, Seto, H, Kurachi, M (2007). Volume reduction of the left planum temporale gray matter associated with long duration of untreated psychosis in schizophrenia: a preliminary report. Psychiatry Research 154, 209–219.CrossRefGoogle ScholarPubMed
Townsend, LA, Norman, RMG, Malla, AK, Rychlo, AD, Ahmed, RR (2002). Changes in cognitive functioning following comprehensive treatment for first-episode patients with schizophrenia spectrum disorders. Psychiatry Research 113, 69–81.CrossRefGoogle ScholarPubMed
Wood, SJ, Pantelis, C, Yung, AR, Velakoulis, D, McGorry, PD (2009). Brain changes during the onset of schizophrenia: implications for neurodevelopmental theories. Medical Journal of Australia 190, 10–13.CrossRefGoogle ScholarPubMed
Wyatt, RJ (1991). Neuroleptics and the natural course of schizophrenia. Schizophrenia Bulletin 17, 325–351.CrossRefGoogle ScholarPubMed
Zhou, F-C, Xiang, Y-T, Wang, C-Y, Dickerson, F, Au, RWC, Zhou, J-J, Zhou, Y, Shum, DHK, Chiu, HFK, Man, D, Lee, EHM, Yu, X, Chan, RCK, Ungvari, GS (2012). Characteristics and clinical correlates of prospective memory performance in first-episode schizophrenia. Schizophrenia Research 135, 34–39.CrossRefGoogle ScholarPubMed
Ziermans, TB, Schothorst, PF, Schnack, HG, Koolschijn, CMP, Kahn, RS, van Engeland, H, Durston, S (2010). Progressive structural brain changes during development of psychosis. Schizophrenia Bulletin 38, 519–530.CrossRefGoogle ScholarPubMed