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Longitudinal studies of cognition in schizophrenia: Meta-analysis

  • Andrei Szöke (a1), Anca Trandafir (a1), Marie-Estelle Dupont (a2), Alexandre Méary (a1), Franck Schürhoff (a1) and Marion Leboyer (a1)...

Abstract

Background

A wide range of cognitive deficits have been demonstrated in schizophrenia, but their longitudinal course remains unclear.

Aims

To bring together all the available information from longitudinal studies of cognitive performance in people with schizophrenia.

Method

We carried out a meta-analysis of 53 studies. Unlike previous reviewers, we included all studies (regardless of the type of medication), analysed each variable separately and compared results with data from controls.

Results

Participants with schizophrenia showed a significant improvement in most cognitive tasks. The available data for controls showed, with one exception (the Stroop test), a similar or greater improvement. Performance in semantic verbal fluency remained stable in both individuals with schizophrenia and controls.

Conclusions

Participants with schizophrenia displayed improvement in most cognitive tasks, but practice was more likely than cognitive remediation to account for most of the improvements observed. Semantic verbal fluency may be the best candidate cognitive endophenotype.

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Copyright

Corresponding author

Dr Andrei Szöke, Service de Psychiatrie Adulte, Hôpital Albert Chenevier, 40 rue de Mesly, 94000 Créteil, France. Email: andrei.szoke@ach.aphp.fr

Footnotes

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Declaration of interest

None.

Footnotes

References

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1 Goldberg, TE, Weinberger, DR, Berman, KF, Pliskin, NH, Podd, MH. Further evidence for dementia of the prefrontal type in schizophrenia? A controlled study of teaching the Wisconsin Card Sorting Test. Arch Gen Psychiatry 1987; 44: 1008–14.
2 Bilder, RM, Lipschutz-Broch, L, Reiter, G, Geisler, S, Mayerhoff, D, Lieberman, JA. Neuropsychological deficits in the early course of first episode schizophrenia. Schiz Res 1991; 5: 198–9.
3 DeLisi, LE, Tew, W, Xie, S, Hoff, AL, Sakuma, M, Kushner, M, Lee, G, Shedlack, K, Smith, AM, Grimson, R. A prospective follow-up study of brain morphology and cognition in first-episode schizophrenic patients: preliminary findings. Biol Psychiatry 1995; 38: 349–60.
4 Rund, BR. A review of longitudinal studies of cognitive functions in schizophrenia patients. Schiz Bull 1998; 24: 425–35.
5 Gold, JM. Cognitive deficits as treatment targets in schizophrenia. Schiz Res 2004; 72: 21–8.
6 McCaffrey, RJ, Duff, K, Westervelt, HJ (eds). Practitioner's Guide to Evaluating Change with Intellectual Assessment Instruments. Springer, 2000.
7 McCaffrey, RJ, Duff, K, Westervelt, HJ (eds). Practitioner's Guide to Evaluating Change with Neuropsychological Assessment Instruments. Springer, 2000.
8 Hedges, LV, Olkin, I. Statistical Methods for Meta-analysis. Academic Press, 1985.
9 Higgins, J, Thompson, S. Quantifying heterogeneity in a meta-analysis. Stat Med 2002; 21: 1539–58.
10 Arthur, W, Bennett, W, Huffcutt, A. Conducting Meta-Analysis Using SAS. Erlbaum, 2001.
11 DerSimonian, R, Laird, N. Meta-analysis in clinical trials. Control Clin Trials 1986; 7: 177–88.
12 Wang, MC, Bushman, BJ. Integrating Results Through Meta-analytic Review Using SAS Software. SAS Institute, 1999.
13 Stip, E, Remington, GJ, Dursun, SM, Reiss, JP, Rotstein, E, MacEwan, GW, Chokka, PR, Jones, B, Dickson, RA; on behalf of the Canadian Switch Study Group. A Canadian multicenter trial assessing memory and executive functions in patients with schizophrenia spectrum disorders treated with olanzapine. J Clin Psychopharmacol 2003; 23: 400–4.
14 Purdon, SE, Jones, BDW, Stip, E, Labelle, A, Addington, D, David, SR, Breier, A, Tollefson, GD. Neuropsychological change in early phase schizophrenia during 12 months of treatment with olanzapine, risperidone or haloperidol. Arch Gen Psychiatry 2000; 57: 249–58.
15 Purdon, SE, Malla, A, Labelle, A, Lit, W. Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol. J Psychiatry Neurosc 2001; 26: 137–49.
16 Penades, R, Boget, T, Catalan, R, Bernardo, M, Gasto, C, Salamero, M. Cognitive mechanisms, psychosocial functioning and neurocognitive rehabilitation in schizophrenia. Schizophr Res 2003; 63: 219–27.
17 Green, MF, Marshall, BD, Wirshing, WC, Ames, D, Marder, SR, McGurk, S, Kern, RS, Mintz, J. Does risperidone improves verbal working memory in treatment-resistant schizophrenia? Am J Psychiatry 1997; 154: 799804.
18 Spohn, HE, Strauss, ME. Relation of neuroleptic and anticholinergic medication to cognitive functions in schizophrenia. J Abnorm Psychol 1989; 98: 367–80.
19 Keefe, RS, Silva, SG, Perkins, DO, Liebermann, JA. The effects of atypical antipsychotic drugs on neurocognitive impairment in schizophrenia: a review and meta-analysis. Schizophr Bull 1999; 25: 201–22.
20 Harvey, PD, Keefe, RS. Studies of cognitive change in patients with schizophrenia following novel antipsychotic treatment. Am J Psychiatry 2001; 158: 176–84.
21 Woodward, ND, Purdon, SE, Meltzer, HY, Zald, DH. A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine and risperidone in schizophrenia. Int J Neuropsychopharmacol 2005; 8: 457–72.
22 Heinrichs, RW, Zakzanis, KK. Neurocognitive deficit in schizophrenia: a quantitative review of the evidence. Neuropsychology 1998; 12: 426–45.
23 Szoke, A, Schürhoff, F, Mathieu, F, Meary, A, lonescu, S, Leboyer, M. Tests of executive functions in first-degree relatives of schizophrenic patients: a meta-analysis. Psychol Med 2005; 35: 771–82.
24 Snitz, BE, Macdonald, AW, Carter, CS. Cognitive deficits in unaffected first-degree relatives of schizophrenia patients: a meta-analytic review of putative endophenotypes. Schizophr Bull 2006; 32: 179–94.
25 Bokat, CE, Goldberg, TE. Letter and category fluency in schizophrenic patients: a meta-analysis. Schizophr Res 2003; 64: 73–8.
26 Henry, JD, Crawford, JR. A meta-analytic review of verbal fluency deficits in schizophrenia relative to other neurocognitive deficits. Cognit Neuropsychiatry 2005; 10: 133.
27 Albus, M, Hubmann, W, Scherer, J, Dreikorn, B, Hecht, S, Sobizack, N, Mohr, F. A prospective 2-year follow-up study of neurocognitive functioning in patients with first-episode schizophrenia. Eur Arch Psychiatry Clin Neurosci 2002; 252: 262–7.
28 Bilder, RM, Goldman, RS, Volavka, J, Czobor, P, Hoptman, M, Sheitman, B, Lindenmayer, JP, Citrome, L, McEvoy, J, Kunz, M, Chakos, M, Cooper, TB, Horowitz, TL, Lieberman, JA. Neurocognitive effect of clozapine, olanzapine, risperidone and haloperidol in patients with chronic schizophrenia or schizoaffective disorder. Am J Psychiatry 2002; 159: 1018–28.
29 Bryson, G, Tamasine, G. Longitudinal Wisconsin card sorting performance in schizophrenia patients in rehabilitation. Appl Neuropsychol 2002; 4: 203–9.
30 Buchanan, RW, Holstein, C, Breier, A. The comparative efficacy and long-term effect of clozapine treatment on neuropsychological test performance. Biol Psychiatry 1994; 36: 717–25.
31 Chua, L, Chong, SA, Pang, SA, Ng, VP, Chan, YH. The effect of risperidone on cognitive functioning in a sample of Asian patients with schizophrenia in Singapore. Singapore Med J 2001; 42: 243–6.
32 Cuesta, MJ, Peralta, V, Zarzuela, A. Effects of olanzapine and other antipsychotics on cognitive function in chronic schizophrenia: a longitudinal study. Schizophr Res 2001; 48: 1728.
33 de Beaurepaire, C, de Beaurepaire, R, Cleau, M, Borenstein, P. Bromocriptine improves digit symbol substitution test scores in neuroleptic-treated chronic schizophrenic patients. Eur Psychiatry 1993; 8: 8993.
34 Deutsch, SI, Schwartz, BL, Rosse, RB, Mastropaolo, J, Marvel, CL, Drapalski, AL. Adjuvant topiramate administration: a pharmacological strategy for addressing NMDA receptor hypofunction in schizophrenia. Clin Neuropharmacol 2003; 26: 199206.
35 Fields, RB, Van Kammen, DP, Peters, JL, Rosen, J, Van Kammen, WB, Nugent, A, Stipetic, M, Linnoila, M. Clonidine improves memory function in schizophrenia independently from change in psychosis. Schizophr Res 1988; 1: 417–23.
36 Fujii, DE, Ahmed, I, Jokumsen, M, Compton, JA. The effects of clozapine on cognitive functioning in treatment-resistant schizophrenic patients. J Neuropsychiatry Clin Neurosci 1997; 9: 240–5.
37 Gold, S, Arndt, S, Nopoulos, P, O'Leary, DS, Andreasen, N. Longitudinal study of cognitive function in first-episode and recent-onset schizophrenia. Am J Psychiatry 1999; 156: 1342–8.
38 Goldberg, TE, Greenberg, RD, Griffin, SJ, Gold, JM, Kleinman, JE, Pickar, D, Schulz, SC, Weinberger, DR. The effect of clozapine on cognition and psychiatric symptoms in patients with schizophrenia. Br J Psychiatry 1993; 162: 43–8.
39 Grawe, RW, Levander, S. Neuropsychological impairments in patients with schizophrenia: stability and prediction of outcome. Acta Psychiatr Scand 2001; 104: 60–4.
40 Green, MF, Marder, SR, Glynn, SM, McGurk, SR, Wirshing, WC, Wirshing, DA, Liberman, RP, Mintz, J. The neurocognitive effects of low-dose haloperidol: a two-year comparison with risperidone. Biol Psychiatry 2002; 51: 972–8.
41 Hagger, C, Buckley, P, Kenny, J, Friedman, L, Ubogy, D, Meltzer, HY. Improvement in cognitive functions and psychiatric symptoms in treatment-refractory schizophrenic patients receiving clozapine. Biol Psychiatry 1993; 34: 702–12.
42 Harris, MJ, Heaton, RK, Schalz, A, Bailey, A, Patterson, TL. Neuroleptic dose reduction in older psychotic patients. Schizophr Res 1997; 27: 241–8.
43 Harvey, PD, Lombardi, J, Liebman, M, White, L, Parella, M, Powchik, P, Davidson, M. Cognitive impairment and negative symptoms in geriatric chronic schizophrenic patients: a follow-up study. Schizophr Res 1996; 22: 223–31.
44 Harvey, PD, Meltzer, H, Simpson, GM, Potkin, SG, Loebel, A, Siu, C, Romano, SJ. Improvement in cognitive function following a switch to ziprasidone from conventional antipsychotics, olanzapine, or risperidone in outpatients with schizophrenia. Schizophr Res 2004; 66: 101–13.
45 Harvey, PD, Palmer, BW, Heaton, RK, Mohamed, S, Kennedy, J, Brickman, A. Stability of cognitive performance in older patients with schizophrenia: an 8-week test-retest study. Am J Psychiatry 2005; 162: 110–17.
46 Hill, SK, Schuepbach, D, Herbener, ES, Keshavan, MS, Sweeney, JA. Pretreatment and longitudinal studies of neuropsychological deficits in antipsychotic-naïve patients with schizophrenia. Schizophr Res 2004; 68: 4963.
47 Hoff, AL, Faustman, WO, Wieneke, M, Espinoza, S, Costa, M, Wolkowitz, O, Csernansky, JG. The effects of clozapine on symptom reduction, neurocognitive function, and clinical management in treatment-refractory state hospital schizophrenic inpatients. Neuropsychopharmacology 1996; 15: 361–9.
48 Hoff, AL, Svetina, C, Shields, G, Stewart, J, DeLisi, LE. Ten year longitudinal study of neuropsychological functioning subsequent to a first episode of schizophrenia. Schizophr Res 2005; 78: 2734.
49 Hughes, C, Kumari, V, Soni, W, Das, M, Binneman, B, Drozd, S, O'Neil, S, Mathew, V, Sharma, T. Longitudinal study of symptoms and cognitive function in chronic schizophrenia. Schizophr Res 2002; 59: 137–46.
50 Killian, G, Holzman, PS, Davis, JM, Gibbons, R. Effects of psychotic medication on selected cognitive and perceptual measures. J Abnorm Psychol 1984; 1: 5870.
51 Ljubin, T, Zakic-Milas, D, Mimica, N, Folnegović-Smalc, V, Makarić, G. A preliminary study of the comparative effects of olanzapine and fluphenazine on cognition in schizophrenic patients. Hum Psychopharmacol 2000; 15: 513–19.
52 Lysaker, P, Bell, M. Performance on repeated administrations of the Wisconsin Card Sorting Test. J Nerv Ment Dis 1994; 182: 656–60.
53 Manschreck, TC, Redmond, DA, Candela, SF, Maher, BA. Effects of clozapine on psychiatric symptoms, cognition and functional outcome in schizophrenia. J Neuropsychiatry Clin Neurosci 1999; 11: 481–9.
54 McGrath, J, Scheldt, S, Welham, J, Clair, A. Performance on tests sensitive to impaired executive ability in schizophrenia and well controls: acute and subacute phases. Schizophr Res 1997; 26: 127–37.
55 McGurk, SR, Moriarty, PJ, Harvey, PD, Parrella, M, White, L, Davis, KL. The longitudinal relationship of clinical symptoms, cognitive functioning and adaptative life in geriatric schizophrenia. Schizophr Res 2000; 42: 4755.
56 McGurk, SR, Mueser, KT, Harvey, PD, LaPuglia, R, Marder, J. Cognitive and symptom predictors of work outcomes for clients with schizophrenia in supported employment. Psychiatr Serv 2003; 54: 1129–35.
57 Nopoulos, P, Flashman, L, Flaum, M, Arndt, S, Andreasen, N. Stability of cognitive functioning early in the course of schizophrenia. Schizophr Res 1994; 14: 2937.
58 Prescott, CA, Strauss, ME, Tune, LE. Test-retest reliability of information-processing measures among chronic schizophrenics. Psychiatry Res 1986; 17: 199202.
59 Purdon, SE, Labelle, A, Boulay, L. Neuropsychological change in schizophrenia after 6 weeks of clozapine. Schizophr Res 2001; 48: 5767.
60 Rosmark, B, Ösby, U, Engelbrektson, K, Nyman, H. Stability of performance on neuropsychological tests in patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 1999; 249: 299304.
61 Rossi, A, Mancini, F, Stratta, P, Mattei, P, Gismondi, R, Pozzi, F, Casacchia, M. Risperidone, negative symptoms and cognitive deficit in schizophrenia: an open study. Acta Psychiatr Scand 1997; 95: 40–3.
62 Rund, BR. Distractibility and recall capability in schizophrenics, a 4 year longitudinal study of stability in cognitive performance. Schizophr Res 1989; 2: 265275.
63 Scottish Schizophrenia Research Group. The Scottish First Episode Schizophrenia Study v. One-year follow-up. Br J Psychiatry 1988; 152: 470476.
64 Seidman, LJ, Pepple, JR, Faraone, SV, Kremen, WS, Cassens, G, McCarley, RW, Tsuang, MT. Wisconsin Card Sorting Test performance over time in schizophrenia, preliminary evidence from clinical follow-up and neuroleptic reduction studies. Schizophr Res 1991; 5: 233242.
65 Seidman, LJ, Pepple, JR, Faraone, SV, Kremen, WS, Green, AI, Brown, WA, Tsuang, MT. Neuropsychological performance in chronic schizophrenia in response to neuroleptic dose reduction. Biol Psychiatry 1993; 33: 575584.
66 Sharma, T, Hughes, C, Soni, W, Kumari, V. Cognitive effects of olanzapine and clozapine treatment in chronic schizophrenia. Psychopharmacology 2003; 169: 398403.
67 Smith, TE, Hull, JW, Huppert, JD, Silverstein, SM. Recovery from psychosis in schizophrenia and schizoaffective disorder: symptoms and neurocognitive rate-limiters for the development of social behavior skills. Schizophr Res 2002; 55: 229237.
68 Stirling, J, White, C, Lewis, S, Hopkins, R, Tantam, D, Huddy, A, Montague, L. Neurocognitive function and outcome in first-episode schizophrenia: A 10-year follow-up of an epidemiological cohort. Schizophr Res 2003; 65: 7586.
69 Sweeney, JA, Hass, GL, Kelip, JG, Long, M. Evaluation of the stability of neuropsychological functioning after acute episodes of schizophrenia: one-year follow-up study. Psychiatry Res 1991; 38: 6376.
70 Townsend, L, Norman, RMG, Malla, AK, Rychlo, AD, Ahmed, RR. Changes in cognitive functioning following comprehensive treatment for first episode patients with schizophrenia spectrum disorder. Psychiatry Res 2002; 113: 6981.
71 Van der Gaag, M, Kern, RS, van den Bosch, RJ, Liberman, RP. A controlled trial of cognitive remediation in schizophrenia. Schizophr Bull 2002; 28: 167176.
72 Velligan, DI, Newcomer, J, Pultz, J, Csernansky, J, Hoff, AL, Mahurin, R, Miller, AL. Does cognitive function improve with quetiapine in comparison to haloperidol. Schizophr Res 2002; 53: 239248.
73 Verdoux, H, Magnin, E, Bourgeois, M. Neuroleptic effects on neuropsychological test performance in schizophrenia. Schizophr Res 1995; 14: 133139.
74 Wölwer, W, Gaebel, W. Impaired Trail-Making Test–B performance in patients with acute schizophrenia is related to inefficient sequencing of planning and acting. J Psychiatr Res 2002; 36: 407416.
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Longitudinal studies of cognition in schizophrenia: Meta-analysis

  • Andrei Szöke (a1), Anca Trandafir (a1), Marie-Estelle Dupont (a2), Alexandre Méary (a1), Franck Schürhoff (a1) and Marion Leboyer (a1)...
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eLetters

The jury is still out � waiting for new data not new analyses!

Andrei Sz�, MD
17 April 2009

Balanza-Martinez et al. made a detailed review of our article (Szoke et al, 2008) and also provided several suggestions for future research.

Although we agree with the authors that the conclusions of our article are by no means definitive, we disagree with them on the followingimportant issues.

First, Balanza-Martinez et al. suggest that our “meta-analysis (…) more likely overestimates the potential for cognitive improvement” as compared with other reviews (the authors cite as an example the review done by Rund (Rund, 1989)). On the contrary, we think that the comparison of results in schizophrenic subjects with controls, which is an original feature of our review, has a sobering effect as it points out that “practice (is) more likely than cognitive remediation to account for most of the improvements observed”. On the other hand reviews (such as the one cited earlier), in which performances in schizophrenic subjects are not compared with those of controls, could mistake improvement in results for improvement in cognitive abilities.

Second, commenting on the methods we used in our meta-analysis, Balanza-Martinez et al. criticize three of our options:

-The inclusion of studies with a test-retest duration under 1 year;

-The inclusion of open trials (especially clozapine trials);

-The fact that we did not differentiate between “first-episode, chronic and geriatric patients”.

As such, the cited authors suggest that it would be better to limit the analyses to a subset of the available data assuming, without formally testing, that some of the studies’ characteristics significantly influenceresults.

At the time we made our analysis there were only 11 studies with morethan a year test-retest interval and only four of them reported data for acontrol group. It was not possible to limit our analysis only to this subset of studies, let alone further exclude studies or separately analysesubgroups of studies.

Instead, we chose to include all methodological sound studies and test the role of potentially confounding variables (including test-retest interval). By using this method, we limited the loss of important available information. It is our belief that we could not gain more insight from less data.

As we report in our article, only 2 variables, out of the 17 tested, showed a larger improvement in studies with shorter test-retest intervals.Thus, for the vast majority of variables, excluding studies with shorter test-retest intervals would lead to an unjustified loss of information.

Third, Balanza-Martinez et al. consider that their suggestions may lead to results “more helpful for clinicians, patients and caregivers”. Wethink that limiting the analysis to studies with large test-retest intervals (which usually have high attrition rates) or excluding the more naturalistic, open trials would achieve just the contrary.

In conclusion, although we agree with Balanza-Martinez et al. that the conclusions of our meta-analysis are not definitive, we also consider that to improve our knowledge on the subject we need new data, not new analyses in subsets of (the same) data.

References

1. Szöke A, Trandafir A, Dupont ME, Méary A, Schürhoff F, Leboyer M. (2008) Longitudinal studies of cognition in schizophrenia: meta-analysis. British Journal of Psychiatry, 192, 248-257.

2. Rund BR. (1989) A review of longitudinal studies of cognitive functions in schizophrenia patients. Schizophr Bulletin, 24, 425-435.
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Conflict of interest: None Declared

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Longitudinal course of cognition in schizophrenia - the jury is still out!

Vicent Balanz�-Mart�nez, Associate Professor of Psychiatry and Psychological Medicine
19 March 2009

In their meta-analysis(1), Szöke et al. found significant improvements in most neuropsychological variables, along with well-known potential practice effects, and also that semantic verbal fluency holds promise as a suitable cognitive endophenotype in schizophrenia. We acknowledge that this review is a step forward, attempting to merge and quantify the evidence from both naturalistic observational studies(2) and clinical trials(3).

We agree with the authors that the current literature is limited by the virtual absence of healthy control groups. Since only 9 out of 53 studies reported longitudinal neurocognitive data for controls, it is difficult to disentangle whether patients´ cognitive changes are true improvements or confounded by the non-specific effects of practice-relatedlearning(4). The use of healthy subjects from test-retest studies (´external controls´) is also problematic and the parallel assessment of controls would rule out the possibility that patients´ apparent cognitive stability is not deterioration in disguise, as the authors accurately suggest.

In addition, we would like to highlight other critical issues that may limit the conclusions. Firstly, the authors´ choice to lower the minimum study duration to one month led to the median test-retest intervalbeing only 4 months, which is shorter than the recommended trial duration to evaluate cognitive changes, e.g. at least 6 months(5). This also may have biased the review towards short-term clinical trials intended to improve cognitive deficits, especially with second-generation antipsychotics. Had a more stringent and clinically relevant 1-year follow-up cut-off(2) been used, only 24 out of 53 studies would have been reviewed. Secondly, approximately half of the 20 clinical trials previously reviewed(3) are open, and these are mostly clozapine trials of treatment-resistant patients. Significant associations between cognitive change and change in negative symptoms are more likely to occur in these studies than in naturalistic follow-up studies(5). Thirdly, we feel the authors missed an opportunity to include the distinction between first-episode, chronic, and geriatric patients as a potential moderator variable. This could have contributed to a better understanding of the probably complex cognitive pathways during the lifespan.

Despite the number of longitudinal neurocognitive reports, less is known than was originally supposed about the course of cognition in schizophrenia. Only a small subset (n=4) of longitudinal reports have compared these neurocognitive pathways with those of healthy controls overat least one year. When reviews(2) are not focused on the neurocognitive effects of antipsychotics, stable long-term performances and, in some cases, cognitive gains could be expected, thus offering a rather pessimistic picture for cognitive enhancement. This approach seems more useful for understanding the long-term natural history of cognition in schizophrenia. Conversely, this meta-analysis(1) relies on short-term data, mostly from clinical trials(3), and therefore more likely overestimates the potential for cognitive improvement.

In sum, it would be misleading if the conclusions were regarded as a major leap forward instead of as tentative hypotheses awaiting further investigation. Since the possibility remains that the current findings aremore valuable to researchers, a new meta-analysis that takes into consideration these and other limitations might be more helpful for clinicians, patients and caregivers.

References

1. Szöke A, Trandafir A, Dupont ME, Méary A, Schürhoff F, Leboyer M. Longitudinal studies of cognition in schizophrenia: meta-analysis. Br J Psychiatry. 2008;192(4):248-57.

2. Rund BR. A review of longitudinal studies of cognitive functions in schizophrenia patients. Schizophr Bull. 1998;24(3):425-35.

3. Woodward ND, Purdon SE, Meltzer HY, Zald DH. A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in schizophrenia. Int J Neuropsychopharmacol. 2005; 8(3): 457-72.

4. Goldberg TE, Goldman RS, Burdick KE, Malhotra AK, Lencz T, Patel RC, Woerner MG, Schooler NR, Kane JM, Robinson DG. Cognitive improvement after treatment with second generation antipsychotic medications in first-episode schizophrenia: is it a practice effect? Arch Gen Psychiatry. 2007;64(10):1115-22.

5. Buchanan RW, Davis M, Goff D, Green MF, Keefe RS, Leon AC, Nuechterlein KH, Laughren T, Levin R, Stover E, Fenton W, Marder SR. A summary of the FDA-NIMH-MATRICS workshop on clinical trial design for neurocognitive drugs for schizophrenia. Schizophr Bull 2005; 31(1):5-19.
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How long is longitudinal

Ahmed S huda, Consultant, Early Intevention in Psychosis
25 April 2008

One of the authors' aims was to distinguish if cognitive deficits were progressive. They used studies which retested after at least one month. The means for half of the studies included retesting occurred btween 1-4 months but with a few "outliers" pulling the mean to 12 months.This is a relatively short period of time to deterimine if cognitive deficits are progressive. The data supplement did not state the period of time between tests for the studies. It suggests there were few studies included with retesting beyond 12 months.

I think we can accept the autohrs' conclusions of improvement in cognitive testing. However we have to add the further caveat that this seems to be in the short term only (12 months or less given the likley paucity of data from after this period included in the study).

This paper can not address the issue of whether schizophrenia is associated with progressive cognitve deficits in the long term as it does not include enough studies with time between tests measured in years/ decades.

For example:V. S. Gabrovska-Johnson et al (2003),"Right-hemisphere encephalopathy in elderly subjects with schizophrenia: evidence from neuropsychological and brain imaging studies" Psychopharmacology Volume 169, p. 367-375 found evidence of neurocognitive deficits in elderly patients with schizophreniathat were different than those found in Alzheimer's disease.

Perhaps the authors' were too restrictive in their entry criteria andexcluded a lot of the longer term studies.

It would be unfortunate if the authors' study was to be referenced infuture as proof that there is no long term cognitive deteriotation in schizophrenia.
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