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Relapse Duration, Treatment Intensity, and Brain Tissue Loss in Schizophrenia: A Prospective Longitudinal MRI Study
Nancy C. Andreasen, M.D., Ph.D.; Dawei Liu, Ph.D.; Steven Ziebell, B.A.; Anvi Vora, M.D.; Beng-Choon Ho, M.D.
Am J Psychiatry 2013;170:609-615. doi:10.1176/appi.ajp.2013.12050674
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Dr. Andreasen has received investigator-initiated research funding from Janssen Scientific Affairs. Dr. Ho has received research grant support from Ortho-McNeil Janssen Scientific Affairs, NIMH, NARSAD (Vicente Foundation Investigator), and the Nellie Ball Research Trust. The other authors report no financial relationships with commercial interests.

From the Psychiatric Iowa Neuroimaging Consortium, University of Iowa Carver College of Medicine, Iowa City.

Address correspondence to Dr. Andreasen (nancy-andreasen@uiowa.edu).

Copyright © 2013 by the American Psychiatric Association

Received May 23, 2012; Revised September 18, 2012; Revised December 22, 2012; Accepted January 14, 2013.

An erratum to this article has been published | view the erratum
Abstract

Objective  Longitudinal structural MRI studies have shown that patients with schizophrenia have progressive brain tissue loss after onset. Recurrent relapses are believed to play a role in this loss, but the relationship between relapse and structural MRI measures has not been rigorously assessed. The authors analyzed longitudinal data to examine this question.

Methods  The authors studied data from 202 patients drawn from the Iowa Longitudinal Study of first-episode schizophrenia for whom adequate structural MRI data were available (N=659 scans) from scans obtained at regular intervals over an average of 7 years. Because clinical follow-up data were obtained at 6-month intervals, the authors were able to compute measures of relapse number and duration and relate them to structural MRI measures. Because higher treatment intensity has been associated with smaller brain tissue volumes, the authors also examined this countereffect in terms of dose-years.

Results  Relapse duration was related to significant decreases in both general (e.g., total cerebral volume) and regional (e.g., frontal) brain measures. Number of relapses was unrelated to brain measures. Significant effects were also observed for treatment intensity.

Conclusions  Extended periods of relapse may have a negative effect on brain integrity in schizophrenia, suggesting the importance of implementing proactive measures that may prevent relapse and improve treatment adherence. By examining the relative balance of effects, that is, relapse duration versus antipsychotic treatment intensity, this study sheds light on a troublesome dilemma that clinicians face. Relapse prevention is important, but it should be sustained using the lowest possible medication dosages that will control symptoms.

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FIGURE 1. Plot of Duration of Relapse By Interscan Interval in a Longitudinal Study of 202 Schizophrenia Patientsa

a Scatterplot depicts the pattern of symptomatic relapse in schizophrenia patients during the longitudinal follow-up period. Duration of relapse is plotted against each interscan interval (years). Early phases of the illness are characterized by multiple relapses of shorter durations.

FIGURE 2. Relationships Between Brain Volumes and Relapse Duration in a Longitudinal Study of 202 Schizophrenia Patientsa

a Longer duration of symptomatic relapse was significantly associated with smaller total cerebral brain tissue volume (panel A; β2=–1.55 cc/year), frontal lobe white matter volume (panel B; β2=–0.48 cc/year), and temporal lobe white matter volume (panel C; β2=–0.17 cc/year). Linear regression lines with negative slopes were generated based on longitudinal brain volume measures.

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TABLE 1.Effect of Interscan Interval Relapse Duration on Brain Volume Measures in a Longitudinal Study of 202 Schizophrenia Patients
Table Footer Note

a Tissue decrease during interscan intervals due to relapse duration in cc/year.

Anchor for Jump
TABLE 2.Effect of Number of Relapses on Brain Volume Measures in a Longitudinal Study of 202 Schizophrenia Patients
Table Footer Note

a Tissue decrease during interscan intervals due to number of relapses in cc/year.

Anchor for Jump
TABLE 3.Effect of Interscan Interval Antipsychotic Treatment (Dose-Years) on Brain Volume Measures in a Longitudinal Study of 202 Schizophrenia Patients
Table Footer Note

a Tissue decrease during interscan intervals due to antipsychotic treatment intensity (dose-years) in cc/4 dose-years.

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