Elsevier

Biological Psychiatry

Volume 43, Issue 11, 1 June 1998, Pages 783-793
Biological Psychiatry

Original Articles
Ventricular Enlargement in Poor-Outcome Schizophrenia

https://doi.org/10.1016/S0006-3223(97)00553-2Get rights and content

Abstract

Background: A subset of patients with schizophrenia, defined on the basis of longitudinal deficits in self-care, may show a classic (“Kraepelinian”) degenerative course. An independent validator of the phenomenologically defined Kraepelinian subtype might be provided by a structural indicator of possible brain degeneration: ventricular size as measured by computed tomography (CT).

Methods: To examine whether Kraepelinian patients would show a differential increase in ventricular size over time, two CT scans were conducted at intervals separated by >4 years, an average of 5 years. Fifty-three male patients with DSM-III-R diagnoses of chronic schizophrenia were subdivided into Kraepelinian (n = 22; mean age = 42 ± 8.6 years) and non-Kraepelinian (n = 31; mean age = 38 ± 12.2 years) subgroups. Kraepelinian patients were defined on the basis of longitudinal criteria: >5 years of complete dependence on others for life necessities and care, lack of employment, and sustained symptomatology. Thirteen normal elderly volunteers (mean age = 60 ± 17.8) were also scanned at 4-year intervals. CT measurements were made by raters without knowledge of subgroup membership. A semiautomated computer program was used to trace the anterior horn, lateral ventricles, and temporal horns for each slice level on which they were clearly seen.

Results: The ventricles showed a bilateral increase in size over the 4-year interval in the Kraepelinian subgroup, more marked in the left hemisphere than the right. By contrast, neither the non-Kraepelinian subgroup nor the normal volunteers showed significant CT changes from scan 1 to scan 2.

Conclusions: Thus, the longitudinal dysfunctions in self-care that characterize the Kraepelinian patients were associated with an independent indicator of brain abnormality.

Introduction

Although there is a general consensus that ventricular enlargement is present in patients with schizophrenia (for review, see Shelton and Weinberger 1986), there is less agreement in more recent reviews about whether this enlargement is a static change early in the course of illness (Vita et al 1997) or a progressive lesion (DeLisi et al 1997). Longitudinal studies are critical to answer this question, since in cross-sectional studies the patient’s age, age of illness onset, duration of illness, and duration of treatment are confounded. Some longitudinal studies have found no change in ventricular size over time Nasrallah et al 1986, Illowsky et al 1988, Vita et al 1988, Vita et al 1994, Degreef et al 1991, Sponheim et al 1991, Vita 1991, Jaskiw et al 1994, whereas others have found increased size with repeat scans Kemali et al 1989, Woods et al 1990, DeLisi et al 1995, DeLisi et al 1997, Nair et al 1997. The possibility that only a subgroup of patients with more severe or unremitting illness might show progressive ventricular enlargement is suggested by the finding of ventricular enlargement on repeat scans in patients who had undergone repeated hospitalizations (Woods et al 1990), those who failed to remit Frecska et al 1994, Lieberman et al 1996, and those who were less medication compliant (DeLisi et al 1997). In contrast, patients studied in their first episodes of schizophrenia, for whom the chronicity of course is as yet unknown, were more likely to show no progressive change in the ventricular system Degreef et al 1991, Sponheim et al 1991, Jaskiw et al 1994, Vita et al 1994, DeLisi et al 1995. Recent cluster-analytic strategies to assess the rate of ventricular volume change also support the existence of a subgroup with enlarging ventricles (Nair et al 1997).

Computed tomographic (CT) studies, including the current report, typically produce somewhat less reliable measurement of ventricular size than high-resolution magnetic resonance imaging (MRI) due to relatively thick (8–10 mm) slices; however, 1-mm-thick MRI planes were not available 10 years ago when this study began, and at present only CT is available for long-term follow-up. Relatively short follow-up intervals may also have diminished the statistical power of some studies to detect progressive change and favored the null hypothesis. Higher resolution volumetric studies with larger sample sizes and longer follow-up intervals have tended to be more likely to reveal progressive enlargement. For example, a 2-year follow-up by DeLisi et al (1992) did not reveal the progressive enlargement that became apparent at 4 (DeLisi et al 1995) and 5 years (DeLisi et al 1997). Thus, the issue of progressivity versus stability of ventricular size remains not entirely resolved.

Based on these data, a reformulated “progressivity of ventricular enlargement hypothesis” would seek to contrast poor and better prognosis schizophrenic patients. Such a design would have the advantage of controlling for nuances involved in repeated CT scans, by contrasting two sets of schizophrenic patients who have undergone two scans on the same scanner. This hypothesis would be best tested if the scanning interval were relatively long in duration and the sample comprised patients with ages toward the fifth decade of life, the time at which age-related changes in ventricular size begin to accelerate (Waddington et al 1991).

Over the last decade, a group of schizophrenic patients with very poor outcome, termed “Kraepelinian,” have been characterized (Keefe et al 1987). These are patients who have been shown to have at least 5 years of continuous inability to provide themselves with food, clothing, or shelter without the help of a caretaker. Evidence indicates that Kraepelinian patients differ from less chronic (non-Kraepelinian) patients in being less responsive to neuroleptics, having more severe positive and negative symptoms, and having a poorer level of premorbid social and sexual adjustment (Keefe et al 1988, Keefe et al 1989, Keefe et al 1990, Keefe et al 1991, Keefe et al 1993, Keefe et al 1996, Losonczy et al 1986a, Losonczy et al 1986b). Hence, this population is a reasonable one in which to test the hypothesis that poor-outcome patients constitute the schizophrenic subgroup that shows progressive ventricular enlargement. Thus, the present study compared a relatively large group of Kraepelinian and non-Kraepelinian schizophrenic patients who underwent two CT scans on the same scanner, with at least 4 years between scans, and who were entering the fifth decade of life.

Section snippets

Subjects

CT scans were acquired from 53 male patients with chronic schizophrenia and 13 normal volunteers on two occasions at least 4 years apart. Patients were recruited from the inpatient and outpatient programs of the Schizophrenia Biological Research Center of the Bronx Department of Veterans Affairs Medical Center, Pilgrim Psychiatric Center, and Mount Sinai Medical Center. All patients met DSM-III-R criteria for chronic schizophrenia (American Psychiatric Association 1987) as determined by a

Ventricular size in schizophrenia subtypes

The VBRs were entered in a five-way analysis of variance (ventricular size × hemisphere × slice level × date × patient group). At the time of the first scan on entrance into the study, the Kraepelinian and non-Kraepelinian subgroups did not differ in total relative ventricular volume when averaged across ventricular region and hemisphere (1.32, SD = 1.06 vs. 1.27, SD = 1.16, respectively). When regional differences were examined, however, Kraepelinian patients had larger values in the anterior

Discussion

Poor-outcome (i.e., Kraepelinian) schizophrenic patients showed significantly greater increases in total ventricular volume over an approximate 5-year interval between baseline and follow-up CT scans than did better-prognosis (i.e., non-Kraepelinian) patients. Although all areas of the ventricular system showed increases in size in the Kraepelinian subgroup, only the lateral ventricles were statistically significantly enlarged compared with values in the non-Kraepelinian subgroup over the

Acknowledgements

This research was supported in part by the Schizophrenia Biological Research Center and the Program in Biological Psychiatry (grants from the Veterans Administration to K.L. Davis), and MH40071 to M.S. Buchsbaum from the National Institute of Mental Health.

Cheuk Tang, Vladimir Tkach, and Dr. Tse-Chung Wei provided programming support, and Rita Amato and Granada Stephens assisted in the graphical analysis of the images. Bradley R. Buchsbaum assisted in additional graphics and statistical

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