Reduced cerebellar volume and neurological soft signs in first-episode schizophrenia

https://doi.org/10.1016/j.pscychresns.2005.02.011Get rights and content

Abstract

Recent studies indicate that morphological and functional abnormalities of the cerebellum are associated with schizophrenia. Since the cerebellum is crucial for motor coordination, one may ask whether the respective changes are associated with motor dysfunction in the disease. To test these hypotheses in a clinical study, we investigated cerebellar volumes derived from volumetric magnetic resonance imaging of 37 first-episode patients with schizophrenia, schizophreniform or schizoaffective disorder and 18 healthy controls matched for age, gender and handedness. To control for potential interindividual differences in head size, intracranial volume was entered as a covariate. Neurological soft signs (NSS) were examined after remission of acute symptoms. Compared with the controls, patients had significantly smaller cerebellar volumes for both hemispheres. Furthermore, NSS in patients were inversely correlated with tissue volume of the right cerebellar hemisphere partialling for intracranial volume. No associations were detected between cerebellar volumes and psychopathological measures obtained at hospital admission when patients were in the acute psychotic state or after remission, treatment duration until remission, treatment response or prognostic factors, respectively. These findings support the hypothesis of cerebellar involvement in schizophrenia and indicate that the respective changes are associated with NSS.

Introduction

Recently, an elaborate model of cortical–subcortical–cerebellar circuitry has been proposed (Andreasen et al., 1998), encompassing frontal, cerebellar and thalamic regions. The concept of “cognitive dysmetria” hypothesizes a disruption in this cortico–cerebellar–thalamic–cortical circuit (CCTCC) leading to impaired sequencing and coordination of mental processes, manifested in symptoms associated with schizophrenia (Andreasen et al., 1996a). This model is supported by functional neuroimaging studies demonstrating an involvement of the cerebellum in higher cognitive functions such as recalling complex narrative material (Andreasen et al., 1996a), episodic memory retrieval (Andreasen et al., 1999), verbal fluency (Schlösser et al., 1998) and reasoning (Osherson et al., 1998) and their related deficits in patients with schizophrenia. The important role of the cerebellum in motor coordination is well established. These functions are known to be deficient not only in patients with manifest schizophrenia, but also in probands with an increased genetic liability (Niethammer et al., 2000). Clinically these deficits present as neurological soft signs (NSS). However, the association between cerebellar changes and NSS has not to date been sufficiently addressed.

Morphological changes of the cerebellum were reported in a number of computed tomography (CT) and magnetic resonance imaging (MRI) studies (Table 1, Table 2). While these studies yielded conflicting results, only one CT study and one MRI study concentrated on first-episode patients. An association between cerebellar changes and NSS in first-episode patients would facilitate the hypothesis that cerebellar changes, like NSS, may precede clinical manifestation of the disease.

The purpose of the present study was to examine possible cerebellar volume differences between subjects with schizophrenia, schizophreniform disorder or schizoaffective disorder and healthy control subjects. To rule out potential medication effects and to address the question of whether changes accompany or even precede the initial episode, we enrolled first-episode patients only. Moreover, potential cerebellar volume changes were investigated with respect to NSS and other important clinical characteristics of the disease.

Section snippets

Subjects

Data of 37 patients and 18 healthy controls (see Table 3) entered statistical analyses. All subjects were dominantly right-handed (Oldfield, 1971). The patient group consisted of first-episode patients with diagnoses of schizophrenia, schizophreniform disorder or schizoaffective disorder who had been consecutively admitted to the inpatient unit of the University of Heidelberg Psychiatric Hospital. Subjects were excluded if they had a lifetime history of major head trauma with loss of

Results

In a first step, demographic variables were tested for significant group differences. Patients and controls did not significantly differ regarding gender, age or handedness.

In a second step it was ruled out that type of sequence caused a systematic effect. Then, volumetric data were investigated. Table 4 gives cerebellar volumes for the two hemispheres separately in patients and normal controls. The ANCOVA revealed a significant group effect for both hemispheres, with schizophrenic patients

Discussion

Our study yielded two major findings: (1) first-episode patients with schizophrenia have reduced cerebellar volumes bilaterally compared with healthy controls, and (2) decreased volumes of the right cerebellar hemisphere in patients are associated with increased NSS scores.

The present investigation provides evidence of cerebellar volume reduction in first-episode schizophrenia. This significant difference was demonstrated independent of ICV and did not refer to potential confounding factors, in

Acknowledgments

The present study was supported in part by the Medical Faculty, University of Heidelberg and the Stanley Medical Research Institute.

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