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