Volumetric Evaluation of the Thalamus in Schizophrenic Male Patients Using Magnetic Resonance Imaging

Abstract

Background: The thalamus, an important subcortical brain region connecting limbic and prefrontal cortices, has a significant role in sensory and cortical processing. Although inconsistently, previous studies have demonstrated neuroanatomical abnormalities in the thalamus of schizophrenic patients.

Methods: This structural magnetic resonance imaging study, based on segmentation of contiguous coronal 1.5-mm images, compared thalamic brain volumes of 15 chronic, male schizophrenic patients with 15 normal controls matched on age, sex, handedness, and parental socioeconomic status.

Results: There were no significant differences between patients and controls in thalamic volumes, right or left, adjusted for total brain volume; however, there were significantly different correlations of thalamic volumes with prefrontal white matter and lateral ventricles among patients, but not among controls. Thalamic volumes among patients were also significantly correlated with bizarre behavior, hallucinations, and thought disorder.

Conclusions: Findings suggest that connectivity between thalamic nuclei and prefrontal cortical areas are abnormal in chronic male schizophrenic patients. In addition, ventricular enlargement may be, in part, due to subtle reduction in thalamic volume and/or in volume of thalamocortical and corticothalamic fibers secondary to thalamic abnormalities. Finally, correlations with positive symptomatology underscore the role of the thalamus in gating or filtering of sensory information and coordination of cortical processing.

Introduction

The primary brain areas implicated in schizophrenia are prefrontal cortex e.g., Weinberger et al 1986; Andreasen et al 1990; Seidman et al 1996, and limbic and medial temporal lobe structures e.g., Bogerts et al 1985, Bogerts et al 1990; Shenton et al 1992; Falkai et al 1988. A few recent in vivo imaging studies have also implicated the thalamus in schizophrenia Andreasen et al 1990, Andreasen et al 1994; Buchsbaum et al 1996; Flaum et al 1995; Goldstein et al 1996; Jernigan et al 1991; Seidman et al 1996. The idea that thalamic abnormalities may contribute to understanding the pathology in schizophrenia is not new, in particular in its role in attention and language processing e.g., Mirsky et al 1991; Seidman 1983; Crosson and Hughes 1987; Kolb 1977. Moreover, the thalamus is an important part of the subcortical network, connecting, among other regions, limbic, basal ganglia, and prefrontal cortical regions Kolb 1977; Groenewegen et al 1990; Pandya and Yeterian 1990. Since cortical activity is controlled and integrated, in part, by the thalamic nuclei, abnormalities in these areas may play a role in the pathogenesis of schizophrenia Crosson and Hughes 1987; Gold and Weinberger 1991; Dolan et al 1993; Silverweig et al 1995.

Early postmortem studies did not show any significant difference in the total thalamic volume of schizophrenic patients compared to the thalamic volume of control subjects Rosenthal and Bigelow 1972; Lesch and Bogerts 1984; Kelsoe et al 1988. However, three postmortem studies did find a significant reduction in the total number of neurons in the brains of schizophrenic patients compared to normal control brains, specifically in the mediodorsal thalamic nucleus Hempel and Treff 1959; Baumer 1954; Pakkenberg 1990Pakkenberg 1992. In contrast, one postmortem study reported no significant difference in nerve cell density in the mediodorsal thalamus Dom et al 1981.

Finally, comparing schizophrenic patients with normal controls, a number of recent in vivo magnetic resonance imaging (MRI) studies have reported significant reductions in thalamic volume Flaum et al 1995; Goldstein et al 1996, thalamic area Andreasen et al 1990; Buchsbaum et al 1996, or in differences between averaged pixel signal intensities reflecting abnormal increases or decreases in thalamic parenchyma or in adjacent white matter fiber tracts Andreasen et al 1994. Further, a recent study indicated significant thalamic volume reductions in first-degree relatives of schizophrenics compared to normal controls Seidman et al 1996. Although there have been seven previous structural MRI studies of the thalamus in schizophrenia, only a few have produced volumetric data, and have used slice thicknesses of 3 mm with 1.5-mm gaps between slices Flaum et al 1995, 3 mm with no gaps Goldstein et al 1996; Seidman et al 1996, and 5 mm with 2.5-mm gaps for diencephalon gray-matter structures Jernigan et al 1991. In the present study, we used contiguous thin slice (1.5 mm) MR high-resolution images, on which automated and manual segmentation and three-dimensional (3D) surface rendering techniques were used to evaluate thalamic volumes in schizophrenic patients and controls.