Thalamic Abnormalities in Schizophrenia Visualized Through Magnetic Resonance Image Averaging

Abstract

Schizophrenia is a complex illness characterized by multiple types of symptoms involving many aspects of cognition and emotion. Most efforts to identify its underlying neural substrates have focused on a strategy that relates a single symptom to a single brain region. An alternative hypothesis, that the variety of symptoms could be explained by a lesion in midline neural circuits mediating attention and information processing, is explored. Magnetic resonance images from patients and controls were transformed with a "bounding box" to produce an "average schizophrenic brain" and an "average normal brain." After image subtraction of the two averages, the areas of difference were displayed as an effect size map. Specific regional abnormalities were observed in the thalamus and adjacent white matter. An abnormality in the thalamus and related circuitry explains the diverse symptoms of schizophrenia parsimoniously because they could all result from a defect in filtering or gating sensory input, which is one of the primary functions of the thalamus in the human brain.

A quantitative MR measure of the fornix in schizophrenia

“…Bogerts et al, 1990;Suddath et al, 1990;Egan et al, 1994); (2) reduction in the volume of the superior temporal gyrus (STG) (Barta et al, 1990;Shenton et al, 1992; see also reviews noted above); and (3) a decrease in thalamic volume (e.g. Andreasen et al, 1994;Buchsbaum, 1996). Analyses of other areas of the brain, such as the frontal and parietal lobes, have yielded more equivocal results (again, see our reviews in Shenton et al, 1997Shenton et al, , 2000McCarley et al, 1999).…”

“…These structures were chosen, based on previous work that showed a link between them and schizophrenia (e.g. Barta et al, 1990;Shenton et al, 1992;Bogerts et al, 1993;Buchanan et al, 1993;Andreasen et al, 1994;Rossi et al, 1994;Schlaepfer et al, 1994;Zipursky et al, 1994;Portas et al, 1998). To investigate the difference in the correlations between the two groups, a Fischer Z transformation was performed.…”

“…Abnormalities in the thalamus (e.g. Andreasen et al, 1994;Portas et al, 1998) as well as structures associated with the limbic system and medial temporal region, such as the hippocampus, have also been implicated (e.g. Bogerts et al, 1985;Falkai et al, 1988;Shenton et al, 1997).…”

“…In fact, there are no reliable MR studies of the fornix in schizophrenia. This is particularly surprising given that the fornix is a key fiber tract connecting two structures, the hippocampus and thalamus, both of which have been implicated in schizophrenia (for the role of the hippocampus in schizophrenia, see review in Shenton et al, 1997;McCarley et al, 1999; for the role of the thalamus in schizophrenia, see Andreasen et al, 1990Andreasen et al, , 1994Corey-Bloom et al, 1995;Flaum et al, 1995;Buchsbaum, 1996;Andreasen, 1997;Shenton et al, 1997Shenton et al, , 2000Portas et al, 1998).…”

Alterations of Thalamic Activity in Schizophrenia and in Response to Antipsychotic Drugs Studies in the Legacy of Seymour S. Kety

“…Post mortem analyses consistently show neuronal reductions in thalamus, particularly mediodorsal thalamus, in schizophrenia (Pakkenberg 1990;Bogerts 1993;Shapiro 1993). MRI studies have not only repeatedly demonstrated reductions of thalamic volume (Andreasen et al 1994;Buchsbaum et al 1996), but these reductions have been observed early in illness, during first episode of psychosis (Ettinger et al 2001), and in children with psychotic disorders (Kumra et al 2000).…”