Neuroreceptor Imaging Studies in Schizophrenia

Abstract

The ability of SPECT and PET to image specific biomolecules in the living brain provides a unique tool for clinical researchers. It is therefore not surprising that the use of neuroreceptor-imaging techniques has become more widespread over the past decade. This article reviews the application of these techniques to the study of schizophrenia. The design of neuroreceptor-imaging studies performed in the field of schizophrenia research can be broadly divided into two categories: (1) studies of pathophysiology and (2) studies of pharmacology. The former examines neuroreceptor and neurotransmitter parameters in individuals with schizophrenia compared to control subjects in order to provide a better understanding of the disease process. Studies of pharmacology seek to elucidate the mechanism of action for the treatments utilized in schizophrenia. This review will consider both studies of pathophysiology and pharmacology, with a discussion of the application of these techniques to drug development.

A Possible Role for the Striatum in the Pathogenesis of the Cognitive Symptoms of Schizophrenia

“…For example, some, though not all, post mortem studies have detected an increase in the level of dopamine in the striatum or an increase, even in unmedicated patients, in the levels of the dopamine metabolite HVA (for a review, see Davis et al, 1991). This is consistent with the numerous findings of an increase in striatal uptake of dopamine in patients with schizophrenia, as determined by an increase in the uptake of Fluoro-Dopa, by the dopamine-synthesizing enzyme L-amino acid decarboxylase (Frankle, 2007; Hietala et al, 1999; Hietala et al, 1995; Lindström et al, 1999; Meyer-Lindenberg et al, 2002; Reith et al, 1994). Similarly, PET imaging has also found that in patients with schizophrenia, there is an increase in the striatum of amphetamine-induced displacement of D2 receptor binding, consistent with increased dopamine release (Abi-Dargham et al, 1998; Breier et al, 1997; Laruelle et al, 1996).…”

The applicability of SRTM in [18F]fallypride PET investigations: Impact of scan durations

“…Some, but not all, investigations of second-generation antipsychotics report increased receptor binding in extrastriatal regions compared with striatal binding (Frankle, 2007). All PET studies describing this preferential extrastriatal binding effect have been performed using FP as the radioligand.…”

Functional Brain Imaging in Schizophrenia: Selected Results and Methods

“…Other chapters in this volume will discuss metabolic and structural imaging. We also refer readers to Frankle's recent review of neuroreceptor imaging studies in schizophrenia (Frankle 2007; see also Urban and Abi-Dargham, this text). Readers interested in the technical details of the functional imaging methods used in the studies reviewed are referred to Andreasen (1989) especially for its excellent chapters on single-photon emission computed tomography (SPECT) and positron emission tomography (PET), to Wood (1987) for descriptions of cerebral blood flow (CBF) methods, and to Buxton (2009) and Huettel et al (2009) for descriptions of functional magnetic resonance imaging (fMRI).…”