Positron emission tomography and single photon emission CT molecular imaging in schizophrenia

We reviewed findings from PET and SPECT studies that have contributed to our understanding of the pathophysiology and treatment of schizophrenia. The most robust set of findings pertains to imaging of presynaptic dopaminergic function in the striatum. The results of these studies have been consistent in showing that schizophrenia, at least during episodes of illness exacerbation, is associated with increased activity of DA neurons; this increased presynaptic activity is associated with positive symptoms and good therapeutic response. Studies of cortical DA function are less numerous and less consistent. In the future, technical advances in PET instrumentation and radioligand development should contribute to a clarification of the role of prefrontal DA in the cognitive impairment that is presented by these patients. An important drawback of the literature in this field is the generally low number of subjects that are included in studies (typically less than 20 per group). Small samples are necessitated by the cost of these investigations, but also, in some instances, to the difficulty in recruiting appropriate clinical subjects (such as drug-free patients who have schizophrenia). In conditions that are characterized by marked heterogeneity, such as major depressive disorders, this factor is bound to yield divergent results across studies. Another source of discrepancy is the variety of technical approaches to data acquisition and analysis. For example, analytical methods range from "empirical" or "semiquantitative" (typically a region of interest to a region of reference ratio measured at one time point) to model-based methods that use an arterial input function. The limitations that are associated with empirical analytical methods might account for artifactual results, especially when the effect size of the between-group difference and the number of subjects are small [149]. In addressing these limitations it will be important to increase the availability of these techniques beyond a few academic centers, to promote multi-center studies in well-characterized populations, and to standardize analytical methods. Until recently, SPECT was the only widely available technique, and SPECT studies have provided a substantial contribution to this field. With the current increase in PET camera availability, the development of [18F]-based molecular imaging probes will provide unique opportunities for further dissemination of these techniques. The article reviewed seminal findings obtained with PET and SPECT molecular imaging of schizophrenia. These techniques do not play a major role in the diagnosis and treatment of this disorder, remain essentially research tools. The results that have been produced by this field to date suggest that PET will significantly contribute to unraveling the biologic bases of psychiatric disorders and may contribute to their clinical management. Moreover, it is foreseeable that PET will become increasingly involved in the development of new psychiatric medications. Expanding the availability of PET and the current radiopharmaceutical portfolio will be critical for these predictions to become reality.