Imaging dopamine transmission in schizophrenia

Over the last ten years, several positron emission tomography (PET) and sin gle photon computerized tomography (SPECT) studies of the dopamine (DA) sys tem in patients with schizophrenia were performed to test the hypothesis th at DA hyperactivity is associated with this illness. In this paper, we revi ewed the results of fifteen brain imaging studies comparing indices of DA f unction in drug naive or drug free patients with schizophrenia and healthy controls: thirteen studies included measurement of DA D-2 receptors density , two studies compared amphetamine-induced DA release, and two studies meas ured DOPA decarboxylase activity, an enzyme involved in DA synthesis. We co nducted a meta-analysis of the studies measuring D-2 receptor density param eters, under the assumption that all tracers labeled the same population of D-2 receptors. This analysis revealed that, compared to healthy controls, patients with schizophrenia present a significant but mild elevation of D-2 receptor density parameters and a significant larger variability of these indices. We found no statistical evidence that studies performed with radio labeled butyrophenones detected a larger increase in D-2 receptor density p arameters than studies performed with other radioligands, such as benzamide s. Studies of presynaptic activity revealed an increase in DA transmission response to amphetamine challenge, and an increase in DOPA decarboxylase ac tivity. Together, these data are compatible with both pre- and post-synapti c alterations of DA transmission in schizophrenia. Future studies should ai m at a better characterization of these alterations, and at defining their role in the pathophysiology of the illness.