Imaging as tool to investigate psychoses and antipsychotics

The results of imaging studies have played an important role in the formulation of hypotheses regarding the etiology of psychosis and schizophrenia, as well as in our understanding of the mechanisms of action of antipsychotics. Since this volume is primarily directed to molecular aspects of psychosis and antipsychotics, only the results of molecular imaging techniques addressing these topics will be discussed here.One of the most consistent findings of molecular imaging studies in schizophrenia is an increased uptake of DOPA in the striatum, which may be interpreted as an increased synthesis of L-DOPA. Also, several studies reported an increased release of dopamine induced by amphetamine in schizophrenia patients. These findings played an important role in reformulating the dopamine hypothesis of schizophrenia. To study the roles of the neurotransmitters γ-aminobutyric acid (GABA) and glutamate in schizophrenia, SPECT as well as MR spectroscopy have been used. The results of preliminary SPECT studies are consistent with the hypothesis of NMDA receptor dysfunction in schizophrenia. Regarding the GABA deficit hypothesis of schizophrenia, imaging results are inconsistent. No changes in serotonin transporters were demonstrated in imaging studies in schizophrenia, but studies of several serotonin receptors showed conflicting results. The lack of selective radiotracers for muscarinic receptors may have hampered examination of this system in schizophrenia as well as its role in the induction of side effects of antipsychotics. Interestingly, preliminary molecular imaging studies on the cannabinoid-1 receptor and on neuroinflammatory processes in schizophrenia have recently been published. Finally, a substantial number of PET/SPECT studies have examined the occupancy of receptors by antipsychotics and an increasing number of studies is now focusing on the effects of these drugs using techniques like spectroscopy and pharmacological MRI.