The impact of genetic polymorphisms on neuroreceptor binding: Results from PET and SPECT neuroreceptor imaging studies

Abstract

Major psychiatric disorders are highly heritable. Nevertheless, more than three decades of candidate gene studies and genome-wide association studies have yielded few, if any, unambiguous and replicable results that would be strong enough as to direct research toward new pharmacological targets. This is in part due to the complex non-Mendelian inheritance patterns and difficult-to-define phenotypes of psychiatric disorders. In addition, the relationship between genetic risk and phenotypic expression is blurred by the strong contribution of environmental factors and epigenetic modification. A research strategy that has successfully been pursued over the last years with magnetic resonance-based methods is imaging of endophenotypes. However, these techniques have the drawback that their results are not easily transferable to a molecular level potentially accessible to therapeutic drugs. Neuroreceptor imaging methods such as positron emission tomography (PET) and single photon emission computer tomography (SPECT) make it possible to explore the impact of genetic variation on neuroreceptor binding and function of transporters and other molecules that play a central role in neuropsychiatric disorders, besides certain aspects of molecules that play a central role in our understanding and treatment of psychiatric disorders. This chapter tries to cover the current state of knowledge about the impact of genetic variation on the behavior of PET and SPECT radioligands in the living human brain.