Dopamine and Psychosis: Disease and Treatment

Abstract

Dopamine dysregulation is central to the pathophysiology of psychosis and underpins the mechanisms of antipsychotic treatment. Recent clinical and preclinical findings have refined our understanding of dopaminergic dysfunction. MRI-based techniques such as quantitative susceptibility mapping (QSM) and neuromelanin imaging are advancing our understanding of iron and dopamine metabolism in psychosis. In parallel, PET imaging, including combined PET–MRI amphetamine challenge studies in healthy controls, provide an integrative understanding of the relationship between striatal dopamine function and cortical activity. Finally, I will consider emerging targets such as trace amine–associated receptor 1 (TAAR1), and the translational value of linking preclinical models with multimodal human imaging. Together, these approaches point toward a more integrated and biologically informed understanding of psychosis and its treatment.

Bio

Rob McCutcheon (MRCPsych, PhD) is an associate professor and consultant psychiatrist at the University of Oxford. Following a Chemistry BSc, he studied medicine, and subsequently undertook combined clinical academic training at King’s College London and South London and Maudsley.  His research investigates both how to use existing treatments more effectively, and how to develop new treatments for people with psychotic disorders like schizophrenia.  This involves testing treatments in both humans and animal models of the illness. Techniques employed include positron emission tomography and functional MRI to better understand the mechanisms underlying both symptoms, and effects of treatment. In his clinical work he runs the TUNE-UP clinic, a service that focuses on cognitive, negative, and resistant positive symptoms that may be neglected in routine care.