LAUSR

Overall Abstract: Animal models of psychosis indicate a new focus on altered GABAergic neurotransmission as the source of subcortical dopamine dysfunction in schizophrenia. While neuroimaging research allows testing the relevance of these models in humans, the extent to which GABAergic neurotransmission is altered in patients with psychosis and people at clinical high risk for psychosis (CHR) is less clear. This symposium will address this issue by integrating findings from state-of-the-art preclinical research, neuropathology studies in schizophrenia, and human neuroimaging studies before and after the development of psychosis. Tony Grace (Pittsburgh) will describe preclinical evidence for a central role of prefrontal and hippocampal GABA interneuron dysfunction in the neurobiological cascade driving subcortical dopamine dysfunction and will show new data on the prevention of schizophrenia-like GABA cell loss by pharmacologically intervening on the GABAergic system. Francine Benes (Harvard) will report new neuropathological data on reduced hippocampal GABA interneurons in schizophrenia, which allow for a detailed understanding of corticolimbic GABAergic changes in the disorder and show specificity with regard to other psychotic disorders. Hilleke Hulshoff Pol (Netherlands) will present new findings on reduced prefrontal GABAergic function in patients with schizophrenia through magnetic resonance spectroscopy research, and its relationship with cognitive functioning. Finally, these data will be complemented by novel multimodal imaging evidence of alterations in prefrontal GABA levels and their relationship to hippocampal perfusion in CHR subjects, presented by Gemma Modinos (London). Philip McGuire, who leads one of the world’s largest groups working with neuroimaging in psychosis and high-risk groups, will integrate this set of complementary findings from different disciplines.