My research has been focused on identifying neurobiologic mechanisms underlying the occurrence of psychotic symptoms, delusions and hallucinations. These symptoms are inextricably linked to cognitive and perceptual impairments. The ultimate goal is identification of molecular determinants of psychosis liability, and identifying the resulting structural and protein alterations within the cerebral cortex circuitry which may serve as targets for novel treatments with enhanced specificity and greater efficacy. I have focused these efforts on the two most prevalent psychotic syndromes, schizophrenia and psychosis occurring in individuals with Alzheimer disease. My research program is highly translational and interdisciplinary, applying genomics, targeted and discovery proteomics, quantitative fluorescent microscopy, and behavioral assays to study: 1) the cognitive and behavioral trajectories of living individuals with Alzheimer disease; 2) post-mortem brain tissue from subjects with Alzheimer disease and schizophrenia; 3) primary cortical neuronal culture; 4) genetic mouse models; and 5) brain tissue from non-human primate and mouse models of drug treatment and postmortem interval effects.
Javitt DC & Sweet RA. Auditory dysfunction in schizophrenia: Integrating clinical and basic features. Nat Rev Neurosci. 2015 Aug 20;16(9):535-50. PMCID: PMC4692466
MacDonald ML, Alhassan J, Newman JT, Richards M, Gu H, Sampson AR, Fish KN, Penzes P, Wills ZP, Lewis DA, Sweet RA. Selective Loss of Smaller Spines in Schizophrenia, Am J Psychiatry. 2017. Jun 1;174(6):586-594. PMCID: PMC5800878.
Shelton MA, Newman JT, Gu H, Sampson AR, Fish KN, MacDonald ML, Moyer CE, DiBitetto JV, Dorph-Petersen KA, Penzes P, Lewis DA, Sweet RA. Loss of microtubule-associated protein 2 immunoreactivity linked to dendritic spine loss in schizophrenia. Biol Psychiatry. 2015 Sep 15;78(6):374-85. PMCID: PMC4520801
DeMichele-Sweet MA, Weamer EA, Klei L, Vrana DR, Hollingshead DJ, Seltman HJ, Sims R, Foroud T, Hernandez I, Moreno-Grau S, Tárraga L, Boada M, Ruiz A, Williams J, Mayeux R, Lopez OL, Sibille EL, Kamboh MI, Devlin B, Sweet RA. Genetic risk for schizophrenia and psychosis in Alzheimer disease. Mol Psychiatry. 2018 Apr;23(4):963-972. PMCID: PMC5668212.
Krivinko JM, Erickson SL, Ding Y, Sun Z, Penzes P, MacDonald ML, Yates NA, Ikonomovic MD, Lopez OL, Sweet RA, Kofler J. Synaptic proteome compensation and resilience to psychosis in Alzheimer's disease. Am J Psychiatry. 2018 Oct 1;175(10):999-1009. PMCID: PMC6167138.