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.
DeMichele-Sweet MAA, Klei L, Creese B, Harwood JC, Weamer EA, McClain L, Sims R, Hernandez I, Moreno-Grau S, Tárraga L, Boada M, Alarcón-Martín E, Valero S; NIA-LOAD Family Based Study Consortium, Alzheimer’s Disease Genetics Consortium (ADGC), Liu Y, Hooli B, Aarsland D, Selbaek G, Bergh S, Rongve A, Saltvedt I, Skjellegrind HK, Engdahl B, Stordal E, Andreassen OA, Djurovic S, Athanasiu L, Seripa D, Borroni B, Albani D, Forloni G, Mecocci P, Serretti A, De Ronchi D, Politis A, Williams J, Mayeux R, Foroud T, Ruiz A, Ballard C, Holmans P, Lopez OL, Kamboh MI, Devlin B, Sweet RA. Genome-wide association identifies the first risk loci for psychosis in Alzheimer disease. Mol Psychiatry. 2021 Jun 10. doi: 10.1038/s41380-021-01152-8. Epub ahead of print. PMID: 34112972.
Grubisha MJ, Sun X, MacDonald ML, Garver M, Sun Z, Paris KA, Patel DS, DeGiosio RA, Lewis DA, Yates NA, Camacho C, Homanics GE, Ding Y, Sweet RA. MAP2 is differentially phosphorylated in schizophrenia, altering its function. Mol Psychiatry. 2021 Feb 1:10.1038/s41380-021-01034-z. doi: 10.1038/s41380-021-01034-z. Epub ahead of print. PMID: 33526823; PMCID: PMC8325721.
MacDonald ML, Garver M, Newman J, Sun Z, Kannarkat J, Salisbury R, Glausier J, Ding Y, Lewis DA, Yates N, Sweet RA. Synaptic Proteome Alterations in the Primary Auditory Cortex of Individuals With Schizophrenia. JAMA Psychiatry. 2020 Jan 1;77(1):86-95. doi: 10.1001/jamapsychiatry.2019.2974. PMID: 31642882; PMCID: PMC6813579.
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. doi: 10.1176/appi.ajp.2018.17080858. Epub 2018 Jul 19. PMID: 30021459; PMCID: PMC6167138.