PET neuroimaging reveals histone deacetylase dysregulation in schizophrenia
Autor: | Stephen J. Haggarty, Roy H. Perlis, Jacob M. Hooker, Baileigh G. Hightower, Minhae Kim, Tonya M. Gilbert, Anisha Bhanot, Joshua L. Roffman, Marco L. Loggia, Hsiao-Ying Wey, Thomas M. Morin, Changning Wang, Frederick A. Schroeder, Daphne J. Holt, Daniel S. Albrecht, Kamber L. Hart, Nicole R. Zürcher, Steven M. Stufflebeam, Amelia M. Pellegrini, Hannah E. Brown, Misha M. Riley, Anais Rodriguez-Thompson, Christine J. Wu |
---|---|
Rok vydání: | 2018 |
Předmět: |
Adult
Male 0301 basic medicine Oncology medicine.medical_specialty Prefrontal Cortex Neuroimaging Schizoaffective disorder Gene Expression Regulation Enzymologic Histone Deacetylases 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Humans Effects of sleep deprivation on cognitive performance Martinostat business.industry Cognition General Medicine Middle Aged medicine.disease Dorsolateral prefrontal cortex 030104 developmental biology medicine.anatomical_structure Psychotic Disorders Schizophrenia Case-Control Studies Positron-Emission Tomography Female Histone deacetylase business 030217 neurology & neurosurgery Research Article |
Zdroj: | Journal of Clinical Investigation. 129:364-372 |
ISSN: | 1558-8238 0021-9738 |
Popis: | BACKGROUND. Patients with schizophrenia (SCZ) experience chronic cognitive deficits. Histone deacetylases (HDACs) are enzymes that regulate cognitive circuitry; however, the role of HDACs in cognitive disorders, including SCZ, remains unknown in humans. We previously determined that HDAC2 mRNA levels were lower in dorsolateral prefrontal cortex (DLPFC) tissue from donors with SCZ compared with controls. Here we investigated the relationship between in vivo HDAC expression and cognitive impairment in patients with SCZ and matched healthy controls using [(11)C]Martinostat positron emission tomography (PET). METHODS. In a case-control study, relative [((11))C]Martinostat uptake was compared between 14 patients with SCZ or schizoaffective disorder (SCZ/SAD) and 17 controls using hypothesis-driven region-of-interest analysis and unbiased whole brain voxel-wise approaches. Clinical measures, including the MATRICS consensus cognitive battery, were administered. RESULTS. Relative HDAC expression was lower in the DLPFC of patients with SCZ/SAD compared with controls, and HDAC expression positively correlated with cognitive performance scores across groups. Patients with SCZ/SAD also showed lower relative HDAC expression in the dorsomedial prefrontal cortex and orbitofrontal gyrus, and higher relative HDAC expression in the cerebral white matter, pons, and cerebellum compared with controls. CONCLUSIONS. These findings provide in vivo evidence of HDAC dysregulation in patients with SCZ and suggest that altered HDAC expression may impact cognitive function in humans. FUNDING. National Institute of Mental Health (NIMH), Brain and Behavior Foundation, Massachusetts General Hospital (MGH), Athinoula A. Martinos Center for Biomedical Imaging, National Institute of Biomedical Imaging and Bioengineering (NIBIB), NIH Shared Instrumentation Grant Program. |
Databáze: | OpenAIRE |
Externí odkaz: |