Journal article

Elevated ubiquitinated proteins in brain and blood of individuals with schizophrenia

Chad A Bousman, Sandra Luza, Serafino G Mancuso, Dali Kang, Carlos M Opazo, Md Shaki Mostaid, Vanessa Cropley, Patrick McGorry, Cynthia Shannon Weickert, Christos Pantelis, Ashley I Bush, Ian P Everall

Scientific Reports | NATURE RESEARCH | Published : 2019

Abstract

Dysregulation of the ubiquitin proteasome system (UPS) has been linked to schizophrenia but it is not clear if this dysregulation is detectable in both brain and blood. We examined free mono-ubiquitin, ubiquitinated proteins, catalytic ubiquitination, and proteasome activities in frozen postmortem OFC tissue from 76 (38 schizophrenia, 38 control) matched individuals, as well as erythrocytes from 181 living participants, who comprised 30 individuals with recent onset schizophrenia (mean illness duration = 1 year), 63 individuals with 'treatment-resistant' schizophrenia (mean illness duration = 17 years), and 88 age-matched participants without major psychiatric illness. Ubiquitinated protein ..

View full abstract

Grants

Awarded by National Health and Medical Research Council of Australia


Awarded by National Institute of Alcohol Abuse and Alcoholism (NIH (NIAAA))


Awarded by National Health and Medical Research Council of Australia (NHMRC) Career Development Fellowship


Awarded by NHMRC Senior Principal Research Fellowship


Funding Acknowledgements

The authors acknowledge the financial support of the CRC for Mental Health. The Cooperative Research Centre (CRC) programme is an Australian Government Initiative. The authors also wish to acknowledge the CRC Scientific Advisory Committee, in addition to the contributions of study participants, clinicians at recruitment services, staff at the Murdoch Children's Research Institute, staff at the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Aging, and research staff at the Melbourne Neuropsychiatry Centre, including coordinators Phassouliotis, C., Merritt, A., and research assistants, Burnside, A., Cross, H., Gale, S., and Tahtalian, S. Participants for this study were sourced, in part, through the Australian Schizophrenia Research Bank (ASRB), which is supported by the National Health and Medical Research Council of Australia (Enabling Grant No. 386500), the Pratt Foundation, Ramsay Health Care, the Viertel Charitable Foundation and the Schizophrenia Research Institute. Postmortem tissues were received from the New South Wales Tissue Resource Center at the University of Sydney, which is supported by the National Health and Medical Research Council of Australia, Schizophrenia Research Institute, National Institute of Alcohol Abuse and Alcoholism (NIH (NIAAA) R24AA012725). C.A.B. was supported by a National Health and Medical Research Council of Australia (NHMRC) Career Development Fellowship (1127700). C.P. was supported by NHMRC Senior Principal Research Fellowship (628386 & 1105825). A.I.B. was supported by NHMRC Senior Principal Research Fellowship (1103703). None of the funding sources played any role in the study design; collection, analysis or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. We thank the Chief Investigators and ASRB Manager: Carr, V., Schall, U., Scott, R., Jablensky, A., Mowry, B., Michie, P., Catts, S., Henskens, F., Pantelis, C., Loughland, C. We acknowledge the help of Jason Bridge for ASRB database queries.