Astrogliosis Marker [11C]SL25.1188 After COVID-19 With Ongoing Depressive and Cognitive Symptoms

Joeffre Braga; Emily J Y Kuik; Mariel Lepra; Pablo M Rusjan; Stephen J Kish; Erica L Vieira; Zahra Nasser; Natasha Verhoeff; Neil Vasdev; Thomas Chao; Michael Bagby; Isabelle Boileau; Stefan Kloiber; M Ishrat Husain; Nathan Kolla; Yuko Koshimori; Khunsa Faiz; Wei Wang; Jeffrey H Meyer

doi:10.1016/j.biopsych.2024.09.027

Astrogliosis Marker [¹¹C]SL25.1188 After COVID-19 With Ongoing Depressive and Cognitive Symptoms

Biol Psychiatry. 2024 Oct 10:S0006-3223(24)01656-1. doi: 10.1016/j.biopsych.2024.09.027. Online ahead of print.

Authors

Joeffre Braga¹, Emily J Y Kuik², Mariel Lepra¹, Pablo M Rusjan³, Stephen J Kish⁴, Erica L Vieira², Zahra Nasser², Natasha Verhoeff², Neil Vasdev⁵, Thomas Chao⁶, Michael Bagby⁷, Isabelle Boileau⁴, Stefan Kloiber⁴, M Ishrat Husain⁴, Nathan Kolla⁸, Yuko Koshimori², Khunsa Faiz⁹, Wei Wang², Jeffrey H Meyer¹⁰

Affiliations

¹ Brain Health Imaging Centre, Azrieli Centre for Neuro-Radiochemistry, and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
² Brain Health Imaging Centre, Azrieli Centre for Neuro-Radiochemistry, and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
³ Douglas Research Centre and Department of Psychiatry, McGill University, Montreal, Québec, Canada.
⁴ Brain Health Imaging Centre, Azrieli Centre for Neuro-Radiochemistry, and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁵ Brain Health Imaging Centre, Azrieli Centre for Neuro-Radiochemistry, and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
⁶ Institute of Mental Health, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada.
⁷ Brain Health Imaging Centre, Azrieli Centre for Neuro-Radiochemistry, and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
⁸ Brain Health Imaging Centre, Azrieli Centre for Neuro-Radiochemistry, and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Waypoint Centre for Mental Health Care, Penetanguishene, Ontario, Canada.
⁹ Department of Diagnostic Radiology, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada.
¹⁰ Brain Health Imaging Centre, Azrieli Centre for Neuro-Radiochemistry, and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada. Electronic address: [email protected].

PMID: 39395470
DOI: 10.1016/j.biopsych.2024.09.027

Abstract

Background: After acute COVID-19, 5% of people experience persistent depressive symptoms and reduced cognitive function (COVID-DC). Theoretical models propose that astrogliosis is important in long COVID, but measures primarily indicative of astrogliosis have not been studied in the brain of long COVID or COVID-DC. The objective of the current study was to measure [¹¹C]SL25.1188 total distribution volume ([¹¹C]SL25.1188 V_T), an index of monoamine oxidase B density and a marker of astrogliosis, with positron emission tomography in participants with COVID-DC and compare with healthy control participants.

Methods: In 21 COVID-DC cases and 21 healthy control participants, [¹¹C]SL25.1188 V_T was measured in the prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum. Depressive symptoms were measured with the Beck Depression Inventory-II, and cognitive symptoms were measured with neuropsychological tests.

Results: [¹¹C]SL25.1188 V_T was higher in participants with COVID-DC in the prefrontal cortex, anterior cingulate cortex, hippocampus, dorsal putamen, and ventral striatum than in healthy control participants. Depressive symptom severity negatively correlated with [¹¹C]SL25.1188 V_T across prioritized brain regions. More recent acute COVID-19 positively correlated with [¹¹C]SL25.1188 V_T, reflecting higher values since predominance of the Omicron variant. Exploratory analyses found greater [¹¹C]SL25.1188 V_T in the hippocampus, dorsal putamen, and ventral striatum of COVID-DC participants than control participants with a major depressive episode with no history of COVID-19, and there was no relationship to cognitive testing in prioritized regions.

Conclusions: Results strongly support the presence of monoamine oxidase B-labeled astrogliosis in COVID-DC throughout the regions assessed, although the association of greater astrogliosis with fewer symptoms raises the possibility of a protective role. The magnitude of astrogliosis in COVID-DC is greater since the emergence of the Omicron variant.

Keywords: COVID-19; Depression; MAO-B; Neuroimaging; PET; [(11)C]SL25.1188.