In a recent study published within the JAMA Psychiatry Journal, researchers discuss the occurrence of neuroinflammation after coronavirus disease 2019 (COVID-19) characterised by cognitive and depressive symptoms.
Study: Neuroinflammation After COVID-19 With Persistent Depressive and Cognitive Symptoms. Image Credit: tadamichi/Shutterstock.com
Background
COVID-19 disease and depression with or without other cognitive symptoms (COVID-DC) are significant public health concerns. The gliosis observed in postmortem samples of severe to critical acute COVID-19 patients shouldn’t be similar to in COVID-DC patients.
It’s uncertain whether individuals with COVID-DC have gliosis of their brains, despite suspicions of its presence.
In neuropsychiatric diseases characterised by brain inflammation, translocator protein total distribution volume (TSPO VT) binding is especially related to activated microglia and astroglia. Basically, it’s primarily present in endothelial cells.
Concerning the study
In the current study, researchers investigate whether individuals with COVID-DC have increased TSPO VT, an index of gliosis (inflammatory change).
The study was conducted over a period of 15 months, starting on April 1 2021, and ending on June 30 2022. The positron emission tomography (PET) imaging protocol was accomplished by 40 participants aged between 18 and 72 years.
The team compared 20 individuals with COVID-DC to twenty healthy controls chosen based on their matching rs6971 genotype, which affected radiotracer binding to TSPO. The control cohort of comparable age and gender were recruited before the COVID-19 outbreak.
The fundamental inclusive criteria for COVID-DC patients was the diagnosis of a novel major depressive episode (MDE) inside three months of acute COVID-19, as documented by the Structured Clinical Interview for DSM-5-Research Version.
Verification of COVID-19 illness was performed through rapid antigen testing or polymerase chain response. Healthy participants were required to satisfy specific criteria, including good health in keeping with a health questionnaire and no documented history of psychiatric illness as determined by the Structured Clinical Interview for DSM-5- Research Version.
Imaging data were acquired for 120 minutes using a three-dimensional high-resolution research tomograph PET scanner. Arterial sampling was conducted through automatic and manual blood sampling systems in the course of the emission PET scan.
A two-tissue compartment model was used to calculate the TSPO VT data. Trained staff administered psychological and neuropsychological tests to COVID-DC participants and the Structured Clinical Interview for DSM-5-Research Version.
The study’s primary measures were motor speed using the general severity of MDE estimated in keeping with the 17-item Hamilton Depression Rating Scale (HDRS) rating, finger-tapping test, and self-perceived deficits in cognitive functioning calculated as per the Cognitive Failures Questionnaire (CFQ) rating.
Results
The study analyzed 40 participants, consisting of 20 COVID-DC patients and 20 healthy controls. The fundamental symptoms of COVID-DC include anhedonia, energy problems on account of low motivation, motor speed slowing, and cognitive issues.
Individuals with COVID-DC exhibit higher TSPO VT in prioritized regions resembling the ventral striatum, anterior cingulate cortex, prefrontal cortex, dorsal putamen, and hippocampus. The study found that the dorsal putamen and ventral striatum regions had significantly higher values than the control group.
Between COVID-DC patients and controls, the team noted a 22% difference within the ventral striatum and a 20% difference within the dorsal putamen. Individuals with COVID-DC exhibited higher TSPO VT in all brain regions analyzed than healthy controls, although this difference’s degree and statistical significance varied.
Higher TSPO VT within the dorsal putamen was linked to reduced motor speed in individuals with COVID-DC, as estimated by average T-scores within the finger-tapping test. COVID-DC patients with the slowest pace had the next average dorsal putamen TSPO VT than healthy individuals by 2.3.
No notable correlation was found between the anterior cingulate or prefrontal cortex TSPO VT and the HDRS rating. Moreover, there was no significant correlation between the hippocampal TSPO VT and the full CFQ rating.
Conclusion
The study found evidence of increased gliosis within the brains of COVID-DC patients, particularly within the dorsal putamen and ventral striatum. COVID-DC individuals often exhibited symptoms of anhedonia, motor retardation, and low motivation leading to low energy. These symptoms collectively suggest a possible injury to the dorsal putamen and ventral striatum.
In COVID-DC cases, a correlation was found between lower scores on the finger-tapping test and greater TSPO VT, indicating the potential for ongoing injury within the dorsal putamen.
Investigating therapies that alleviate or specifically goal the detrimental consequences of gliosis may benefit patients with COVID-DC.