Is translocator protein distribution volume elevated in the brain after acute COVID-19 infection with sequelae of depressive and cognitive symptoms?

In a recent study published in the JAMA Psychiatry Journal, researchers discuss the occurrence of neuroinflammation after coronavirus disease 2019 (COVID-19) characterized 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 is not the same as in COVID-DC patients.

It is uncertain whether individuals with COVID-DC have gliosis in their brains, despite suspicions of its presence.

In neuropsychiatric diseases characterized by brain inflammation, translocator protein total distribution volume (TSPO V_T) binding is mainly associated with activated microglia and astroglia. In general, it is primarily present in endothelial cells.

About the study

In the present study, researchers investigate whether individuals with COVID-DC have increased TSPO V_T, 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 completed by 40 participants aged between 18 and 72 years.

The team compared 20 individuals with COVID-DC to 20 healthy controls selected 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 main inclusive criteria for COVID-DC patients was the diagnosis of a novel major depressive episode (MDE) within 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 reaction. Healthy participants were required to meet specific criteria, including good health according to 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 during the emission PET scan.

A two-tissue compartment model was used to calculate the TSPO V_T 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 overall severity of MDE estimated according to the 17-item Hamilton Depression Rating Scale (HDRS) score, finger-tapping test, and self-perceived deficits in cognitive functioning calculated as per the Cognitive Failures Questionnaire (CFQ) score.

Results

The study analyzed 40 participants, consisting of 20 COVID-DC patients and 20 healthy controls. The main symptoms of COVID-DC include anhedonia, energy problems due to low motivation, motor speed slowing, and cognitive issues.

Individuals with COVID-DC exhibit higher TSPO V_T in prioritized regions such as 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 in the ventral striatum and a 20% difference in the dorsal putamen. Individuals with COVID-DC exhibited higher TSPO V_T in all brain regions analyzed than healthy controls, although this difference's degree and statistical significance varied.

Higher TSPO V_T in the dorsal putamen was linked to reduced motor speed in individuals with COVID-DC, as estimated by average T-scores in the finger-tapping test. COVID-DC patients with the slowest pace had a higher average dorsal putamen TSPO V_T than healthy individuals by 2.3.

No notable correlation was found between the anterior cingulate or prefrontal cortex TSPO VT and the HDRS score. Additionally, there was no significant correlation between the hippocampal TSPO VT and the total CFQ score.

Conclusion

The study found evidence of increased gliosis in the brains of COVID-DC patients, particularly in the dorsal putamen and ventral striatum. COVID-DC individuals frequently exhibited symptoms of anhedonia, motor retardation, and low motivation resulting in low energy. These symptoms collectively suggest a potential 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 in the dorsal putamen.

Investigating therapies that alleviate or specifically target the detrimental consequences of gliosis could benefit patients with COVID-DC.

Written by

Bhavana Kunkalikar

Bhavana Kunkalikar is a medical writer based in Goa, India. Her academic background is in Pharmaceutical sciences and she holds a Bachelor's degree in Pharmacy. Her educational background allowed her to foster an interest in anatomical and physiological sciences. Her college project work based on ‘The manifestations and causes of sickle cell anemia’ formed the stepping stone to a life-long fascination with human pathophysiology.