PET detected reduced dopamine signaling in the brains of some people with long COVID

PET detected reduced dopamine signaling in the brains of some people with long COVID

A Toronto research group compared 24 people with the neuropsychiatric subtype of long COVID with 24 healthy peers. The patients had lower VMAT2 signal in the striatum, a brain system involved in motivation, movement speed, and memory. Lower signal was associated with more severe apathy and slowing.

Apathy, brain fog, and slowing after COVID often appear as a collection of symptoms that is difficult to trace to a single process in the brain. In an article published on July 10 in eBioMedicine, researchers identified a measurable feature in a specific group of patients with these symptoms.

They used positron emission tomography, or PET. A radioactive tracer is injected into the bloodstream, and the scanner shows where it binds in the brain. In this study, the tracer bound to VMAT2, a protein that loads dopamine into tiny vesicles at nerve terminals. When a neuron transmits a signal, dopamine is released from these vesicles into the synapse.

Among the 24 participants with long COVID, VMAT2 signal in the striatum was lower than among the 24 healthy people of the same age, with mean values of 1.60 and 1.91, respectively. The difference remained when the control group was expanded to 43 people. The striatum connects dopamine pathways with several functions. Its ventral region contributes to motivation, the putamen contributes to the initiation and speed of movement, and the caudate nucleus contributes to some memory processes.

The associations within the patient group followed this functional map. Lower signal in the ventral striatum was associated with more severe apathy. Lower signal in the putamen was associated with slower performance on a finger tapping test. Weaker signal in the caudate nucleus was associated with poorer word recall after a delay. The authors had not planned this analysis in advance, so the finding requires independent confirmation.

The sample was deliberately narrow. All patients had experienced mild or moderate acute COVID and subsequently developed apathy and at least five neuropsychiatric symptoms. The result therefore applies to the subtype of long COVID defined by this set of symptoms. The participants had no neurological disorders before the infection.

VMAT2 has long been used as a marker of the condition of dopamine nerve terminals. Reduced signal may reflect fewer terminals, fewer dopamine containing vesicles, or a change in the amount of the transporter protein. The authors propose testing whether an intervention that increases dopamine transmission at synapses can improve brain function in these patients. This will require repeated PET measurements and treatment trials that select patients based on this biological marker.

In some people, infection may alter the neural systems that support the motivation to act, movement speed, and the retention of information. Researchers now have a specific signal that may help them identify these cases and test treatments.