PET Imaging Reveals Dopamine System Injury, Not Widespread Inflammation, as Hallmark of Long COVID Brain Pathology
核心洞察
A CAMH study provides the first direct evidence of dopamine neuron loss in long COVID (搜索), with PET scans showing significantly reduced dopamine transporter markers across all major striatal regions.
Lower dopamine markers correlated with specific symptoms: reduced motivation linked to ventral striatum, slower movement to dorsal putamen, and poorer memory to caudate putamen.
A separate Finnish study found no evidence of widespread neuroinflammation in long COVID (搜索) patients compared to healthy controls, though increased cellular activity in the hippocampus and amygdala was tied to anxiety and depression severity.
A pair of new brain imaging studies is reshaping the scientific understanding of long COVID (搜索)'s neurological underpinnings, challenging the prevailing hypothesis that persistent brain inflammation drives the condition's most debilitating symptoms. Instead, researchers at the Centre for Addiction and Mental Health (CAMH) in Toronto have produced what they describe as the first direct evidence of injury to the brain's dopamine system, while a separate Finnish investigation found no signs of widespread neuroinflammation in long COVID patients.
The CAMH findings, published in eBioMedicine, used positron emission tomography (PET) imaging to examine dopamine neuron integrity in individuals diagnosed with long COVID (搜索). The results revealed significantly lower levels of a well-established imaging marker of dopamine nerve terminal density across all major regions of the striatum—a brain structure central to motivation, movement, and cognitive function.
"Our findings provide compelling evidence that long COVID (搜索) involves the loss of dopamine-releasing neurons," said Dr. Jeffrey Meyer, senior scientist at CAMH's Brain Health Imaging Centre and senior author of the study. "This kind of injury is well known to produce symptoms like lack of motivation and motor slowing, and may contribute to memory difficulties in other neurological conditions. Our results suggest a similar process is occurring in long COVID."
Dopamine Deficits Map onto Specific Symptoms
The reductions in dopamine markers were not uniform in their clinical consequences. Lower dopamine markers in the ventral striatum were associated with greater loss of motivation. Reduced activity in the dorsal putamen corresponded with slower movement, while decreases in the caudate putamen were linked to poorer memory performance. This symptom-to-region mapping strengthens the case for a causal relationship between dopamine system injury and the neurological complaints that patients have reported for years.
The new findings build on the team's earlier work demonstrating elevated inflammation in the brains of people with long COVID (搜索), particularly in areas rich in dopamine-producing neurons. "We know that inflammation can injure dopamine neurons," Meyer explained. "While our earlier research showed high levels of inflammation in those regions, this study provides direct evidence that the dopamine neuron marker is reduced in the same regions, and that this loss correlates with patients' symptoms."
According to the researchers, long COVID (搜索) affects an estimated 5% of the global population, including approximately 2 million Canadians, with symptoms persisting for at least three months after the initial infection.
Finnish Study Challenges the Inflammation Hypothesis
Complementing the CAMH findings, researchers at the University of Turku in Finland conducted PET and MRI scans on 14 people with long COVID (搜索), 11 healthy volunteers, and 13 individuals with multiple sclerosis (MS)—a neurological disease known to cause brain inflammation. The results, published in the Journal of Neurology, showed that people with long COVID had much lower inflammatory activity in the brain's white matter than patients with MS. Researchers also found no differences between long COVID patients and healthy participants in markers associated with brain inflammation or neurodegeneration.
"We did not observe evidence of widespread brain inflammation in patients with long COVID (搜索) when compared to healthy controls," said Professor of Neuroimmunology Laura Airas, who led the study.
However, the Finnish team did identify a temporal pattern: among participants with long COVID (搜索), those who underwent brain scans within 16 months of their infection showed higher levels of inflammatory activity in white matter than those who had been living with the condition for a longer period. This suggests that inflammation may be more prominent during earlier disease stages and gradually decline over time.
Emotional Brain Regions and Symptom Severity
One of the Finnish study's most notable findings involved the hippocampus and amygdala, two brain regions that help regulate emotions, memory, and stress responses. People reporting higher levels of anxiety and depression, as well as poorer quality of life, tended to show increased cellular activity in these regions. These observations suggest that changes in activity within emotion-regulating areas of the brain may be connected to symptom severity in at least some people with long COVID (搜索).
The findings raise the possibility that some patients could benefit more from treatments focused on stress management and emotional regulation rather than therapies aimed solely at reducing inflammation. "This study highlights the need to continue investigating the complex biological mechanisms underlying long COVID (搜索). Understanding these processes is essential for developing targeted treatments," Airas noted.
Toward Dopamine-Targeted Therapeutics
The CAMH team's discovery could open the door to new treatment approaches by shifting attention from inflammation alone toward restoring dopamine function. "These results indicate that long COVID (搜索) is, at least in part, a disorder of the brain's dopamine system," Meyer said. "This suggests that repurposing medications that augment the function of dopamine-releasing neurons, including dopamine precursors and inhibitors of dopamine metabolism, could be a promising approach."
Based on the findings, CAMH researchers plan to launch a clinical trial within the next few months, in collaboration with University Health Network (UHN), to evaluate whether medications targeting dopamine activity can improve fatigue, motivation, and memory problems in people with long COVID (搜索).
For patients, the research offers validation that their symptoms have a biological basis. "For five years, I have been seeking answers on what happened to me after I contracted COVID in 2021," said Susan Deuville, a lived-experience research adviser who worked with the CAMH team. "It was a crushing loss of the life I had and the person I was before. The research of Dr. Meyer brings hope. It also validates what long COVID (搜索) sufferers have always known: long COVID is real, and the effects are devastating."