Brain health is rooted in mindset, study finds

Having more positive life experiences is associated with a lower risk of developing brain disorders like Alzheimer’s disease, slower cognitive decline with age, and even a longer life.

But how feelings and experiences translate into physical changes that protect or harm the brain remains unclear.

A study led by Columbia researchers now suggests that the brain’s mitochondria could play a fundamental role. The study is published in the journal Proceedings of the National Academy of Sciences.

Mitochondria provide energy to the brain, and the new study shows that the molecular machinery used by mitochondria to transform energy is boosted in older adults who have experienced less psychological stress during their lives than in older adults. who have had more negative experiences.

“We show that older adults’ state of mind is linked to the biology of their brain mitochondria, which is the first time that subjective psychosocial experiences have been linked to brain biology,” explains Caroline Trumpff, assistant professor of medical psychology, who led the research with Martin Picard, associate professor of behavioral medicine at Columbia University’s Vagelos College of Physicians and Surgeons and the Robert N. Butler Columbia Aging Center.

“We think that the mitochondria in the brain are like antennas, picking up molecular and hormonal signals and transmitting information to the cell nucleus, thereby changing the life course of each cell,” explains Picard. “And if mitochondria can change cellular behavior, they can also change the biology of the brain, the mind and the person as a whole.”

The new research used data collected from two comprehensive studies of nearly 450 older adults in the United States. Each study collected detailed psychosocial information from participants over two decades over the course of their lives. Study participants donated their brains after death for further analysis, which provided data on the state of the participants’ brain cells.

Trumpff created indices that converted patients’ reports of positive and negative psychosocial factors into a single overall psychosocial experience score. She also scored each participant on seven domains that represent distinct genetic networks active in mitochondria.

“The use of multivariate mitotype indices is an important innovation because we could more easily interpret the biological state of mitochondria with networks of related genes than an analysis of thousands of individual genes,” says Picard.

Results showed that a mitochondrial domain, which assessed the energy transformation machinery of the organelle, was associated with psychosocial scores.

“Greater well-being was linked to a greater abundance of protein in the mitochondria needed for energy processing, while negative mood was linked to lower protein,” says Trumpff.

“This may be why chronic psychological stress and negative experiences are bad for the brain, because they damage or impair mitochondrial energy processing in the dorsolateral prefrontal cortex, the part of the brain responsible for tasks. high-level cognitive skills.”

The researchers also analyzed mitochondria in specific cell types in the brain and found that associations between mitochondria and psychosocial factors were not determined by the brain’s neurons, but by its glial cells, which may play more than their traditionally assumed “support” role.

“This part of the study, made possible through our collaboration with the Columbia Center for Translational and Computational Neuroimmunology, is what I think makes it particularly significant,” Picard said. “Asking questions at this level of cellular resolution in the brain is unprecedented in the mitochondrial field.

“Neuroscience is the focus of neuroscience research, but we are becoming aware that other brain cells could be the cause of diseases.”

Do mitochondria change mood, or does mood change mitochondria?

Although the current study cannot determine whether the participant’s psychosocial experiences altered their brain mitochondria or whether innate or acquired mitochondrial states contributed to these experiences, other studies suggest that the relationship between mitochondria and mood works. in both ways.

In animal studies, the evidence is very strong, says Picard, that chronic stress affects the energy transformation of mitochondria. And in humans, a recent study led by Picard and his collaborator Elissa Epel at UCSF found the first evidence that mood can affect mitochondria in humans. In this study, positive mood predicted greater mitochondrial energy production in participants’ blood cells on subsequent days, but mitochondrial activity did not predict mood on subsequent days.

A growing body of work in animals and humans also indicates that mitochondria themselves can modify behavior.

“It is possible that these mechanisms reinforce each other,” believes Trumpff. “Chronic stress could alter an individual’s mitochondrial biology in ways that subsequently affect their perception of social events, thereby creating more stress. The picture emerging in the literature is that all of these pathways are interactive. “

Next steps

Although the brain’s energy transformation machinery is greater in participants with higher psychosocial scores, researchers do not yet know whether this leads to greater energy transformation. Trumpff and Picard are currently conducting these studies with hundreds of brains from the same cohorts of participants.

The team is also exploring a way to measure the brain’s mitochondrial health, which could be used in doctors’ offices in the future.

“Mitochondria are the source of health and life, but we have no way to quantify health, only disease,” says Picard. “We need health science. We need tests that show how healthy and resilient a person is.

“This would be clinically useful for monitoring changes in health status before disease onset, and it could transform medical research by giving scientists a focus other than decades of accumulated protein deposits or d other forms of long-term damage.”