UC research examines role of spinal cord neural pathways in depression

UC research examines role of spinal cord neural pathways in depression

Expert presents at international conference, publishes literature review on yearslong project

Ongoing University of Cincinnati research is contributing to a more comprehensive understanding of how spinal cord neural pathways affect major depressive disorder and is making a stronger case for new therapeutic targets that take brain-body connections into account.

UC's Francisco Romo-Nava, MD, PhD, recently presented data at the International Society for Bipolar Disorders and published a review in the journal Discover Mental Health, providing more evidence that spinal interoceptive pathways (SIP) may be a novel, feasible target to treat conditions including major depressive disorder (MDD).

How did this research begin?

Romo-Nava's research focuses on how brain-body communication is involved in psychiatric disorders.

"We think that the connection between the brain and the body is essential for psychiatric disorders," said Romo-Nava, associate professor in the Department of Psychiatry and Behavioral Neurosciences at UC, associate chief research officer for the Research Institute at the Lindner Center of HOPE and a UC Health physician scientist. "Emerging evidence suggests that many of the symptoms of mood disorders, or eating disorders, and anxiety disorders have to do with what one could interpret as dysregulation in this brain-body interaction."

SIPs function as a "highway" for neurons to transmit information to the brain, which then senses, interprets and integrates these signals. Romo-Nava hypothesizes that one contributor to MDD could be that this pathway becomes overloaded with information, similar to a traffic jam on a highway.

The research team used EEG data to confirm a laser stimulation delivered in participants' feet traveled along spinal interoceptive pathways and reached the brain as intended.

What has the research found so far?

Since 2020, Romo-Nava and colleagues have been testing a patented noninvasive spinal cord electrical stimulation method designed to decrease the amount of traffic in SIPs as a treatment for mood disorders. Preliminary data showed the method as feasible and well-tolerated to treat depressive symptoms, but the actual mechanism involved was still unknown.

To learn more, the researchers investigated the path of the electrical stimulation from the spinal cord to the brain with a noninvasive laser whose signal traveling from the foot to the brain through SIPs can be observed via brain wave data.

Using electroencephalogram (EEG) data in this NIMH-funded study, the team confirmed that the laser stimulation, and therefore the electrical stimulation, delivered on the pathway reaches the brain as intended. This allows the team to then measure aspects of these signals called laser-evoked potentials.

"These preliminary findings suggest a novel association between laser-evoked potentials as measures of spinal interoceptive pathways' function and depressive syndrome symptom domains," Romo-Nava said.

The data suggests an increasing importance of this brain-body circuit and bodily states that are regulated through SIPs, including sleep/wake cycles, metabolism and eating, and reproductive behavior. The team found widespread physiological consequences when SIPs are dysregulated.

"It appears bodily states may be relevant to understand aspects of the depressive syndrome and identify new therapeutic targets," Romo-Nava said. "The collected data provides us preliminary information on how the function of spinal interoceptive pathways may ultimately become relevant to enable a more comprehensive understanding of major depressive disorder, and perhaps other psychiatric disorders."

Francisco Romo-Nava, MD, PhD

What are the next steps?

Romo-Nava said the team will continue to recruit participants in the ongoing double-blinded randomized controlled trial to learn more about the effects of modulating SIPs with electrical stimulation. Additionally, they hope to develop specific markers to better quantify and measure the function of the electrical stimulation.

"Our team has been able to implement a sophisticated study design that we anticipate will generate valuable data that will contribute to understanding the role of brain-body interaction networks in psychiatric disorders and whether these pathways could become novel therapeutic targets for personalized noninvasive neuromodulation interventions," he said.

Doing science the right way takes a thorough, methodical approach, and Romo-Nava and colleagues have spent nearly a decade pursuing this potential treatment pathway.

"I am very proud of what our team has achieved throughout these years," he said. "We think it is necessary to conduct this work because we need to improve our understanding of the depressive syndrome to offer more and improved therapeutic alternatives for patients that experience depression. While we are optimistic about our approach, we remain cautious, and results will continue to inform our next steps."

Frequently asked questions about UC's spinal interoceptive pathway research

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Featured photo at top of Romo-Nava preparing to apply the laser pulse to a participant. All photos/Andrew Higley/UC Marketing + Brand.

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