Recent advances in brain scanning may bring welcome news to people with depression. Two new types of MRI appear able to spot distinct brain characteristics of the condition.

The researchers say that their findings deepen knowledge about how depression affects the brain and should lead to better treatments.

One of the new types of MRI reveals differences in the blood—brain barrier (BBB), and the other highlights differences in the brain's complex network of connections.

Scientists recently used the novel MRI technologies in people with or without major depressive disorder (MDD).

Presentations on the findings are featuring this week at RSNA 2019, the 105th annual meeting of the Radiological Society of North America, which is taking place in Chicago, IL.

According to the World Health Organization (WHO), depression affects more than 264 million people worldwide.

Depression and the BBB

Depression is more than the feelings of sadness that most people experience in day-to-day life. It can be a serious health condition, especially when symptoms persist. The most severe forms of depression can lead to suicide.

Loss of interest in daily activities, feelings of hopelessness, and fatigue are some of the main symptoms of MDD.

While scientists know that brain changes accompany the symptoms of MDD, their understanding of the underlying mechanisms is insufficient to meet the urgent need for better treatments.

Kenneth T. Wengler, PhD, a researcher in the Department of Psychiatry at Columbia University, in New York, was the first author of the study that examined links between MDD and changes to the BBB.

"Unfortunately," says Wengler, "with current treatments [for MDD] there is a large chance of relapse or recurrence."

"To develop new, more effective treatments, we must improve our understanding of the disorder," he adds.

The BBB is a unique set of properties in the brain's blood vessels that allow them to control the movement of molecules and cells between them and the tissues that they serve.

The BBB shields the brain from harmful toxins and pathogens that might be in the bloodstream.

Reduced water permeability in the BBB

Wengler and colleagues used a new type of MRI that they had developed themselves. The method, which they named "intrinsic diffusivity encoding of arterial labeled spins," or IDEALS, allows scientists to investigate the movement of water across the BBB.

They used the new MRI to investigate the BBBs of 14 individuals with MDD and 14 healthy control participants.

Scans of the participants' brains revealed that those with MDD had reduced water permeability in their BBBs; water moved less readily from their blood vessels into brain tissue than it did in the healthy controls.

The difference in BBB water permeability was particularly marked in two brain regions: the amygdala and the hippocampus. Previous imaging research in people with MDD has also highlighted these two regions.

"We observed disruption of the BBB in gray matter regions known to be altered in [MDD]," Wengler explains.

Disruption to the connectome

The second study investigated disruptions to what scientists call the connectome, or the "complete, point-to-point spatial connectivity of neural pathways in the brain."

Previous studies that have examined the connectome in relation to MDD have tended to focus on connectivity among brain regions.

The new study is different, in that it takes a deeper look at the connectome within brain regions.

Guoshi Li, PhD, a researcher from the Image Display, Enhancement, and Analysis Group at the University of North Carolina School of Medicine, in Chapel Hill, was the first author.

Li and colleagues used functional MRI (fMRI) accompanied by a new tool called a multiscale neural model inversion framework. They used the new method to scan 66 adults with MDD and 66 healthy control participants.

These techniques allowed the team to look at activity in microscopic circuits in relation to large-scale brain activity. They assessed excitation and inhibition among circuits of brain cells. A healthy brain works best when there is a balance between excitation and inhibition.

The fMRI scan results showed that in the dorsal lateral prefrontal cortex, individuals with MDD had different patterns of excitation and inhibition, compared with the individuals who did not have MDD.

The dorsal lateral prefrontal cortex is a region of the brain that helps regulate self-control and emotions. Its function includes the regulation of the amygdala. Scientists have long believed that depressive symptoms can arise when the brain fails to inhibit the amygdala correctly.

"In our study," says Li, "we found that excitation and inhibition in the brain regions in control of executive functions and emotional regulation were reduced in patients with MDD."

"This suggests that control functions in MDD are impaired, which may lead to elevated responses in the amygdala, resulting in increased anxiety and other negative moods," he adds.

The researchers also found that another brain area involved in emotion regulation, the thalamus, tended to show higher recurrent excitation in individuals with MDD.

Li says that the new findings will help scientists fathom the deeper brain connectivity features of depression. He explains that until now, all they had was a "superficial understanding of connectivity."

"This method allows us to identify impaired connectivity within each brain region, making it a potentially more powerful tool to study the neuromechanism of brain disorders and develop more effective diagnosis and treatment."

Guoshi Li, PhD

The RSNA 2019 program gives the following details about the two studies, which have yet to feature in peer-reviewed journals:

"Blood-Brain Barrier Water Permeability Disruption in Major Depressive Disorder" was presented at session SSM19-05 on Wednesday, December 4th, 2019.

"Multiscale Modeling of Intra-Regional and Inter-Regional Connectivities and Their Alterations in Major Depressive Disorder" was presented at session SSJ19-04 on Tuesday, December 3rd, 2019.