Ottawa-led breakthrough could hold key to ‘holy grail’ of depression research

Ground-breaking research could lead to personalized therapy for bipolar sufferers
By Stu Mills, CBC News

New research published today unlocks some of the mysteries of bipolar disorder and could lead to effective therapy for those suffering from the illness, the Ottawa-based researcher who led the study says.

Bipolar disorder is a debilitating mental illness that affects more than 350,000 people across Canada. Sufferers typically fluctuate between periods of depression and bouts of mania, when their mood is euphoric.

A study led by Dr. Georg Northoff at The Royal’s Institute of Mental Health Research uncovered interrelated changes in the brain’s two distinct neurological networks that could hold the key to better understanding those mood shifts.

A patient’s depressed or a manic state shows up in functional magnetic resonance imaging as changes in the default mode network (DMN) and the sensorimotor network (SMN), the researchers found.

“Our findings showed that the more the balance is tipped to the DMN, the more depressed a person is; the more it is tipped to the SMN, the more manic,” said Northoff in a statement published by The Royal.

“It’s the interaction between these two networks that is new. This interaction has never been measured before, not even in healthy people.”

MRI imaging reveals depression

Northoff and his co-authors used a functional MRI machine to look into the brains of healthy people and those suffering from depression and mania related to bipolar disorder and compared the differences.

“People suffering from depression are locked in their own thoughts. Everything revolves around them and they don’t  connect with the external world,” said Northoff.

The opposite was true when bipolar sufferers entered a manic state. Researchers found abnormally low signaling in the DMN, revealing very few internal thoughts, and abnormally high signaling levels in the sensorimotor area.

“A manic person is distracted by everything. They have lots of movement and their thoughts are not about themselves but more oriented to the external world.”

The paper, titled “Contrasting variability patterns in the default mode and sensorimotor networks balance in bipolar depression and mania,” was published today in the Proceedings of the National Academy of Sciences of the United States.

Northoff said the findings could lead to new therapies for bipolar disorder.

Personalized therapy

More exciting, he says, is the possibility that the discovery could eventually lead to personalized and individualized, therapy, the “holy grail” of depression research.

“When you go to your family doctor for blood tests and she sees that your glucose level is abnormal, she will make a decision about your treatment. If your glucose level is extremely high, you will get insulin and she will know exactly how much to give you depending on your  level. If your glucose level is just slightly above average, she might just change your diet,” said Northoff.

“That’s what I’m attempting to do with this research. I want to get individualized ranges of just how depressed or manic a person is. This is essentially my blood test. Based on the results, I can then say, ‘OK, you get this therapy.'”

Northoff said brain stimulation is one such leading-edge therapy that would allow doctors to “reboot” the brain of a person suffering from bipolar disorder and bring the signaling between the DMN and the SMN into balance.

That therapy would be applied as small electrical currents delivered through a transcranial magnetic stimulation  machine to increase activity in a specific area of the brain.

“So, if someone is depressed we may want to increase the activity in the SMN to create a better balance in signaling between activity in that network and in the DMN. Or if someone is manic, we would increase activity in the DMN.”

​Dr. Northoff is set to launch a large-scale, multi-year clinical study aimed at determining whether individualized therapy based on the results of brain imaging is more effective than therapy prescribed without the use of brain imaging.

This study will take advantage of The Royal’s new Brain Imaging Centre, opening this spring.


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