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Neuroimaging techniques making inroads as a diagnostic tool


 

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HUNTINGTON BEACH, CALIF. – Five years ago, Dr. Bradley S. Peterson was about to give up on the idea that advanced neuroimaging could one day be used as a diagnostic tool for clinical practice in child psychiatry.

“I thought it was completely hopeless; I really did,” Dr. Peterson told attendees at the annual meeting of the American College of Psychiatrists. “I’m extremely optimistic now.”

Dr. Bradley S. Peterson

Dr. Bradley S. Peterson

Thanks to advances in technology and more rigorously designed studies, imaging will aid clinical diagnoses in the foreseeable future, predicted Dr. Peterson, director of the Institute for the Developing Mind at Children’s Hospital Los Angeles.

“I sincerely believe it’s around the corner,” he said. “I think the biggest challenge may be addressing regulatory issues, as some of these computer algorithms, depending on how they are used, may constitute a medical device. Getting things through the [Food and Drug Administration] can be prohibitively expensive, time consuming, and arduous.”

Using examples from studies conducted by his lab and that of colleagues in the field, he discussed four cutting-edge new uses of imaging studies in childhood disorders psychiatry.

Identifying biological vulnerabilities

In an ongoing study conducted with Myrna M. Weissman, Ph.D., division chief of epidemiology in the department of psychiatry at Columbia University, New York, researchers are prospectively following a three-generation cohort for more than 25 years in an effort to understand families at high and low risk for major depressive disorder. A large sample of patients with chronic, severe, highly impairing depression was recruited in and around New Haven, Conn., along with a group of community controls who, according to self-report, spouses, and other family members, had never suffered from depression. Longitudinal studies of that cohort to date have demonstrated that grandchildren in families with multiple generations of major depressive disorder are at high risk for depression and anxiety disorders.

In a study that Dr. Peterson conducted with Dr. Weissman and colleagues, the brains of 131 study participants were imaged “to identify in the brain what is transmitted between these generations that place these biological offspring of depressed people at risk for depression,” he explained. He presented published brain measurement findings from 66 subjects in the high-risk group and 65 in the low-risk group (PNAS 2009;105:6273-8). The primary measurement of interest was the cortical mantle, which he described as “the gray matter at the surface of the brain, which contains most of the nerve cell bodies and synapses of the brain that carry information from one part of the brain to another. This is generally about 6 mm thick on average, but it varies slightly across the brain.”

Dr. Peterson and his associates found that subjects at high risk for depression had a 28% average reduction in cortical thickness, compared with their counterparts in the low-risk group, primarily in the right hemisphere of the brain. He characterized this as “a massive finding in two respects. It’s massive in its spatial extent, from the back of the brain to the front. It’s also massive at each point of the brain. The average reduction of 28% in offspring of the high-risk people is a massive biological effect. It’s astounding that we can find this in offspring. Even people who are offspring of depressed individuals two generations removed carry this abnormality, and it’s there even if they’ve never been sick in their lifetime. This high-risk approach is one way of identifying true biological vulnerability to illness.”

Identifying brain-based causal mechanisms

This effort involves yoking MRI or other imaging technology to randomized, controlled trials. “Instead of having a change in symptoms be an outcome measure, here it’s a change in MRI or brain-based measure,” said Dr. Peterson, who is also director of child and adolescent psychiatry at the University of Southern California, Los Angeles.

In a recent study, he and other researchers, including Dr. David J. Hellerstein and Dr. Jonathan Posner at Columbia University, conducted functional MRIs to determine whether antidepressant medication normalizes default mode network connectivity in adults with dysthymia. They imaged 25 healthy controls at one point in time and imaged 41 dysthymic adults twice: once before and once after a 10-week trial of duloxetine (JAMA Psychiatry 2013;70:373-82). They were interested in the effects of duloxetine on the default mode network of the brain, a “circuit” of brain regions that include the ventral anterior cingulate, the posterior cingulate, and the inferior parietal lobule.

“It’s called the default mode [circuit] because when you daydream or mind wander or introspect, this set of circuits is highly active,” Dr. Peterson said. “If you have to perform a task rather than let your mind wander, that system has to shut off. This region has been implicated many times in depression, because it’s been shown to be hyperactive in currently depressed people. It’s been especially related to ruminations. So the more people ruminate, the more this default system is active.”

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