Mood Disorders: More Alike Than Distinct?

Pauline Anderson

May 11, 2015

Patients with bipolar disorder (BP) and those with major depressive disorder (MDD) may have more in common than previously thought, new research suggests.

These patient groups performed similarly on a cognitive task, and both groups were slower and less accurate than healthy control participants.

"We couldn't differentiate the diagnosis based on their performance on this test," lead author Kelly Ryan, PhD, clinical assistant professor, Department of Psychiatry, Neuropsychology Program, University of Michigan Medical School and Depression Center, Ann Arbor, told Medscape Medical News.

The study was published in the May issue of Brain.

Slow Response Time

For the study, the researchers performed two separate experiments with women. The researchers used only women in the study to remove any potential sex effects.

The first experiment included 266 patients with MDD, 202 with BD, and 150 matched control individuals. Patients ranged in age from 17 to 84 years. Patients with BD were in the euthymic, depressed, or mixed state but not in a manic state. MDD patients were in the depressed or euthymic states.

Researchers used the 3-minute first level of the Parametric Go/No-Go Task, which measures attention and response time, resulting in two dependent measures of cognitive control.

Cognitive control, explained Dr Ryan, refers to how the brain works to manage cognitive processes such as attention, reasoning, and problem solving.

During this experiment, participants sat at a computer while a serial stream of letters was flashed on the screen. They were asked to press the keyboard as quickly and as accurately as possible when a target letter appeared.

The study showed that the patients with mood disorder did worse than control participants (P < .001 for both accuracy and response time). Post hoc analyses confirmed that the healthy control individuals performed better than both mood disorder groups for accuracy (MDD, P = .02; BD, P = .03) and response time (both MDD and BD, P < .001). There were no significant differences for accuracy or response time between the MDD and BD groups.

The results were the same after matching groups with regard to age and after matching patent groups with regard to depression severity.

For response times, there were significantly more patients below the 16th percentile, the ninth percentile, and the fifth percentile cutoffs relative to healthy control participants. For accuracy, there were significantly more patients below the 16th percentile, the ninth percentile, and the fifth percentile relative to healthy control individuals.

"The patients with mood disorders were slower at responding, and they were also less accurate, meaning that they weren't responding correctly to the target letter," said Dr Ryan.

In the second experiment, 52 women from the first sample (19 with MDD and 16 with BD) underwent functional MRI while carrying out the same test as in the first experiment.

Healthy control individuals had shorter response times compared with both patient groups (P < .05), similar to the first experiment. The BD group performed worse than the healthy control participants and the MDD group for accuracy and response time (for both, P < .01).

When comparing each group's performance in experiment 1 to that in experiment 2, each group showed significant slower response time. The differences in performance of some participants inside vs outside the scanner might be partly explained by anxiety or distractibility, say the authors.

Brain Imaging

Using whole brain imaging, the researchers could see which parts of the brain were activated in each group.

"We were able to see what parts of the brain lit up while they were performing the task," said Dr Ryan.

The study showed that there were no regions with greater activation in the healthy control group relative to the BD and MDD patients.

The mood disorder groups had greater activation relative to the healthy control group in the left superior temporal gyrus and the right superior parietal lobule and cerebellum.

Attention difficulties among mood disorder patients "appear to be localized in a performance-specific and disease-shared way to the right posterior parietal cortex," which is an important node in the executive network.

However, in MDD patients, this involved "hyperactivation" of this area compared with control individuals. In contrast, these areas lit up less in bipolar patients than control participants. Dr Ryan described this as "hypoactivation."

In MDD patients, this region appeared to be engaged to a greater extent when they responded correctly. "Patients were using a lot of activity, which suggests some compensation," said Dr Ryan.

Neuropsychological deficits in the prefrontal cortex and other functionally and structurally connected regions negatively affect emotional and behavioral regulation, say the authors.

The National Institutes of Health is keen to learn whether mood disorders share neurobiology and genetics, said Dr Ryan.

Dr Kelly Ryan

"I think this study kind of points us in that direction. Maybe these mood disorders are part of a continuum and are more alike than they are distinct." Although such theories were floating around before, emerging science is helping to "link some of the neurobiology together," she added.

The new information will not affect clinical practice, at least not immediately. "It's not going to change how we practice now, but I think we are getting closer to understanding some of the underlying neurobiology of mood disorders, and, hopefully, in future it will help us identify those who are at risk for developing them," said Dr Ryan.

A Bit of Embroidery

Reached for a comment, Gail Erlick Robinson MD, director, Women's Mental Health Program, University Health Network, and professor of psychiatry, University of Toronto, in Canada, said that the study "offers a bit of embroidery on our preexisting knowledge of cognitive dysfunction in mood disorders."

She added that there has been relatively less emphasis on differences between the sexes, "so that part's interesting."

However, she said that the study does not provide any major breakthroughs in our knowledge of the connection between mood disorders and neurobiological disruptions.

She concluded that it is an article "I would not call high impact."

The research was supported by a National Alliance for Research on Schizophrenia and Depression Award, a K-23 award, the University of Michigan Department of Psychiatry Research Committee, the University of Michigan fMRI laboratory, the Heinz C. Prechter Bipolar Research Fund at the University of Michigan Depression Center and the Richard Tam Foundation.

Brain. 2015;138:1424-1434. Full text

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