Impaired Cognitive Control in Major Depression and Bipolar Disorder

Those suffering from depression or bipolar disorder can often feel their thinking ability has gotten fuzzy, or less sharp than before their symptoms began. Now, researchers have shown in a very large study that effect is indeed real.

And the effect is rooted in brain activity differences that are visible on advanced brain scans.

Further, the results add to the mounting evidence that both these conditions exist on a spectrum of mood disorders, instead of being completely unrelated. This view could transform the way doctors and patients think about, diagnose and treat these disorders.

Researchers from the University of Michigan Medical School and Depression Center and their colleagues reported the results of tests they gave to 612 women, more than two-thirds of whom had experienced either major depression or bipolar disorder. The researchers also presented data from detailed brain scans of 52 of the women, who took tests while brain scans were conducted.

The number of patients involved is rather large for this kind of mental health study. That fact makes the findings even more meaningful.

Cognitive Control Lowered

Researchers pooled data from several U-M studies, including the Prechter Longitudinal Study of Bipolar Disorder. They focused on results from women to take gender differences out of the mix.

Seen as groups, women with depression or bipolar disorder did equally badly on the test, which required sustained concentration. The test asked them to react rapidly when certain letters flashed briefly on a screen, amid a random sequence of other letters.

Compared with the group with no mental health conditions, the groups with either diagnosis lagged noticeably on this standard test of cognitive control.

And while many individual women with depression or bipolar scored as well on the test as healthy participants, nearly all the test-takers in the bottom 5 percent of performers had one of the two mood disorders.

On the brain scans, the researchers found that the women with depression or bipolar disorder had different levels of activity than healthy women in a particular area of the brain called the right posterior parietal cortex.

In those with depression, the activity in this area was higher than in healthy individuals, while in those with bipolar disorder it was lower.

The area where the differences were seen helps control executive function activities such as working memory, problem solving and reasoning.

Shared Cognitive Dysfunction

Lead author Kelly Ryan, Ph.D., a U-M neuropsychologist said of the study:

“In all, we show a shared cognitive dysfunction in women with mood disorders, which were pronounced in the cognitive control tests and more nuanced in scans.

These findings support the idea of seeing mood disorders dimensionally, as a continuum of function to dysfunction across illnesses that are more alike than distinct.”

Ryan, who sees patients as a clinical assistant professor in the U-M Department of Psychiatry, adds:

“Traditionally in psychiatry we look at a specific diagnosis, or category. But the neurobiology is not categorical—we’re not finding huge differences between what clinicians see as categories of disease. This raises questions about traditional diagnoses.”

Ryan and her colleagues note that this view of mood disorders is growing in favor, and even the National Institute of Mental Health has put it forth as an area of research focus under the name Research Domain Criteria.

But they do not suggest that mental health clinicians should use the test or brain scans given to the study participants to spot risks for or diagnose a mood disorder.

Senior author Scott Langenecker, Ph.D., formerly at U-M and now at the University of Illinois, Chicago, adds,

“The RDoC initiative is not meant to replace this clinical diagnostic system. It is designed to extend ways of understanding neurobiology, performance, and genetics at natures’ seams, rather than at groupings of clinical symptoms based on a patient’s current memory of recent symptoms and clinician observations of signs. The RDoC initiative is a recognition that we need to rely more heavily on what these neurobiological results are telling us – mental diseases have more overlap in the basic brain and genetic signatures.”

The researchers hope that their findings will help other researchers, who could use these tests as a way to divide participants up for further study, an “intermediate phenotype” for mood disorders.

For example, researchers could focus on studying people with and without classical mood disorders by first giving them the cognitive control test, and then using the expensive brain-scanning option only on those with poor performance. This could influence strategies future clinical screening, diagnosis and treatment.

Kelly A. Ryan , Erica L. Dawson , Michelle T. Kassel , Anne L. Weldon , David F. Marshall , Kortni K. Meyers , Laura B. Gabriel , Aaron C. Vederman , Sara L. Weisenbach , Melvin G. McInnis , Jon-Kar Zubieta , Scott A. Langenecker
Shared dimensions of performance and activation dysfunction in cognitive control in females with mood disorders
Brain, May 2015 DOI: http://dx.doi.org/10.1093/brain/awv070