Key Neurological Differences Between Youth with Bipolar Disorder and Unipolar Depression

This week we will be discussing an article published in the Journal of Psychiatry Research: Neuroimaging in December 2020. In this article, titled “Differentiating bipolar disorder from unipolar depression in youth: A systematic literature review of neuroimaging research studies”, authors Kelberman and colleagues present their review of literature examining differences in brain functioning between youth with and without bipolar disorder. 

Why did they do it?

As the authors highlight, differentiating bipolar disorder from unipolar depression in children presents clinicians with a significant challenge. Incorrect diagnosis can lead to incorrect intervention, which poses a serious consequence to the misdiagnosed child.

While debates related to the occurrence and prevalence of bipolar disorder in children are not novel, controversy surrounding the topic increased greatly in the mid 1990’s when the DSM-IV criteria of bipolar symptoms were adapted to allow for the diagnosis of bipolar disorder in children (American Psychiatric Association [APA], 2000). Since then, debate around the clinical and ethical considerations related to the diagnosis of bipolar disorder has only continued to grow.

Obtaining objective data, from which clinicians can base a diagnosis of bipolar disorder, is a challenge. Most data are collected using rating scales and many providers do not utilize the necessary breadth of scales to fully evaluate the presence of mania. In this systematic review, the authors shine light on the ability to use brain-based data to differentiate children with bipolar disorder from those with unipolar depression and/or healthy peers.

How did they do it?

The authors searched across scientific databases for existing literature focusing on neuroimaging, bipolar, and unipolar depression in children. Inclusion and exclusion criteria are outlined in detail in the published article. Overall, nine studies were included in the review with a total of 228 participants diagnosed with bipolar disorder, 268 diagnosed with major depressive disorder, and 299 healthy controls. It is important to note that the authors reviewed findings from structural and functional neuroimaging research.

What did they find?

In total, six neuroimaging studies documented that brain structure, function, connectivity, and chemistry in the cortico-limbic-striatal neural system differentiated children with bipolar disorder and unipolar depression. Two papers showed significant differences in the anterior cingulate cortex (ACC), such that children with bipolar disorder had increased right and left ACC white matter volumes compared to those with unipolar disorders. Importantly, these results are consistent with the adult literature. 

The insula also emerged as a potentially important area of interest, as three papers included in the systematic review demonstrated between-group differences in insular activity. In addition to the ACC and insula, many other brain areas were found to differentiate bipolar disorder and unipolar depression. Many of these brain regions/structures play a significant role in neural systems that support emotion processing and regulation, cognition, and reward processing.

What does it all mean (our take)?

This work is exciting and important and we thank the authors for their review of the current literature. The challenge continues to be in the generalizability of findings. These findings were derived from relatively small sample sizes, indicating that the generalizability of the work is limited. 

So, what do we do? Well, it is critical that researchers continue to use neuroimaging techniques to evaluate the neural structure and function of children with bipolar disorder and other mental illnesses. While doing so, however, it is important to continue thinking through the translation of that work. For example: Is it possible to expect that all children with suspected bipolar disorder could undergo an MRI? Are there other neurocognitive correlates that we could evaluate in lieu of a more costly MRI? The work is complex, but necessary.

Nevertheless, we are excited about the future of this work. We’re looking forward to continuing to review great articles like the article reviewed today and watch the world of behavioral health continue to develop answers to some of its most unique and challenging questions.