doctor looking at brain scans

Bipolar disorder is a complex mental health condition that is characterized by dramatic fluctuations in mood, attitude, and energy.

For decades, mental health experts have attempted to answer an important question. How do various environmental, biological, and neurological factors influence a person’s risk for developing this disorder?

Researchers are particularly interested in how structural and functional differences in the brain impact bipolar disorder.

In recent years, researchers have explored the connection between bipolar disorder and the brain from a different perspective. Instead of attempting to identify brain features that can cause bipolar disorder, they did the opposite. They focused on determining how bipolar disorder may lead to changes in the brain.

At least two studies offer clues.

One is a large international effort. The other is a smaller and more localized endeavor. Both found convincing evidence that certain aspects of bipolar disorder can lead to significant alterations in brain structure.

Linking Manic Episodes with Structural Brain Changes

In September 2021, the Journal Biological Psychiatry published a large study on the link between bipolar disorder and structural changes in the brain.

The study had been conducted by members of the Enhancing Neuro Imaging Genetics through Meta Analysis (ENIGMA) Bipolar Disorder Working Group, or ENIGMA-BD. As described on its website, ENIGMA is an international consortium that “brings together researchers in imaging genomics, neurology and psychiatry, to understand brain structure and function.”

The goals of the September 2021 study, according to the ENIGMA-BD team’s report were twofold. First, they sought to identify if bipolar disorder can cause progressive structural abnormalities in the brain. Second, they sough to determine if these abnormalities are related to manic episodes.

To accomplish these goals, the ENIGMA-BD team reviewed 2,464 brain MRI scans. The team collected scans from study subjects at 14 sites in nine nations:

  • The study involved a total of 1,232 subjects.
  • 307 subjects had bipolar disorder.
  • 925 subjects were in the healthy control (HC) group.
  • The mean age of the subjects was 40.

The research team reviewed two sets of MRI brain scans. They also reviewed related clinical data for each study subject. The length of time between the scans varied from subject to subject. The shortest gap between scans was six months. The longest was nine years.

Research Highlights: What They Found

  • There was a negative correlation between the number of mood episodes that subjects had during the course of the study and the rate of cortical changes they experienced. This indicated that patients who had a greater number of mood episodes experienced more rapid cortical thinning.
  • The researchers identified “significant negative correlations” between the number of manic episodes a person had and the annual rate of change in two areas of the brain: left lingual thickness and frontal pole.
  • The total number of manic, hypomanic, and mixed episodes that a person had in the period between their two MRI scans was inversely correlated with changes in the thickness of multiple frontal, prefrontal, and temporal brain areas.

“Compared with healthy control subjects, patients with [bipolar disorder] showed faster enlargement of ventricular volumes and slower thinning of the fusiform and parahippocampal cortex,” the researchers wrote. “More (hypo)manic episodes were associated with faster cortical thinning, primarily in the prefrontal cortex.”

In a November 2021 Neuroscience News article, study author Christoph Abe said that the team’s findings may account for why some people with bipolar disorder experience an intensification of symptoms over time.

“The abnormal ventricle enlargements and importantly the associations between cortical thinning and manic symptoms indicate that bipolar disorder may in fact be a neuroprogressive disorder, which could explain the worsening of bipolar symptoms in some patients,” he indicated.

‘Potential Severe Consequences of a Single Manic Episode’

The ENIGMA-BD study was not the first research effort that explored a connection among bipolar disorder, manic episodes, and structural brain changes.

In fact, a group led by the ENIGMA-BD team’s lead author, Christoph Abe, had published a similar (but much smaller) study six years earlier.

In November 2015, the journal Brain published a study that involved 31 adult subjects (16 men and 15 women). All of the subjects had bipolar I disorder. Researcher recruited subjects from a program at an outpatient treatment unit in Stockholm, Sweden.

All 31 subjects completed a baseline MRI brain scan, All subjecgts then completed a follow-up scan six years later. After comnpleting both scans, the research team divided the subjects into two groups:

  • 18 subjects who had no manic episodes between the baseline MRI scan and the follow-up
  • 13 subjects who had at least one manic episode during the six-year period between scans

As was the case with the ENIGMA-BD research effort, the November 2015 study also found that “progressive frontal cortical abnormalities were strongly related to manic episodes.”

After reaching this conclusion, the November 2015 team then removed all members of the mania group who had experienced more than one manic episode during the six-year period between brain scans. They then compared those who remained with the no-mania group, and found no differences cortical volume after excluding individuals with multiple manic episodes from the comparison.

“This indicates that a significant decrease of cortical volume in frontal regions can be attributed to one single manic episode, further emphasizing potential severe consequences of a single manic episode,” Abe wrote.

The Importance of the Prefrontal Cortex

Both the ENIGMA-BD study and the November 2015 research found that, among other effects, manic episodes can have a considerable impact on the structure of the prefrontal cortex.

To understand the significance of this, let’s take a moment to review what, exactly, the prefrontal cortex is (and what it does).

As described by Amy F.T. Arnsten, PhD, of Yale University School of Medicine’s Department of Neurobiology, the prefrontal cortex (PFC) is responsible for regulating cognitive functions such as thoughts, actions, and emotions. It does this via a complex network of connections with various other regions of the brain.

The prefrontal cortex controls executive function. This category can include the following:

  • Short-term (working) memory
  • Mental flexibility
  • Focus and attention
  • Establishing priorities
  • Resisting urges and impulses
  • Regulating one’s behavior
  • Adhering to societal norms
  • Predicting consequences

Unfortunately, although the prefrontal cortex plays such a vital role in so many essential cognitive functions, stress can easily disrupt its function.

“Even quite mild acute uncontrollable stress can cause a rapid and dramatic loss of prefrontal cognitive abilities,” Dr. Arnsten wrote, “and more prolonged stress exposure causes architectural changes in prefrontal dendrites.”

This suggests that, in addition to exacerbating symptoms of manic episodes, the ability of bipolar disorder to cause structural alterations within the prefrontal cortex may also have a profound negative impact on cognition and executive functioning.

Find Help for Bipolar Disorder in Southern California

If someone that you care about experiences severe symptoms of bipolar disorder,  there is help. Crownview Psychiatric Institute may have the solutions you seek. At our treatment center in San Diego, California, adults who have bipolar disorder and other complex mental health concerns receive comprehensive, personalized care in a dynamic community-oriented environment.

With our help, your loved one can experience improved health and achieve the best possible quality of life. To learn more, please visit our Contact Us page or call us today.