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A new study published in the American Journal of Psychiatry looked at longitudinal changes in structural connectivity in young people at a high genetic risk for bipolar disorder.

“Bipolar disorder is characterized by severe and impairing swings of mood, varying from the chaos and impaired judgment of mania to the slowed thinking and suicidal despair of depression,” study author Philip Mitchell told us. “It is a very strongly genetic condition, with close relatives of someone with this condition having ten times the population risk of developing this.”

Bipolar disorder normally first presents between the ages of 15 and 25 years, causing a major impact on the lives of the young people affected, disrupting education, relationships and families. At present, there are no means of predicting who will develop this, apart from the increased risk in these families. 

“Treatment can only be initiated once the first manic episode occurs, with these episodes often requiring involuntary hospitalization,” Mitchell told us. “This study examined children and siblings of people with bipolar disorder who had not yet developed bipolar disorder themselves at the beginning of the study.”

Researchers followed the original participants for up to ten years, tracking their mental health symptoms, brain imaging, and genetics. The main purpose of the study is to identify changes in clinical presentation or brain imaging that predict who will go on to develop manic episodes. 

“This particular study reported on the brain scans undertaken at the baseline assessment then two years later,” Mitchell told us. “In this paper, we report on structural connectivity which allows us to quantitate the strength of pathways in the brain. We studied young people aged between 12 and 30 years – studying both a ‘high risk’ group with a parent or sibling with bipolar disorder, and a ‘control’ group of young people with no family history of any mental illness.” 

There have been only two prior studies that have reported on repeated brain scans in young people at high risk, and none that have reported on structural connectivity. In other words, this is the first report internationally on changes in structural connectivity over time in a group of young people at high risk of bipolar disorder. 

“This approach allows us to examine the trajectory of any changes in the development of brain networks/circuits involved in mood and thinking in this population,” Mitchell told us. “The young people were in their late teens/early twenties at the time of the second scan.”

Researchers hypothesized that changes in brain networks involved in mood would precede the development of manic episodes and may predict their occurrence.

“We found that there was a brain network involved in mood regulation and cognition that strengthened over the two years in young people with no family history, but weakened in those with a family history of bipolar disorder,” Mitchell told us. “This was a strongly significant difference that could not be explained by other factors such as medication use.” 

While there were only a few individuals who had developed mania over the two years, the findings were stronger in those subjects (though because of the small numbers, this was not statistically significant). 

“This world-first novel finding is important as it indicates that the brain networks involving mood and cognition are already less efficient before the illness first manifests, and is more marked in those who go on to develop mania,” Mitchell told us. “In other words, these brain networks are not functioning efficiently even before bipolar disorder first presents clinically.”

Mitchell believes the study highlights the need for early intervention for this condition to delay progress of detrimental brain changes and illness severity.