Weighty matters in bipolar I

And you can take that to the bank

The session was kicked off by Professor Mark Frye of the Mayo Clinic Bipolar Biobank, who described how, since its establishment in 2009, the Biobank has aimed to be a repository where DNA can be matched to rigorous clinical phenotypes to facilitate genomic studies of disease risk and treatment response.

In this era of personalised medicine, there is an ongoing need for granular, easily-accessible data, and it’s great to see organisations like Prof Frye’s Biobank striving to create clinically useful resources that could make a real difference to patients.

Fat chance

As you can probably guess from the name of the symposium, one of the focuses of Prof Frye’s work with the Biobank was the link between obesity and bipolar. This topic was also brought up by Professor Roger McIntyre in one of the question sessions during the Lundbeck symposium ‘Identifying patients suffering from mania with depressive symptoms’.

Prof Frye presented analysis that showed that while obesity is present in bipolar patients at twice the rate of the general population, the direct links between the impulsiveness seen in bipolar patients, binge eating disorder (BED), obesity, and cardiovascular disease may not be as simple as first thought.

It seems that while obesity and cardiovascular disease are associated with a greater medical burden in patients with bipolar disorder, obesity does not increase the psychiatric burden in these patients. However, there was a greater psychiatric burden seen in bipolar patients suffering from BED (about two thirds of whom are also obese).

Medicine man

With the discussion focused on unravelling the impact of obesity and other factors, one of the attendees questioned whether there was any evidence that exposure to medications increased the cardiovascular risk. Dr Frye pointed to data from Scandiavian studies from the premedication era that showed that patients with bipolar were still dying from cardiovascular disorders.

Gordian knot

As with much in life, the more we find out, the more there is to find out. While the data that Prof Frye presented may seem to only lead to more questions, the more data that can be analysed by institutes such as the Mayo Clinic Bipolar Biobank, the more we can untangle these complex interactions between the various factors impacting bipolar patients, and the better we can improve these patients’ outcomes.

Gene genie

Prof Frye’s presentation was followed by an in-depth but enthralling analysis by Professor Alfredo B. Cuellar Barboza of the role of the TCF/7L2 gene in obesity in bipolar I patients.

Prof Barboza started with an overview of the genetics of bipolar – a highly heritable (60-85%), highly heterogeneous disease with many potential confounding genes.

He then pointed to the phenomological similarities between bipolar and obesity, with FTO (the gene most commonly associated with obesity) also being associated with impulsivity.

People power

Using a large scale genetic study in 388 bipolar patients and 1020 controls, Prof Barboza’s team identified TCF/7L2 gene variants as being responsible for increasing BMI modifying the risk of bipolar disorder. This may be because TCF/7L2 is involved in neurodevelopment, neurogenesis, neuroplasticity, and mood-stabilisation affects.

TCF/7L2 influences these processes through the WnT pathway, which is linked to brain patterning (as well as type 2 diabetes and some cancer types), and protective variants of the TCF/7L2 gene appear to lose their effects as BMI increases. Obesity has also been noted to block WnT’s activity in rodents.

TCF/7L2 may therefore be one of the facilitators for the influence of obesity on the brain of bipolar I patients.

Every journey starts with the smallest step

Scientific progress, particularly on the genetic level, is painstaking. So understanding an incredibly complex and diverse disease such as bipolar, and how it links with obesity, was never going to be a simple task.

But it’s heartening to see how leveraging the large-scale data sets of projects like Prof Mark Frye’s Mayo Clinic Bipolar Biobank can help to uncover fine-grain details, such as the role of TCF/7L2, bringing us ever closer to a true understanding of bipolar I disorder.

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