Unraveling the genetic code of bipolar disorder

In a recent study posted to the medRxiv* preprint server, researchers investigate the genetic associations and heritability between categorical and dimensional bipolar disorder (BD) models.

Study: Strong Genetic Overlaps Between Dimensional and Categorical Models of Bipolar Disorders in a Family Sample. Image Credit: My Ocean Production / Shutterstock.com

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

What is BD?

BD is a mental health disorder characterized by cyclical variations between depressive and manic mood and behavioral states that make it difficult to function and perform daily activities. According to recent estimates, 2-4% of adults in the United States will experience BD at some stage in their lifespan. Importantly, BD is commonly misdiagnosed or unrecognized for years after symptoms initially appear. 

Subclinical BD symptoms that do not reach categorical diagnostic standards affect many of people. As a result, there is now a greater emphasis on dimensional psychopathology assessments like the mood disorder questionnaire (MDQ) that may better depict the full range of BD symptoms.

Despite the high prevalence of BD, little is known about the underlying environmental and genetic variables that cause this condition. Previous studies indicate that BD is highly heritable, with estimates varying from 60-85%. Nevertheless, there is limited information regarding the genetic and heritability relationships between categorical and dimensional BD models.

About the study

In the current study, researchers evaluate the genetic continuity between categorical and dimensional BD models. To this end, data from the Amish-Mennonite Bipolar Genetics (AMBiGen) study, which includes families with BD and associated disorders from Mennonite and Amish communities in South and North America, were utilized.

Structured psychiatric interviews were conducted, during which study participants were asked to complete the MDQ evaluating the lifetime history of cardinal manic symptoms and related impairments.

A total of 726 individuals were included in the current study, 212 of whom had a categorical diagnosis of a major mood disorder. A vital tool was created to evaluate heritability which integrated genomic data and genomic relationship matrix (GRM) using high-quality single nucleotide polymorphism (SNP) information.

Principal component analysis (PCA) was performed to assess the dimensions of the MDQ. Genetic overlaps and heritability between categorical diagnoses and MDQ-derived measures were estimated across genotyped participants.

The aim of the current study was to validate MDQ as a dimensional assessment of BD and gain insights into the environmental and genetic variables that contribute to the development of this disorder. These findings could have an immense impact on how BD and associated diseases are diagnosed, treated, and prevented.

Study findings

Significant genetic overlaps were observed between categorical and dimensional BD models among a family sample. Moreover, study participants diagnosed with BD possessed higher MDQ scores than those without a BD diagnosis, thus demonstrating the reliability of MDQ as a dimensional BD measurement criterion.

Strong genetic connections and considerable heritability were observed for most of the MDQ's components, thus reflecting that categorical and dimensional measures of BD have significant genetic overlap.

The MDQ assesses three features, including depressive symptoms, maniac symptoms, and impairment. The MDQ symptom score had 30% heritability and was distributed equally among its three main components.

Categorical diagnoses and impairment had the strongest genetic associations, thus indicating that impairment may significantly contribute to the genetic continuity between categorical and dimensional models of BD.

Conclusions

The study findings indicate a genetic continuity between categorical and dimensional models of BD across a family sample. These findings suggest that the MDQ might be a valuable tool for determining those at risk for BD and other associated disorders. 

In addition to providing valuable insights into the environmental and genetic elements influencing BD and similar illnesses, the study results may enhance the precision of preventing, treating, and diagnosing BD and associated disorders.

Furthermore, future studies on the genetic continuity between categorical and dimensional models of psychiatric illnesses may benefit from the methods and results discussed in this study. The study findings may also support the development of more efficient psychiatric disorder treatments by allowing better comprehension of the environmental and genetic components that contribute to these illnesses.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Shanet Susan Alex

Written by

Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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