Dr. Vladimir I. Vladimirov | Uncovering the Genetic and Molecular Underpinnings of Psychiatric Disorders

While genetic research for psychiatric disorders can be based on the analysis of blood or skin, studying molecular processes in the brain requires samples of real human brain tissue. Except for special cases, such samples cannot be readily obtained from living people.

Instead, Dr. Vladimir Vladimirov at the University of Arizona has been exploring the potential of analyzing postmortem brain tissue. His research aims to reveal the molecular processes underpinning different psychiatric conditions towards the development of preventative strategies and effective treatments.

While obtaining brain tissue from deceased psychiatric patients is difficult, due to logistical, ethical, and cultural hurdles, numerous samples have been collected, preserved, and maintained by several research centers around the world.

In a recent paper, Dr. Vladimirov and his colleagues explored past research that analyzed postmortem brain tissue from patients with various psychiatric conditions, including bipolar disorder, major depressive disorder, and schizophrenia. These analyses were able to pinpoint genetic expression patterns that are common to each of these disorders.

However, Dr. Vladimirov’s team found that these studies were mostly based on tissues from White patients of European descent. This lack of ethnic diversity in postmortem samples limits the ability of researchers to carry out generalizable studies that represent humanity as a whole.

The team has thus established close collaborations with several research institutions, such as the Lieber Institute for Brain Development and others across the world, to create new databases that include brain samples from numerous different populations.

In another recent study, Dr. Vladimirov wished to identify the molecular processes underpinning a common and devastating condition – namely alcohol use disorder. He and his collaborators honed in on a specific brain region, named nucleus accumbens, which plays a key role in alcohol addiction and other reward-seeking behaviors.

By studying samples from patients diagnosed with the disorder, the researchers analyzed gene expression and RNA activity in this brain region. They compared these samples to those from individuals without alcohol addiction.

RNA is a molecule found in all living things that resembles DNA but consists of a single strand instead of two. This substance is responsible for translating genetic information into molecular processes in the body. By analyzing different sub-types of RNA, Dr. Vladimirov’s team identified unique molecular mechanisms in the nucleus accumbens region of patients with alcohol use disorder, which were not typically found in those of people without the disorder.

Most notably, the researchers found that a sub-type of RNA, known as circular RNA or CircRNA, played a key role in controlling the expression of relevant genes in the nucleus accumbens with alcohol use disorder. Delving deeper, the researchers found that the molecular mechanism by which CircRNA controls gene expression in this brain region is by interacting with another sub-type of RNA called miRNA within the nucleus accumbens.

The recent work by Vladimirov and his colleagues highlights the huge potential of postmortem brain research as a way to learn more about the genetic and molecular underpinnings of psychiatric disorders. Their findings pave the way for further exciting discoveries that could inform the development of targeted prevention and treatment strategies.