June 13, 2024
Brain Health

Unraveling the Complex Interplay of Molecular Dysregulations in PTSD and Depression

Researchers at McLean Hospital, a member of the Mass General Brigham health care system, in collaboration with The University of Texas at Austin and Lieber Institute for Brain Development, have shed new light on the shared and distinct molecular alterations in post-traumatic stress disorder (PTSD) and major depressive disorder (MDD) by examining various brain regions, genomic layers, cell types, and blood samples.

The team, led by first author Nikolaos P. Daskalakis, MD, Ph.D., director of the Neurogenomics and Translational Bioinformatics Laboratory at McLean Hospital, and an associate professor of psychiatry at Harvard Medical School, aimed to capture the intricate biological networks underlying stress-related disorders.

Stress-induced disorders, such as PTSD and MDD, are intricate conditions that develop over time due to the interplay between genetic susceptibility and traumatic stress exposure. Previous research has identified hormonal, immune, methylomic (epigenetic), and transcriptomic (RNA) factors in peripheral samples contributing to these disorders. However, limited access to postmortem Brain Health from diseased PTSD patients has restricted a comprehensive understanding of brain-based molecular changes.

Senior author Kerry Ressler, MD, Ph.D., chief scientific officer and director of Division of Depression and Anxiety Disorders and Neurobiology of Fear Laboratory at McLean Hospital, and a professor of psychiatry at Harvard Medical School, explained, “Our primary objectives for this study were to interpret and integrate differential gene and protein expression, epigenetic alterations, and pathway activity across our postmortem brain cohorts in PTSD, depression, and neurotypical controls.”

By combining circuit biology with advanced multi-omics tools, the researchers delved into the molecular pathology behind these disorders, potentially paving the way for novel therapeutics and biomarkers.

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