Study elucidates complex differences in the brains of people with PTSD and depression

Stress-related disorders such as post-traumatic stress disorder and clinical depression are complex conditions influenced by both genetics and the environment. Despite much research, the molecular mechanisms behind these disorders remain elusive. However, researchers at the University of Texas at Austin, Dell Medical School, have broken new ground with a study uncovering complex differences in the brains of patients with PTSD and depression and neurologically normal controls. The study, published this week, Sciencemay provide potential avenues for new therapeutic approaches and biomarkers.

“Understanding why some people develop PTSD and depression and others do not is a major challenge,” said study researcher Charles B. Nemeroff, M.D., Ph.D., of the American Psychiatric Association. Psychiatry The study was conducted by co-investigators Kelly Lessler, MD, chief scientific officer at McLean Hospital and professor of psychiatry at Harvard Medical School, of Dell Medical's Department of Psychiatry and Behavioral Sciences, and Joel Kleinman, MD, associate director of clinical sciences at the Lieber Institute for Brain Development.

“We found that the brains of people with these disorders have clear molecular differences, particularly in the prefrontal cortex. These changes appear to affect the immune system, neuronal function, and even the function of stress hormones.”

Charles B. Nemeroff, M.D., Chief, Department of Psychiatry and Behavioral Sciences, Dell Med

The 231-person study used a cutting-edge technique called multi-omic analysis to investigate molecular changes across multiple brain regions, which integrates different layers of data, including gene structure and protein expression, to provide a complete picture of the molecular changes associated with PTSD and depression.

Key findings from the survey include:

• Identifying specific genes and pathways associated with PTSD and depression, highlighting the role of immune mechanisms, neuroregulation, and stress hormone signaling
• Discovery of gender-specific differences in molecular signatures, particularly in clinical depression
• Correlation between childhood trauma, suicide, and molecular mutations in both disorders
• Identifying shared and unique molecular patterns in PTSD and depression may aid in the creation of new treatments and the development of blood-based biomarkers.

Additionally, the study explored the intersection of brain multiomics and blood proteins, opening up the possibility of using blood-based biomarkers to distinguish risk and disease processes. This could provide insight into the neurobiological changes underlying the development of PTSD and severe depression, allowing researchers to tailor new, effective treatments specifically for these disorders, Nemerov said.

The researchers' main goal in this study was to understand how different genes and proteins affect patients, and how epigenetic changes and different brain pathways relate to PTSD and depression in the participants.

“We've essentially combined circuit biology with powerful multi-omics tools to delve into the molecular pathology behind these disorders,” said Ressler, who is also director of McLean Hospital's Division of Depression and Anxiety Disorders and the Neurobiology of Fear Laboratory.

The researchers' findings offer hope for improved understanding and treatment of PTSD and depression and highlight the importance of multi-omic analyses in unraveling the complexities of psychiatric disorders.

“Learning more about the molecular basis of these disorders, such as PTSD and clinical depression in the brain, paves the way for discoveries that will lead to more effective treatment and diagnostic tools,” Kleinman said. “This research is made possible thanks to brain tissue donations to the Lieber Institute Brain Repository from families who have lost loved ones to these disorders. We hope that our research will one day bring comfort to people suffering from these disorders and their loved ones.”

The study was funded by a five-year grant from the National Institute of Mental Health.