By Deeksha Kemthur / May 16, 2024
Researchers from McLean Hospital and collaborating institutions have discovered distinct and shared molecular aspects, especially in relation to brain regions, genomic layers, blood, and cell types in individuals who have PTSD or Depression.
The complexity of these diseases makes these new molecular findings so important; lead author Nikolaos P. Daskalakis, MD, PhD., states, “PTSD is a complex pathological condition. We had to extract information across multiple brain regions and molecular processes to capture the biological networks at play” (McLean Hospital, 2024). The complex interactions of numerous factors lead to the formation of these diseases. Although researchers have information on hormonal, immune, and transcriptomic influences, the information on brain-based molecular factors is flimsy due to limited resources for postmortem tissue.
Researchers targeted this using specific techniques to understand and integrate the epigenetic alterations and pathway activity in neurotypical and depression controls; Kerry Ressler, MD, PhD, states how they “essentially combined circuit biology with powerful multi-omics tools to delve into the molecular pathology behind these disorders” (McLean Hospital, 2024). The team analyzed data from 231 control subjects who had PTSD, MDD, or were neurotypical and 114 individuals to conclude differences in brain regions such as the medial prefrontal cortex (mPFC). The single-nucleus RNA sequencing of 118 PFC samples led to information on cell-type-specific patterns and blood-based proteins, ultimately isolating key biomarkers associated with these stress-related disorders. Genome-wide association studies (GWAS) were compared to the critical brain-based process genes involved in these diseases to identify specific risks.
Results show how individuals with PTSD and MDD shared altered gene expression and exons in the mPFC while they differed in the localization of these epigenetic changes. They were able to find how childhood trauma and biological sex, with a stronger association of males to disease signals, were significant influences of molecular differences.
The researchers assert their limitations in data with overall bias, with population selection, clinical assessment, comorbidities, and also how they did not fully delve into subtypes and how there will need to be more studies to understand signals across brain regions or “omics.” However, the data they have found lays the groundwork for a deeper understanding of the complex interplay of environment and genetics. These findings can be used to develop new treatments and bring aid to those suffering from PTSD or MDD.
Citations:
Hospital, M. (2024, June 11). Unveiling the molecular mechanisms behind PTSD and depression: Latest findings. SciTechDaily. https://scitechdaily.com/unveiling-the-molecular-mechanisms-behind-ptsd-and-depression-latest-findings/
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