Objective:

To investigate molecular changes associated with chronic posttraumatic stress disorder (PTSD) and their potential link to accelerated biological aging.

Approach:

• Study Population: Analyzed plasma samples from 393 World Trade Center responders, including 232 PTSD patients and 161 trauma-exposed controls.
• Methodology: Utilized the SomaScan platform to measure 9,404 protein analytes and performed targeted metabolomic profiling of 145 metabolites.
• Primary Outcome: Identified differential protein and metabolite expression associated with PTSD.
• Secondary Analyses: Evaluated integrated proteomic-metabolomic networks, enriched biological pathways, and organ-specific proteomic aging.

Key Findings:

• 121 significantly altered protein analytes corresponding to 114 unique proteins and seven differentially expressed metabolites were identified.
• Alterations in proteins NCAN, BCAN, NCAM1, and GDF15 were prominent.
• Increased metabolites included lactate, glutamic acid, cystathionine, hydroxylysine, proline, and sphingomyelin, while serotonin levels decreased.
• Molecular signatures were associated with alterations in energy metabolism, amino acid metabolism, oxidative stress, and neuronal signaling.
• Accelerated biological aging was observed among PTSD patients, particularly in the pancreas and lungs.

Interpretation:

Chronic PTSD may be linked to coordinated redox-metabolic alterations and accelerated biological aging across multiple organ systems.

Limitations:

• Cross-sectional design limits conclusions about causality or temporal relationships.
• Study population was exclusively World Trade Center responders, limiting generalizability.
• Plasma-based biomarkers may not fully reflect biological processes in specific organs or the brain.
• Residual confounding could not be excluded.

Conclusion:

Longitudinal studies are needed to determine if these molecular signatures predict disease progression, treatment response, or long-term health outcomes.

Sources:

• Nature Communications