Effectiveness of Interventions for Interpersonal Functioning Among Adolescents With Posttraumatic Stress Symptoms: A Meta-Analysis.

Post-traumatic stress disorder (PTSD) is a chronic and often debilitating psychiatric condition that can arise after exposure to traumatic events. About 6.1% of U.S. adults are estimated to experience PTSD at some point in their lives, highlighting its significance as a public health concern. PTSD affects more than mental health: individuals with the disorder also face higher risks of cardiovascular disease, metabolic problems, neurodegeneration, and premature death. These observations suggest that trauma leaves lasting marks on the body, though we still do not fully understand the molecular processes that link psychological stress to long-term physical illness. Current treatments, including psychotherapy and medications, are only partially effective, as seen in populations like World Trade Center (WTC) responders, where high rates of PTSD persist nearly two decades after 9/11. Thus, it is critical to delineate the molecular processes underlying PTSD to develop therapies that can prevent physical morbidity in people with PTSD. For many years, biological studies of PTSD have focused on stress-responsive systems, especially hypothalamic-pituitary-adrenal axis signaling and immune activity. While these pathways explain immediate stress reactions, they do not capture the long-lasting, multisystem effects or aging-related consequences of PTSD. In animal studies, chronic stress is shown to affect processes shared across the brain, blood vessels, immune system, and other tissues including redox balance, mitochondrial function, and metabolism. Disruptions in these processes appear to contribute to aging-related disease and may link trauma exposure to downstream tissue dysfunction. Yet few human studies have examined whether stress produces coordinated molecular changes across multiple organ systems in PTSD. High-dimensional molecular profiling offers a promising way to fill these gaps. Plasma proteomics allows for the direct measurement of proteins that control nearly all physiological processes, from intracellular to intercellular signaling. Metabolomic profiling, which examines small molecules reflecting upstream gene and protein activity, provides a complementary view of biochemical states across the body. By integrating proteomic and metabolomic data, we can uncover coordinated molecular networks that might be missed when each type of data is analyzed separately. This approach gives a more comprehensive, systems-level understanding of the biological changes associated with trauma.