Abstract
GDF15 (growth differentiation factor 15) is a marker of cellular and mitochondrial energetic stress linked to physical-mental illness, aging, and mortality. Here, we describe the psychobiological regulation of plasma and saliva GDF15 in four human studies including 3,599 samples from 148 healthy individuals. We report two main observations establishing GDF15 as a novel tractable biomarker of psychosocial stress. 1) In two experimental laboratory studies, socio-evaluative stress rapidly elevates GDF15 and lactate, two molecular markers of energetic/reductive stress. 2) Similar to other stress-related metabolic hormones, we also find that saliva GDF15 exhibit a robust awakening response, being highest at the time of waking up and declining by ∼42-92% within 30-45 minutes. These data position GDF15 as a dynamic biomarker of psychosocial stress accessible in human blood and saliva, pointing towards a shared psychobiological pathway linking mental and mitochondrial energetic stress. These foundational observations open the door to large-scale studies using GDF15 to non-invasively probe how acute psychosocial factors promote cellular and mitochondrial and energetic stress contributing to the stress-disease cascade across the lifespan.
Significance statement This study uncovers the dynamic psychobiological regulation of plasma and saliva GDF15, establishing it as a biomarker of acute psychosocial stress. Using over 3,500 samples we demonstrate that acute socio-evaluative stress increases within minutes both GDF15 and lactate, reflecting reductive stress. High-intensity sampling over multiple weeks also confirms novel dynamics around the saliva GDF15 awakening response. These findings highlight a connection between acute psychosocial stress and mitochondrial energetic stress, offering new opportunities to investigate how stress becomes biologically embedded and contributes to health trajectories across the human lifespan.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
Updated preprint to include new analysis.
