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Review Paper | Physiology Science | Volume 15 Issue 7, July 2026 | Pages: 652 - 657 | India
The GDF15-GFRAL Axis in Stress Signalling: A Novel Neuroendocrine Link to Post-Traumatic Stress Disorder (PTSD)
Abstract: Post-Traumatic Stress Disorder (PTSD) is a complex neuropsychiatric condition that arises following trauma, yet its biological mechanisms remain poorly defined, complicating the identification of reliable diagnostic markers and effective treatments. Traditional models have focused on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, but these frameworks often overlook the systemic comorbidities, such as metabolic issues and chronic inflammation, that frequently accompany PTSD. This review proposes an innovative neuroendocrine model centered on the Growth Differentiation Factor 15 (GDF15) and its receptor, GFRAL, suggesting that this pathway is hyperactive in PTSD. GDF15, initially recognized as a marker of metabolic distress, is chronically elevated due to the cellular and metabolic stress induced by severe trauma. Once it enters the central nervous system, GDF15 interacts with GFRAL receptors located in specific brain regions, leading to the activation of neural circuits that contribute to persistent PTSD symptoms, including avoidance behaviors and heightened anxiety. This neuroendocrine pathway serves as a crucial link between the psychological impact of trauma and its physical manifestations. By elucidating the GDF15-GFRAL axis, the review underscores the potential of GDF15 as a biomarker for psychiatric classification and biotype identification. Targeting this pathway through pharmacological or metabolic interventions could represent a promising avenue for developing new therapeutic strategies for PTSD, grounded in a deeper understanding of its biological underpinnings.
Keywords: Post-Traumatic Stress Disorder (PTSD), Growth Differentiation Factor 15 (GDF15), GFRAL Receptor, Stress Signalling, HPA Axis, Biomarker, Cellular Distress
How to Cite?: Sudipta Banerjee, Ishita Chatterjee, "The GDF15-GFRAL Axis in Stress Signalling: A Novel Neuroendocrine Link to Post-Traumatic Stress Disorder (PTSD)", Volume 15 Issue 7, July 2026, International Journal of Science and Research (IJSR), Pages: 652-657, https://www.ijsr.net/getabstract.php?paperid=SR26708123109, DOI: https://dx.doi.org/10.21275/SR26708123109