Ruoting Yang ^1* Bernie Daigle ^2,3 Ryan Rampersaud ⁴ Katharina Schultebraucks ⁵

• ¹ Walter Reed Army Institute of Research, Silver Spring, United States
• ² Department of Computer Science, University of Memphis, Memphis, Tennessee, United States
• ³ Deparment of Biological Sciences, University of Memphis, Memphis, Tennessee, United States
• ⁴ Department of Psychiatry and Behavioral Sciences, University of California San Francisco School of Medicine, San Francisco, CA, San Francisco, United States
• ⁵ Department of Psychiatry, New York University Grossman School of Medicine, New York, United States

One central theme in this Research Topic is the role of metabolites as intermediaries of trauma response. Gary et al. highlighted dysregulated pathways in acute stress disorder (ASD), including amino acid metabolism and lipid signaling, revealing potential metabolic biomarkers for early diagnosis and intervention (Gary, Misganaw et al. 2024). Similarly, Patel et al. examined how dietary polyunsaturated fatty acids (PUFAs) modulate neuronal resilience to traumatic brain injury (TBI) and stress, implicating diet as a critical factor in mitigating visual and neuronal deficits (Patel, Yang et al. 2024). Transcriptomic analyses showed that DHA-enriched diets activate pathways such as SNARE signaling, endocannabinoid synapse pathways, and synaptic long-term depression, while suppressing inflammatory cytokine signaling (e.g., IL-6, IL-8) and ferroptosis, underscoring the interaction between PUFA treatment, TBI, and brain signaling networks. These findings emphasize the need to consider both endogenous and environmental influences in understanding stress resilience and vulnerability.Another key focus is the gut-brain axis and its role in stress and mood disorders. Chakraborty et al. reviewed how microbial metabolites mediate the host's response to environmental stressors, suggesting a bidirectional relationship influencing neuroinflammation and behavior (Chakraborty 2024). Furthering our understanding of the gut-brain axis in the context of mental health, Pinakhina et al. investigated the intronic variant rs521851 in the MAGI2 (S-SCAM) gene significantly associated with depression symptoms in individuals with a high risk of eating disorders, highlighting its influence on gut-brain axis dysregulation (Pinakhina, Kasyanov et al.). Their results underscore the genetic underpinnings of psychiatric conditions and reinforce the interplay between genetic predisposition and environmental stressors. Such insights underscore the potential of targeting microbiome-related pathways and considering genetic factors in addressing trauma-related disorders.Beyond the gut-brain axis, researchers also employed cutting-edge tools to investigate the complexities of stress response systems. Parker et al. employed neural ordinary differential equations (NODEs) to model the hypothalamic-pituitary-adrenal (HPA) axis dynamics, offering a machine-learning-based framework to predict stress responses in depressive disorders (Parker, Nelson et al. 2024). This innovative approach highlights the growing importance of integrating computational models with biological data to enhance diagnostic accuracy and therapeutic precision.In summary, this Research Topic underscores the complexity and interconnectedness of molecular systems in trauma and stress responses. By fostering interdisciplinary collaboration and innovative methodologies, these studies pave the way for more holistic approaches to understanding and mitigating the impacts of trauma on health.