Innovation in Anxiety Management: An Integrative Review of Genetic, Physiological, and Behavioral Factors ^†

Introduction: Anxiety is a complex pathology modulated by the interaction among genetic vulnerabilities, neural physiology, inflammatory system activity, and behavioral and environmental factors such as parental stress or lifestyle. The purpose of this review is to integratively analyze how genetic, neurophysiological, and behavioral axes interrelate and influence the management of anxiety in adults, revealing more personalized and effective intervention pathways. Methodology: This study is an integrative systematic review, given its hybrid nature, based on randomized controlled trials (RCTs) and systematic reviews retrieved from PubMed and SciELO, published within the last five years. Guided by the PRISMA protocol, the study encompassed three distinct variables: (1) genetic, investigating serotonergic vulnerability in 51 healthy participants genotyped for TPH2; (2) physiological, evaluating the inflammatory pathway in an RCT with n = 142 genotyped for IL-1β; and (3) behavioral, exploring the association between paternal anxiety and emotional problems in offspring through a meta-analysis of 98 studies (n = 54,998). Results: The TPH2 genotype was associated with increased subjective anxiety. Carriers of the IL-1β A allele showed a significantly higher risk of anxiety and greater symptom reduction following psychobiotic intervention. Parental anxiety exhibited a small but significant association with emotional and behavioral problems in offspring (r = 0.16). Conclusion: Genetic variations (TPH2, IL-1β) act as vulnerability markers predicting specific responses to physiological interventions. These findings emphasize the need for personalized therapies targeting neural regulation, inflammatory modulation, and behavioral optimization. This research aims to inspire future collaborations and funding that will advance innovative, evidence-based approaches to anxiety management, strengthening the bridge between translational neuroscience and integrative clinical practice.