Background: Stress-related disorders, including PTSD, acute stress disorders, adjustment disorder, and attachment disorders, arise from complex interactions between genetic susceptibility and environmental stressors. While early environmental factors play a central role in the development of these disorders, there is growing evidence that genetic predisposition also contributes to individual differences in vulnerability and resilience. This narrative review examines current evidence on genetic predisposition and resilience mechanisms in stress-related psychopathology during developmental age. Methods: A literature search was performed using PubMed, Cochrane, MedRxiv, and Medline databases, focusing on studies published between 2010 and 2025, written in English, in the pediatric and adolescent population. Priority was given to original research articles and high-impact reviews. Studies were selected based on relevance to the genetic mechanisms underlying vulnerability and resilience to stress. 71 of 317 were selected. Two hundred forty-six articles were excluded due to a lack of relevance to the topic or because they included an adult population. Results: Polymorphisms and epigenetic modifications in genes involved in hypothalamus–pituitary–adrenal axis (FKBP5, NR3C1, ADCYAP1R1 and ACE), serotoninergic (SLC6A4 and HTR2A), noradrenergic and dopaminergic system (COMT and MAOA), BDNF, estrogen receptor and excitatory amino acid transporters are associated with increased risk of psychopathology following early trauma, but are also implicated in the development of resilience. Conclusions: Genetic factors influence both vulnerability and resilience to stress-related disorders. However, further studies based on the role of genetics are needed to advance precision and personalized medicine, which is still largely underexplored to this day in the field of stress-induced disorders.

Genetic Predisposition and Genetic Resilience Factors in Stress-Related Disorders During the Developmental Age: A Narrative Review

Raffagnato, Alessia;Toldo, Irene
2025

Abstract

Background: Stress-related disorders, including PTSD, acute stress disorders, adjustment disorder, and attachment disorders, arise from complex interactions between genetic susceptibility and environmental stressors. While early environmental factors play a central role in the development of these disorders, there is growing evidence that genetic predisposition also contributes to individual differences in vulnerability and resilience. This narrative review examines current evidence on genetic predisposition and resilience mechanisms in stress-related psychopathology during developmental age. Methods: A literature search was performed using PubMed, Cochrane, MedRxiv, and Medline databases, focusing on studies published between 2010 and 2025, written in English, in the pediatric and adolescent population. Priority was given to original research articles and high-impact reviews. Studies were selected based on relevance to the genetic mechanisms underlying vulnerability and resilience to stress. 71 of 317 were selected. Two hundred forty-six articles were excluded due to a lack of relevance to the topic or because they included an adult population. Results: Polymorphisms and epigenetic modifications in genes involved in hypothalamus–pituitary–adrenal axis (FKBP5, NR3C1, ADCYAP1R1 and ACE), serotoninergic (SLC6A4 and HTR2A), noradrenergic and dopaminergic system (COMT and MAOA), BDNF, estrogen receptor and excitatory amino acid transporters are associated with increased risk of psychopathology following early trauma, but are also implicated in the development of resilience. Conclusions: Genetic factors influence both vulnerability and resilience to stress-related disorders. However, further studies based on the role of genetics are needed to advance precision and personalized medicine, which is still largely underexplored to this day in the field of stress-induced disorders.
2025
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3576699
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