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<p>Identity dissociation is challenging to detect and treat, and its etiology remains incompletely understood. Childhood maltreatment and FKBP5 polymorphisms, which modulate the stress response, may contribute by disrupting the integration of autobiographical experiences essential for identity development. We examined whether gene-environment interactions involving childhood maltreatment and <i>FKBP5</i> polymorphisms predict clinically significant identity dissociation. In a cohort of <i>N</i> = 377 participants, we assessed childhood maltreatment and identity dissociation using validated questionnaires and genotyped CATT haplotypes within <i>FKBP5</i> linked to stress reactivity. Identity dissociation was dichotomized using an established clinical threshold. An elastic net regularized logistic regression model incorporating maltreatment subtypes, CATT haplotype count, and their interactions was trained (<i>N</i> = 194) and validated (<i>N</i> = 183). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and Matthews correlation coefficient. Decision curve analysis assessed clinical utility across varying risk thresholds. The model demonstrated fair discrimination (AUC = 0.709) with 58.6% sensitivity and 79.9% specificity. While the positive predictive value was modest (35.0%) due to the low prevalence of identity dissociation (15.9%), decision curve analysis revealed a net clinical benefit across a broad range of threshold probabilities (6–76%), indicating practical utility for risk stratification in clinical settings. The negative predictive value was 0.91. These findings provide initial evidence that gene-environment interactions between childhood maltreatment and <i>FKBP5</i> variation may contribute to the risk of identity dissociation. While predictive precision remains limited, this study demonstrates the feasibility of applying machine learning approaches to dissociation and highlights the need for further research into their traumatic and biological underpinnings to improve detection, prevention, and treatment.</p>

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Predicting identity dissociation using childhood maltreatment and genetic variation in the stress-response gene FKBP5: a machine learning analysis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月6日

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  • Leonhard Kratzer,
  • Hans Knoblauch,
  • Abigail Powers,
  • Seyma Katrinli,
  • Vasiliki Michopoulos,
  • Negar Fani,
  • Charles F. Gillespie,
  • Tanja Jovanovic,
  • Kerry J. Ressler,
  • Alicia K. Smith,
  • Bertram Müller-Myhsok,
  • Stefan Tschöke

摘要

Identity dissociation is challenging to detect and treat, and its etiology remains incompletely understood. Childhood maltreatment and FKBP5 polymorphisms, which modulate the stress response, may contribute by disrupting the integration of autobiographical experiences essential for identity development. We examined whether gene-environment interactions involving childhood maltreatment and FKBP5 polymorphisms predict clinically significant identity dissociation. In a cohort of N = 377 participants, we assessed childhood maltreatment and identity dissociation using validated questionnaires and genotyped CATT haplotypes within FKBP5 linked to stress reactivity. Identity dissociation was dichotomized using an established clinical threshold. An elastic net regularized logistic regression model incorporating maltreatment subtypes, CATT haplotype count, and their interactions was trained (N = 194) and validated (N = 183). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and Matthews correlation coefficient. Decision curve analysis assessed clinical utility across varying risk thresholds. The model demonstrated fair discrimination (AUC = 0.709) with 58.6% sensitivity and 79.9% specificity. While the positive predictive value was modest (35.0%) due to the low prevalence of identity dissociation (15.9%), decision curve analysis revealed a net clinical benefit across a broad range of threshold probabilities (6–76%), indicating practical utility for risk stratification in clinical settings. The negative predictive value was 0.91. These findings provide initial evidence that gene-environment interactions between childhood maltreatment and FKBP5 variation may contribute to the risk of identity dissociation. While predictive precision remains limited, this study demonstrates the feasibility of applying machine learning approaches to dissociation and highlights the need for further research into their traumatic and biological underpinnings to improve detection, prevention, and treatment.