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. 2025 Dec;16(1):2480884.
doi: 10.1080/20008066.2025.2480884. Epub 2025 May 14.

Childhood maltreatment and mental health: causal links to depression, anxiety, non-fatal self-harm, suicide attempts, and PTSD

Zheng Zhang  1   2 , Chenggang Jiang  2 , Xinglian Wang  1 , Haitang Qiu  1 , Jiazheng Li  3 , Yating Wang  3 , Qinghua Luo  1 , Yuanzhi Ju  1
Affiliations

Childhood maltreatment and mental health: causal links to depression, anxiety, non-fatal self-harm, suicide attempts, and PTSD

Zheng Zhang et al. Eur J Psychotraumatol. 2025 Dec.

Abstract
in English, Spanish

Background: This study aims to elucidate the causal relationship between childhood maltreatment (CM) and subsequent mental health outcomes, including major depressive disorder (MDD), anxiety (ANX), post-traumatic stress disorder (PTSD), suicide attempts, and non-fatal self-harm. Utilising Mendelian Randomisation (MR) and genome-wide association studies (GWAS) data from individuals of European descent, this research applies a rigorous analytical methodology to large-scale datasets, overcoming the confounding variables inherent in previous observational studies.Methods: Genetic data were obtained from publicly available GWAS on individuals of European ancestry, focusing on Childhood Maltreatment (CM), Major Depressive Disorder (MDD), Anxiety (ANX), Post-Traumatic Stress Disorder (PTSD), Age at First Episode of Depression, Number of Depression Episodes, Non-fatal self-harm, and Suicide Attempts. Mendelian Randomisation (MR) analyses were conducted to investigate the causal impact of CM on these outcomes. Sensitivity analyses included IVW, MR Egger, WM, and MR-PRESSO. FDR corrections were applied to account for multiple testing. Results were presented as odds ratios (ORs) with confidence intervals (CIs).Results: Significant associations were identified between CM and the likelihood of developing MDD (IVW: OR = 2.28, 95% CI = 1.66-3.14, PFDR < .001), ANX (IVW: OR = 1.01, 95% CI = 1.00-1.02, PFDR =.032), and PTSD (IVW: OR = 2.29, 95% CI = 1.43-3.67, PFDR =.001). CM was also linked to increased non-fatal self-harm (IVW: OR = 1.06, 95% CI = 1.04-1.08, PFDR <.001), higher frequency of depressive episodes (IVW: β=0.31, 95% CI = 0.17-0.46, PFDR <.001), and earlier onset of depression (IVW: β=-0.17, 95% CI = -0.32 to - 0.02, PFDR =.033). No significant association was found between CM and suicide attempts (IVW: OR = 1.09, 95% CI = 0.81-1.45, PFDR =.573).Conclusion: This study provides robust evidence that CM is a significant causal factor for MDD, ANX, PTSD, and non-fatal self-harming behaviours. It is associated with a higher frequency of depressive episodes and earlier onset of depression. These findings highlight the need for early intervention and targeted prevention strategies to address the long-lasting psychological impacts of CM.

Antecedentes: Este estudio busca dilucidar la relación causal entre el maltrato infantil (MI) y las consecuencias posteriores en la salud mental, incluyendo el trastorno depresivo mayor (TDM), la ansiedad (ANS), el trastorno de estrés postraumático (TEPT), los intentos de suicidio y las autolesiones no letales. Utilizando datos de aleatorización mendeliana (AM) y estudios de asociación de todo el genoma (GWAS, por sus siglas en inglés) de personas de ascendencia europea, esta investigación aplica una rigurosa metodología analítica a conjuntos de datos a gran escala, superando las variables de confusión inherentes a estudios observacionales previos.

Métodos: Los datos genéticos se obtuvieron de GWAS públicos en individuos de ascendencia europea, centrándose en maltrato infantil (MI), trastorno depresivo mayor (TDM), ansiedad (ANS), trastorno de estrés postraumático (TEPT), edad al primer episodio de depresión, número de episodios de depresión, autolesiones no fatales e intentos de suicidio. Se realizaron análisis de aleatorización mendeliana (AM) para investigar el impacto causal del MI en estos resultados. Los análisis de sensibilidad incluyeron IVW, MR Egger, WM y MR-PRESSO. Se aplicaron correcciones FDR para considerar la multiplicidad de pruebas. Los resultados se presentaron como probabilidades (OR, por sus siglas en inglés) con intervalos de confianza (IC).

Resultados: Se identificaron asociaciones significativas entre MI y la probabilidad de desarrollar TDM (IVW: OR = 2,28, IC 95% = 1,66–3,14, PFDR < 0,001), ANS (IVW: OR = 1,01, IC 95% = 1,00–1,02, PFDR = 0,032) y TEPT (IVW: OR = 2,29, IC 95% = 1,43–3,67, PFDR = 0,001). El MI también se relacionó con un aumento de las autolesiones no fatales (IVW: OR = 1,06; IC del 95% = 1,04–1,08; PFDR <0,001), una mayor frecuencia de episodios depresivos (IVW: β = 0,31; IC del 95% = 0,17–0,46; PFDR <0,001) y un inicio más temprano de la depresión (IVW: β = −0,17; IC del 95% = −0,32 a – 0,02; PFDR = 0,033). No se encontró una asociación significativa entre el MI y los intentos de suicidio (IVW: OR = 1,09; IC del 95% = 0,81–1,45; PFDR = 0,573).

Conclusión: Este estudio proporciona evidencia sólida de que el MI es un factor causal significativo para el TDM, la ansiedad, el TEPT y las conductas de autolesión no letales. Se asocia con una mayor frecuencia de episodios depresivos y una aparición más temprana de la depresión. Estos hallazgos resaltan la necesidad de una intervención temprana y estrategias de prevención específicas para abordar los impactos psicológicos a largo plazo del MI.

Keywords: Childhood maltreatment; Maltrato infantil; Mendelian randomisation; aleatorización mendeliana; ansiedad; anxiety; major depressive disorder; post traumatic stress disorder; trastorno depresivo mayor; trastorno por estrés postraumático.

Plain language summary

Our study employs Mendelian randomisation to demonstrate that CM directly increases the risk of developing major depressive disorder, anxiety, non-fatal self-harm, suicide attempts, and post traumatic stress disorder in later life.The findings indicate that individuals who experienced CM are significantly more likely to suffer from depression, PTSD and anxiety, underscoring the long-term negative impacts of early adverse experiences.The research highlights the critical need for early prevention and intervention strategies. It reveals that CM not only elevates the likelihood of more frequent and earlier-onset depression but also underscores the necessity for specialised support for affected individuals.

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Conflict of interest statement

No potential conflict of interest was reported by the authors.

Figures

Flowchart of the two-sample Mendelian Randomisation study process, detailing data sources, SNP selection criteria, and key assumptions for analyzing causal links between childhood maltreatment and mental health outcomes.
Figure 1.
Schematic representation of the three hypotheses of the MR study. Note. Solid arrow lines indicate MR analysis processes and can only influence the outcome by exposure. Dashed arrows indicate instrumental variables independent of any confounding variables. IVW: inverse-variance weighted; LD: linkage disequilibrium; SNP: single-nucleotide polymorphism.
Forest plot showing the odds ratios and confidence intervals for the association between childhood maltreatment and various mental health outcomes, including major depressive disorder anxiety, post-traumatic stress disorder, non-fatal self-harm, and suicide attempts.
Figure 2.
Forest plot of the causal relationships between CM and MDD, ANX, PTSD, non-fatal self-harm, and suicide attempts based on three MR methods.
Forest plot showing causal relationships between childhood maltreatment and the onset age of depression and number of episodes. Three MR methods used: IVW, WM, and MR Egger regression. ORs with 95% CIs are displayed for each method.
Figure 3.
Forest plot of the causal relationships between CM and the onset age of depression and the number of episodes, based on three MR methods. Note. OR: odds ratio; CI: confidence interval; IVW: inverse variance weighting; WM: weighted median; MR Egger: MR Egger regression; nSNP: number of single-nucleotide polymorphism.
A scatter plot demonstrating the causal effects of childhood maltreatment on MDD, ANX, PTSD, non-fatal self-harm, suicide attempts, and the age and frequency of the first depressive episode. Black dots represent IVs used in MR analysis.
Figure 4.
Scatter Plot of MR on the Causal Effects of CM on MDD, ANX, PTSD, Non-fatal self-harm, Suicide Attempts, and the Age and Frequency of the First Depressive Episode. Note. The horizontal x-axes indicate the genetic instruments linked to the exposure data, while the vertical y-axes represent the genetic instruments associated with the outcome data. The IVs employed in the MR analysis are indicated by black dots. Light blue: inverse-variance weighted; green: weighted-median estimator; deep blue: MR-Egger. As the inverse-variance weighted and weighted-median estimator methods produced highly similar estimates in the analysis, these figures exhibit a visual overlap.
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