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Adverse childhood experiences were linked to higher risk of treatment-resistant depression

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Two adult women sit on a gray couch in a bright modern office with plants; one woman in a patterned dark jacket listens while the other in a pink cardigan holds a tablet and speaks, suggesting a professional consultation or counseling session.
Research area:PsychiatryClinical PsychologyPsychiatry and Mental health

What the study found

The study found that people who reported more adverse childhood experiences (ACEs, such as abuse, neglect, or witnessing family violence before age 19) had higher odds of treatment-resistant depression (TRD), a form of major depressive disorder that does not respond after multiple antidepressant changes. The association remained in analyses comparing twins within the same family.

Why the authors say this matters

The authors conclude that the findings highlight the importance of preventing ACEs and of including ACE history in clinical assessment to identify people with major depressive disorder who may be at elevated risk for treatment resistance.

What the researchers tested

The researchers studied twin pairs from two Swedish Twin Registry cohorts, linked to national patient and prescription registers for follow-up through the end of 2016. They used a co-twin control design to examine the association between ACEs and TRD while accounting for unmeasured familial confounding, including shared genetic and family environmental factors.

What worked and what didn't

In the main analysis, each additional ACE was associated with increased odds of TRD. The association also appeared within both monozygotic and dizygotic twin analyses. Among individual ACE types, physical neglect and sexual abuse showed the largest associations with TRD.

What to keep in mind

The abstract does not describe all possible limitations beyond the study design and the attempt to account for familial confounding. The ACEs were measured with seven yes-or-no items adapted from a checklist, and TRD was defined using clinical or symptom-based major depressive disorder plus antidepressant switching criteria.

Key points

  • The study included 17,814 twins in the main analysis.
  • 31.2% reported at least 1 adverse childhood experience, and 5.6% reported 3 or more.
  • The overall prevalence of treatment-resistant depression was 1.3% (230 people).
  • Each additional ACE was associated with higher odds of TRD (OR 1.69).
  • Physical neglect and sexual abuse had the strongest associations with TRD.

Disclosure

Research title:
Adverse childhood experiences were linked to higher risk of treatment-resistant depression
Authors:
Ying Xiong, Philip Lindersten, Tong Gong, P. O. Magnusson, S. Liu, Yi Lu
Institutions:
Karolinska Institutet, Karolinska Institutet, Karolinska Institutet, Karolinska Institutet, Karolinska Institutet, Karolinska Institutet, University of Edinburgh
Publication date:
2026-03-12
DOI:
10.1001/jamanetworkopen.2026.0222
OpenAlex record:
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AI provenance: This post was generated by gpt-5.4-mini (OpenAI). The original authors did not write or review this post.