Adverse Childhood Experiences Linked to Higher Risk of Treatment-Resistant Depression

Each additional adverse childhood experience increased the odds of treatment-resistant depression by about 70%

Mar. 27, 2026 at 11:50am

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A new study found that exposure to adverse childhood experiences (ACEs) was associated with an increased risk for treatment-resistant depression (TRD) in adulthood. The strongest associations were with physical neglect and sexual abuse, which each conferred more than a fivefold higher risk for TRD compared to no history of ACEs.

Why it matters

This research highlights the long-term mental health impacts of childhood adversity and the importance of addressing ACEs through prevention and early intervention efforts. Understanding the link between ACEs and treatment-resistant depression can help clinicians identify high-risk patients and tailor mental health treatments accordingly.

The details

The population-based study used data from two Swedish Twin Registry cohorts, analyzing responses from over 17,800 twins born between 1959-1992. Participants reported on exposure to various ACEs before age 19, including emotional neglect or abuse, physical neglect, physical abuse, sexual abuse, rape, hate crime, and witnessing family violence. Overall, 31% of participants reported at least one ACE, and 6% had experienced three or more. The primary outcome was TRD, defined as major depressive disorder with self-reported symptoms and two or more failed antidepressant treatments.

  • The study followed participants from 2005-2006 or 2013-2014 until 2016.

The players

Ying Xiong

The lead author of the study, a researcher at Karolinska Institutet in Stockholm, Sweden.

Erin C. Dunn

The author of an accompanying editorial, a researcher at Purdue University in Indianapolis.

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What they’re saying

“Findings from this cohort study emphasize the importance of primary prevention of ACEs and suggest that routine assessment of ACE history may help clinicians identify patients who are at elevated risk for MDD treatment resistance.”

— Ying Xiong, Researcher

“Researchers and their funders should now address key issues that support translation: reliably and validly measuring childhood adversity exposure, incorporating ACE history into clinical assessment and treatment planning, understanding biological mechanisms within and across generations, developing effective postexposure interventions that mitigate risk, and maybe even preventing ACEs in the first place.”

— Erin C. Dunn, Researcher

What’s next

Researchers plan to further investigate the biological mechanisms linking ACEs to treatment-resistant depression, as well as develop interventions to prevent and mitigate the impacts of childhood adversity.

The takeaway

This study underscores the profound and lasting effects of adverse childhood experiences on mental health, highlighting the critical need for comprehensive approaches to address ACEs and support those at high risk of treatment-resistant depression.