TOPLINE:

Exposure to adverse childhood experiences (ACEs) was associated with an increased risk for treatment-resistant depression (TRD) in adulthood, with each additional ACE increasing the odds by about 70%, new research showed. The strongest associations were with physical neglect and sexual abuse, with each conferring a more than fivefold higher risk for TRD compared to no history of ACEs.

METHODOLOGY:

• A population-based study used data from two Swedish Twin Registry cohorts, for more than 17,800 twins (mean age, 32 years; 57% women) born from 1959 to 1985 and from 1986 to 1992 who completed surveys in 2005-2006 or 2013-2014. All were followed until 2016.
• Exposure to ACE was assessed using questions adapted from the Life Stressor Checklist-Revised, which covered emotional neglect or abuse, physical neglect, physical abuse, sexual abuse, rape, hate crime, and witnessing family violence before the age of 19 years. Among all, 31% of participants reported experiencing at least one ACE, and 6% had at least three ACEs.
• The primary outcome was TRD, defined as major depressive disorder (MDD) diagnosed clinically or based on the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria with self-reported symptoms plus having two or more antidepressant treatment changes. Secondary analyses examined ACE subtypes , dose-response relationships, and associations between the exposure to ACE and the risk for MDD.
• Additional co-twin control analyses adjusted for shared genetic and environmental factors.

TAKEAWAY:

• The overall prevalence of TRD was 1.3%; the prevalence was 5% for those who reported at least three ACEs vs 0.7% for those with no ACEs. Each additional ACE was associated with increased odds of TRD (odds ratio [OR], 1.69), which remained significant in co-twin control analyses (OR, 2.23).
• Participants with one or two ACEs had higher odds of TRD (ORs, 2.31 and 4.25, respectively) than those with no ACEs, with the highest odds for those with at least three ACEs (OR, 6.83).
• All ACE subtypes except hate crime were linked to increased TRD odds, with physical neglect (OR, 5.73) and sexual abuse (OR, 5.01) showing the strongest associations. Only emotional neglect or abuse remained significant in co-twin control analyses, but the 95% CI range was wide (OR, 19.99; 95% CI, 2.35-170.03).
• Exposure to ACEs was more strongly associated with the risk for TRD than with the risk for overall MDD, with exposure to each additional ACE linked to ORs of 1.69 vs 1.57.

IN PRACTICE:

“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,” the investigators wrote.

The author of anaccompanying editorial noted that 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.”

SOURCE:

This study was led by Ying Xiong, PhD, Karolinska Institutet, Stockholm, Sweden. The accompanying editorial was authored by Erin C. Dunn, ScD, MPH, Purdue University, Indianapolis. Both articles were published online on March 12 in JAMA Network Open.

LIMITATIONS:

ACEs were assessed retrospectively using self-reported measures, introducing potential recall bias, misclassification, and differential reporting. Temporal relationships could not be fully established; and treatment resistance was inferred from prescription patterns without direct assessment of treatment adherence or clinical response.

DISCLOSURES:

This study was funded by the National Institute of Mental Health, the European Union’s Horizon 2020 research and innovation program, the Swedish Research Council, and the European Research Council. The investigators reported having no relevant conflicts of interest. The editorialist reported serving as the principal investigator on two grants from the National Institute of Mental Health.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.