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Area of Science:

  • Psychiatry
  • Epidemiology
  • Genetics

Background:

  • Adverse childhood experiences (ACEs) are established risk factors for major depressive disorder (MDD).
  • The specific association between ACEs and treatment-resistant depression (TRD) remains under-investigated, particularly concerning unmeasured familial confounding.

Purpose of the Study:

  • To investigate the link between ACEs and TRD.
  • To control for unmeasured confounding factors, such as shared genetic and environmental influences within families.

Main Methods:

  • Utilized a co-twin control design within two large Swedish Twin Registry cohorts (STAGE and YATSS).
  • Linked twin survey data with national patient and prescription registers for comprehensive follow-up.
  • Assessed ACEs using a validated checklist and defined TRD based on clinical diagnosis and treatment history.

Main Results:

  • Each additional ACE exposure was associated with significantly increased odds of TRD (OR, 1.69).
  • The association between ACEs and TRD persisted within monozygotic and dizygotic twin pairs, indicating robustness.
  • Physical neglect and sexual abuse emerged as ACE types with the strongest association with TRD.

Conclusions:

  • ACE exposure is independently associated with an elevated risk of developing TRD.
  • Findings underscore the importance of ACEs in understanding depression treatment resistance.
  • Clinical assessment should include screening for ACE history to identify individuals at higher risk for TRD.