What are the implications of childhood trauma for depression and its response to therapy?

Childhood trauma is an important risk factor for major depressive disorder (MDD).1 It is significantly more common in people with MDD than in healthy controls,1 and is associated with a greater risk of early-onset, recurrence and a more chronic course of MDD.2 Childhood trauma is also associated with a poor response to standard antidepressant therapy.1

Many people with MDD have experienced childhood trauma

The many types of childhood trauma (or adverse childhood experience [ACE]) include emotional, sexual and physical interpersonal abuse; family separation, breakup or conflict; and experiences of natural disaster.1,2

Associated with a more chronic course of MDD

Among 1008 participants in the international Study to Predict Optimized Treatment for Depression (iSPOT-D), 62.5% reported at least two childhood traumatic events compared with 28.4% of 336 healthy controls (p<0.01).1


Negative effects on mental, psychosocial and physical health

An adverse effect on cognitive and brain development

Childhood trauma has a detrimental effect on cognitive development associated with lower IQ, complex visual attention, verbal memory, learning, planning, problem-solving, processing speed, language, reading and mathematics scores.3

Having had at least one ACE is significantly associated (p<0.0001) with risk-taking behaviours in adolescents (cigarette smoking, alcohol use, street drug use, at least one suicide attempt) compared with individuals with no ACE.2

More ACEs are also associated with a higher rate of serious family, job and financial problems, and a higher rate of stress, substance abuse and MDD in adult life.2,4

Adverse effects on physical health include a shorter telomere length in children at 5 and 10 years of age,5 general low-grade inflammation in adulthood with higher levels of inflammatory biomarkers,6 a higher blood pressure7 and a higher prevalence of obesity.7


A poor response to standard antidepressants

Patients with MDD experiencing childhood trauma between 4 and 7 years of age are 1.6 times less likely to respond to SSRI or SNRI1

Patients with MDD experiencing childhood trauma between 4 and 7 years of age are 1.6 times less likely to achieve response or remission at 8 weeks when treated with selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs).1 Among 722 participants in iSPOT-D:

  • the response rate was only 17.7% compared with 82.3% for patients with no history of childhood abuse1
  • the remission rate was only 15.9% compared with 84.1% for patients with no history of childhood abuse1

The more chronic course of MDD experienced by people with a history of childhood trauma is compounded by its poor response to standard antidepressant therapy.1

AU-NOTPR-0425 . August 2021

  1. Williams LM, et al. Transl Psychiatry 2016;6:799.
  2. Hillis SD, et al. Pediatrics 2004;113:320–7.
  3. De Bellis MD, et al. Child Adolesc Psychiatr Clin N Am 2014;23(2):185–222.
  4. Got Your ACE Score? https://acestoohigh.com/got-your-ace-score/ Accessed 17 August 2021.
  5. Shalev I, et al. Mol Psychiatry 2013;18:576–81.
  6. Danese A, et al. PNAS 2007;104:1319–24.
  7. McIntyre RS, et al. Int J Psychiatry Med 2012;43:165–77.
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