The effect of adverse childhood experiences on chronic pain and major depression in adulthood: a systematic review and meta-analysis

Georgia Antoniou (Lead / Corresponding author), Emilie Lambourg, J. Douglas Steele, Lesley A. Colvin

Research output: Contribution to journalReview articlepeer-review

10 Citations (Scopus)
127 Downloads (Pure)


Background: Adverse childhood experiences have been linked to increased multimorbidity, with physical and mental health consequences throughout life. Chronic pain is often associated with mood disorders, such as major depressive disorder (MDD); both have been linked to adverse childhood experiences. It is unclear how the effect of adverse childhood experiences on neural processing impacts on vulnerability to chronic pain, MDD, or both, and whether there are shared mechanisms. We aimed to assess evidence for central neural changes associated with adverse childhood experiences in subjects with chronic pain, MDD, or both using systematic review and meta-analysis.

Methods: Electronic databases were systematically searched for neuroimaging studies of adverse childhood experiences, with chronic pain, MDD, or both. Two independent reviewers screened title, abstracts, and full text, and assessed quality. After extraction of neuroimaging data, activation likelihood estimate meta-analysis was performed to identify significant brain regions associated with these comorbidities.

Results: Forty-nine of 2414 studies were eligible, of which 43 investigated adverse childhood experiences and MDD and six investigated adverse childhood experiences and chronic pain. None investigated adverse childhood experiences, chronic pain, and MDD together. Functional and structural brain abnormalities were identified in the superior frontal, lingual gyrus, hippocampus, insula, putamen, superior temporal, inferior temporal gyrus, and anterior cerebellum in patients with MDD exposed to adverse childhood experiences. In addition, brain function abnormalities were identified for patients with MDD or chronic pain and exposure to adverse childhood experiences in the cingulate gyrus, inferior parietal lobule, and precuneus in task-based functional MRI studies.

Conclusions: We found that adverse childhood experiences exposure can result in different functional and structural brain alterations in adults with MDD or chronic pain compared with those without adverse childhood experiences.

Systematic review protocol: PROSPERO CRD42021233989
Original languageEnglish
Pages (from-to)729-746
Number of pages18
JournalBritish Journal of Anaesthesia
Issue number6
Early online date20 Apr 2023
Publication statusPublished - Jun 2023


  • Adverse childhood experiences
  • Chronic Pain
  • Depression
  • Early life adversity
  • Major depressive disorder
  • MRI
  • Neuroimaging
  • Neuropathic pain
  • chronic pain
  • neuroimaging
  • neuropathic pain
  • early life adversity
  • major depressive disorder
  • depression
  • adverse childhood experiences

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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