Negative early life events, often referred to as Adverse Childhood Experiences (ACEs), are common and have been associated with increased multimorbidity and long-term psychological and physical consequences, such as psychiatric disorders and chronic diseases. Moreover, there is likely a bidirectional relationship between chronic pain and depression, both of which have been linked to ACEs. However, a detailed understanding of mechanisms and moderators remains unclear. The overall objective was to study the effect of ACEs on brain neurobiology, particularly identifying structural and functional differences in individuals with and without chronic pain and/or depression. The study synthesises knowledge on the neural correlates of ACEs with comorbid chronic pain and/or depression during adulthood. This was achieved through a systematic review and meta-analysis of existing literature. Notably, a gap was identified, with only six studies examining chronic pain and ACEs and none investigating the comorbidity of chronic pain, depression, and ACEs, while the meta-analysis revealed structural and functional brain abnormalities. For the primary investigation, neural changes linked to ACEs in individuals with chronic pain and/ or depression were explored using tasks such as the probabilistic reward learning task, implicit emotional processing of fearful and neutral faces task, and structural T1 images. Focusing on the blunted activation of the reward circuitry—a replicated finding in depression— the study sought to determine if self-reported chronic pain and various ACEs exhibit similar neural correlates. Results indicated that reduced reward activation in the striatum is associated with chronic pain severity, as well as with experiences of sexual abuse and depression severity. The study also explored the insulo-thalamo-cingulate network, selected for its crucial role in pain processing and intricate connections with emotion-regulating regions, by performing a Dynamic Causal Modelling analysis. Of particular interest were emotional neglect and abuse ACEs sub-scores, aligning with the negative emotionally valanced nature of the implicit facial emotional recognition task. The results showed that participants with chronic pain and participants with chronic pain and who experienced emotional abuse and neglect in childhood exhibited alterations in effective connectivity within the insulo-thalamo-cingulate network. Additionally, the work examined grey matter alterations in chronic pain and ACEs, both separately and comorbidly, by conducting a voxel-based morphometry and a region of interest analysis. The results indicated that chronic pain and ACEs independently affect the nucleus accumbens grey matter. Importantly, their combined effect was more than merely additive, suggesting complex interactions or influences that lead to a more pronounced decrease in grey matter volume. Presentation of this essential set of information linking the reward-related, pain-related and emotional regulation-related regions with chronic pain and ACEs provides a crucial foundation for comprehending their mutual impact. This vital insight underscores the intricate relationships between these factors. Nonetheless, a more in-depth exploration is necessary to fully understand the mechanisms underlying this relationship and further investigate the effect of the comorbidity of chronic pain, depression, and ACEs.
Georgia Antoniou (Wed,) studied this question.