Childhood maltreatment influences adult brain structurethrough its effects on immune, metabolic, and psychosocialfactors

• 成果类型: Article
• 署名作者: Orellana, Sofia C.; Bethlehem, Richard A. I.; Simpson-Kent, Ivan L.; van Harmele, Anne-Laura; Vertes, Petra E.; Bullmore, Edward T.
• 署名单位: University of Cambridge; University of Cambridge; Leiden University; Leiden University - Excl LUMC; UK Research & Innovation (UKRI); Medical Research Council UK (MRC); University of Cambridge; University of Pennsylvania; Leiden University - Excl LUMC; Leiden University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13054
• DOI: 10.1073/pnas.2304704121
• 发表日期: 2024-04-16
• 关键词: body-mass index; gray-matter volume; posttraumatic-stress-disorder; early-life adversity; peripheral inflammation; structural alterations; hippocampal volume; cortical thickness; major depression; association

摘要

Childhood maltreatment (CM) leads to a lifelong susceptibility to mental ill-healthwhich might be reflected by its effects on adult brain structure, perhaps indirectlymediated by its effects on adult metabolic, immune, and psychosocial systems. Indexingthese systemic factors via body mass index (BMI), C-reactive protein (CRP), and ratesof adult trauma (AT), respectively, we tested three hypotheses: (H1) CM has direct orindirect effects on adult trauma, BMI, and CRP; (H2) adult trauma, BMI, and CRP areall independently related to adult brain structure; and (H3) childhood maltreatmenthas indirect effects on adult brain structure mediated in parallel by BMI, CRP, andAT. Using path analysis and data fromN=116,887 participants in UK Biobank,we find that CM is related to greater BMI and AT levels, and that these two variablesmediate CM's effects on CRP [H1]. Regression analyses on the UKB MRI subsample(N=21,738) revealed that greater CRP and BMI were both independently related toa spatially convergent pattern of cortical effects (Spearman's(sic)= 0.87) characterized byfronto-occipital increases and temporo-parietal reductions in thickness. Subcortically,BMI was associated with greater volume, AT with lower volume and CPR with effectsin both directions [H2]. Finally, path models indicated that CM has indirect effectsin a subset of brain regions mediated through its direct effects on BMI and AT andindirect effects on CRP [H3]. Results provide evidence that childhood maltreatmentcan influence brain structure decades after exposure by increasing individual risk towardadult trauma, obesity, and inflammation.