Childhood maltreatment influences brain structure through immune, metabolic and psychosocial factors
Poster No:
2310
Submission Type:
Abstract Submission
Authors:
Sofia Orellana1, Richard Bethlehem2, Ivan Simpson-Kent3, Anne-Laura van Harmelen4, Petra Vértes5, Edward Bullmore1
Institutions:
1University of Cambridge, Cambridge, United Kingdom, 2Autism Research Centre, Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom, 3Leiden University, Cambridge, Netherlands, 4Leiden University, Leiden, Netherlands, 5University of Cambridge, Cambridge, Cambridgeshire
First Author:
Co-Author(s):
Richard Bethlehem
Autism Research Centre, Department of Psychiatry, University of Cambridge
Cambridge, United Kingdom
Autism Research Centre, Department of Psychiatry, University of Cambridge
Cambridge, United Kingdom
Introduction:
Childhood maltreatment (CM) has long term effects on risk for mental and physical ill-health (Danese et al., 2009; Nelson et al., 2020). Protracted psychiatric susceptibility might reflect CM's effects on adult brain structure, perhaps indirectly mediated by its effects on adult metabolic (Danese & Tan, 2014), immune (Danese et al., 2007), and psychosocial systems (Edalati & Nicholls, 2019). Indexing the latter three variables via body mass index (BMI), C-reactive protein (CRP) and rates of adult trauma (AT) respectively, we tested three hypotheses: (H1) CM has direct or indirect effects on AT, BMI and CRP; (H2) adult trauma, BMI and CRP are all independently related to adult brain structure; and (H3) effects of CM on adult brain structure are mediated by its effects on adult trauma, BMI and CRP.
Methods:
We used measurements of CM, AT, BMI and CRP from N=136,625 participants in UK Biobank to test H1 by path analysis of direct and indirect causal effects of childhood maltreatment on adult variables. For a subsample of N=21,738 participants with T1-weighted MRI data, we used regression and path analysis to test the effects of adult variables (H2) and childhood maltreatment (H3) on cortical thickness of 180 areas and volume of 7 subcortical nuclei, controlling for multiple comparisons with FDR = 5%.
Results:
CM had significant direct effects on BMI and AT, and significant indirect (but not direct) effects on CRP through AT and BMI (Fig 1A). H2: Greater CRP and BMI were both related to a spatially convergent pattern of cortical effects (Spearman's R=0.87, Fig 1B & 1C) characterized by fronto-occipital increases and temporo-parietal reductions in thickness. AT had little to no cortical effects but was related to decreases across 6 subcortical structures. BMI was related to volumetric increases in all limbic structures. H3: Two nested path models considering indirect effects of CM on brain structure through its direct effects on AT, BMI and indirect effects on CRP each had good fit across two disjoint subsets of regions (Fig 1D-G).
Conclusions:
Human brain cortical structure was significantly associated with adult immune (CRP) and metabolic (BMI) status, and subcortically with metabolic (BMI) and psychosocial (AT) status, which in turn were partly predicted by prior exposure to childhood maltreatment. Long term effects of childhood adversity on adult brain structure may be mediated indirectly via increased risk of adult trauma, obesity or inflammation.
Lifespan Development:
Early life, Adolescence, Aging 2
Lifespan Development Other
Novel Imaging Acquisition Methods:
Anatomical MRI 1
Physiology, Metabolism and Neurotransmission :
Physiology, Metabolism and Neurotransmission Other
Keywords:
ADULTS
Affective Disorders
Development
Modeling
MRI
Psychiatric
Social Interactions
STRUCTURAL MRI
Other - Environment
1|2Indicates the priority used for review
Provide references using author date format
Danese, A., Pariante, C. M., Caspi, A., Taylor, A., & Poulton, R. (2007). Childhood maltreatment predicts adult inflammation in a life-course study. Proceedings of the National Academy of Sciences of the United States of America, 104(4), 1319–1324.
Danese, A., & Tan, M. (2014). Childhood maltreatment and obesity: Systematic review and meta-analysis. Molecular Psychiatry, 19(5), 544–554.
Edalati, H., & Nicholls, T. L. (2019). Childhood Maltreatment and the Risk for Criminal Justice Involvement and Victimization Among Homeless Individuals: A Systematic Review. Trauma, Violence & Abuse, 20(3), 315–330.
Nelson, C. A., Bhutta, Z. A., Harris, N. B., Danese, A., & Samara, M. (2020). Adversity in childhood is linked to mental and physical health throughout life. BMJ, 371, m3048. https://doi.org/10.1136/bmj.m3048