Chabert, Jonathan, Laidi, Charles, Caseras, Xavier  ORCID: https://orcid.org/0000-0002-8490-6891, Harrison, Neil ORCID: https://orcid.org/0000-0002-9584-3769 and Leboyer, Marion
2026.
Complement component C4 and neuroimaging in psychiatry: A systematic review.
Brain, Behavior, and Immunity
137
, 106873.
10.1016/j.bbi.2026.106873
|
Preview |
PDF
- Published Version
Available under License Creative Commons Attribution. Download (2MB) | Preview |
Abstract
Introduction Genomic, transcriptomic, and proteomic studies suggest that the complement system contributes to the pathophysiology of various psychiatric disorders partly through neurodevelopmental effects linked to C4A protein levels variations. We conducted a systematic review to characterize how brain micro- and macrostructure and connectivity vary with proxies of in vivo brain C4A protein levels in both psychiatric and general-population cohorts. Methods We used Medline, Web of Science, and Embase, and included all studies published before April 14, 2025. Inclusion criteria were: (1) inclusion of healthy controls and/or individuals with psychiatric disorders assessed according to recognized diagnostic manuals (DSM or ICD); (2) use of MRI-based neuroimaging; and (3) use of genomic, transcriptomic and/or proteomic approaches as proxies of in vivo brain C4A proteins levels. Results From 317 identified articles, 11 were included. Associations between C4A levels and brain structure were heterogeneous across regions. Only the mOFC, dlPFC, and entorhinal cortex were implicated in more than one study. Findings for the mOFC and dlPFC varied by the type of metrics and clinical status, whereas higher C4A levels were more consistently associated with smaller entorhinal cortex surface area and cortical thickness in pediatric, middle-aged, and older general-population cohorts. In addition, one study found higher genetically predicted C4A expression to be associated with higher TSPO levels. Conclusion The limited number of available studies and their methodological heterogeneity make synthesis challenging. However, biological hypotheses such as excessive synaptic pruning or broader inflammatory effects on the brain may provide plausible explanatory frameworks for the reported associations.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Research Institutes & Centres > Cardiff University Brain Research Imaging Centre (CUBRIC) Schools > Medicine |
| Publisher: | Elsevier |
| ISSN: | 0889-1591 |
| Date of First Compliant Deposit: | 9 July 2026 |
| Date of Acceptance: | 13 June 2026 |
| Last Modified: | 09 Jul 2026 15:39 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/188038 |
Actions (repository staff only)
 |
Edit Item |
Dimensions
Dimensions