Comparison of volumetric brain analysis in subjects with rheumatoid arthritis and ulcerative colitis

Objectives Rheumatoid arthritis (RA) and ulcerative colitis (UC) are two autoimmune diseases where patients report high levels of fatigue, pain, and depression. The effect of systemic inflammation from these diseases is likely affecting the brain, however, it is unknown whether there are measurable neuroanatomical changes and whether these are a contributing factor to these central symptoms. Methods We included 258 RA patients with 774 age and sex matched controls and 249 UC patients with 747 age and sex matched controls in a case control study utilising the UK Biobank dataset. We used imaging derived phenotypes (IDPs) to determine whether there were differences in (1) hippocampal volume and (2) additional subcortical brain volumes between patients compared to controls and if there were common regions affected between these two diseases. Results Patients with UC had moderately smaller hippocampi compared to age and sex matched controls (difference: 134.15 mm3, SD ± 64.76, p = 0.035). This result was not seen in RA patients. RA patients had a significantly smaller amygdala volume than age and sex matched controls (difference: 91.27 mm3, SD ± 30.85, p = 0.0021, adjusted p value = 0.012). This result was not seen in UC patients. All other subcortical structures analysed were comparable between the patients and control groups. Conclusion These results indicate there are subcortical brain differences between UC, RA and controls but different regions of the limbic system are preferentially affected by UC and RA. This study may provide evidence for different neurodegenerative mechanisms in distinct autoimmune diseases. Key Messages ### Competing Interest Statement Jennifer Cox is an industry funded PhD student funded by GSK. Dr. de Groot is an employee of, and holds shares in GSK. GSK had no role in the design or conduct of the study. Dr. Kempton was funded by an MRC Career Development Fellowship (grant MR/J008915/1). Dr. Williams has received research funding from Bionomics, Eli Lilly, the Engineering and Physical Sciences Research Council, GlaxoSmithKline, Johnson and Johnson, Lundbeck, the National Institute of Health Research, Pfizer, Takeda, and Wellcome Trust. The authors acknowledge financial support from the Wellcome Trust and the Engineering and Physical Sciences Research Council for the Kings Medical Engineering Centre and the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and Kings College London. The views expressed here are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. The other authors report no financial relationships with commercial interests. ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The UK Biobank gave approval for this work under application number 40933. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present work are contained in the manuscript