Abstract

BackgroundAutoimmune diseases represent a large and heterogeneous group of disorders that afflict specific target organs. However, multiple factors point to common links between the differing presentations of autoimmune disorders.With increased interest in further understanding the neuro-immune axis, autoimmune diseases represent an important opportunity to explore whether systemic inflammation from these autoimmune pathways has a central effect and, if so, whether there is a common or discrete central effect caused by different autoimmune diseases.ObjectivesThe present study aimed to analyse hippocampal volume in patients with rheumatoid arthritis (RA) and ulcerative colitis (UC) as compared to healthy control groups. The hippocampus was chosen as a region of interest given the regulatory role it exhibits in the hypothalamic–pituitary–adrenal (HPA) axis2. Additionally, the hippocampus has been identified as a region that is affected in other autoimmune diseases such as systemic lupus erythematosus (SLE).MethodsData from 1,040 individuals in the UKBiobank Imaging sub-study were included in the present study. This was divided into two separate patient populations with separate control groups. Data from 267 individuals (mean age ± SD =65.52 ± 7.02, 70.8% females) were included in the RA patient group with 267 age and sex matched controls (mean age ± SD = 65.51 ± 7, 70.8% females). Data from 253 individuals (mean age ± SD = 64.09 ± 7.03, 51.6% females) were included in the UC patient group with 253 age and sex matched controls (mean age ± SD = 63.4 ± 7.02, 51.6% females).The UKBiobank is a prospective observational study with a proposed cohort of 500,000 participants. The imaging substudy is planned to scan 100,000 of those participants with a standardised scanning protocol including MRI of the brain. Multi-modal images were acquired on a 3T scanner3. From the T1w data, volumetric imaging derived phenotypes (IDPs) are provided using the FMRIB Integrated Registration and Segmentation Tool (FIRST); http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/FIRST. This study utilised the right and left hippocampal volume outputs from that tool.ResultsWe observed a smaller hippocampal volume in UC patients when compared to healthy controls (difference right: 99.78 mm3, SD ± 38.97, p = 0.01; left: 74.30 mm3, SD ± 39.41, p = 0.06). The Cohen’s effect size was d = -0.24 [95% CI -0.43, -0.05] for right hippocampal volume and d = -0.18 [95% CI -0.36, 0.00] for left hippocampal volume.Figure 1.Right and left hippocampal volume in UC patients versus controls and right and left hippocampal volume in RA patients versus controls.There was no significant difference seen in hippocampal volume in RA patients compared to controls (difference right: 61.32 mm3, SD ± 40.33, p = 0.13; left: 39.00 mm3, SD ± 38.19, p = 0.31). The Cohen’s effect size was d = -0.12 [95% CI -0.30, 0.06] for right hippocampal volume and d = -0.08 [95% CI -0.27, 0.10] for left hippocampal volume.ConclusionThis study provides evidence of moderate reduction in hippocampal volumes in patients with ulcerative colitis as compared to age and sex matched healthy controls. This same effect was not seen in a similarly matched rheumatoid arthritis patient population. Further analysis of additional subcortical regions could provide further context for whether there are alternative regions affected in both RA and UC.

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