The relationship between systemic lupus erythematosus and psychiatric morbidity

Abstract

SLE is associated with neuropsychiatric (NP) symptoms. The roles of various genotypes and autoantibodies (Abs) in NPSLE remain unknown. Before overt central nervous system (CNS) involvement, it is important to study the psychiatric morbidity, cognitive functions, structural and functional changes in the brain in SLE patients.

Two meta-analyses were performed to understand the aetiology and pathogenesis of NPSLE. The first meta-analysis identified that genetic polymorphisms in the pathways of immune complex clearance, such as the IgG Fc (Fcγ) receptor IIIa, Fcγ RIIIb and Integrin alpha M (ITGAM) genotypes were found to be susceptibility genes for NPSLE. The second meta-analysis found that NPSLE patients are more likely to have elevated serum levels of anti-cardiolipin (AcL), lupus anticoagulants (LA), anti-phospholipid (APL), anti-ribosomal P Abs and anti-neuronal Abs compared with SLE patients without NP manifestations.

Clinical studies were performed on SLE patients without overt CNS involvement. A cross-sectional study comparing depression, anxiety and health status in patients suffering from SLE, rheumatoid arthritis (RA) and gout found that SLE patients were more likely to be anxious compared to RA and gout patients. Impaired mental health and a low satisfaction with life were significantly associated with anxiety in SLE patients. The relationship between illness perception, rumination and negative emotions/fatigue in patients with RA and SLE were examined. SLE patients reported higher levels of perceived chronicity of illness, rumination and anxiety compared to RA patients. Identity, causes and consequences of illness, were associated with a greater severity of negative emotions and fatigue in patients suffering from RA and SLE and mediated by ruminations. When comparing the cognitive function in SLE patients and healthy controls, SLE patients with high levels of anxiety/depression demonstrated significantly lower processing speeds and visuospatial constructional abilities compared to SLE patients with low levels of anxiety/depression and healthy controls. When performing a set-shifting task during functional magnetic resonance imaging (fMRI), SLE patients demonstrated increased shift-related activations in the frontal and parietal areas. The shift-related deactivations in the anterior cingulate gyrus in SLE patients suggest impaired attentional network for conflict and error detection. The shift-related deactivations in the hippocampus infer that there are early damages in the hippocampus in SLE. As compared to healthy controls, structural MRI analysis revealed significant reductions in the grey matter volumes (GMV) at baseline and 16-month follow-up in the left inferior temporal gyrus, the right middle frontal gyrus, orbital part, the right superior frontal gyrus, the right rolandic operculum, the bilateral inferior frontal gyrus, orbital part and the bilateral middle cingulate cortex, as well as in the white matter volumes (WMV) at baseline and 16-month follow-up in the bilateral superior longitudinal fasciculus, the bilateral corticospinal tract, the bilateral cingulum cingulated gyrus, the bilateral inferior fronto-occipital fasciculus and the bilateral anterior thalamic radiation. This thesis discovers new findings to help liaison psychiatrists and rheumatologists to understand the pathogenesis in NPSLE and psychiatric morbidity in SLE without overt CNS involvement. Most importantly, this thesis provides a platform for further research in the non-organic, non-psychotic psychopathology of SLE.