Multivariate relationships between peripheral inflammatory marker subtypes and cognitive and brain structural measures in psychosis

Abstract

Elevations in peripheral inflammatory markers have been reported in patients with psychosis. Whether this represents an inflammatory process defined by individual or subgroups of markers is unclear. Further, relationships between peripheral inflammatory marker elevations and brain structure, cognition, and clinical features of psychosis remain unclear. We hypothesized that a pattern of plasma inflammatory markers, and an inflammatory subtype established from this pattern, would be elevated across the psychosis spectrum and associated with cognition and brain structural alterations. Clinically stable psychosis probands (Schizophrenia spectrum, n=79; Psychotic Bipolar disorder, n=61) and matched healthy controls (HC, n=60) were assessed for 15 peripheral inflammatory markers, cortical thickness, subcortical volume, cognition, and symptoms. A combination of unsupervised exploratory factor analysis and hierarchical clustering was used to identify inflammation subtypes. Levels of IL6, TNFα, VEGF, and CRP were significantly higher in psychosis probands compared to HCs, and there were marker-specific differences when comparing diagnostic groups. Individual and/or inflammatory marker patterns were associated with neuroimaging, cognition, and symptom measures. A higher inflammation subgroup was defined by elevations in a group of 7 markers in 36% of Probands and 20% of HCs. Probands in the elevated inflammatory marker group performed significantly worse on cognitive measures of visuo-spatial working memory and response inhibition, displayed elevated hippocampal, amygdala, putamen and thalamus volumes, and evidence of gray matter thickening compared to the proband group with low inflammatory marker levels. These findings specify the nature of peripheral inflammatory marker alterations in psychotic disorders and establish clinical, neurocognitive and neuroanatomic associations with increased inflammatory activation in psychosis. The identification of a specific subgroup of patients with inflammatory alteration provides a potential means for targeting treatment with anti-inflammatory medications.

Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis

“…using composite scores analyses [44], regularized regression [45], k-means clustering [26,46,47], or through a combination of unsupervised exploratory factor analysis and hierarchical clustering [48]. Consistent with our findings, the majority of these previous studies demonstrated that inflammatory profiles in patients with psychotic disorders can be sub-grouped into two main clusters, namely "high inflammatory" and a "low inflammatory" subgroups.…”

TNFα and MMP1 in brain microvascular endothelial cells regulate blood-brain barrier dysfunction in psychotic disorders

“…2f and g). Similar to existing clinical studies 7,[15][16][17]30,31 , our results demonstrate there is a BBB-deficit subgroup in psychotic disorders characterized by more extensive BBB disruption as evidenced by decreased TEER, increased permeability, lower CLDN5 intensity, and aberrant tight junctional morphology.…”

“…Conversely, transcriptomic and genetic studies indicate the presence of disruptions in paracellular 6 and transcellular [7][8][9][10][11][12][13] mechanisms related to BMEC function. There is also increasing evidence for increased BBB permeability in subgroups of patients with SZ 7,14,15 and BD 16,17 . These findings suggest BMEC involvement in the pathogenesis of SZ and BD in specific subgroups of patients, but there is no study to date that has directly investigated the role of BMECs in SZ and BD.…”

Assessing the Effect of Interaction Between C-Reactive Protein and Gut Microbiome on the Risks of Anxiety and Depression

“…Although previous studies have found the functional relevance of gut microbiome and CRP with the development of anxiety and depression (30,31), the biological mechanism underlying the effects of interaction between gut microbiome and CRP on the risks of anxiety and depression remains to be elucidated (32). In this study, we explored the interaction between CRP and 114 gut microbiome-related traits and observed a signi cant interaction between them for depression and anxiety.…”