Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain

Longitudinal course of inflammatory-cognitive subgroups across first treatment severe mental illness and healthy controls

“…The main finding is that inflammatory-cognitive subgroups based on CRP as a measure of inflammation and a cognitive composite score, is stable over one year in first treatment SMI and HC. These findings also confirm the inflammatory-cognitive subgroup pattern that we previously identified using broad panels of inflammatory and immune-related markers and cognitive domains (Sæther et al, 2023, 2024). Importantly, while cognition, symptoms, and level of functioning generally improved over the first year of treatment for SMI participants, we observed stable differences between the subgroups at both time-points, with the higher inflammation – lower cognition subgroup having worse cognition, higher inflammation, more symptoms, and lower functioning.…”

“…Thus, to ensure the highest possible N, corresponding tests from the two batteries were standardized separately (Z-scores) before combining to cover nine cognitive domains: Fine-motor speed, psychomotor processing speed, mental processing speed, attention, verbal learning, verbal memory, semantic fluency, working memory and cognitive control . We have previously shown robust between-battery correspondence of test performance for SZ, BD and HC (Sæther et al, 2024). The cognitive batteries consisted of tests from the MATRICS Consensus Cognitive Battery (MCCB) (Nuechterlein et al, 2008), Halstead-Reitan (Klove, 1963), the Wechsler Adult Intelligence Scale (WAIS-III) (Wechsler, 1997), Delis Kaplan Executive Functioning System (D-KEFS) (Delis et al, 2001), the California Verbal Learning Test (CVLT-II) (Delis et al, 1987), and the Hopkins Verbal Learning Test-Revised (HVLT-R) (Benedict et al, 1998).…”

“…The trajectory of CRP levels from baseline to 1 year follow-up in first treatment SZ and BD is, however, unknown. Based on a similar approach to our previous work (Sæther et al, 2024, 2023), we used hierarchical clustering to identify transdiagnostic inflammatory-cognitive subgroups using CRP and a cognitive composite score at baseline. The subgroups were assessed longitudinally across demographic, clinical, and cognitive measures.…”

“…Recent evidence from machine learning suggests higher accuracy of case-control prediction when both cognition and inflammatory markers are evaluated together (Fernandes et al, 2020). Using hierarchical clustering, we recently identified a transdiagnostic subgroup with cognitive impairment and higher inflammation using different immune and inflammatory marker panels (Sæther et al, 2023, 2024). This subgroup also had more symptoms and lower functioning, compared to a subgroup with milder impairments and lower inflammation.…”