Circulating inflammatory and neurotrophic markers as moderators and/or mediators of cognitive remediation outcome in people with bipolar disorders

Abstract

BACKGROUND: Immune dysregulation appears involved in affective disorder pathophysiology. Inflammatory biomarkers have been linked with the cognitive impairment observed in people with bipolar disorders and as such are candidate markers that may improve with, and/or predict outcomes to, cognitive remediation therapies (CRT). AIMS: Nine candidate biomarkers were examined as putative mediators and/or moderators to improvements following CRT compared with treatment as usual (TAU) from a randomised controlled trial. METHOD: Euthymic adults with bipolar disorders who had been randomised to CRT (n = 23) or TAU (n = 21) underwent blood testing before and after a 12 week intervention period. Five cytokines and four growth factor proteins, selected a priori, were examined in association with global cognition and psychosocial functioning outcomes. RESULTS: CRT attenuated a reduction in the brain-derived neurotrophic factor (BDNF), basic fibroblast growth factor and vascular endothelial growth factor-C compared to TAU. For the BDNF, lower baseline levels predicted better functional outcomes across the sample but was more pronounced in TAU versus CRT participants and indicated larger CRT effects in those with a higher BDNF. A moderation effect was also apparent for tumour necrosis factor-β and interleukin-16, with greater CRT versus TAU effects on functioning for participants with lower baseline levels. CONCLUSIONS: Although preliminary, results suggest that CRT may exert some protective biological effects, and that people with lower levels of neurotrophins or cytokines may benefit more from CRT. We note an absence of associations with cognitive (versus functional) outcomes. These findings require further examination in large well-controlled studies.