Associations between immuno-metabolic markers, working memory, and functional brain activation in depressive and
Simon Braak1,2, Laura K M Han1,2,3, Chris Vriend1,4,5
1Amsterdam UMC, Location Vrije Universiteit Amsterdam, Department of Psychiatry, De Boelelaan 1117, Amsterdam, the Netherlands.
Background:
Cognitive impairment and immuno-metabolic dysregulation are commonly observed in depressive and anxiety disorders, but underlying brain processes remain unclear. This study examined relationships between immuno-metabolic markers, working memory performance, and task-related functional brain activation in persons with depressive and anxiety disorders and healthy controls (HC).
Methods:
Functional MRI data acquired during an n-back task were analyzed in 54 persons with depressive and anxiety disorders and 69 HC to assess working memory load-related activation. Working memory performance was indexed using d-prime and reaction time. Peripheral immuno-metabolic characteristics were assessed using an inflammation composite index (c-reactive protein, interleukin-6, tumor necrosis factor-alpha, interferon-gamma), a metabolic syndrome index, and a principal component analysis-derived metabolomics factor based on 72 circulating metabolites.
Results:
Across all participants, the working memory task significantly induced functional activation in canonical task-related brain regions (Z-max = 3.72, p < 0.05), although independent of test performance (p > 0.05). No significant associations were found between immuno-metabolic measures and either working memory performance or functional activation, nor were any interaction effects with diagnostic status observed (p > 0.05).
Conclusions:
We found no evidence to support a link between peripheral immuno-metabolic markers and working memory performance or related functional brain activation in persons with depressive and anxiety disorders and HC. Longitudinal and interventional studies incorporating more direct assessments of neuroinflammation will be necessary to further clarify the role of immuno-metabolic factors in cognition.
