Carrol, D; Busse, WW; Frye, CJ; Klaus, DR; Bach, JC; Floerke, H; Bendlin, BB; ... Rosenkranz, MA; + view all Carrol, D; Busse, WW; Frye, CJ; Klaus, DR; Bach, JC; Floerke, H; Bendlin, BB; Zetterberg, H; Blennow, K; Heslegrave, A; Hoel, R; Rosenkranz, MA; - view fewer (2025) Regional brain structural alterations in reward and salience networks in asthma. Brain, Behavior, and Immunity , 126 pp. 80-97. 10.1016/j.bbi.2025.01.028.

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Abstract

Introduction: Chronic systemic inflammation is highly prevalent and has deleterious effects on the brain, impacting both function and structure, and manifesting in elevations in psychological symptoms transdiagnostically. Asthma is a chronic inflammatory disease of the airway that affects more than 300 million people worldwide and is known to be highly comorbid with psychological and cognitive dysfunction. Though a growing corpus of work has identified functional brain abnormalities associated with asthma, limited research has investigated structural differences which may partially underlie functional changes. Identifying and characterizing asthma-related structural brain changes will shed light on the neurobiology through which asthma impacts mental function and has the potential to inform prophylaxis and treatment. Methods: We examined differences in regional brain volume, cortical thickness, and surface area, in 128 individuals with asthma compared to 134 non-asthma healthy controls. Five regions of interest were examined a priori, based on their previous implication in inflammation-related functional consequences (dorsal and ventral striatum, pallidum, and insula), or previous evidence of asthma-related structural impact (hippocampus and thalamus). We supplemented our region of interest approach with a voxel-wise whole-brain analysis. Additionally, we examined the association of brain structure with depression symptoms, asthma severity, degree of inflammation, and plasma biomarkers of neuroinflammation, neurodegeneration, and Alzheimer's disease specific pathology. Results: Compared to non-asthma control participants, those with asthma had smaller nucleus accumbens volumes, thicker orbitofrontal cortices, larger middle frontal cortex surface areas, and greater diencephalon volumes. Those with more severe asthma had smaller nucleus accumbens and dorsal striatal volumes, reduced anterior cingulate cortex surface area, and greater amygdala volume compared to those with mild asthma. In untreated asthma patients, greater depressive symptoms were associated with smaller striatal volume, suggesting a potential CNS-protective effect of medications that reduce airway inflammation in asthma. In addition, a plasma marker of astrogliosis was associated with larger diencephalon, cerebellum, brainstem, and thalamus volumes, but reduced insula thickness and surface area. Conclusions: Patterns of structural brain changes in participants with asthma encompass key regions of reward and salience networks, which may in part give rise to the functional alterations in these networks characteristic of chronic systemic inflammation.

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