Association between altered brain morphology and elevated peripheral endothelial markers - Implications for psychotic disorders

SCHIZOPHRENIA RESEARCH

卷:161

Article

Dieset, Ingrid^1,2  Haukvik, Unn Kristin^1,2,3  Melle, Ingrid^1,2  Rossberg, Jan Ivar^1,2  Ueland, Thor⁴  Hope, Sigrun^1,2  Dale, Anders M.^7,8,9  Djurovic, Srdjan^1,2,6  Aukrust, Pal^4,5  Agartz, Ingrid^1,2,3  Andreassen, Ole A.^1,2 

[1] Oslo Univ Hosp, KG Jebsen Ctr Psychosis Res, Div Mental Hlth & Addict, Oslo, Norway

[2] Univ Oslo, Inst Clin Med, N-0407 Oslo, Norway

[3] Diakonhjemmet Hosp, Dept Psychiat Res, Oslo, Norway

[4] Univ Oslo, Fac Med, Oslo Univ Hosp, Res Inst Internal Med,Rikshosp, N-0407 Oslo, Norway

[5] Oslo Univ Hosp, Rikshosp, Sect Clin Immunol & Infect Dis, Oslo, Norway

[6] Univ Oslo, Ulleval Hosp, Dept Med Genet, N-0407 Oslo, Norway

[7] Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA

[8] Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA

[9] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA

关键词: Inflammation;    Endothelial markers;    Basal ganglia;    Brain morphology;   

DOI  :  10.1016/j.schres.2014.11.006

来源: Elsevier

【 摘 要 】

Background: Increased inflammation, endothelial dysfunction, and structural brain abnormalities have been reported in both schizophrenia and bipolar disorder, but the relationships between these factors are unknown. We aimed to identify associations between markers of inflammatory and endothelial activation and structural brain variation in psychotic disorders. Methods: We measured von Willebrand factor (vWf) as a marker of endothelial cell activation and six inflammatory markers (tumor necrosis factor-receptor 1, osteoprotegerin, interleukin-1-receptor antagonist, interleukin-6, C-reactive protein, CD40 ligand) in plasma and 16 brain structures obtained from MRI scans of 356 individuals (schizophrenia spectrum; n = 121, affective spectrum; n = 95, healthy control subjects; n = 140). The relationship between the inflammatory and endothelial markers and brain measurements were investigated across groups. Results: There was a positive association (p = 2.5 x 10(-4)) between plasma levels of vWf and total volume of the basal ganglia which remained significant after correction for multiple testing. Treatment with first generation antipsychotics was associated with basal ganglia volume only (p = 0.009). After adjusting for diagnosis and antipsychotic medication, vWf remained significantly associated with increased basal ganglia volume (p = 0.008), in particular the right globus pallidus (p = 3.7 x 10(-4)). The relationship between vWf and basal ganglia volume was linear in all groups, but the intercept was significantly higher in the schizophrenia group (df = 2, F = 8.2, p = 3.4 x 10(-4)). Conclusion: Our results show a strong positive correlation between vWf levels and basal ganglia volume, in particular globus pallidus, independent of diagnosis. vWf levels were significantly higher in schizophrenia, which could indicate a link between endothelial cell activation and basal ganglia morphology in schizophrenia patients. (C) 2014 Elsevier B.V. All rights reserved.

【 授权许可】

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