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

Ingrid Dieset; Unn Kristin Haukvik; Ingrid Melle; Jan Ivar Røssberg; Thor Ueland; Sigrun Hope; Anders M Dale; Srdjan Djurovic; Pål Aukrust; Ingrid Agartz; Ole A Andreassen

doi:10.1016/j.schres.2014.11.006

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

Schizophr Res. 2015 Feb;161(2-3):222-8. doi: 10.1016/j.schres.2014.11.006. Epub 2014 Nov 27.

Authors

Affiliations

¹ KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway. Electronic address: ingrid.dieset@medisin.uio.no.
² KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
³ KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
⁴ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Faculty of Medicine, University of Oslo, Oslo, Norway.
⁵ Department of Radiology, University of California San Diego, La Jolla, CA, USA; Department of Neuroscience, University of California San Diego, La Jolla, CA, USA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
⁶ KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Medical Genetics, Oslo University Hospital Ullevål, Oslo, Norway.
⁷ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Faculty of Medicine, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Norway.

PMID: 25433965
DOI: 10.1016/j.schres.2014.11.006

Abstract

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=2.5×10(-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=3.7×10(-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=3.4×10(-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.

Keywords: Basal ganglia; Brain morphology; Endothelial markers; Inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Blood Proteins / metabolism*
Brain / pathology*
C-Reactive Protein / metabolism
Cytokines / blood*
Female
Humans
Image Processing, Computer-Assisted
Linear Models
Magnetic Resonance Imaging
Male
Middle Aged
Osteoprotegerin / blood
Psychiatric Status Rating Scales
Psychotic Disorders / blood*
Psychotic Disorders / pathology*
Young Adult
von Willebrand Factor / metabolism

Substances

Blood Proteins
Cytokines
Osteoprotegerin
von Willebrand Factor
C-Reactive Protein