Abstract:
BACKGROUND:Bipolar Disorder (BD) is associated with elevated biomarkers of cell-mediated immune activation and inflammation and with signs of widespread disruption of white matter (WM) integrity in adult life. Consistent findings in animal models link WM damage in inflammatory diseases of the brain and serum levels of cytokines. METHODS:With an exploratory approach, we tested the effects of 22 serum analytes, including pro- and anti-inflammatory cytokines and neurotrophic/hematopoietic factors, on DTI measures of WM microstructure in a sample of 31 patients with a major depressive episode in course of BD. We used whole brain tract-based spatial statistics in the WM skeleton with threshold-free cluster enhancement of DTI measures of WM microstructure: axial (AD), radial (RD), and mean diffusivity (MD), and fractional anisotropy (FA). RESULTS:The inflammation-related cytokines TNF-α, IL-8, IFN-γ and IL-10, and the growth factors IGFBP2 and PDGF-BB, shared the same significant associations with lower FA, and higher MD and RD, in large overlapping networks of WM fibers mostly located in the anterior part of the brain and including corpus callosum, cingulum, superior and inferior longitudinal fasciculi, inferior fronto-occipital fasciculi, uncinate, forceps, corona radiata, thalamic radiation, internal capsule. CONCLUSIONS:Higher RD is thought to signify increased space between fibers, suggesting demyelination or dysmyelination. The pattern of higher RD and MD with lower FA suggests that inflammation-related cytokine and growth factor levels inversely associate with integrity of myelin sheaths. The activated inflammatory response system might contribute to BD pathophysiology by hampering structural connectivity in critical cortico-limbic networks.
journal_name
J Affect Disordjournal_title
Journal of affective disordersauthors
Benedetti F,Poletti S,Hoogenboezem TA,Mazza E,Ambrée O,de Wit H,Wijkhuijs AJ,Locatelli C,Bollettini I,Colombo C,Arolt V,Drexhage HAdoi
10.1016/j.jad.2016.05.047subject
Has Abstractpub_date
2016-09-15 00:00:00pages
1-9eissn
0165-0327issn
1573-2517pii
S0165-0327(15)31431-2journal_volume
202pub_type
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