TY - JOUR
T1 - Blood-brain barrier pathology in patients with severe mental disorders
T2 - a systematic review and meta-analysis of biomarkers in case-control studies
AU - Futtrup, Jesper
AU - Margolinsky, Rebecca
AU - Benros, Michael Eriksen
AU - Moos, Torben
AU - Routhe, Lisa Juul
AU - Rungby, Jørgen
AU - Krogh, Jesper
N1 - Publisher Copyright:
© 2020
PY - 2020/7
Y1 - 2020/7
N2 - Background: Blood-brain barrier (BBB) pathology may be associated with mental disorders. The aim of this systematic review and meta-analysis is to identify, evaluate and summarize available evidence on whether potential biomarkers of BBB pathology are altered in patients with schizophrenia spectrum disorders, major depression and bipolar disorder compared to healthy controls. Methods: The primary outcome is blood S100B, while secondary outcomes include biomarkers in blood and/or cerebrospinal fluid, i.e. albumin ratio, fibrinogen, immunoglobulin G, glial fibrillary acidic protein, amyloid beta (Aβ), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases, endothelial glycocalyx constituents, and cell adhesion molecules (CAMs). A systematic search in PubMed, Embase and PsycINFO resulted in 131 eligible studies, of which 93 were included in the meta-analysis. Meta- and subgroup analyses were undertaken using random-effects modelling. The protocol was a priori registered on PROSPERO (CRD42020152721). Results: S100B was increased in schizophrenia spectrum disorders (24 studies; 1107 patients; standardized mean difference (SMD) = 0.82; 95% confidence interval (CI) = 0.51 to 1.13; I2 = 90%), major depression (13 studies; 584 patients; SMD = 0.57; 95% CI = 0.31 to 0.83; I2 = 73%) and bipolar disorder (4 studies; 142 patients; SMD = 0.55; 95% CI = 0.16 to 0.94; I2 = 48%). Similarly, numerous secondary outcomes, including albumin ratio, fibrinogen, Aβ, MMPs and CAMs, were altered. Results of the included studies varied considerably, and important confounders were often not accounted for. Conclusions: The findings implicate occurrence of BBB pathology in patients with schizophrenia spectrum disorders, major depression and bipolar disorder compared to healthy controls. However, definite conclusions cannot be drawn, mainly because the investigated biomarkers are indirect measures of BBB pathology.
AB - Background: Blood-brain barrier (BBB) pathology may be associated with mental disorders. The aim of this systematic review and meta-analysis is to identify, evaluate and summarize available evidence on whether potential biomarkers of BBB pathology are altered in patients with schizophrenia spectrum disorders, major depression and bipolar disorder compared to healthy controls. Methods: The primary outcome is blood S100B, while secondary outcomes include biomarkers in blood and/or cerebrospinal fluid, i.e. albumin ratio, fibrinogen, immunoglobulin G, glial fibrillary acidic protein, amyloid beta (Aβ), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases, endothelial glycocalyx constituents, and cell adhesion molecules (CAMs). A systematic search in PubMed, Embase and PsycINFO resulted in 131 eligible studies, of which 93 were included in the meta-analysis. Meta- and subgroup analyses were undertaken using random-effects modelling. The protocol was a priori registered on PROSPERO (CRD42020152721). Results: S100B was increased in schizophrenia spectrum disorders (24 studies; 1107 patients; standardized mean difference (SMD) = 0.82; 95% confidence interval (CI) = 0.51 to 1.13; I2 = 90%), major depression (13 studies; 584 patients; SMD = 0.57; 95% CI = 0.31 to 0.83; I2 = 73%) and bipolar disorder (4 studies; 142 patients; SMD = 0.55; 95% CI = 0.16 to 0.94; I2 = 48%). Similarly, numerous secondary outcomes, including albumin ratio, fibrinogen, Aβ, MMPs and CAMs, were altered. Results of the included studies varied considerably, and important confounders were often not accounted for. Conclusions: The findings implicate occurrence of BBB pathology in patients with schizophrenia spectrum disorders, major depression and bipolar disorder compared to healthy controls. However, definite conclusions cannot be drawn, mainly because the investigated biomarkers are indirect measures of BBB pathology.
KW - Albumin ratio
KW - Bipolar disorder
KW - Blood-brain barrier
KW - Major depression
KW - S100B
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=85116781237&partnerID=8YFLogxK
U2 - 10.1016/j.bbih.2020.100102
DO - 10.1016/j.bbih.2020.100102
M3 - Journal article
AN - SCOPUS:85116781237
SN - 2666-3546
VL - 6
JO - Brain, Behavior, and Immunity - Health
JF - Brain, Behavior, and Immunity - Health
M1 - 100102
ER -