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; I 2 = 90%), major depression (13 studies; 584 patients; SMD = 0.57; 95% CI = 0.31 to 0.83; I 2 = 73%) and bipolar disorder (4 studies; 142 patients; SMD = 0.55; 95% CI = 0.16 to 0.94; I 2 = 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.
ObjectivesRecent large cohort studies suggest an association between high plasma prolactin and cardiovascular mortality. The objective of this systematic review was to systematically assess the effect of reducing prolactin with dopamine agonist on established cardiovascular risk factors in patients with prolactinomas.DesignBibliographical search was done until February 2019 searching the following databases: PubMed, EMBASE, WHO and LILAC. Eligible studies had to include participants with verified prolactinomas where metabolic variables were assessed before and after at least 2 weeks treatment with dopamine agonists.MethodsBaseline data and outcomes were independently collected by two investigators. The study was registered with PROSPERO (registration number CRD42016046525).ResultsFourteen observational studies enrolling 387 participants were included. The pooled standardized mean difference of the primary outcome revealed a reduction of BMI and weight of −0.21 (95% CI −0.37 to −0.05; P = 0.01; I2 = 71%), after treatment. Subgroup analysis suggested that the reduction of weight was primarily driven by studies with high prolactin levels at baseline (P = 0.04). Secondary outcomes suggested a small decrease in waist circumference, a small-to-moderate decrease in triglycerides, fasting glucose levels, HOMA-IR, HbA1c and hsCRP, and a moderate decrease in LDL, total cholesterol and insulin.ConclusionThis systematic review suggests a reduction of weight as well as an improved lipid profile and glucose tolerance after treatment with dopamine agonist in patients with prolactinomas. These data are based on low-quality evidence.
Background: Previous studies indicate that levels of plasma norepinephrine (p-NE) are altered in depressed patients. However, it is unclear whether altered NE metabolism is involved in the pathogenic association between depression and cardiovascular disease. The aim of the present study was, firstly, to investigate if p-NE levels differ between patients with major depression and healthy controls. Secondly, the study sought to assess the associations between p-NE and metabolic variables in all participants. The third and final aim of the study was to assess if the associations between p-NE and metabolic variables are influenced by disease status (depression vs. healthy). Methods: 108 patients with major depression and 44 healthy controls were tested for levels of p-NE and metabolic variables that affect cardiovascular risk. Results: The median level of p-NE in depressed patients (DSM-IV) was 2636 pg/ml, (IQR 2094-3143) and 2279 pg/ml (IQR 2007-2562) in non-depressed controls (p = 0.013). However, the difference between p-NE levels was non-significant when adjusted for daily smoking (p = 0.138). Significant associations (p ≤ 0.05) were observed between p-NE and p-lipids, mean arterial blood pressure, p-insulin, quantitative insulin sensitivity check index as well as inflammatory markers. Conclusions: Elevated levels of p-NE observed in patients with major depression were attributable to daily smoking, rather than to the depressive disorder. Important associations were found between p-NE and metabolic variables that affect cardiovascular risk. This is interesting from a clinical point of view, since affected individuals may benefit from simple and inexpensive treatments that influence sympathetic activity. All associations were independent of disease status.
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