Trace elements play a crucial role in many biochemical processes, mainly as components of vitamins and enzymes. Although small amounts of metal ions have protective properties, excess metal levels result in oxidative injury, which is why metal ion homeostasis is crucial for the proper functioning of the brain. The changes of their level in the brain have been proven to be a risk factor for Alzheimer's, Parkinson's, and Huntington's diseases, as well as amyotrophic lateral sclerosis. Therefore, it is currently an important application of various analytical methods. This review covers the most important of them: inductively coupled ground mass spectrometry (ICP-MS), flame-induced atomic absorption spectrometry (FAAS), electrothermal atomic absorption spectrometry (GFAAS), optical emission spectrometry with excitation in inductively coupled plasma (ICP-OES), X-ray fluorescence spectrometry (XRF), and neutron activation analysis (NAA). Additionally, we present a summary of concentration values found by different research groups.
Background
Current treatment of major depressive disorder (MDD) often does not achieve full remission of symptoms. Therefore, new forms of treatment and/or adjunct therapy are needed. Evidence has confirmed the modulation of the gut–brain–microbiota axis as a promising approach in MDD patients. The overall purpose of the SANGUT study—a 12-week, randomized, double-blind, and placebo-controlled Study Evaluating the Effect of Probiotic Supplementation on the Mental Status, Inflammation, and Intestinal Barrier in Major Depressive Disorder Patients Using Gluten-free or Gluten-containing Diet — is to determine the effect of interventions focused on the gut-brain-microbiota axis in a group of MDD patients.
Methods
A total of 120 outpatients will be equally allocated into one of four groups: (1) probiotic supplementation+gluten-free diet group (PRO-GFD), (2) placebo supplementation+ gluten-free diet group (PLA-GFD), (3) probiotic supplementation+ gluten containing diet group (PRO-GD), and (4) placebo supplementation+gluten containing diet group (PLA-GD). PRO groups will receive a mixture of psychobiotics (
Lactobacillus helveticus
R0052 and
Bifidobacterium longum
R0175), and GFD groups will follow a gluten-free diet. The intervention will last 12 weeks. The primary outcome measure is change in wellbeing, whereas the secondary outcome measures include physiological parameters.
Discussion
Microbiota and its metabolites have the potential to influence CNS function. Probiotics may restore the eubiosis within the gut while a gluten-free diet, via changes in the microbiota profile and modulation of intestinal permeability, may alter the activity of microbiota-gut-brain axis previously found to be associated with the pathophysiology of depression. It is also noteworthy that microbiota being able to digest gluten may play a role in formation of peptides with different immunogenic capacities. Thus, the combination of a gluten-free diet and probiotic supplementation may inhibit the immune-inflammatory cascade in MDD course and improve both psychiatric and gut barrier-associated traits.
Trial registration
NCT03877393
.
Introducing the Minimum Spanning Tree (MST) algorithms to neural networks science eliminated the problem of arbitrary setting of the threshold for connectivity strength. Despite these advantages, MST has been rarely used to study network abnormalities in schizophrenia. An MST graph mapping a network structure is its simplification, therefore, it is important to verify whether the reconfigured network is significantly related to the behavioural dimensions of the clinical picture of schizophrenia. 35 first-episode schizophrenia patients and 35 matched healthy controls underwent an assessment of information processing speed, cognitive inter-trial variability modelled with ex-Gaussian distributional analysis of reaction times and resting-state EEG recordings to obtain frequency-specific functional connectivity matrices from which MST graphs were computed. The patients’ network had a more random structure and star-like arrangement with overloaded hubs positioned more posteriorly than it was in the case of the control group. Deficient processing speed in the group of patients was predicted by increased maximal betweenness centrality in beta and gamma bands, while decreased consistency in cognitive processing was predicted by the betweenness centrality of posterior nodes in the gamma band, together with duration of illness. The betweenness centrality of posterior nodes in the gamma band was also significantly correlated with positive psychotic symptoms in the clinical group.
There is an increasing amount of evidence which links the pathogenesis of irritable bowel syndrome (IBS) with food IgG hyperreactivity. Some authors have suggested that food IgG hyperreactivity could be also involved in the pathophysiology of major depressive disorder (MDD). The aim of this study was to compare levels of serum IgG against 39 selected food antigens between three groups of participants: patients with MDD (MDD group), patients with IBS (IBS group) and healthy controls (HC group). The study included 65 participants (22 in the MDD group, 22 in the IBS group and 21 in the HC group). Serum IgG levels were examined using enzyme-linked immunosorbent assay (ELISA). Medical records, clinical data and laboratory results were collected for the analysis. IgG food hyperreactivity (interpreted as an average of levels of IgG antibodies above 7.5 µg/mL) was detected in 28 (43%) participants, including 14 (64%) from the MDD group, ten (46%) from the IBS group and four (19%) from the HC group. We found differences between extreme IgG levels in MDD versus HC groups and in IBS versus HC groups. Patients with MDD had significantly higher serum levels of total IgG antibodies and IgG against celery, garlic and gluten compared with healthy controls. The MDD group also had higher serum IgG levels against gluten compared with the IBS group. Our results suggest dissimilarity in immune responses against food proteins between the examined groups, with the highest immunoreactivity in the MDD group. Further studies are needed to repeat and confirm these results in bigger cohorts and also examine clinical utility of IgG-based elimination diet in patients with MDD and IBS.
Depressive episodes are associated not only with changes in neurotransmission in the central nervous system, but also may lead to structural changes in the brain through neuroendocrine, inflammatory, and immunological mechanisms. The aim of this article is to present a new hypothesis connecting the inflammatory theory of depression with IgG food hypersensitivity and leaky gut syndrome. This new potential pathway that may mediate the pathogenesis of depression implies the existence of subsequent developmental stages. Overproduction of zonulin triggered, for example, by gliadin through activation of the epidermal growth factor receptor and protease-activated receptor causes loosening of the tight junction barrier and an increase in permeability of the gut wall ('leaky gut'). This results in a process allowing larger molecules that would normally stay in the gut to cross into the bloodstream and in the induction of IgG-dependent food sensitivity. This condition causes an increased immune response and consequently induces the release of proinflammatory cytokines, which in turn may lead to the development of depressive symptoms. It seems advisable to assess the intestinal permeability using as a marker, for example, zonulin and specific IgG concentrations against selected nutritional components in patients with depression. In the case of increased IgG concentrations, the implementation of an elimination-rotation diet may prove to be an effective method of reducing inflammation. This new paradigm in the pathogenesis of depressive disorders linking leaky gut, IgG-dependent food sensitivity, inflammation, and depression is promising, but still needs further studies to confirm this theory.
The aim of this study was to compare neural network topology of 30 patients with first episode schizophrenia (FES) and 30 multiepisode schizophrenia (mean number of psychotic relapses =4 years, duration of illness >5 years) patients, who were assessed with graph theory methods. This comparison was designed to identify network differences, which might be assigned to the burden of a mental disease. To estimate functional connectivity, we applied the phase lag index algorithm and the minimum spanning tree (MST) for the characterization of network topology. Group comparison revealed significant between-group differences of maximal betweenness centrality and tree hierarchy in the beta-band and hierarchy in the gamma-band. MST results showed that in the beta-band the network of patients with longer duration of illness (LDI) was characterized by more centralized network, while subjects with short duration of illness (FES) showed more decentralized topology. Furthermore, in the gamma-band, our results suggest that illness duration can disturb the balance between overload prevention and large-scale integration in the brain network. A qualitative analysis proved that the topological displacement of hubs also differentiated the FES and LDI groups. Our findings suggest that the duration of illness significantly affects the topology of resting-state functional network, supporting the “disconnectivity hypothesis’ in schizophrenia.
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