Maria Radziwoń-Zaleska

The central nervous system (CNS) is closely related to the gastrointestinal tract, mainly through regulating its function and homeostasis. Simultaneously, the gut flora affects the CNS and plays an essential role in the pathogenesis of neurologic and neuropsychological disorders such as Parkinson’s and Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis or autism spectrum disorder. The population of gut microorganisms contains more than one billion bacteria. The most common are six phyla: Proteobacteria, Actinomyces, Verucomicrobia, Fusobacteria, and dominant Bacteroides with Firmicutes. The microbiota–gut–brain axis is a bidirectional nervous, endocrine, and immune communication between these two organs. They are connected through a variety of pathways, including the vagus nerve, the immune system, microbial metabolites such as short-chain fatty acids (SCFAs), the enteric nervous system, and hormones. Age, diet, antibiotics influence the balance of gut microorganisms and probably lead to the development of neurodegenerative disorders. In this article, a review is presented and discussed, with a specific focus on the changes of gut microbiota, gut–brain axis, related disorders, and the factors that influence gut imbalance.

So far, there is no consistent and convincing theory explaining the pathogenesis of migraines. Vascular disorders, the effect of oxidative stress on neurons, and the contribution of magnesium-calcium deficiencies in triggering cortical depression and abnormal glutaminergic neurotransmission are taken into account. However, there are no reliable publications confirming the role of dietary deficits of magnesium and latent tetany as factors triggering migraine attacks. The aim of the study was to evaluate the influence of latent magnesium deficiency assessed with the electrophysiological tetany test on the course of migraine. The study included: a group of 35 patients (29 women and six men; in mean age 41 years) with migraine and a control group of 24 (17 women and seven men; in mean age 39 years) healthy volunteers. Migraine diagnosis was based on the International Headache Society criteria, 3rd edition. All patients and controls after full general and neurological examination were subjected to a standard electrophysiological ischemic tetany test. Moreover, the level of magnesium in blood serum was tested and was in the normal range in all patients. Then, the incidence of a positive tetany EMG test results in the migraine group and the results in the subgroups with and without aura were compared to the results in the control group. Moreover, the relationship between clinical markers of spasmophilia and the results of the tetany test was investigated in the migraine group. As well as the relationship between migraine frequency and tetany test results. There was no statistically significant difference in the occurrence of the electrophysiological exponent of spasmophilia between the migraine and control group. Neither correlation between the occurrence of clinical symptoms nor the frequency of migraine attacks and the results of the tetany test was stated (p > 0.05). However, there was an apparent statistical difference between the subgroup of migraine patients with aura in relation to the control group (p < 0.05). The result raises hope to find a trigger for migraine attacks of this clinical form, the more that this factor may turn out to be easy to supplement with dietary supplementation.

Animal studies using tests and models have demonstrated that magnesium exerts an antidepressant effect. The literature contains few studies in humans involving attempts to augment antidepressant therapy with magnesium ions. The purpose of our study was to assess the efficacy and safety of antidepressant treatment, in combination with magnesium ions. A total of 37 participants with recurrent depressive disorder who developed a depressive episode were included in this study. As part of this double-blind study, treatment with the antidepressant fluoxetine was accompanied with either magnesium ions (120 mg/day as magnesium aspartate) or placebo. During an 8-week treatment period, each patient was monitored for any clinical abnormalities. Moreover, serum fluoxetine and magnesium levels were measured, and pharmaco-electroencephalography was performed. The fluoxetine + magnesium and fluoxetine + placebo groups showed no significant differences in either Hamilton Depression Rating Scale (HDRS) scores or serum magnesium levels at any stage of treatment. Multivariate statistical analysis of the whole investigated group showed that the following parameters increased the odds of effective treatment: lower baseline HDRS scores, female gender, smoking, and treatment augmentation with magnesium. The parameters that increased the odds of remission were lower baseline HDRS scores, shorter history of disease, the presence of antidepressant-induced changes in the pharmaco-EEG profile at 6 h after treatment, and the fact of receiving treatment augmented with magnesium ions. The limitation of this study is a small sample size.

The clinical efficacy of current antidepressant therapies is unsatisfactory; antidepressants induce a variety of unwanted effects, and, moreover, their therapeutic mechanism is not clearly understood. Thus, a search for better and safer agents is continuously in progress. Recently, studies have demonstrated that zinc and magnesium possess antidepressant properties. Zinc and magnesium exhibit antidepressant-like activity in a variety of tests and models in laboratory animals. They are active in forced swim and tail suspension tests in mice and rats, and, furthermore, they enhance the activity of conventional antidepressants (e.g., imipramine and citalopram). Zinc demonstrates activity in the olfactory bulbectomy, chronic mild and chronic unpredictable stress models in rats, while magnesium is active in stress-induced depression-like behavior in mice. Clinical studies demonstrate that the efficacy of pharmacotherapy is enhanced by supplementation with zinc and magnesium. The antidepressant mechanisms of zinc and magnesium are discussed in the context of glutamate, brain-derived neurotrophic factor (BDNF) and glycogen synthase kinase-3 (GSK-3) hypotheses. All the available data indicate the importance of zinc and magnesium homeostasis in the psychopathology and therapy of affective disorders.

Previously, we demonstrated antidepressant-like effect of magnesium (Mg) in the forced swim test (FST). Moreover, the joint administration of Mg and imipramine (IMI) at ineffective doses per se, resulted in a potent reduction in the immobility time in this test. In the present study, we examined the effect of immobility stress (IS), and Mg and/or IMI administration on FST behavior. IS induced enhancement of immobility time, which was reversed by Mg or IMI at doses ineffective in non-stressed mice (10 mg/kg and 15 mg/kg, respectively). The joint administration of Mg and IMI was effective in both IS and non-stressed animals in FST. IS did not significantly alter locomotor activity, while IMI or Mg + IMI treatment in IS mice reduced this activity. We also measured serum and brain Mg, IMI and its metabolite desipramine (DMI) concentration in mice subjected to FST and injected with Mg + IMI, both restrained and non-restrained. In the present study we demonstrated a significant increase (by 68%) in the brain IMI and a slight, non-significant reduction in DMI concentration in IS + Mg + IMI + FST vs. Mg + IMI + FST groups, which might indicate the reduction in brain IMI metabolism. The IS-induced reduction in brain IMI metabolism did not participate in the activity in FST, since no differences in such activity were noticed between IS + Mg + IMI + FST and Mg + IMI + FST groups. The present data suggest that IS-induced increase in immobility time in FST is more sensitive for detection antidepressant-like activity. However, further studies are needed to examine the effect of other antidepressants in such an experimental paradigm.

34 patients with diagnosis of depressive episode (ICD-10) were treated for 8 weeks with tricyclic antidepressants (TCA) 22 patients were treated with clomipramine 75-175 mg daily, 11 with imipramine 75-150 mg and 1 with amitriptyline 150 mg. Following parameters were analysed: plasma concentration (FPIA, HPLC), pharmaco-EEG (spectrum power for delta, theta, alfa1, 2, beta 1, 2, 3 by the use of FFT), clinical improvement (HAMD, HARS, SGI, SERS). 50% reduction in HAMD was regarded as improvement. No relationship between mental state and plasma concentration of TCA was found, initial results in SERS were prognostic for the course of treatment, pharmaco-EEG was typical for antidepressants after two weeks of treatment and reflects clinical improvement and stabilization of plasma concentration. Comparing the plasma concentration of TCA measured by the use of FPIA and HPLC method may be useful for the implementation of monitoring therapy.