Maria Radziwoń-Zaleska

Vitamin D and the central nervous system.

Vitamin D is formed in human epithelial cells via photochemical synthesis and is also acquired from dietary sources. The so-called classical effect of this vitamin involves the regulation of calcium homeostasis and bone metabolism. Apart from this, non-classical effects of vitamin D have recently gained renewed attention. One important yet little known of the numerous functions of vitamin D is the regulation of nervous system development and function. The neuroprotective effect of vitamin D is associated with its influence on neurotrophin production and release, neuromediator synthesis, intracellular calcium homeostasis, and prevention of oxidative damage to nervous tissue. Clinical studies suggest that vitamin D deficiency may lead to an increased risk of disease of the central nervous system (CNS), particularly schizophrenia and multiple sclerosis. Adequate intake of vitamin D during pregnancy and the neonatal period seems to be crucial in terms of prevention of these diseases.

Magnesium in depression

Magnesium is one of the most essential mineral in the human body, connected with brain biochemistry and the fluidity of neuronal membrane. A variety of neuromuscular and psychiatric symptoms, including different types of depression, was observed in magnesium deficiency. Plasma/serum magnesium levels do not seem to be the appropriate indicators of depressive disorders, since ambiguous outcomes, depending on the study, were obtained. The emergence of a new approach to magnesium compounds in medical practice has been seen. Apart from being administered as components of dietary supplements, they are also perceived as the effective agents in treatment of migraine, alcoholism, asthma, heart diseases, arrhythmias, renal calcium stones, premenstrual tension syndrome etc. Magnesium preparations have an essential place in homeopathy as a remedy for a range of mental health problems. Mechanisms of antidepressant action of magnesium are not fully understood yet. Most probably, magnesium influences several systems associated with development of depression. The first information on the beneficial effect of magnesium sulfate given hypodermically to patients with agitated depression was published almost 100 years ago. Numerous pre-clinical and clinical studies confirmed the initial observations as well as demonstrated the beneficial safety profile of magnesium supplementation. Thus, magnesium preparations seem to be a valuable addition to the pharmacological armamentarium for management of depression.

Serum cortisol concentration in patients with major depression after treatment with fluoxetine

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol levels is characteristic of the pathophysiology of major depressive disorder (MDD). The aim of this study was to determine whether increased plasma cortisol levels appear in patients with major depression and if effective antidepressant treatment by fluoxetine leads to regulation of cortisol level. This aim was realized by describing and validation of methods of determining fluoxetine and cortisol in serum and searching for correlation between their concentrations in patients with endogenous depression, the therapeutic effect as assessed in Hamilton Depression Rating Scale (HDRS), age and sex of patients. Plasma cortisol and fluoxetine levels were measured using high performance liquid chromatography (HPLC) methods with applying Shimadzu chromatograph with UV detection. Plasma cortisol and fluoxetine levels were measured at time zero (before therapy) and after 6h, 24h, 2, 4, 6 and 8 weeks of fluoxetine administration in patients with major depression qualified for therapeutic drug monitoring (TDM). The study included 21 patients (14 women, 7 men; mean age 29-75 years) and 24 healthy comparison subjects. The patients had a mean score on the 21-item HDRS. As the effect of fluoxetine administration the decrease of the level of cortisol was observed in patients who responded to the therapy (the reduction of points in HDRS scale in at least 50%). The validation parameters of HPLC method of fluoxetine and cortisol determination indicate the possibility of applying them for determination of both: the level of concentration of the drug in therapeutic drug monitoring and the level of cortisol in serum of patients with endogenous depression.

Serum cortisol concentration in patients with major depression after treatment with clomipramine.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and elevated cortisol (CORT) levels are characteristics of the pathophysiology of major depressive disorder. The aim of this study was to determine whether increased plasma CORT levels appear in patients with major depression and if effective antidepressant treatment by clomipramine (CLO) leads to regulation of CORT level. Plasma CORT levels were measured using high performance liquid chromatography (HPLC) methods in patients with major depression at time zero (before therapy) and after 3 h, 24 h, 4, 6 and 8 weeks of CLO administration. The study included 17 patients (12 women, 5 men; mean age 54.5 years, SD =12.3) and 21 healthy comparison subjects. The patients had a mean score on the 21-item Hamilton Depression Rating Scale (HDRS) of 26.8 (range 22-35). Eight of the patients with major depression recruited for the study showed a 46% increase in CORT concentration compared to the established standard. In 13 patients treated with CLO, serum CLO levels reached a therapeutic range. In recovered depressed patients, antidepressant treatment significantly reduced HDRS scores from the 6th week of treatment. A drop in plasma CORT levels in recovered depressed subjects occurred 0 to 6 weeks after CLO treatment (n = 5, p < 0.046). However, neither subject group exhibited any definitive markers of CORT secretion. In the population studied, patients had distinct profiles of HPA axis dysregulation. Finding a linear correlation between lower CORT secretion and therapeutic plasma CLO levels is the first aim of monitored therapy and may be important for understanding the pathophysiology of major depressive disorder.

Zinc in the Monoaminergic Theory of Depression: Its Relationship to Neural Plasticity

Preclinical and clinical studies have demonstrated that zinc possesses antidepressant properties and that it may augment the therapy with conventional, that is, monoamine-based, antidepressants. In this review we aim to discuss the role of zinc in the pathophysiology and treatment of depression with regard to the monoamine hypothesis of the disease. Particular attention will be paid to the recently described zinc-sensing GPR39 receptor as well as aspects of zinc deficiency. Furthermore, an attempt will be made to give a possible explanation of the mechanisms by which zinc interacts with the monoamine system in the context of depression and neural plasticity.

Effects of Magnesium Supplementation on Unipolar Depression: A Placebo-Controlled Study and Review of the Importance of Dosing and Magnesium Status in the Therapeutic Response

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 usefulness of monitored therapy using Clozapine concentration in the blood serum for determining drug dose in Polish schizophrenic patients.

BACKGROUND The aim of the study is to evaluate the advisability of systematic monitoring of clozapine (CLO) concentration in serum during treatment of schizophrenia in Polish psychiatric patients. METHOD The concentration of CLO and its metabolites: norclozapine (NCLO) and clozapine N-oxide (CLO-NO) in serum obtained from 107 patients suffering from schizophrenia was determined by high performance liquid chromatography (HPLC) method. There were two groups of patients. In the first group of patients (n=95) the concentration of drug and its metabolites was determined by one-time testing. Correlations were tested using the test statistics. In the second group of patients (n=12), 51 samples of serum were provided by the same patient in different time spans (from 6days to 14 months after the beginning of the treatment). RESULTS Concentrations of CLO and its metabolites in blood serum do not always show a linear dependence on the applied dose for individual patients. CONCLUSION The high volatility of CLO concentrations in blood serum of patients treated with identical doses of the drug confirmed the validity of the monitored therapy.