Krzysztof Styczeń

The serum zinc concentration as a potential biological marker in patients with major depressive disorder.

Despite many clinical trials assessing the role of zinc in major depressive disorder (MDD), the conclusions still remain ambiguous. The aim of the present clinical study was to determine and comparison the zinc concentration in the blood of MDD patients (active stage or remission) and healthy volunteers (controls), as well as to discuss its potential clinical usefulness as a biomarker of the disease. In this study 69 patients with current depressive episode, 45 patients in remission and 50 controls were enrolled. The zinc concentration was measured by electrothermal atomic absorption spectrometry (ET AAS). The obtained results revealed, that the zinc concentration in depressed phase were statistically lower than in the healthy volunteers [0.89 vs. 1.06xa0mg/L, respectively], while the zinc level in patients achieve remission was not significantly different from the controls [1.07 vs. 1.06xa0mg/L, respectively]. Additionally, among the patients achieve remission a significant differences in zinc concentration between group with and without presence of drug-resistance in the previous episode of depression were observed. Also, patients in remission demonstrated correlation between zinc level and the average number of depressive episodes in the last year. Serum zinc concentration was not dependent on atypical features of depression, presence of psychotic symptoms or melancholic syndrome, age, age of onset or duration of disease, number of episodes in the life time, duration of the episode/remission and severity of depression measured by the Hamilton Rating Scale for Depression (HDRS), and the Montgomery-Asberg Depression Rating Scale (MADRS). Concluding, our findings confirm the correlation between zinc deficit present in the depressive episode, and are consistent with the majority of previous studies. These results may also indicate that serum zinc concentration might be considered as a potential biological marker of MDD.

Associations of Serum Cytokine Receptor Levels with Melancholia, Staging of Illness, Depressive and Manic Phases, and Severity of Depression in Bipolar Disorder.

To examine cytokine receptor biomarkers in bipolar disorder (BD), we recruited 133 well-phenotyped BD patients and 50 normal controls and measured serum levels of soluble interleukin 1 receptor antagonist (sIL-1RA), soluble interleukin-2 receptor (sIL-2R), sIL-6R, and tumor necrosis factor receptor 60 and 80xa0kDa (sTNFR60/80). sIL-1RA and sTNFR80 are significantly higher in BD than in controls and sTNFR80 and higher in melancholic than in non-melancholic patients and controls. Kapczinski’s stages 3 + 4 are characterized by lowered sIL-2R and increased sTNFR80 levels. Acute phase depression is characterized by increased sTNFR80 levels as compared with controls, manic, and euthymic patients. Both sTNFR60 and sTNFR80 levels are significantly and positively related with severity of depression but not mania. Logistic regression analysis showed that the significant predictors for BD are increased sIL-1RA levels, nicotine dependence and a family history of depression and alcoholism. The risk factors for stages 3 + 4 are lowered sIL-2R levels and nicotine dependence. Melancholia is predicted by higher sTNFR80 levels and female sex. Severity of depression is predicted by female sex, nicotine dependence, and increased sTNFR60 and sTNFR80 levels. Cell-mediated immunity is activated during a current episode of depression but not (hypo)mania or the euthymic state. There are no associations between the biomarkers and age at onset, duration of illness, severity of mania, bipolar (BP)2 or BP1 subtypes, rapid cycling, atypical depression, psychotic or suicidal symptoms, and a family history of psychiatric disease. The results show that increased sIL-1RA may be a trait marker of BD, increased sTNFR80 a state marker of the depressive phase, especially melancholia, while lower sIL-2R but higher sTNFR80 may be staging biomarkers.

Decreased serum zinc concentration during depressive episode in patients with bipolar disorder

OBJECTIVESnZinc may be involved in the pathophysiology and treatment of depressive disorder. However, data on this issue in bipolar disorder (BD) are limited. The aim of the study was to assess zinc concentrations in the blood serum of patients at various phases and stages of bipolar disorder.nnnMETHODSnThe study included 129 patients with a diagnosis of bipolar disorder type I (n=69) or type II (n=60). Fifty-eight were in a depressive episode, 23 in a manic episode and 48 in remission. Fifty healthy volunteers made a control group. Zinc concentration was measured using flame atomic absorption spectrometry.nnnRESULTSnSerum zinc level in patients diagnosed with BD type I in the depressive phase was significantly reduced as compared with mania, remission and healthy subjects. In the BD type II, serum zinc level in hypomania, depression or remission phase was not significantly different from the control group. In the whole group, lower level of zinc in depression compared to remission and control subjects was found during late stage of the illness but not in the early stage. Zinc concentration was not dependent on the severity of manic or depressive symptoms and subtype of depression but correlated positively with the number of manic/hypomanic relapses in the past year.nnnLIMITATIONSnLack of prospective model, heterogeneity of pharmacological treatment, small number of subgroups presenting specified clinical features.nnnCONCLUSIONSnDecreased serum zinc concentration occurs in depression in BD type I and probably in depression in the late stage of BD.

Phospholipid-protein balance in affective disorders: Analysis of human blood serum using Raman and FTIR spectroscopy. A pilot study.

Raman and FTIR (Fourier Transform Infra Red) spectroscopies provide information on the chemical structure of compounds through identification and analysis of functional groups. In the present study, both spectroscopic techniques were used for investigating the phospholipid - protein balance in blood serum of depressed subjects (major depressive disorder and bipolar disorder type I or II) taking also into account their age and gender. The obtained results were compared with those of healthy subjects. The Raman and FTIR (using ATR (Attenuated Total Reflectance) technique), spectra show that a correlation between the level of phospholipids and proteins exists. Indeed, in depressed subjects the quantity of phospholipids and proteins is lower, compared to healthy ones. The second derivative of FTIR spectra shows that phospholipids directly affect the structure of proteins and their functions. In all male depressed subjects a higher amount of phospholipids and proteins compared to female depressed subjects was measured, offering them faster recovery perspectives. Spectroscopy results show that the phospholipids and proteins levels are lower in depressed subjects from 41 to 65 compared to the age group between 20 and 40, independently from the gender. Consequently, this study shows that Raman and infrared spectroscopies might be applied as a diagnostic tool to evaluate the balance between phospholipids and proteins in blood serum as a potential biomarker in depressive disorders.

Lipid Peroxidation and Immune Biomarkers Are Associated with Major Depression and Its Phenotypes, Including Treatment-Resistant Depression and Melancholia

To examine immune-inflammatory and oxidative (I&O) biomarkers in major depression (MDD) and its related phenotypes, we recruited 114 well-phenotyped depressed patients and 50 healthy controls and measured serum levels of interleukin (IL)-1α, soluble IL-1 receptor antagonist (sIL-1RA), soluble IL-2 receptor (sIL-2R), soluble IL-6 receptor (sIL-6R), soluble tumor necrosis factor receptor 60 and 80xa0kDa (sTNF-R1/R2), and thiobarbituric acid reactive substances (TBARS). Obtained results indicate that MDD is characterized by increased sIL-1RA, sTNF-R1, and TBARS concentrations. Melancholic depression is associated with increased sIL-6R but lowered IL-1α levels. A current episode of depression is accompanied by significantly increased sIL-6R compared to the remitted state. Treatment-resistant depression (TRD) is accompanied by increased sIL-6R and TBARS but lowered sTNF-R2 levels compared to non-TRD patients. These immune markers are not significantly correlated with Hamilton Depression Rating Scale (HDRS), Montgomery-Asberg Depression Scale (MADRS), number episodes, or age at onset. Our findings show that increased sIL-1RA, sTNF-R1, and TBARS levels may be trait markers of depression, while increased sIL-6R levels may be a state marker of melancholia and an acute phase of depression. MDD is accompanied by increased lipid peroxidation and simultaneous activation of immune pathways, and the compensatory anti-inflammatory reflex system (CIRS). TRD is characterized by highly increased oxidative stress and probably increased TNFα and IL-6 trans-signalling. Novel treatments for major depression should target oxidative stress pathways, while new treatments for TRD should primary target lipid peroxidation and also activated immune-inflammatory pathways.

Lurasidone: The 2016 update on the pharmacology, efficacy and safety profile

The aim of this paper was to review the up-to-date evidence base on pharmacology and clinical properties of lurasidone. Lurasidone is an atypical antipsychotic, approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia and bipolar depression. Lurasidone exhibits both an antipsychotic and antidepressant action. Based on its pharmacodynamics profile, it is believed that the drugs clinical action is mediated mainly through the D2, 5-HT2A and 5-HT7 receptors inhibition. In patients with schizophrenia the recommended dose range is 40-80mg/day. In bipolar depression broader dosage ranges (20-120mg/day) were found to be effective. In terms of side effects, higher rates of akathisia, parkinsonism and hyperprolactinemia were observed in individuals receiving lurasidone (as compared to patients treated with other atypical antipsychotics). On the other hand, treatment with lurasidone yields relatively lower risk for developing sedation or overweight/obesity.

Study of the Serum Copper Levels in Patients with Major Depressive Disorder

Copper may be involved in the pathophysiology of depression. Clinical data on this issue are very limited and not conclusive. The purpose of the study was to determine the copper concentration in the serum of patients with major depressive disorder and to discuss its potential clinical usefulness as a biomarker of the disease. A case–control clinical study included 69 patients with current depressive episode, 45 patients in remission and 50 healthy volunteers. Cu concentration was measured by electrothermal atomic absorption spectrometry (ETAAS). The mean serum copper level in depressed patients was slightly lower (by 11xa0%; not statistically significant) than in the control group. Furthermore, there was no significant difference in Cu2+ concentration between depressive episode and remission, nor between remission and control group. In the remission group were observed significant correlations between copper levels and the average number of relapses over the past years or time of remission. There was no correlation between serum copper and severity of depression, as measured by HDRS and MADRS. The obtained results showed no significant differences between the copper concentration in the blood serum of patients (both with current depressive episode and in remission) and healthy volunteers, as well as the lack of correlations between the copper level in the active stage of the disease and clinical features of the population. Our study is the first conducted on such a large population of patients, so the results may be particularly important and reliable source of knowledge about the potential role of copper in depression.

Are there differences in lipid peroxidation and immune biomarkers between major depression and bipolar disorder: Effects of melancholia, atypical depression, severity of illness, episode number, suicidal ideation and prior suicide attempts

Background: There is evidence that major depression (MDD) and bipolar disorder (BD) are accompanied by activated immune & oxidative (I&O) pathways. Methods: To compare I&O biomarkers between MDD and BD we assessed serum levels of thiobarbituric acid reactive substances (TBARS; a lipid peroxidation marker), soluble interleukin‐2 receptor (sIL‐2R), sIL‐6R, IL‐&agr;, sIL‐1R antagonist (sIL‐1RA), tumor necrosis factor receptor 60 kDa/80 kDa (sTNFR60/R80) in 114 MDD and 133 BD patients, and 50 healthy controls. We computed z‐unit weighted indices reflecting the 5 cytokine receptor levels (zCytR), cell‐mediated immunity (zCMI) and I&O pathways (zCMI + TBARS). Results: There are no significant differences in biomarkers between MDD and BD. BD/MDD with atypical features is characterized by increased sIL‐6R and TBARS, whereas melancholia is associated with higher TBARS and lower sTNFR60 levels. Severity of illness, as measured with the Hamilton Depression Rating Scale, is correlated with increased sIL‐6R, sTNFR80, TBARS, zCytR and zCMI + TBARS. The number of episodes the year prior to blood sampling is positively associated with sTNFR80, TBARS, zCMI, zCMI + TBARS, while number of hospitalizations is positively associated with sIL‐1RA. Prior suicidal attempts are associated with increased sIL‐1RA, IL‐1&agr;, zCMI, TBARS and zCMI + TBARS, while TBARS is associated with current suicidal ideation. Conclusions: There are no I&O biomarker differences between MDD and BD. Atypical depression is associated with increased IL‐6 trans‐signaling and lipid peroxidation. Severity of depression, number of episodes and suicidal attempts are associated with activated I&O pathways. Increased TBARS is the single best predictor of BD/MDD, atypical depression, melancholia and current suicidal ideation. HighlightsThere are no immune & oxidative (I&O) biomarker differences between major depression (MDD) and bipolar disorder (BD).Atypical depression is associated with increased IL‐6 trans‐signaling and lipid peroxidation.Severity of depression, number of episodes and suicidal attempts are associated with activated I&O pathways.Increased TBARS is the single best predictor of BD/MDD, atypical depression, melancholia and current suicidal ideation.

Vortioxetine: A review of the pharmacology and clinical profile of the novel antidepressant

The aim of this paper was to review the up-to-date evidence base on pharmacology and clinical properties of vortioxetine. Vortioxetine is a novel antidepressant, approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). Because vortioxetine exhibits both an antidepressant and anxiolytic effect, it may be effective in treating both depressive and anxiety disorders, such as generalized anxiety disorder (GAD). Based on its pharmacodynamics profile and preclinical studies, it is believe that the drugs clinical action is mediated mainly by selective blockade of serotonin reuptake (by inhibiting the serotonin transporter [SERT]) and direct modulation of 5-HT receptors activity (such as 5-HT3, 5-HT7, 5-HT1D and 5-HT1B). In patients with MDD the recommended doses range is 5-20mg/day. Vortioxetine was shown to be more effective than placebo both in MDD and GAD. In terms of side effects, nausea, vomiting, diarrhea, and dry mouth were most commonly observed in individuals receiving vortioxetine. In direct comparison to duloxetine, vortioxetine is found to have a smaller efficacy but had a lower risk of developing the common antidepressant-induced adverse effects.

A web-based study of bipolarity and impulsivity in athletes engaging in extreme and high-risk sports

Background We hypothesised that men and women who engage in extreme or high-risk sports would score higher on standardised measures of bipolarity and impulsivity compared to age and gender matched controls. Methods Four-hundred and eighty extreme or high-risk athletes (255 males and 225 females) and 235 age-matched control persons (107 males and 128 females) were enrolled into the web-based case-control study. The Mood Disorder Questionnaire (MDQ) and Barratt Impulsiveness Scale (BIS-11) were administered to screen for bipolarity and impulsive behaviours, respectively. Results Results indicated that extreme or high-risk athletes had significantly higher scores of bipolarity and impulsivity, and lower scores on cognitive complexity of the BIS-11, compared to controls. Further, there were positive correlations between the MDQ and BIS-11 scores. Conclusion These results showed greater rates of bipolarity and impulsivity, in the extreme or high-risk athletes, suggesting these measures are sensitive to high-risk behaviours.