In schizophrenia,non-remitters and partial remitters to treatment with antipsychotics are qualitatively distinct classes with respect to neurocognitive deficits and neuro-immune biomarkers: results of soft independent modeling of class analogy

Around one third of schizophrenia patients are non-responders to antipsychotic therapy. The present study aimed to delineate the pathway-phenotypes of non-remitters (NRTT) and partial remitters (PRTT) to treatment with antipsychotics as defined using the Global Clinical Impression scales. We recruited 60 NRTT, 50 PRTT and 43 healthy controls and measured schizophrenia symptoms, neurocognitive tests, plasma CCL11, interleukin-(IL)-6, IL-10, Dickkopf protein 1 (DKK1), high mobility group box-1 protein (HMGB1), κ- and μ-opioid receptors (KOR and MOR, respectively), endomorphin-2 (EM-2), and β-endorphin. Soft independent modeling of class analogy (SIMCA) showed that NRTT and PRTT are significantly discriminated with a cross-validated accuracy of 94.7% and are qualitatively distinct classes using symptomatome, and neuro-immune-opioid-cognitome (NIOC) features as modeling variables. Moreover, a NIOC pathway phenotype discriminated PRTT from healthy controls with an accuracy of 100% indicating that PRTT and controls are two qualitative distinct classes. Using NIOC features as discriminatory variables in SIMCA showed that all PRTT were rejected as belonging to the normal control class and authenticated as belonging to their target class. In conclusion, a non-response to treatment can best be profiled using a SIMCA model constructed using symptomatome and NIOC features. A partial response should be delineated using SIMCA by authenticating patients as controls or PRTT instead of using scale-derived cut-off values or a number of scale items being rated mild or better. The results show that PRTT is characterized by an active NIOC pathway phenotype and that both NRTT and PRTT should be treated by targeting neuro-immune and opioid pathways.

     

Chronic fatigue syndrome and fibromyalgia-like symptoms are an integral component of the phenome of schizophrenia: neuro-immune and opioid system correlates

Metabolic Brain Disease - Physiosomatic symptoms are an important part of schizophrenia phenomenology. The aim of this study is to examine the biomarker, neurocognitive and symptomatic correlates...     

Total and ionized calcium and magnesium are significantly lowered in drug-naïve depressed patients: effects of antidepressants and associations with immune activation

Metabolic Brain Disease - Major depressive disorder (MDD) is associated with alterations in calcium (Ca) and magnesium (Mg), as well as circulating pro- and anti-inflammatory cytokines....     

Cytokine dependent hematopoietic cell linker (CLNK) is highly elevated in blood transfusion dependent beta-thalassemia major patients

BackgroundTransfusion-dependent β-thalassemia (TDT) is a severe form of thalassemia caused by mutations in the β-globin gene, resulting in partial or complete deficiency of β-globin chains. This deficiency results in oxidative stress, dyserythropoiesis, and chronic anemia. Cytokine-dependent hematopoietic cell linker (CLNK) belongs to adaptor proteins that have the capacity to interact with multiple signalling proteins and function in the organisation of the molecular components required for signal transduction.ObjectivesThis is the first study which measured serum CLNK in TDT patients and examines the correlation between CLNK and iron overload biomarkers.Patients and methodsSixty children with TDT and 30 normal children (aged 3–12 years old) participated in the present study. The patients were on blood transfusion as a part of their treatment regimen. Serum C-reactive protein was negative in all samples.ResultsThe results showed significantly higher (P < 0.001) serum CLNK levels in TDT patients as compared with controls. The TDT diagnosis explained 19.4% of the variance in CLNK levels. The increased levels of CLNK were significantly associated with indicants of iron overload, namely increased ferritin levels.ConclusionsIncreased CLNK levels in TDT may be explained by reciprocal effects between immune signalling and immature erythrocytes, which release soluble receptors and signalling molecules, including CLNK, in the blood.     

Effect of serum fibroblast growth factor receptor 2 and CAPS proteins on calcium status in β-thalassaemia major patients who are free from overt inflammation

Bone disorders and disturbed calcium (Ca) homeostasis are common disorders in β-thalassaemia major (β-TM). In the present study, two bone related markers are studied in β-TM patients with negative C-reactive protein for the first time; fibroblast growth factor receptor 2 (FGFR2) and CAPS protein. Another goal is to estimate the correlation between the recent parameters and bone biomaterials as a function of iron status parameters in β-TM patients. The results revealed that, in patients with β-TM serum FGFR2, CAPS, alkaline phosphatase (ALP) and Mg significantly increased while serum Ca levels were low as compared with controls. Ca status is correlated with iron overload in β-TM. A significant correlation was present between CAPS and FGFR2. In conclusion, FGFR2 and CAPS associated with Ca status and subsequent bone disturbances in β-TM patients. Their level can be predicted from the equation: CAPS =0.001ALP +0.48FGFR2-1.26Ca – 3.95Pi +12.76 with acceptable applicability.     

Lowered zinc and copper levels in drug-naïve patients with major depression: Effects of antidepressants,ketoprofen and immune activation

Abstract

Objectives: The aim of the present work is to examine the effects of treatment with sertraline with and without ketoprofen on serum levels of zinc and copper in association with immune-inflammatory biomarkers in drug-naïve major depressed patients.

Methods: We measured serum zinc and copper, interleukin (IL)-1β, IL-4, IL-6, IL-18, interferon-γ, and transforming growth factor-β1 in 40 controls and 133 depressed patients. The clinical efficacy of the treatment was measured using the Beck Depression Inventory-II (BDI-II) at baseline and 8?weeks later.

Results: We found significantly reduced serum zinc and copper in association with upregulation of all cytokines, indicating activation of the immune-inflammatory responses system (IRS) and the compensatory immune regulatory system (CIRS). Treatment with sertraline significantly increased zinc and decreased copper. During treatment, there was a significant inverse association between serum zinc and immune activation. The improvement in the BDI-II during treatment was significantly associated with increments in serum zinc coupled with attenuation of the IRS/CIRS.

Conclusions: Lower zinc is a hallmark of depression, while increments in serum zinc and attenuation of the immune-inflammatory response during treatment appear to play a role in the clinical efficacy of sertraline.     

Lack of correlation between non-labile iron parameters,total carbonyl and malondialdehyde in major thalassemia

Thalassemia patients are at high risk of iron-induced toxicity and oxidative stress consequences. The present cross-sectional study is conducted to determine whether or not lipid peroxidation or protein oxidation is correlated with iron parameters in patients with thalassemia major. To prove this hypothesis, malondialdehyde and total carbonyl were correlated with the degree of excess iron concentration in the patients. A total of 118 Arabic Iraqi patients and 30 healthy children were participated in the present study. Results showed a significant increase (p<0.05) in serum total carbonyls, malondialdehyde and the iron indices of patients as compared with the control group. Total iron binding capacity and transferrin concentrations decreased significantly (p<0.05) in patients with thalassemia compared with the control group. The results also showed a lack of a significant correlation between each serum malondialdehyde and total carbonyl with each component of iron status. In conclusion, total carbonyls and malondialdehyde were increased in thalassemia patients indicating the vulnerability of these patients to tissue injury caused by oxidative stress. The formation of total carbonyl and malondialdehyde are independent of excess non-labile iron concentration, indicating that different mechanisms are involved in injury caused by the labile iron and in the formation of oxidation end products.