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Clozapine is the gold standard for treatment-resistant schizophrenia; however, its superior efficacy is accompanied by potentially serious adverse events (neutropenia, seizures, constipations, pneumonia), many of which are also concentration-dependent. As such, clozapine dose titration should be guided by therapeutic drug monitoring (TDM). However, access to TDM is often limited. The present study describes a new deep neural network that can predict the concentrations, toxicity and therapeutic dose range for clozapine and norclozapine. The model was trained on basic clinical data (biological sex, age, clozapine daily dose, BMI, CRP and number of CYP 1A2 and 3A4 substrates, inhibitors and inducers) from 69 patients treated with different clozapine doses. Our findings provide the training efficacy data for the model, as well as an analysis of clozapine and norclozapine blood concentrations in a test group of three additional patients, to demonstrate its practical capabilities. The model is licensed on a free and permissive 2-Clause BSD license and is available to all clinicians; it can be accessed as a web application, available at https://csk.umed.pl/clotop., Competing Interests: Declaration of competing interest Nothing to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Deprivation of sleep (DS) and its effects on circadian rhythm gene expression are not well understood despite their influence on various physiological and psychological processes. This study aimed to elucidate the changes in the expression of circadian rhythm genes following a night of sleep and DS. Their correlation with sleep architecture and physical activity was also examined. The study included 81 participants who underwent polysomnography (PSG) and DS with actigraphy. Blood samples were collected after PSG and DS. Expression levels of brain and muscle ARNT-like 1 (BMAL1), circadian locomotor output cycles kaput (CLOCK), neuronal PAS domain protein 2 (NPAS2), period 1 (PER1), cryptochrome 1 (CRY1) and nuclear receptor subfamily 1 group D member 1 (NR1D1) were analyzed using qRT-PCR. DS decreased the expression of CLOCK and BMAL1 while increasing PER1. PER1 expression correlated positively with total sleep time and non-rapid-eye-movement (NREM) sleep duration and negatively with sleep latency, alpha, beta and delta waves in the O1A2 lead. Physical activity during DS showed positive correlations with CLOCK, BMAL1, and CRY1. The findings highlight the role of PER1 in modulating sleep patterns, suggesting potential targets for managing sleep-related disorders. Further research is essential to deepen the understanding of these relationships and their implications.

Background: The molecular underpinnings of insufficient sleep remain underexplored, with disruptions in the neurotrophic signaling pathway emerging as a potential explanation. Neurotrophins (NTs), including brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT3), neurotrophin 4 (NT4), and glial-cell-line-derived growth factor (GDNF), play crucial roles in nerve cell growth and repair. However, their associations with sleep patterns are poorly understood. This study aimed to investigate the relationship between the chosen neurotrophins and objective sleep parameters., Methods: The study involved 81 participants subjected to polysomnography (PSG). Blood samples were collected after PSG. The mRNA expression and serum protein concentrations of BDNF, GDNF, NT3, and NT4 were measured using real-time quantitative reverse-transcription PCR (qRT-PCR) or enzyme-linked immunosorbent assay (ELISA) methods, respectively., Results: BDNF and NT3 proteins were negatively correlated with NREM events, while NT4 protein positively correlated with REM events. Electroencephalography power analysis revealed BDNF protein's negative correlation with delta waves during rapid eye movement and non-rapid eye movement sleep., Conclusion: The study highlights associations between neurotrophins and sleep, emphasizing BDNF's role in regulating NREM and REM sleep. The EEG power analysis implicated BDNF in delta wave modulation, shedding light on potential neurotrophic mechanisms underlying sleep effects on cognitive and mood processes.

Sarcosine (N-methylglycine), a glutamatergic modulator, reduces the primary negative symptoms of schizophrenia. These beneficial changes might be mediated by trophic factors such as epidermal growth factor (EGF). We assessed associations between initial serum EGF levels or changes in serum EGF levels and symptom severity during the addition of sarcosine to stable antipsychotic treatment and thereby evaluated the associations between glutamatergic modulation, clinical changes and peripheral EGF concentrations. Fifty-eight subjects with a diagnosis of chronic schizophrenia with dominant negative symptoms, stably treated with antipsychotics, completed a prospective 6-month, randomized, double-blind, placebo-controlled study. Subjects received orally 2 g of sarcosine ( n = 28) or placebo ( n = 30) daily. Serum EGF levels and symptom severity (using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS)) were assessed at baseline, 6-week and 6-month follow-up. Augmentation antipsychotic treatment with sarcosine had no effect on EGF serum levels at any time points. Only the sarcosine group showed a significant improvement in negative symptoms, general psychopathology subscales and the overall PANSS score. We found a reduction in serum EGF levels in the placebo group, but levels in the sarcosine remained stable during the study. Our data indicate that improvement in negative symptoms due to sarcosine augmentation is not directly mediated by EGF, but effective treatment may induce the production or block the decrease in EGF concentrations, which indicates the neuroprotective effect of treatment and confirms the relationship between neuroprotection and EGF levels.

Introduction: The objective of the study was to evaluate safety and tolerability of tDCS treatment in schizophrenia patients. Our results confirm already established evidence that tDCS is a very safe and well tolerated method of non-invasive brain stimulation for patients with schizophrenia., Subjects and Methods: Database of 219 tDCS sessions in patients with paranoid schizophrenia has been analyzed., Results: During 219 tDCS sessions there were no serious adverse effects. All adverse effects were mild to moderate and transitory and the most frequent were: itching/tingling (81%), burning (53%) or heat sensation (48%) and skin reddening (35%). Itching/tingling and burning sensation were also frequently reported as at least moderately severe. All major adverse events (itching/tingling, burning/heat sensation) were more often localized by patients under the anodal pad. Men were more prone to experience some adverse events (itching/tingling, burning/heat sensation, skin reddening, metallic taste and tiredness). Most of the adverse events had their onset at the beginning of tDCS session, resolved by the end of tDCS session (with the exception of skin reddening, which recovered within 30 minutes after stimulation) and were associated with mild or moderate distress., Conclusion: Our results confirm already established evidence that tDCS is a very safe and well tolerated method of non-invasive brain stimulation for patients with schizophrenia.

Competing Interests: The authors have no conflicts of interest or financial disclosures to report.

Introduction: Although schizophrenia is a severe mental illness, whose etiology is still largely unknown, its pathogenesis may be associated with dysregulation of the immune mechanisms. The present study compares the levels of interleukin (IL)-10, interleukin-8 (CXCL8), and fractalkine (CX3CL1) between schizophrenia patients and healthy controls. It also assesses the ability of peripheral peripheral blood mononuclear cells (PBMCs) to produce these cytokines spontaneously and following mitogen-stimulation., Materials and Methods: A prospective study was performed of 60 adult schizophrenia patients and 32 controls. CXCL8, IL-10, and fractalkine concentrations were measured in serum and supernatants from cultured PBMCs. Anthropometric (BMI, WHR) and body composition measurements were taken using bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA)., Results and Conclusion: The schizophrenia patients demonstrated significantly higher levels of serum CXCL8 (schizophrenia: 13.4 ± 15.7 pg/mL, control: 6.9 ± 4.2 pg/mL, p = 0.001) and lower level of serum fractalkine (schizophrenia: 22.8 ± 9.9 pg/mL, control: 45.4 ± 84.5 pg/mL, p = 0.041). Serum IL-10 levels did not significantly differ. No in vitro synthesis of fractalkine was observed. Neither unstimulated or PHA-stimulated CXCL8 secretion differed between the two groups ( p >0.05). The patients not taking mood stabilizers (MS-) demonstrated significantly higher CXCL8 levels than those on mood stabilizers (MS+) ( p = 0.03) and control ( p < 0.001). In addition, the MS- sub-group demonstrated significantly lower serum fraktalkine than controls ( p = 0.009). These effects could be described as pseudo-normalization of CXCL8 and fractalkine in schizophrenia patients taking mood stabilizers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Arabska, Wysokiński, Brzezińska-Błaszczyk and Kozłowska.)

There is growing evidence that immune/inflammatory processes are related to the etiology of schizophrenia. Danger-/damage-associated molecular patterns (DAMPs), also called alarmins, are recognized as inflammatory mediators that play an important role in the development of many infection-induced or sterile inflammatory diseases. The importance of DAMPs particles in various mental disorders is still not clear. Therefore, this study aimed to evaluate serum levels of the most promising alarmins (IL-33, sST2, HMGB1, and S100B), as potent schizophrenia biomarkers. Sixty-eight adult patients with chronic schizophrenia and twenty-nine healthy volunteers were included in this prospective study. Enzyme-linked immunosorbent assay (ELISA) was used to assess the serum concentration of IL-33, sST2, HMGB1, and S100B. We documented that the serum levels of IL-33 (p = 0.006), sST2 (p = 0.02), HMGB1 (p = 0.01), and S100B (p = 0.04) are significantly higher in patients with schizophrenia than in healthy subjects. In male, but not in female, patients with schizophrenia, we found a significant difference in the serum IL-33, sST2, and HMGB1 concentrations as compared to the healthy men. In both male and female patients with schizophrenia, there was no significant difference in the serum concentrations of S100B in comparison to control subjects. In patients with schizophrenia, no significant correlations were noticed neither between any studied alarmins and PANSS scores nor between CDSS scores. Given that all investigated alarmins participate in the course of the neuroinflammatory process, they might be considered as biomarkers of neuroinflammatory process underlying schizophrenia. Based on our observations, it seems that the most useful biological indicator of schizophrenia would be IL-33., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objective: Modulation of glutamatergic neurotransmission in schizophrenia by sarcosine leads to a reduction in primary negative symptoms, while its metabolic profile is safe. In order to extend research in the area, we assessed serum levels of neuropeptide Y (NPY), a hypothalamic hormone related to anxiety and depression, also involved in mechanisms inducing weight gain. Additionally, we analyzed associations between NPY concentrations and its changes with severity of symptoms and metabolic parameters., Methods: A prospective 6-month, randomized, double-blind placebo-controlled trial was completed by 57 subjects with chronic schizophrenia with predominant negative symptoms and stable antipsychotic treatment. The participants received 2 g of sarcosine (n = 28) or placebo (n = 29) daily. We assessed serum NPY concentrations and severity of symptoms (with the Positive and Negative Syndrome Scale [PANSS] and Calgary Depression Scale for Schizophrenia) at the beginning of the study, after 6 weeks and 6 months., Results: Sarcosine did not affect NPY levels in all time points. The highest decrease in NPY concentrations was observed in the subjects who were initially depressed, who became euthymic at the last visit. We noticed an improvement in the total PANSS score, and negative symptom and general psychopathology subscales in the sarcosine group, however, without any correlation with NPY levels., Conclusion: The use of sarcosine does not change NPY levels. Peripheral NPY concentrations may be related to depressive symptoms in schizophrenia., (© 2020 John Wiley & Sons Ltd.)

Introduction: The aim of this study was to determine the mRNA expression profile of dopamine D 1 , D 2 , D 3 , D 4 and serotonin 5-HT 1A , 5-HT 2A , and 5-HT 3A receptors in peripheral blood mononuclear cells (PBMCs) in schizophrenia and the in vitro effect of antipsychotics on the expression of these receptors in PBMCs of healthy subjects. Materials and Methods: Twenty-seven patients with schizophrenia and 29 healthy controls were recruited for the study. All study subjects underwent thorough clinical assessment, including anthropometric and body composition measurements. The expression of mRNA for dopamine D 1-4 and serotonin 5-HT 1A-3A receptors was measured using quantitative RT-PCR in peripheral blood mononuclear cells. In vitro mRNA and protein expression of these receptors was measured using quantitative RT-PCR and Western Blotting in PBMCs cultured with quetiapine, haloperidol, aripiprazole, risperidone, olanzapine or clozapine at IC 50 , half of IC 50 , and one-quarter of IC 50 concentrations. Results: The key finding was that the schizophrenia group demonstrated significantly higher mRNA expression of D 1 , D 2 and D 4 receptors ( p < 0.001), and significantly lower mRNA expression of 5-HT 3A receptors ( p < 0.01). After adjusting for smoking, the mRNA expression of D 1 lost its significance, while that of D 3 , 5-HT 1A , 5-HT 2A became significant (all three were lower in the schizophrenia group). These receptors also demonstrated different ratios of mRNA expression in the schizophrenia group. The in vitro experiments showed that high concentrations of antipsychotics influenced the mRNA and protein expression of all studied receptors. Conclusion: Schizophrenia patients display a distinctive pattern of dopamine and serotonin receptor mRNA expression in blood mononuclear cells. This expression is little affected by antipsychotic treatment and it may therefore serve as a useful diagnostic biomarker for schizophrenia., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Wysokiński, Kozłowska, Szczepocka, Łucka, Agier, Brzezińska-Błaszczyk and Sobierajska.)

It has been suggested that immune-inflammatory processes might be involved in the etiopathogenesis of schizophrenia. Since growing evidence indicates that adipokines strongly modulate the course of immune response and inflammatory processes, it is currently suggested the contribution of those factors in the etiology of schizophrenia as well. The aim of this study was to determine the serum levels of 4 adipokines-apelin, resistin, chemerin, and omentin-in patients with schizophrenia as compared with healthy subjects. Fifty-seven adult patients with schizophrenia and 31 healthy volunteers were included in this prospective study. ELISA was used to measure the serum concentration of resistin, apelin, omentin-1, and chemerin. No difference in the mean concentration of resistin (p=0.20) and chemerin (p=0.30) between patients with schizophrenia and the healthy group was observed. Apelin concentration was significantly (p=0.004) lower in patients with schizophrenia as compared with controls. A significant difference in apelin level between men with schizophrenia and control group (p=0.04) was reported. Apelin concentration was significantly correlated with waist-to-hip ratio, whereas chemerin concentration was significantly correlated with the Positive and Negative Syndrome Scale G score. There exists evidence that apelin might be involved in the pathogenesis of schizophrenia., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction and Objectives: According to immunological theory of schizophrenia, dysfunctions of the immune system are linked with the pathology of schizophrenia. Among cytokines, tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) seem to be correlated with psychopathology of schizophrenia. Both IL-6 and TNF-α are produced in the fat tissue by adipocytes. Thus, cytokine levels in obese patients are increased compared with healthy subjects. These metabolic underlying mechanisms may be an important confounding factor in the studies on cytokines levels in schizophrenia. The aim of this study was to evaluate how metabolic alterations affect peripheral IL-6 and TNF-α levels in schizophrenia patients., Materials and Methods: This was a case-control study, 30 schizophrenia patients were recruited in the study group and 30 healthy subjects were matched by sex and age. Serum levels of TNF-α and Il-6 were measured using ELISA test, together with detailed anthropometric, laboratory and body composition parameters (determined using bioelectric impedance analysis)., Results and Conclusions: Serum TNF-α concentration in the schizophrenia group was 6.05 ± 1.61 ng/mL and 5.94 ± 1.26 ng/mL in the control group. The difference between these two groups was not significant (p = .79). Serum IL-6 concentration in the schizophrenia group was 1.54 ± 1.46 ng/mL and in the control group 1.39 ± 1.39 ng/mL. Again, the difference was not significant (p = .51). We have analysed the relationship between anthropometric and metabolic variables and serum IL-6 and TNF-α concentrations. In conclusion, TNF-α was more sensitive to metabolic alterations compared with IL-6. This observation may be beneficial for further research on immune system in schizophrenia, indicating that studies of IL-6 and TNF-α should be controlled at least for major metabolic parameters (BMI, WHR)., Competing Interests: Declaration of Competing Interest None to declare, (Copyright © 2020 Elsevier B.V. All rights reserved.)

The purpose of the article: Brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (MMP-9) are involved in the processes of neurogenesis, synaptic plasticity, learning and memory. Growing number of studies shows a relationship between BDNF or MMP-9 and schizophrenia. Also, BDNF and MMP-9 levels may be affected by metabolic parameters, such as obesity or dyslipidemia. Our hypothesis is that alterations of BDNF or MMP-9 levels in schizophrenia might be secondary to metabolic abnormalities, often found among schizophrenia patients. Materials and methods: We have compared BDNF and MMP-9 between patients with schizophrenia ( n  = 64, age 49 ± 8.2 y) and healthy controls ( n  = 32, age 51 ± 8.9 y) in the context of cardio-metabolic parameters. Serum levels of BDNF and MMP-9 were measured using ELISA test, body composition parameters were determined using bioelectric impedance analysis. Results and conclusions: Our results showed significantly lowered serum BDNF concentration in the schizophrenia group (schizophrenia: 23.8 ± 7.83 ng/mL, control: 27.69 ± 8.11 ng/mL, p  = 0.03). Serum MMP-9 concentration in schizophrenia group did not differ compared with the control group (schizophrenia: 456.8 ± 278.4 ng/mL, control: 341.5 ± 162.4 ng/mL, p  = 0.07). After adjusting for age, all anthropometric parameters, body composition and laboratory tests BDNF were still significantly lower in the schizophrenia group. However, MMP-9 became significantly elevated in the schizophrenia group after adjusting for several anthropometric and body composition covariates. Our results confirmed reduced serum BDNF concentration in patients with schizophrenia. Also, this reduction seems to be independent of metabolic abnormalities. On the other hand, our hypothesis that MMP-9 level in schizophrenia is altered due to metabolic abnormalities might be true.

Increasing evidence has shown that the immune system is involved in the schizophrenia development, with alterations in immune cell reactivity being one possible factor contributing to its pathogenesis. The purpose of the study was to evaluate in vitro the capability of peripheral blood mononuclear cells (PBMCs) obtained from subjects with schizophrenia and controls to engage in spontaneous and phytohemagglutinin (PHA)-stimulated cytokine production. The concentrations of various cytokines (interleukin (IL)-1β, IL-17A, tumor necrosis factor (TNF), interferon (IFN)-γ and IL-10) in supernatants from cultured PBMCs were measured using the cytometric bead array. No significant differences in the spontaneous production of IL-1β, IL-17A, IFN-γ and IL-10 by PBMCs were detected between individuals with schizophrenia and controls. TNF synthesis by PBMCs was found to be lower among those with schizophrenia. In all subjects and controls, greater cytokine generation was associated with PBMCs treated with PHA compared with those that were not. The PBMCs from people with schizophrenia displayed considerably higher sensitivity to mitogen stimulation, as the production of IL-17A, TNF and IFN-γ was at least threefold of that observed in healthy subjects, which may be driven by antipsychotics taken by patients with schizophrenia. Correlation was observed between spontaneous production of IFN-γ and Positive and Negative Syndrome Scale G subscore (which measures the general symptoms of schizophrenia) and between PHA-stimulated synthesis of IL-17A and G subscore. Our data confirm that the immune system dysregulation may underlie schizophrenia pathophysiology. There is a potential possibility that immunological tests could be used as a diagnostic, therapeutic and side-effects biomarker for schizophrenia, but further studies are needed., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

The objective of this study was to evaluate the association between adiposity parameters and fasting serum levels of appetite-regulating peptides: leptin, neuropeptide Y (NPY), desacyl ghrelin, peptide YY(1-36), obestatin, cocaine- and amphetamine-regulated transcript (CART), and agouti-related protein in 30 healthy, non-obese subjects. Thirty European Caucasian adult participants were included in the study (17 men and 13 women). Body composition (body fat and lean body mass) was determined using bioelectrical impedance analysis. Concentrations of peptides in serum were assessed using the enzyme-linked immunosorbent assay. Women had higher level of leptin (P < 0.001), with no other differences for analyzed peptides. We have found a significant correlation between serum concentrations of CART and NPY (P < 0.001). Fasting leptin level was associated with age (P = 0.002), waist circumference (P < 0.001), and lean body mass (P < 0.001). Levels of ghrelin were lower in participants with dyslipidemia (P = 0.009). Levels of obestatin (P = 0.008) and leptin (P = 0.02) were higher in participants with insulin resistance. Associations between body fat and appetite-regulating peptides are more complex than simple feedback loops. Leptin is probably the first signal in the pathway that regulates body fat content, as of all analyzed peptides leptin was the only one that was associated with body composition or anthropometric measurements., Competing Interests: None

Interpersonal predictive coding (IPC) enables one to use the information conveyed by the communicative action of one agent to predict the response of another agent. IPC relies both on explicit reflective processes (processing of communicative intentions) and automatic reflexive processes (motor resonance). Predictive coding deficits may underlie positive symptoms in people with schizophrenia (SCZ), yet IPC has not been analyzed in SCZ. Thirty-nine SCZ and 22 controls (HC) completed a simultaneous masking detection task, during which they observed either communicative (Com) or individual (Ind) actions of agent A and had to report the presence of the agent B, who was shown in half of the trials. In line with previous findings, detection criterion was lowered after Com as compared to Ind, suggesting a higher tendency to report the presence of a second agent after observing agent A's communicative gestures . Surprisingly, this effect was found to a similar extent in both groups. Communicative criterion was linked to mentalizing abilities, but not to symptoms in SCZ. Finding that SCZ show similar IPC as HC adds to the previous evidence that reflexive processes may be relatively intact in patients. Furthermore, the level of reflective processes may be crucial for patients' social functioning.

Objective: Leptin is produced in the adipose tissue. It controls energy homeostasis by reducing food intake and increasing energy expenditure. According to the "leptin hypothesis of depression", chronic stress leads to reduced leptin concentration and leptin insufficiency may underlie depressive symptoms. However, it is also hypothesized that observed in depressed patients differences in leptin levels may be secondary to differences in adiposity. The aim of this case-control study is to evaluate fasting serum leptin levels in elderly women with major depression disorder and to compare them with non-depressed elderly women., Methods: We measured fasting serum leptins levels and body composition in 32 elderly (age ≥60 years) European Caucasian women with major depression disorder and in 49 non-depressed elderly (age ≥ 60 years) European Caucasian women., Results: There was no statistically significant difference (p=0.14) in fasting serum leptin level between patients with depression (3.04±1.79 ng/mL) and control subjects (2.46±1.70 ng/mL)., Conclusions: In two groups of subjects with comparable adiposity parameters we did not confirm that leptin level is changed in patients with depression. We assume that changes in leptin level in patients with depression may be mediated by adiposity.

Increasing evidence suggests that in addition to neurochemical abnormalities, various immunological alterations are related to the pathogenesis of schizophrenia. Toll-like receptors (TLRs) actively mediate immune/inflammatory processes and play a pivotal role in damage/danger recognizing. Therefore, the aim of this study was to compare the expression of TLRs in peripheral blood mononuclear cells (PBMCs) in schizophrenic patients with those of healthy subjects. It also measures the metabolic status of the study subjects. Twenty-seven adult European Caucasian patients with paranoid schizophrenia and twenty-nine healthy volunteers were included in this prospective study. qRT-PCR assessed TLR mRNA expression levels. Body composition was measured using two methods: bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). The TLR1, TLR2, TLR4, TLR6, and TLR9 expression were down-regulated, in opposite to TLR3 and TLR7 which manifested higher expression in patients with schizophrenia. TLR5 and TLR8 mRNAs did not differ between groups. TLR mRNA expression was highly correlated. Decreased TLR expression may protect against excessive cell stimulation via exogenous and/or endogenous ligands, and may be recognized as a counterbalancing mechanism limiting the excessive development of inflammation., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Sarcosine, glycine transporter inhibitor, increases glycine levels around NMDA receptor, improving primary negative symptoms of schizophrenia. The aim of our study was to find a potential relationship between initial TNF-alpha level, its changes and schizophrenia symptoms severity, resulting from adding sarcosine to a stable antipsychotic treatment. Sixty subjects with stable schizophrenia were randomized to receive either 2 g of sarcosine or placebo and completed a 6-month, double blind, placebo-controlled study. Three patients on sarcosine and one taking placebo did not complete TNF-alpha tests, planned at the beginning, after 6 weeks and after 6 months. For clinical assessments we used PANSS and CDSS scales. No changes in TNF-alpha serum concentrations in both groups at any time-points was noted. The sarcosine group achieved significant improvement in negative symptoms, general psychopathology and total PANSS score group, however without any significant correlations between TNF-alpha levels and PANSS scores in all assessments. Positive correlations between TNF-alpha levels and CDSS score were found in the placebo group and total study group. Initial TNF-alpha concentrations cannot be used as a predictor of the improvement resulting from adding sarcosine. Sarcosine does not significantly affect TNF-alpha levels. TNF-alpha may be involved in mechanisms related to depressive symptomatology in schizophrenia., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aim: Neurotrophin-3 (NT-3) is a neurotrophic factor responsible for promoting development, survival and function of neurons. NT-3 may be involved in the etiopathology of schizophrenia and mood disorders. However it must be cleared up if changes of NT-3 level are associated with schizophrenia itself or are secondary to certain symptoms (e.g. negative or depressive). The aim of this study was to examine whether the presence of negative or depressive symptoms affects peripheral NT-3 concentration in patients with schizophrenia., Methods: Data for 69 Caucasian adult hospitalized patients with chronic paranoid schizophrenia was compared with 27 healthy subjects. Level of NT-3 was measured in blood serum using enzyme-linked immunosorbent assay. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS)., Results: Patients were stratified into three sub-groups: non-depressed with no dominating negative symptoms (DEP-/NEG-), non-depressed with dominating negative symptoms (DEP-/NEG+) and depressed with dominating negative symptoms (DEP+/NEG+). Mean NT-3 concentration was higher in the DEP+/NEG + sub-group (202.61 ± 258.76 pg/mL) compared with the DEP-/NEG+ (83.79 ± 215.75 pg/mL), DEP-/NEG- (83.79 ± 215.75 pg/mL) and control (36.47 ± 73.84 pg/mL) sub-groups (p = 0.016)., Conclusion: We found that in schizophrenia serum level of neurotrophin-3 (NT-3) is increased only if depressive symptoms are present. There was no difference in NT-3 level between schizophrenia patients and controls., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: There are no studies comparing red blood cell parameters between patients with schizophrenia, bipolar disorder and unipolar depression. The aim of this study was to compare differences in erythrocyte parameters (red blood cell count (RBC), hematocrit (HCT), hemoglobin (HGB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red blood cell distribution width (RDW)) in patients with schizophrenia (SHZ), unipolar depression (UD) and bipolar disorder (BIP): bipolar depression (BD) and mania (BM)., Subjects and Methods: This was a retrospective, cross-sectional, naturalistic study of 2381 patients (SHZ n=1244; UD n=794; BIP n=343, BD n=259, BM n=84)., Results: There was significant difference for all red cell parameters between study groups (p<0.001). Age and sex may affect various erythrocyte parameters., Conclusion: There are differences in erythrocyte parameters between schizophrenia, unipolar depression and bipolar disorder. Compared with schizophrenia, significantly higher percentage of patients with affective disorders has anemia or abnormal erythrocyte parameters. Positive correlations between age and MCV and RDW and negative correlation between other parameters and age were found in all study groups.

Association between inflammation and depression, especially in elderly patients, leads to conclusions about their shared influence on risk of cardiovascular disease and death. It might be found useful to predict those issues by monitoring inflammatory parameters, such as neutrophil/lymphocyte ratio (NLR). The aim of this study was to determine the NLR in elderly patients with unipolar depression compared with non-depressed elderly patients. NLR was measured in 684 Caucasian subjects (depressed: n = 465, non-depressed: n = 219), aged ≥ 60 (depressed: mean age 74.8 ± 7.8 years, non-depressed: mean age: 71.1 ± 5.7 years). There were two subgroups within depressed patients: first episode depression (n = 138, 29.6%) and recurrent depression (n = 328, 70.3%). NLR was calculated as ratio between absolute neutrophil count to absolute lymphocyte count. NLR was significantly higher in unmedicated patients with depression compared with healthy control (2.10 ± 2.13 vs. 2.01 ± 0.75, p = 0.004). It was higher in first episode depression compared with recurrent depression (2.11 ± 1.76 vs 1.64 ± 1.04, p < 0.05). There was a positive correlation with severity of symptoms. We found non-specific effect of treatment with antidepressants or antipsychotics on lower NLR. Increased NLR in patients with first episode of depression compared to recurrent depression and healthy control may have important clinical consequences. Severity of symptoms are positively correlated with NLR, which may indicate that with increasing severity of depression, the risk of cardiovascular events is also rising, which leads to higher mortality. In elderly patients with depression even a small reduction of such risk may translate into better prognosis and improve quality of live. The difference between first episode and recurrent depression in terms of inflammatory biomarkers requires further studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Social predictive coding is now a well-established phenomenon in healthy individuals. It has been demonstrated that the communicative gestures of one agent may be effectively used to predict the actions of other agents. Individuals with schizophrenia often present social-cognitive deficits. The aim of this paper is to examine interpersonal predictive coding in patients with schizophrenia. Forty-six participants with schizophrenia and 40 healthy controls (HC) completed a simultaneous masking detection task (Interpersonal Detection Task; IDT), during which they observed point-light displays of two agents (A and B). During the communicative condition, agent A performed a communicative gesture, to which agent B responded accordingly. During the individual condition, agent A performed a noncommunicative action instead of the communicative gesture. Upon completion of the IDT, participants were asked to explicitly classify the actions of two agents based on nonmasked videos of point-light dyads. In line with previous findings, people with schizophrenia presented a reduced masking threshold for biological motion displays, and were less able to correctly recognize the actions of two agents during the explicit recognition task. However, observing the communicative gesture of agent A enhanced the visual discrimination of agent B in participants from all groups. This effect was observed despite the fact that SCZ presented overall diminished sensitivity to biological motion during IDT. Interpersonal predictive coding, which at least partially relies upon implicit processes, may be less impaired in people with schizophrenia than explicit social-cognitive processes (e.g., theory of mind). (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

Objectives: Impairments of Theory of Mind (ToM) have been repeatedly demonstrated in patients with schizophrenia (SCZ). However, only a handful of studies have explored deficits in affective and cognitive subcomponents of ToM. Thus, this study aims to examine affective and cognitive ToM abilities in SCZ by using a novel, verbal paradigm., Methods: Twenty-four SCZ and 22 healthy comparison subjects (HC) completed a battery of tasks, which consisted of: (i) Brief Cognitive Assessment Tool for Schizophrenia (B-CATS), (ii) three well-established tasks measuring social cognitive abilities, and (iii) original tasks which assess ability to infer cognitive and affective mental states based on everyday verbal social interactions., Results: In line with previous findings, SCZ were outperformed by HC in all tasks. However, the interaction effect of the group and the task showed that cognitive (as opposed to affective) ToM was more profoundly impaired in patients with SCZ., Conclusions: It is proposed that in SCZ group cognitive ToM is more impaired as it involves more effortful reflective processes, while affective ToM, which is more automatic and based on reflexive processes, may differentiate patients from healthy comparison subjects to a lesser extent. (JINS, 2018, 24, 305-309).

Objective: Augmentation of sarcosine, a natural inhibitor of the glycine transporter type I, normalizes glutamatergic neurotransmission, having beneficial impact on primary negative symptoms in schizophrenia and may also influence immune system and interleukin 6 (IL-6) levels., Aim: Finding a relationship between initial IL-6 serum concentrations or its changes and severity of symptoms as a result of sarcosine addition to stable antipsychotic treatment., Method: Fifity-eight individuals with schizophrenia with predominantly negative symptoms completed a 6-month randomized, double-blind placebo-controlled prospective study. Patients received 2 g of sarcosine (n = 29) or placebo (n = 30) daily per os. We measured IL-6 levels and severity of symptoms at the beginning, after 6 weeks and 6 months. As main clinical tools, we used Positive and Negative Syndrome Scale (PANSS) and Calgary depression scale for schizophrenia (CDSS)., Results: Augmentation with sarcosine had no effect on IL-6 serum levels in all time points. We noted significant improvements in negative symptoms, general psychopathology, and total PANSS score in the sarcosine group. We found correlation of initial serum IL-6 with severity of positive symptoms and negative association between IL-6 levels reduction and positive symptoms reduction., Conclusions: Sarcosine does not significantly affect IL-6 concentrations but IL-6 may be involved in mechanisms related to the presence of positive symptoms., (Copyright © 2018 John Wiley & Sons, Ltd.)

More and more data seems to imply that immune mechanisms are involved in the pathomechanism of bipolar disorder (BD). However, the primary role of cathelicidin LL-37 is defense against pathogens, more and more data indicated that this peptide strongly modulates immune system functioning and contributes to immune pathology of chronic and inflammatory diseases. No data is available on the level of LL-37 in bipolar patients. The aim of the study was to examine the circulating levels of cathelicidin LL-37 in euthymic patients with BD. Forty patients with BD and fifty-nine healthy volunteers were enrolled into the study. Concentration of LL-37 in serum was assessed using immunoenzymatic test ELISA. The mean LL-37 concentration in bipolar patients and in healthy subjects were 4.60 ± 7.65 ng/mL and 1.92 ± 2.89 ng/mL, respectively, and the difference was statistically significant (p = 0.035). Within the BD group LL-37 level was significantly higher in women than in men (p = 0.045). The evaluation of serum LL-37 concentration during stable 8 week treatment indicated that at baseline (T1) mean level of LL-37 was 5.82 ± 10.59 ng/mL; and after treatment (T2) was 4.33 ± 5.87 ng/mL; the difference between T1 and T2 was not significant. Elevated serum levels of LL-37 in bipolar patients may suggest the role of this peptide in the pathomechanism of BD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The aim of this study is to analyze whether clozapine serum concentration may affect fasting serum levels of several appetite regulating peptides: CART, PYY(1-36), NPY, AgRP, des-acylated ghrelin, leptin and obestatin. Serum concentration of clozapine and fasting serum levels of des-acylated ghrelin, neuropeptide Y (NPY), agouti-related protein (AgRP), peptide YY (PYY(1-36)), cocaine- and amphetamine-regulated transcript (CART), leptin and obestatin were measured in 30 subjects with schizophrenia on clozapine monotherapy. Leptin concentration was negatively correlated with clozapine dose (r = -0.53, p = 0.002), while NPY concentration was negatively correlated with clozapine concentration (r = -0.55, p = 0.01). Correlations with other peptides were not significant. We cannot conclude that serum concentration of clozapine is directly associated with increased or decreased level of appetite-regulating peptides., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Antimicrobial peptides are components of the innate immune system. Cathelicidin LL-37 plays an important role in antimicrobial defense, exerts proinflammatory effect and strongly affects the immune system functioning. Our recent study revealed that serum concentration of LL-37 is increased in elderly women with depression. The aim of this study is to evaluate serum LL-37 levels in elderly women with depression and to compare them with non-depressed elderly women, matched for anthropometric and body composition parameters., Methods: Forty women with unipolar depression and 23 non-depressed women (age ≥60 years) were included into the study. Anthropometric measurements and biochemical analyzes were performed. Concentration of LL-37 in serum was assessed using ELISA method. Body composition was measured using two methods: bioimpedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA)., Results: There was a statistically significant difference (p =.038) in serum LL-37 level between patients with depression (3.55 ± 6.57 ng/mL) and control subjects (2.01 ± 3.88 ng/mL). Apart from visceral adipose tissue mass (%) in the depression group, we found no associations between serum LL-37 and analyzed anthropometric or body composition parameters., Conclusions: Results of this study indicate that with the exception of visceral adipose tissue, LL-37 serum levels are not affected by anthropometric or body composition parameters. The association between visceral adipose tissue and LL-37 may indicate that visceral fat could be responsible for the increased LL-37 production.

Cathelicidin LL-37 is a small cationic that plays an important role in antimicrobial defense, as it kills a broad spectrum of infectious agents by disrupting their membranes, including gram-positive and gram-negative bacteria, some viruses and fungi; and it neutralizes activity of bacterial endotoxins. Moreover, cathelicidin LL-37 exerts proinflammatory effect, while numerous reports indicate the role of inflammation in the development of depression. The purpose of this study was to evaluate the circulating levels of cathelicidin LL-37 in elderly depressed patients. Thirty-nine elderly (age ≥ 60 years) women with major depressive disorder and thirty-eight non-depressed elderly (age ≥ 60 years) women were included into the study. The mean serum cathelicidin LL-37 concentration in patients with depression and in healthy subjects were 2.40 ± 3.00ng/mL and 1.17 ± 3.04ng/mL, respectively, and the difference was statistically significant. No significant differences between mean serum CRP level and WBC count in MDD patients and control group were documented. There were no correlations between LL-37 level and age, BMI, GDS score, CRP level or WBC count. It can be assumed that elevated serum LL-37 levels in depressed patients may reflect inflammatory activation associated with depression., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Blood lipids are widely used in monitoring the risk of cardiovascular diseases; however, atherogenic indices are more precise markers. The aim of the study was to determine differences in atherogenic indices in elderly patients with unipolar depression (DEP) compared with nondepressed elderly patients (nonDEP) using case-control analysis., Methods: Fasting serum lipid profiles were measured in 564 (depressed: n = 282, nondepressed: n = 282, 83.7% (n = 236) women in both groups) Caucasian inpatients aged ≥60, with mean age 76.9 years. Patients from both groups were matched for age and sex. Atherogenic index of plasma (AIP) was calculated as log 10 (triglycerides/HDL cholesterol). Castelli atherogenic indices were calculated as follows: AI LDL/HDL is the ratio of low-density lipoprotein (LDL) cholesterol to high-density lipoprotein (HDL) cholesterol and AI TC/HDL is the ratio of total cholesterol to HDL cholesterol., Results: HDL levels were significantly decreased in depressed patients (48.2 ± 14.4 mg/dL vs. 54.5 ± 17.7 mg/dL). No other differences in lipid profile were found. We found that all three analyzed atherogenic indices were increased in depressed patients (AIP: 0.41 ± 0.28 vs. 0.33 ± 0.27, AI LDL/HDL : 2.90 ± 1.41 vs. 2.42 ± 1.07, AI TC/HDL : 4.51 ± 1.84 vs. 3.79 ± 1.21). We found associations between depression severity and reduced level of HDL (β = -0.02) or increased AIP (β = 1.66)., Conclusions: All three atherogenic indices were increased in elderly patients with depression. Since depression and age are associated with elevated risk of cardiovascular events, elderly patients with depression should be carefully monitored for abnormal lipid status to reduce their cardiovascular risk. The role of lipid abnormalities in the pathogenesis of depression requires further studies.

Social cognition deficits are observed both in patients with schizophrenia (SCZ) and in patients with mesial temporal lobe epilepsy (MTLE). This may be due to dysfunction of the amygdala network, which is a common feature of both diseases. In this study, SCZ (n = 48) or MTLE (n = 31) and healthy controls (HC, n = 47) completed assessments of mentalising (Reading Mind in the Eyes Test, RMET) and basic cognitive processing, e.g., working memory, executive functions and psychomotor speed (Trail-Making Test B and Digit Symbol). SCZ were also assessed with the Positive And Negative Syndrome Scale (PANSS). We found that the RMET scores of the two clinical groups were similar (p > 0.05) and lower than in the HCs (SCZ: p < 0.05; MTLE: p < 0.001). In the next step, SCZ were split into two groups with respect to the level of symptoms. Analysis of the RMET scores revealed no differences between the HC (M = 25.7 ± 4.1) and POS-LO (M = 25.3 ± 4.8); both groups outperformed the POS-HI group (M = 21.3 ± 5.2) and the MTLE group (M = 20.8 ± 4.6). No differences were found for the median-split with regard to negative symptoms. In SCZ, the mind-reading deficit appears to be associated with the level of positive symptoms. Both POS-HI and MTLE patients present significant mentalising deficits compared to healthy controls.

Aim: C-reactive protein (CRP) is the major acute-phase plasma protein. Studies show that patients with depression have elevated levels of CRP. The aim of the study was to determine differences in CRP serum level in elderly patients with unipolar depression (DEP) compared with non-depressed elderly patients (nonDEP) using case-control analysis., Methods: Serum level of CRP was measured in 404 (DEP: n = 202, nonDEP: n = 202) Caucasian inpatients aged ≥60 (350 women, 86.7%; mean age = 76.7 years)., Results: Mean CRP level in the study groups was: DEP 2.67 ± 2.56 mg/dL, nonDEP 2.41 ± 2.19 mg/dL, the difference was not significant (p = 0.96). The overall rate of being above the high level of CRP (set at 3.0 mg/L) was 33.2% for DEP and 29.2% for nonDEP groups (p = 0.39). It was also found that, in the whole study group, CRP level was not correlated with age (p = 0.10)., Conclusions: Elderly patients with depression have no increased CRP levels. A high percentage (∼30%) of all subjects had a CRP level >3 mg/L, which is the cut-off point for increased cardiovascular risk.

Aim: Finding a relationship between schizophrenia symptoms severity and initial level of BDNF and its changes during augmentation of antipsychotic treatment with sarcosine., Method: 57 individuals with schizophrenia with predominantly negative symptoms completed a 6-month RCT prospective study. The patients received 2g of sarcosine (n=27) or placebo (n=30) daily. At the beginning, after 6 weeks and 6 months BDNF levels were measured. Severity of symptoms was assessed using the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS)., Results: BDNF serum levels were stable after 6 weeks and 6 months in both groups. We noted improvement in negative symptoms, general psychopathology and total PANSS score in sarcosine group comparing to placebo, however there was no correlations between serum BDNF concentrations and PANSS scores in all assessments. Initial serum BDNF concentrations cannot be used as a predictor of the improvement resulting from adding sarcosine., Conclusions: Our results indicate that either BDNF is not involved in the NMDA-dependent mechanism of sarcosine action or global changes in BDNF concentrations induced by amino-acid cannot be detected in blood assessments., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: Find changes in matrix metallopeptidase-9 (MMP-9) levels during augmentation of antipsychotic treatment with sarcosine and a relationship between schizophrenia symptoms severity and initial level of MMP-9., Method: Fifty-eight patients with diagnosis of schizophrenia with predominant negative symptoms participated in a six-month prospective RCT (randomized controlled trial). The patients received two grams of sarcosine (n = 28) or placebo (n = 30) daily. At the beginning, after six weeks and after six months MMP-9 levels were measured. Severity of symptomatology was assessed with the Positive and Negative Syndrome Scale (PANSS) and Calgary Depression Scale for Schizophrenia (CDSS)., Results: MMP-9 serum levels were stable after six weeks and six months in both groups. We noted improvement in negative symptoms, general psychopathology and total PANSS score in sarcosine group compared to placebo; however, there was no correlations between serum MMP-9 concentrations and PANSS scores in all assessments. Initial serum MMP-9 concentrations cannot be used as an improvement predictor acquired during sarcosine augmentation., Conclusions: Our results indicate that either MMP-9 is not involved in the N-methyl-d-aspartate (NMDA)-dependent mechanism of sarcosine action in terms of clinical parameters or sarcosine induced changes in peripheral MMP-9 concentrations cannot be detected in blood assessments.

There are no studies comparing platelet parameters platelet parameters (platelet count (PLT), mean platelet volume (MPV) and platelet large cell ratio (P-LCR)) between patients with schizophrenia, bipolar disorder and unipolar depression. Therefore, the aim of this study was to determine and compare differences in PLT, MPV and P-LCR in patients with schizophrenia, unipolar depression and bipolar disorder. This was a retrospective, cross-sectional, naturalistic study of 2377 patients (schizophrenia n=1243; unipolar depression n=791; bipolar disorder n=343, including bipolar depression n=259 and mania n=84). There were significant differences for PLT, MPV and P-LCR values between study groups. A significant percentage of patients with bipolar disorder had abnormal (too low or too high) number of platelets. Negative correlation between PLT and age was found in all study groups and positive correlation between age and MPV and P-LCR was found in patients with schizophrenia., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Aim: Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) are neurotrophins-proteins that induce the survival, development, and function of neurons. Their role in the development of schizophrenia and mood disorders is widely studied. This study was aimed to determine whether depression affects levels of BDNF and NT-3 in patients with schizophrenia., Methods: Data for 53 Caucasian adult hospitalized patients with chronic paranoid schizophrenia was compared with 27 healthy subjects. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and positive, negative and general sub-scores, the Calgary Depression Scale for Schizophrenia (CDSS), the Hamilton Depression Rating Scale (HDRS), and the Clinical Global Impressions scale (CGI). Patients were defined as depressed (SHZ-DEP) with scores CDSS > 6 and HDRS > 7, otherwise they were included into the non-depressed group (SHZ-nonDEP)., Results: In total, 17 patients (32.1%) with schizophrenia met criteria for depression. SHZ-DEP patients had higher scores in HDRS, CDSS, PANSS total, PANSS negative, PANSS general and CGI (p < 0.001 for all comparisons). There were no differences in BDNF or NT-3 levels between patients with schizophrenia and controls. BDNF levels were lower in SHZ-DEP compared to SHZ-nonDEP: 18.82 ± 5.95 versus 22.10 ± 5.31 ng/mL, p = 0.045. NT-3 levels were higher in SHZ-DEP compared to SHZ-nonDEP: 133.31 ± 222.19 versus 56.04 ± 201.28 pg/mL, p = 0.033., Conclusion: There were no differences in neurotrophin levels between patients with schizophrenia and controls. We found lower BDNF and higher NT-3 serum levels in depressed patients with schizophrenia.

Background: Metabolic syndrome (obesity, glucose intolerance, insulin resistance and dyslipidaemia) is a well-known adverse effect of most antipsychotics. It is particularly common in patients treated with olanzapine and clozapine. Currently, the mechanisms underlying its development are not completely understood., Case Report: We present a case of improved body composition (reduced amount of total body fat and visceral adipose tissue), anthropometric measurements (body weight, waist, abdominal and hip circumferences) and lipid profile in a 31-year-old man with schizophrenia following discontinuation of clozapine. During a combined treatment with clozapine, flupentixol and ziprasidone, a routine laboratory test revealed a severe dyslipidaemia (triglycerides > 1800 mg/dL; > 20.3 mmol/L), despite previous lipid-lowering therapy. This abnormality completely recovered after clozapine has been discontinued., Conclusions: Clozapine may cause severe, but reversible metabolic abnormalities, including obesity and hypertriglyceridaemia. Atypical antipsychotic-related lipid abnormalities may have a very rapid onset, occur in relatively young patients, with severe lipid derangements and have potential serious complications. This case confirms how important is to monitor metabolic parameters in patients taking antipsychotics. Discontinuation or switching to another antipsychotic medication may improve components of the metabolic syndrome.

This study was undertaken with the purpose to determine if there are changes in metabolic parameters during 6-month add-on treatment with sarcosine in patients with schizophrenia. This was a randomized double blind, placebo-controlled and parallel group study. Eligible participants were randomly assigned to receive 2g of sarcosine (n=30) or placebo (n=29). Sarcosine was administered as supplementation to the ongoing antipsychotic treatment. Augmentation with sarcosine had no effect on any of the analyzed cardiometabolic parameters. Also, augmentation with sarcosine had no effect on any of the analyzed body composition parameters. This is the first randomized placebo-controlled study to examine the metabolic safety of sarcosine in patients with schizophrenia. Clinically, this observation is of high importance considering how prevalent are metabolic abnormalities in patients with schizophrenia., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Many, even healthy, older people fail to adequately regulate food intake and experience loss of weight. Aging-associated changes in the regulation of appetite and the lack of hunger have been termed as the anorexia of aging. The etiology of the anorexia of aging is multi-factorial and includes a combination of physiological changes associated with aging (decline in smell and taste, reduced central and peripheral drive to eat, delayed gastric emptying), pathological conditions (depression, dementia, somatic diseases, medications and iatrogenic interventions, oral-health status), and social factors (poverty, loneliness). However, exact mechanisms of the anorexia of aging remain to be elucidated. Many neurobiological mechanisms may be secondary to age-related changes in body composition and not associated with anorexia per se. Therefore, further studies on pathophysiological mechanisms of the anorexia of aging should employ accurate measurement of body fat and lean mass. The anorexia of aging is associated with protein-energy malnutrition, sarcopenia, frailty, functional deterioration, morbidity, and mortality. Since this symptom can lead to dramatic consequences, early identification and effective interventions are needed. One of the most important goals in the geriatric care is to optimize nutritional status of the elderly.

Background: We tested the hypothesis that uric acid levels are higher in subjects with schizophrenia treated with clozapine than in healthy control and they correlate with anthropometric measurements, laboratory tests and results of bioimpedance analysis of body composition., Methods: Data for 24 subjects with schizophrenia treated with clozapine and 24 age- and sex-matched healthy volunteers was analyzed., Results: There was no difference of fasting uric acid concentrations between clozapine and control groups (4.5 ± 1.4 vs. 4.3 ± 1.3 mg/dl, P = 0.87). Regarding the whole group, uric acid levels were significantly higher in men (5.2 ± 1.2 vs. 3.6 ± 0.9, P < 0.001). Uric acid levels correlated with weight (R = 0.58, P = 0.003), body mass index (BMI; R = 0.49, P = 0.01), abdominal circumference (R = 0.45, P = 0.03), waist circumference (R = 0.47, P = 0.02), waist-to-hip ratio (R = 0.42, P = 0.04), insulin (R = 0.50, P = 0.01), homoeostasis model assessment of insulin resistance 2 (HOMA2-IR; R = 0.49, P = 0.01), basal metabolic rate (R = 0.56, P = 0.004), lean body mass (R = 0.55, P = 0.005) and body water (R = 0.55, P = 0.005). There were no significant differences of uric acid levels for smoking status, impaired fasting glucose, abdominal obesity, obesity/overweight and dyslipidemia. Uric acid levels did not correlate with age, duration of clozapine treatment, clozapine dose, leg circumference, systolic blood pressure, diastolic blood pressure, total body fat, triglycerides, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), homocysteine, corrected calcium, glucose and homoeostasis model assessment of insulin resistance 1 (HOMA1-IR)., Conclusions: We did not find significant differences in blood uric acid levels between subjects with schizophrenia and controls. Association with weight, BMI, abdominal and waist circumferences, insulin levels and insulin resistance may support uric acid role as an important cardiovascular risk factor. Association with lean weight may explain why men have higher levels of uric acid than women.

Aims: The aim of this study is to investigate differences in triglycerides (TGA), cholesterol (TC), HDL, LDL and glucose (FPG) levels in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania., Results: Results for 2305 Caucasian patients were included in the study (1377 women, 59.7%; mean age 45.6). Mean TGA level was: schizophrenia: 139.9±90.6 mg/dL, unipolar depression: 125.4±70.8 mg/dL, bipolar disorder: 141.1±81.9 mg/dL, bipolar depression: 147.7±82.8 mg/dL mg/dL, bipolar mania: 120.2±76.1 mg/dL, inter-group differences were significant (p<0.001). Mean TC level was: schizophrenia: 188.5±40.4 mg/dL, unipolar depression: 198.8±50.7 mg/dL, bipolar disorder: 194.4±48.3 mg/dL, bipolar depression: 198.9±48.8 mg/dL, bipolar mania: 180.1±43.8 mg/dL, inter-group differences were significant (p<0.001). Mean HDL level was: schizophrenia: 45.3±13.9 mg/dL, unipolar depression: 48.1±14.8 mg/dL, bipolar disorder: 45.4±15.3 mg/dL, bipolar depression: 45.1±15.4 mg/dL, bipolar mania: 46.4±15.1 mg/dL, inter-group differences were significant (p<0.001). Mean LDL level was: schizophrenia: 115.4±34.7 mg/dL, unipolar depression: 125.7±44.1 mg/dL, bipolar disorder: 120.9±42.1 mg/dL, bipolar depression: 124.5±43.1 mg/dL, bipolar mania: 109.3±36.9 mg/dL, inter-group differences were significant (p<0.001). Mean FPG level was: schizophrenia: 95.9±24.9 mg/dL, unipolar depression: 94.8±22.9 mg/dL, bipolar disorder: 97.2±24.4 mg/dL, bipolar depression: 98.3±25.3 mg/dL, bipolar mania: 93.9±21.1 mg/dL, inter-group differences were not significant (p=0.08). Odds ratios for glucose and lipids abnormalities, correlations with age, sex distribution in diagnostic groups for normal ranges of glucose and lipids, differences in glucose and lipids levels between the age groups were also calculated., Conclusions: Our results confirm that there is a high prevalence of lipid and glucose abnormalities in patients with schizophrenia and mood disorders (both unipolar and bipolar). However, we have demonstrated that these diagnostic groups differ in terms of types and frequency of these metabolic dysfunctions. Women and patients aged 40+ are at particularly high risk., (Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objective: C-reactive protein (CRP) is the major acute-phase plasma protein. Studies show that patients with various mental disorders have elevated levels of CRP. The aim of the study was to determine differences in CRP serum level in patients with acute schizophrenia, unipolar depression, bipolar depression and bipolar mania., Method: Serum level of CRP was measured in 950 Caucasian inpatients (589 women, 62.0%; mean age 50.3 years)., Results: Mean concentration of CRP in study groups was: schizophrenia (n = 485) 5.30 mg/l, unipolar depression (n = 319) 5.61 mg/l, bipolar disorder (n = 146) 4.65 mg/l, bipolar depression (n = 114) 3.82 mg/l and bipolar mania (n = 32) 7.36 mg/l. There was no difference for CRP levels between patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania (P = 0.58). The overall rate of being above the high level of CRP (set at 3.0 mg/l) was 35.7% for schizophrenia, 38.6% for unipolar depression, 40.4% for bipolar disorder, 40.4% for bipolar depression and 40.6% for bipolar mania. There were no significant differences in the risk of having high level of CRP between the clinical groups. The rate of patients being above high level was higher in women. We also found that in whole study group CRP level was positively correlated with age (P = 0.002)., Conclusions: Although there is no statistically significant difference in CRP serum level between patients with schizophrenia, unipolar depression, bipolar depression and bipolar mania, our results show that more than one-third (37.4%) of all subjects had CRP level > 3 mg/l, which is the cut-off point for high cardiovascular risk.

Aim: Agouti-related peptide (AgRP) is one of the hypothalamic hormones that works by increasing appetite and decreasing metabolism, thus leading to weight gain. The aim of the study was to find out if AgRP level in subjects with schizophrenia on clozapine monotherapy is higher compared with healthy controls., Methodology: We determined fasting serum AgRP levels in 24 subjects with schizophrenia on clozapine monotherapy and 24 healthy, age- and sex-matched controls. Biochemical and anthropometric measurements were combined with body composition analysis., Results: There was no difference for AgRP levels between patients taking clozapine and control group (15.00±8.65 vs. 15.33±6.82 pg/mL, p =0.37). We found negative correlations between AgRP levels and total body fat (r =-0.34 and -0.48 in the whole study group and clozapine group, respectively) and positive correlations with lean body mass (r =0.38 and 0.49 in the whole study group and clozapine group, respectively), body water (r =0.34 and 0.49 in the whole study group and clozapine group, respectively) and basal metabolic rate (r =0.42 both in the clozapine and control groups). There were no correlations with age, height, weight, body mass index, fat mass index, abdominal, waist or hip circumferences, waist-hip ratio, blood pressure, total cholesterol, HDL, LDL, triglycerides, uric acid, glucose, insulin, clozapine dose or treatment duration, duration of treatment with antipsychotics and markers for insulin resistance., Conclusion: We cannot conclude that treatment with clozapine is associated with increased level of AgRP. We did not find previously described differences in AgRP levels between obese and non-obese subjects or associations between AgRP and various metabolic parameters.