Bartłomiej Stańczykiewicz

Cytokines and C-reactive protein alterations with respect to cognitive impairment in schizophrenia and bipolar disorder: A systematic review

BACKGROUND The aim of this article was to perform a systematic review of studies investigating the association between peripheral levels of cytokines and C-reactive protein (CRP), cytokine gene polymorphisms and cognition in patients with schizophrenia and bipolar disorder (BD). METHODS The following databases: PubMed, CINAHL Complete, Academic Search Complete, ERIC and Health Source: Nursing/Academic Edition databases were searched according to the PRISMA guidelines. We included studies that investigated the association between peripheral levels of CRP and cytokines, cytokine gene polymorphisms and cognitive performance in schizophrenia and/or BD patients. Subsequently, quality assessment of eligible publications was performed. Results were synthesized by discussing main findings around correlations between inflammatory markers and cognition. RESULTS Most consistent results indicate worse cognitive performance in schizophrenia patients with higher CRP levels. Less consistent evidence suggests better cognitive functioning of schizophrenia patients with higher levels of tumour necrosis factor-α (TNF-α). Evidence for the involvement of other cytokines in cognitive impairment in patients with schizophrenia is less convincing due to discordant results or scarcity of studies. Due to low number of studies, it is difficult to draw conclusions on the involvement of CRP and cytokine alterations in the development of cognitive deficits in BD. Single studies suggest the role of CRP, interleukin(IL)-1 receptor antagonist, IL-6 and TNF-α with its receptors in the development of cognitive impairment in BD. CONCLUSIONS Peripheral inflammation might be related to cognitive deficits in schizophrenia and BD. Unequivocal conclusions cannot be made due to methodological heterogeneity and low number of studies investigating particular cytokines.

Profiling inflammatory signatures of schizophrenia: A cross-sectional and meta-analysis study

We aimed to profile a broad panel of inflammatory markers in patients with schizophrenia and healthy controls. Additionally, we performed a meta-analysis of chemokine alterations that have not been subjected to quantitative synthesis so far. We recruited 78 patients with schizophrenia and 78 healthy controls, and measured inflammatory markers using the Luminex technology. After adjustment for multiple testing, we found elevated levels of interleukin (IL)-1 receptor antagonist (IL-1RA), IL-6, IL-7, IL-8, IL-9, IL-10, IL-13, interferon-γ, eotaxin-1, granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein-1 (MCP-1), platelet-derived growth factor with two B subunits (PDGF-BB), macrophage inflammatory protein (MIP)-1α, MIP-1β, vascular endothelial growth factor A (VEGF-A) and RANTES in multiple-episode schizophrenia (MES) patients. These differences, except for the difference in eotaxin-1 levels, appeared to be significant after co-varying for the dosage of antipsychotics. There were no significant differences in the levels of immune markers between first-episode schizophrenia (FES) patients and controls. Our meta-analysis revealed elevated levels of MCP-1 in first-episode psychosis (FEP) patients and MES individuals. Other chemokine alterations (elevated levels of IL-8, eotaxin-1 and MIP-1β) were present only in MES patients. Our results indicate that dysregulation of immune response in schizophrenia develops with illness progression or appears as a long-term medication effect. Chemokine alterations are another example of aberrant immune response in schizophrenia patients. Elevated levels of MCP-1 might represent trait markers since these alterations were found in FEP and MES patients. Other chemokine alterations might be the markers of disease progression or might represent medication effects.

Erratum to: Pro-Cognitive Properties of the Immunomodulatory Polypeptide Complex, Yolkin, from Chicken Egg Yolk and Colostrum-Derived Substances: Analyses Based on Animal Model of Age-Related Cognitive Deficits

The online version of the original article can be found under doi: 10.1007/s00005-016-0392-z .

[Selected mice models based on APP, MAPT and presenilin gene mutations in research on the pathogenesis of Alzheimer's disease].

The research conducted on animal models of Alzheimers disease (AD) has provided valuable information about the pathogenesis of this disease and associated behavioral and cognitive deficits as well as the disease-associated anatomical and histopathological lesions of the brain. Transgenic technologies have enabled the creation of animal models based on mutations in APP, MAPT, presenilin genes, tau protein and apoE. Due to economic reasons studies are mainly conducted on mice. Their brain tissue, depending on the mutation, is characterized by histopathological changes, such as the presence of amyloid plaques, tau protein deposits and dystrophic neurites, gliosis, hippocampal atrophy and amyloid accumulation in vessels. Animal cognitive impairment and behavior, which can be demonstrated in behavioral tests, primarily relate to the working and reference memory, alternation and anxiety. Unfortunately, despite the various modifications specific to AD in the genome of animals, scientists have failed to create an animal model characterized by all the pathological changes that can occur in Alzheimers disease. Nevertheless, the role of transgenic animals is undeniable, both in research on AD neuropathology and for testing new therapies, such as immunotherapy. Despite the occurrence of abundant Alzheimers disease mice models this article is dedicated to selected models with mutations in the APP, MAPT and presenilin genes and their application for behavioral studies.

Whole-body Cryotherapy in Dementia

Current studies have not addressed the impact of extremely low temperatures on the cognitive functions of humans. Determining the etiopathogenesis of dementia is a crucial aspect of studies dealing with cognitive functions. There is a consensus among researchers that vascular lesions, oxidative stress, inflammatory processes and abnormal neurotransmission are associated with the development of dementia, including Alzheimers disease (Grammas 2011). An antioxidative activity of cryotherapy carried out on patients with multiple sclerosis has been shown in several studies. Clinical trials involving patients with secondary progressive multiple slcerosis showed them to have a statistically significant increase in the total antioxidant status (TAS) following 10 cryotherapy sessions (Miller 2010). Due to the anti-inflammatory (a modification of the concentration of proinflammatory cytokines) and antioxidatixe effect of low temperatures as well as the hormonal and lipid changes they cause, they may play an important role in preventing or inhibiting pathophysiological processes leading to dementia. Therefore, carrying out a study concerning the effect of systemic cryotherapy on the body in dementia will allow to assess its efficacy. Grammas P. Neurovascular dysfunction, inflammation and endothelial activation: implications for the pathogenesis of Alzheimer’s disease. J Neuroinflamm 2011;8:26. Miller E, Mrowicka M, Malinowska K, Mrowicki J, Saluk-Juszczak J, Kedziora J. The effects of wholebody cryotherapy on oxidative stress in multiple sclerosis patients, J Therm Biol, vol.35, 2010, s.406410.

The neuropsychiatric aspect of the HCV infection

HCV infection is significantly more prevalent in the population of psychiatric patients, drug addicts and people tending to undertake risky sexual behaviors than in the general population. This article presents a spectrum of psychopathological symptoms and psychological dysfunctions, an outline of current theories on the neuropathology and psychiatric aspects of HCV infection treatment. The unspecific character of the psychopathological symptoms in the HCV infection makes the process of thorough diagnostics and adequate treatment difficult, thus the specific and characteristic features have been emphasized. The aim of this review is to shed light not only on the basic information concerning CNS pathology but also on the conclusions emerging from the studies of different authors, of various methodology, in diverse study groups and also to investigate current topics of research. The results of neuroimaging studies have been presented as well. Attention has also been dedicated separately to specific issues, like psychiatric aspects of co-infection with HCV and HIV viruses, the chronic fatigue in the course of HCV infection, the influence of substance use disorders and difficulties encountered during treatment with interferon. Undiagnosed psychiatric disorders, not only inevitably decrease the already rather low quality of life but also cause non-adherence with recommendations and medications regimes, contributing to a worse treatment outcome. Finally, the above disorders, when left untreated, result in higher rates of risk-taking behaviors among the infected, thus imposing a danger not only to patients themselves but also to the healthy population.

An animal model of the procognitive properties of cysteine protease inhibitor and immunomodulatory peptides based on colostrum.

BACKGROUND The positive effect of human cystatin C on the development of Alzheimers disease has been reported, as it inhibits the formation of β-amyloid oligomers and amyloidogenesis. Cystatin C has been found to have a neuroprotective effect by inhibiting cysteine proteases, inducing autophagy and neurogenesis. There is a growing interest in the procognitive properties of colostrum-based specimens, which could delay dementia and ameliorate memory deterioration. OBJECTIVES The aim of the study was to evaluate the influence of ovocystatin and a Coloco peptide complex on the cognitive functions in reference to Colostrinin, using a model of young (4 month-old) and old (10-month-old) Wistar rats. MATERIAL AND METHODS In the present study, the effects of ovocystatin [100 μg/rat] and the Coloco peptide [4 μg/rat]derived from colostrum were assessed with respect to the reference specimen, Colostrinin [4 μg/rat]. The specimens were administered intraperitoneally and orally for 12 days. Cognitive functions were assessed using the Morris water maze (MWM). RESULTS The group of young rats that received ovocystatin orally obtained significantly better results in the MWM compared to the placebo group (p < 0.05). Similarly, the group of young rats receiving Coloco orally obtained better results in the MWM compared to the placebo group and to the group of rats receiving Colostrinin (p < 0.05). There were no statistically significant differences in the oral and intraperitoneal administration of ovocystatin, Coloco and Colostrinin in the group of old rats. CONCLUSIONS The obtained results suggest that oral administration of ovocystatin and Coloco has beneficial effects on the cognitive functions of young rats.

Effects of Immunomodulatory Peptide Y On Cognitive Functions in Animal Models

Despite the great intensity of studies to explain mechanisms of the Alzheimer’s disease, there’s still lack of effective prevention and treatment. As many specimens had been unadmitted because of their adverse side effects, thus recent attempts to follow natural biological protective mechanisms might open a range of possibilities in developing novel drugs to slow down processes of dementia and cognitive impairment. Promising results were achieved in patients treated with herbal agents, such as Gingko biloba extract, as well as animal derived preparations, i.a. PRP/Colostrinine (proline rich polipeptyde) complex isolated from ovine and bovine colostrum with confirmed immunomodulating properties and pro-cognitive action on memory and learning functions. The contribution of egg yolk (vitellus) ingredients to chicks development appeared similar to mammalian colostrum role in growth and immunity of newborns. Recently discovered polipeptyde complex associated with IgY, named Yolkine,has been put to the series of experiments in order to determine the effects of egg yolk preparations on cognitive functions in young and old rats as a model of cognitive decline and process of brain aging. To estimate Yolkine efficiency, different doses and routes of administration were applied, along with wide range of aging-sensitive behavioral tests, i.a. novel object recognition task and Morris water maze. The authors will present the results of the ongoing study and key findings.

Procognitive Properties of Cysteine Protease Inhibitor – Ovocystatin in Alzheimer's Disease Mice Model.

Background The results obtained in the last decade suggest that cystatin C plays an important role in the development of Alzheimer´s disease (AD) by inhibiting the aggregation of β-amyloid and its deposition. Cystatin C also demonstrate protective role via inhibition of cysteine proteases or by induction of autophagy and induction of proliferation (1–3). Aims/Objectives The aim of the study concerns the influence of the ovocystatin derived from the new generation of eggs on cognitive decline in AD mice model. Methods Animals: Mice B6C3-Tg(APPswe, PSEN1dE9)85Dbo/Mmjax–Genotype HEMI and NCAR (The Jackson Laboratories). Specimen and administration: Ovocystatin [40μg/mouse] were administered with drinking water by 22 weeks. The placebo group received drinking water. The locomotor activity were tested by IR Actimeter. The evaluation of learning and memory was determined by Morris Water Maze test (MWM) (4). The study „Innovative technologies of bio-preparations’ production on the base of new generation of eggs” was co-financed by the European Union from the European Regional Development Fund under the Operational Program Innovative Economy, 2007-2013. Results Mice from group with ovocystatin administration with drinking water have traveled statistically longer distance [D%] at Target quadrant than Placebo mice in MWM (p>0,05). Conclusion Ovocystatin given with drinking water has influence on learning and memory in HEMI group. 1. Gauthier S, Kaur G, Mi W, Tizon B, Levy E. Front Biosci (Schol Ed), 2011; 1(3):541-554. 2. Kaur G, Levy E. Front Mol Neurosci, 2012; 6(5):79. 3. Zerovnik E. BioEssays, 2009; (6):597-599. 4. Bromley-Brits, K., Deng, Y., Song, W. J Vis Exp, 2011, (53):e2920.

Psychiatric symptomatology and personality in a population of primary care patients

INTRODUCTION AND OBJECTIVE Psychiatric disorders (and their high rates of prevalence) in primary care have been widely analyzed, but the problem of underdiagnosis remains unresolved. This becomes increasingly more important in rural health centres in the face of lack of epidemiological data from these centres. The aim of this study is focused on the relationship between general health, psychiatric symptomatology and personality characteristics in the context of an adequate diagnosis. MATERIALS AND METHODS 518 primary care patients in 6 Polish urban clinical centres were studied using (in order of administration): a sociodemographic questionnaire, the General Health Questionnaire (GHQ-28) and Eysenck Personality Questionnaire (EPQ-R). RESULTS The investigated sample was representative for urban primary care patients. The findings confirmed a significant association between neuroticism and general health. The strongest relation with current functioning and mental distress of the patients (GHQ general score) was observed in case of symptoms of anxiety and insomnia. The symptoms of depression may be the most difficult to identify (psychiatric symptoms assessed using GHQ sub-scales). CONCLUSIONS According to the GHQ assumptions and confirmed by the presented study, sub-threshold psychiatric symptomatology affects the functioning of primary care patients and their general health. This correlates with personality factors. Improving adequacy of diagnosis becomes extremely important, as it may often be the only chance for appropriate therapy of mental problems for people living in rural areas due to lower availability of specialistic mental services. Further epidemiological studies concerning rural primary care and prevalence of the spectrum of mental disorders need to be conducted.