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Lit jest lekiem normotymicznym, stosowanym z wyboru w leczeniu profilaktycznym choroby afektywnej dwubiegunowej (ChAD). Skuteczność profilaktyczna litu może być uwarukowana czynnikami genetycznymi, związanymi częściowo z predyspozycją do choroby afektywnej dwubiegunowej. W dziedzinie genetyki w psychiatrii pierwsza dekada XXI wieku została zdominowana przez badania „genów kandydujących”. W niniejszym artykule przedstawiono badania genów kandydujących związanych z profilaktyką litem, prowadzone na Uniwersytecie Medycznym w Poznaniu w latach 2005-2018. W tym czasie badane były polimorfizmy wielu genów, z których część jest również związana z predyspozycją do choroby afektywnej dwubiegunowej. Związek ze skutecznością profilaktyczną litu stwierdzono w przypadku polimorfizmów genów 5HTT, ACP1, ARNTL, BDNF, COMT, DRD1, FKBP5, FYN, GLCC, NR3C1 i TIM. Nie stwierdzono takiego związku w odniesieniu do genów 5HT2A, 5HT2C, DRD2, DRD3, DRD3, GRIN2B, GSK-3β, MMP-9 i NTRK2. Wykazano natomiast asocjację polimorfizmu genu GSK-3β z nerkowymi działaniami niepożądanymi w przebiegu stosowania litem. Omówiona została możliwa rola tych genów zarówno w mechanizmie profilaktycznej skuteczności litu, jak i w patogenezie choroby afektywnej dwubiegunowej.

W ostatnim czasie obserwujemy dużą ilość publikacji, opisujących rolę inhibitorów transportera glicynowego GlyT1 w leczeniu schizofrenii. Koncepcja zastosowania tych leków oparta jest o glutaminową teorię schizofrenii. Teoria ta tłumaczy zaburzenia psychotyczne jako konsekwencję defektu w funkcjonowaniu receptora NMDA. Funkcja wspomnianego receptora zależy głównie od dostępności kofaktorów. Jednym z nich jest najprostszy aminokwas, glicyna. Aminokwas ten oddziałuje z miejscem glicynowym obecnym na podjednostce NR1 receptora NMDA, co ułatwia jego aktywację. Substancje, które mogłyby ułatwić dostępność glicyny dla receptora, hipotetycznie usprawniłyby procesy neuroplastyczności. Większa efektywność tych procesów mogłaby stanowić czynnik ochronny przed pogłębiającymi się deficytami poznawczymi i objawami negatywnymi w przebiegu schizofrenii. W tym artykule przedstawiliśmy przegląd systematyczny dotychczas opublikowanej literatury na temat zastosowania inhibitorów GlyT1 w leczeniu schizofrenii. Najpierw opisano przedkliniczne dowody uzasadniające użycie wzmocnienia działania glicyny. Następnie korzystając z baz danych CINAHL, EMBASE, EMCARE, Medline, PsycINFO, PubMed oraz Google Scholar, wyodrębniliśmy i przeanalizowaliśmy dowody z badań klinicznych. Inhibitory GlyT1 zdają się mieć potencjał w poszukiwaniu nowych substancji w celu leczenia objawów negatywnych, z kolei zdolność tych substancji do redukowania deficytów poznawczych jest niepotwierdzona. Do tej pory sprawdzono przydatność kliniczną wielu substancji, w tym N- metyloglicyny (sarkozyny), bitopertyny oraz syntetycznych pochodnych. Część związków wykazuje korzystny efekt kliniczny, niemniej ilość opublikowanych informacji na ten temat jest niewspółmierna do jakości dowodów.

Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small protein β2-microglobulin (β2m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those containing viral peptides can be detected by CD8+ T lymphocytes that kill infected cells. Many viruses enhance their in vivo survival by encoding genes that downregulate MHC-I expression to avoid CD8+ T cell recognition. Here we report that two accessory proteins encoded by SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, downregulate MHC-I expression using distinct mechanisms. One, ORF3a, a viroporin, reduces global trafficking of proteins, including MHC-I, through the secretory pathway. The second, ORF7a, interacts specifically with the MHC-I heavy chain, acting as a molecular mimic of β2m to inhibit its association. This slows the exit of properly assembled MHC-I molecules from the endoplasmic reticulum. We demonstrate that ORF7a reduces antigen presentation by the human MHC-I allele HLA-A*02:01. Thus, both ORF3a and ORF7a act post-translationally in the secretory pathway to lower surface MHC-I expression, with ORF7a exhibiting a novel and specific mechanism that allows immune evasion by SARS-CoV-2.Significance StatementViruses may down-regulate MHC class I expression on infected cells to avoid elimination by cytotoxic T cells. We report that the accessory proteins ORF7a and ORF3a of SARS-CoV-2 mediate this function and delineate the two distinct mechanisms involved. While ORF3a inhibits global protein trafficking to the cell surface, ORF7a acts specifically on MHC-I by competing with β2m for binding to the MHC-I heavy chain. This is the first account of molecular mimicry of β2m as a viral mechanism of MHC-I down-regulation to facilitate immune evasion.

Cod was one of the most important fish species in the Baltic Sea, but its condition is deteriorating for several reasons, including an increasing parasite burden. The aim of this study was to determine the source of infection of Baltic cod with parasites by examination of invertebrates found in situ in the cod stomach. A total of 1681 cod were sampled during four research cruises in the southern Baltic Sea in 2012, 2013 and 2014 and the composition of their diet was analysed. Each prey item from cod stomach was identified to the lowest possible taxonomic level and a parasitological analysis of all invertebrates collected was performed. Crangon crangon, Saduria entomon and Mysis mixta were the most commonly represented invertebrates among food items. Hysterothylacium aduncum was found only in C. crangon. This host–parasite system is reported here for the first time in situ in the stomach of cod from the Baltic Sea, confirming the role of C. crangon in cod infection with H. aduncum.

Lithium is a mood stabilizer widely used in the pharmacotherapy of bipolar disorder and treatment‑resistant depression. Taking into account dysregulated inflammatory activity in depression and the immunomodulatory role of lithium, we hypothesized that genes associated with inflammatory responses may be potential biomarkers of lithium action. We aimed to compare gene expression changes between the brain and the periphery after chronic lithium administration in an animal model of depression. Depressive behavior was induced by chronic mild stress protocol for 4 weeks. After 2 weeks, rats started to receive lithium (study group) or water (reference group). The control group were rats not exposed to stress. Amygdala, hippocampus, frontal cortex and peripheral blood were analyzed using whole transcriptome expression microarrays. Changes were confirmed with qPCR and ELISA assay. After 2 weeks of lithium administration, we observed significant changes in gene expression between amygdala and peripheral blood. Logistic regression analysis determined Alox15 expression as a predictor of lithium status, as its expression was tissue‑specific and increased in amygdala and decreased in blood. Analysis of serum ALOX15 protein revealed its upregulation after two‑week lithium administration. Our study suggests that lithium may have therapeutic potential in depressive behaviors. These results indicate immunomodulatory effect of lithium and that Alox15 may be a new potential marker of chronic lithium treatment.

Schizophrenia onset in the developmental age has strong neurodevelopmental burden and links with a poorer prognosis. The approach to diagnosis is still based on symptomatic description without objective validation. In the study we aimed to compare the peripheral blood levels of hypothesized biomarker proteins: brain-derived neurotrophic factor (BDNF), proBDNF, p75 neurotrophin receptor (p75NTR) and S100B between early-onset schizophrenia-spectrum adolescents (n = 45) and healthy controls. Assessment of the schizophrenia-spectrum adolescents encompassed symptomatic description with the use of structuralized interviews and executive function objective measurement. Plasma levels of BDNF protein were significantly lower in schizophrenia patients (p NTR levels and positive and negative symptoms scale (PANSS) scores, p75NTR and S100B levels and suicidal parameters, as well as a correlation of BDNF plasma level with the risky decision-making style in Iowa Gambling Task (IGT). The results indicate a potential value of studied proteins as a biomarker in the diagnosis and monitoring of the disease’s course.

Sparse studies have shown that specific biomarkers of a global DNA methylation status may be related to various mental diseases and states, including: bipolar disorder (BD), anxiety and major depression disorder (MDD). The objective of this study was to analyze potential variation of the above mentioned global methylation status in women with depression. 38 women with a current and clinically confirmed depressive episode suffering from BD type I, type II or MDD and 71 women from the general population and at similar age were recruited for the study. Alu and LINE-1 methylation was assayed with the quantitative methylation-specific PCR technique with TaqMan probes, while the 5-mC and 5-hmC level was determined using the ELISA-based method. Significantly higher levels of 5-mC, Alu and LINE-1 methylation were observed in the women with depression as compared to the controls; while the 5-hmC level revealed to be significantly lower. The BD type I patients presented the highest level of 5-mC of all the women with a depressive episode. 5-mC level in the patients was positively and significantly correlated with the severity of the symptoms of depression. Relationships between Alu or LINE-1 methylation and 5-mC level were statistically significant only in the case of the control women. Alu and LINE-1 methylation do not constitute suitable biomarkers of global DNA methylation in the investigated patients. These findings require confirmation in case-control and prospective epidemiological studies.

The research was carried out in the years 2015–2018 on the commercial plantations of a horticultural farm. The analysis focused on the yields of two raspberry cultivars: ‘Polana’ and ‘Polka’, factoring in the influence of cultivation methods (in the ground; in the beds with an agrotextile), soil classes (IIIa; IVb), and plantation age (2–5 and 6–10 years). The commercial yields of fruit intended for processing were determined. The economic efficiency analysis of the production of both varieties was carried out. It was shown that regardless of the factor under scrutiny, higher results (in t·ha–1) were obtained from the ‘Polana’ variety. There were differences in the yields of the two varieties depending on the factors. In the case of both varieties, higher results were obtained in traditional cultivation and in class IIIa soil. The plantation age caused only slight differences in the yields of both varieties. The analyses showed statistical significance only in the case of the impact of the cultivation method on the yields of the ‘Polana’ cultivar. Regardless of the variety, the value of production decreased year after year, which resulted mainly from the downward trend in raspberry prices.

Knowledge about ecological interactions between species is of paramount importance in ecology and ecosystem-based fisheries management. To understand species interactions, studies of feeding habits are required. In the Baltic Sea, there is good knowledge of the diet of cod, but little is known about the diet of flounder, the second most abundant demersal fish in the region. In this study, we investigated the diets of cod and flounder for the first time using stomach content data collected simultaneously in 2015-2017 over a large offshore area of the southern Baltic Sea. The diet of flounder was relatively constant between sizes and seasons and was dominated by benthos, with a high proportion in weight of the benthic isopod Saduria entomon. The diet of cod differed between seasons and showed an ontogenetic shift with a relative decrease of benthic prey and an increase of fish prey with size. Historic diet data of cod were used to explore cod diet changes over time, revealing a shift from a specialized to generalist feeding mode paralleled by a large relative decline in benthic prey, especially S. entomon. Flounder populations have increased in the past 2 decades in the study area, and therefore we hypothesized that flounder have deprived cod of important benthic resources through competition. This competition could be exacerbated by the low benthic prey productivity due to increased hypoxia, which could contribute to explaining the current poor status of the Eastern Baltic cod. The results of this study point to the importance of including flounder in multispecies end ecosystem models.

Introduction: Sexual functioning is an important aspect of maintaining the biopsychosocial balance of a human being. Sexual dysfunctions (SD) are common in societies around the world. Studies on alcoholics have shown that chronic and persistent alcohol consumption induces SD leading to impairment of interpersonal contacts, which may affect mental health. By improving the knowledge of this topic one can work on planning multidimensional treatment programmes. The aim of the study will be to measure the sexual functioning of people addicted to alcohol. Material and methods: The research group consisted of 60 people addicted to alcohol aged 18–65, mainly hospitalized in Pruszkow. The control group is 60 healthy people. The participants filled out a set of questionnaires consisting of: sociodemographic questionnaire, sexological tests: FSFI for women, IIEF for men, KZS, Mell-Krat, KWS for both sexes, and a set of tests for alcohol dependence. Results: The analysis showed a significant effect on the results: on the scale pain during sex for the relationship factor. Persons in a relationship showed lower scores on a scale than those who are not in a relationship; for IIEF variable of question No. 4. Healthy people had higher results in this question; in the group of both sexes for the variables satisfaction with appearance and sexualization measured before the onset of symptoms of the disease in people with alcoholism and in healthy people. People with alcoholism showed significantly higher results than healthy people on the scale of satisfaction with appearance. Conclusions: After the research it can be concluded that the most important factor conditioning the sexual functioning of alcohol addicts is a better perception of sexuality before the onset of the disease.

Genetic research in psychiatry has been developing intensively for over 30 years. The social knowledge on the role of genes in the predisposition to diseases and their importance for treatment effects increases. Psychiatric genetic counselling is a service provided under healthcare around the world. The aim of this paper is to present psychiatric genetic counselling, its role for patients and its application in the clinical practice at the current state of knowledge. We discuss these aspects of genetic consultation which relate to mental health. Psychiatric genetic counselling is rarely available in the Polish psychiatric care system and access to specialist training is limited. We indicate that the patient’s adaptation to the genetic burden can bring potential benefits, e.g. better compliance with doctor’s prescriptions. Based on current expert recommendations, we discuss pharmacogenetic tests which are useful in clinical practice. In particular, we analyse the polymorphisms of CYP2D6, CYP2C19 and histocompatibility complex genes HLA.

For many years Poland and Serbia have played the dominating roles in European raspberry production. However, the growing production in Ukraine might threaten the relative stability of the raspberry market for both countries. It is projected that in the coming years Ukraine will strengthen its competitive position in relation to the current industrial raspberry production leaders. This justifies the need to conduct comparative analyses of competitive power, and its contributory factors, including production costs in individual countries. The aim of this study was to compare economic viability and cost-effectiveness in raspberry production, using the examples of selected horticultural holdings in Poland, Serbia, and Ukraine. The production volumes of raspberries in Poland, Serbia and Ukraine were analysed. The levels of costs and the financial results generated in raspberry cultivation for processing purposes were also determined, using the example of horticultural holdings in this countries. The results indicated that the direct costs in Ukraine, were just over half lower those in Poland and Serbia. The raspberry crop yields in the three investigated countries were similar, and the sales prices in the analysed years made it possible to obtain a surplus of receipts over direct costs.

An increasing incidence of mood disorders in adolescents and young adults is being observed. The assessment of personality traits seems to be an interesting tool in identifying early markers of major depression (MD) or bipolar disorder (BD) as well as predictors of the course of the disease. The aim of this study was to compare the personality profiles in young patients with MD and BD in acute and remitted mood states.Seventy-nine adolescents and young adults with mood disorder diagnoses (MD or BD) were included in the study. The participants were assessed based on structured diagnostic interviews and completed the Temperament and Character Inventory (TCI). The clinical evaluation was conducted during the acute episodes and after reaching the stabilized mood in the course of follow-up visits in a 2-year study observation.At baseline, MD patients had higher scores on the harm avoidance (HA) with more pronounced anticipatory worry and fatigability subscale than BD patients. Conversely, BD patients reached higher scores in the total self-directedness (SD) character dimension and its sub-dimensions. MD patients with acute depressive symptoms had higher scores in the HA dimension and its subscale: anticipatory worry, shyness, and fatigability compared with their euthymic states. No significant differences in TCI dimensions between baseline and euthymia in the BD subgroup were found, and no differences between euthymic MD and BD patients.Higher ST and SD sub-dimensions may constitute a personality profile specific to BD, while high HA seems to be related to major depression in both acute and remitted states in young patients.

Plastic litter is widespread on our planet and is recognized as a contaminant of high concern. Plastic ingestion and retention in gills were studied in two key Baltic fish species: herring (Clupea harengus L.) and cod (Gadus morhua L.). In total, 183 fish from the southern Baltic Sea were analysed. Plastic litter was found in digestive tracts of 12.7 and 14.8% of herrings and cods, respectively. In addition, gills were shown to constitute an important transfer route of plastic to cod (9.9% of cods) but not to herring thus likely reflecting species-specific differences in fish lifestyles and/or water filtering capacity. No more than one plastic item per individual was found except for three fish with two items in their stomachs. Dominant microplastics (5 mm) (MPs) (88.6% of all items) composed of irregular fragments, fibres and foils (61.3%, 25.8% and 12.9% of all MPs, respectively) were followed by meso- (5-25 mm) and macro-plastics (25 mm) (5.7% each of all items). Plastic ingestion and retention in gills did not affect fish body condition assessed by Fulton's K index, although herrings that ingested plastic particles beyond the microplastic size range (i.e.5 mm) were characterized by the lowest condition indices. All plastic items recovered from fish exhibited clear signs of weathering and surface extended due to their roughness and fragmentation which may enhance both sorption properties for chemical compounds and/or their leaching. Nevertheless, chemical contaminant levels in herring muscles were not different than in a plastic-free group. The vast majority of fibres found in fish was identified as air-borne or procedural contamination and were excluded from further analyses. In addition, the vessel's paint dust found in fish stressed the need for strict quality assurance also during fish sampling.

Introduction This study aimed to find the expression biomarkers of pharmacological treatment response in a naturalistic hospital setting. Through gene expression profiling, we were able to find differentially-expressed genes (DEGs) in unipolar (UD) and bipolar (BD) depressed women. Methods We performed gene expression profiling in hospitalized women with unipolar (n=24) and bipolar depression (n=32) who achieved clinical improvement after pharmacological treatment (without any restriction). To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. Results After pharmacological treatment, UD and BD varied in the number of regulated genes and ontological pathways. Also, the pathways of neurogenesis and synaptic transmission were significantly up-regulated. Our research focused on DEGs with a minimum fold change (FC) of more than 2. For both types of depression, 2 up-regulated genes, OPRM1 and CELF4 (p=0.013), were significantly associated with treatment response (defined as a 50% reduction on the Hamilton Depression Rating Scale [HDRS]). We also uncovered the SHANK3 (p=0.001) gene that is unique for UD and found that the RASGRF1 (p=0.010) gene may be a potential specific biomarker of treatment response for BD. Conclusion Based on transcriptomic profiling, we identified potential expression biomarkers of treatment outcomes for UD and BD. We also proved that the Ras-GEF pathway associated with long-term memory, female stress response, and treatment response modulation in animal studies impacts treatment efficacy in patients with BD. Further studies focused on the outlined genes may help provide predictive markers of treatment outcomes in UD and BD.

Cognitive deficits are the core factors impacting quality of life among patients diagnosed with schizophrenia. Effective method of treatment for this domain of symptoms remains lacking. Recent evidence suggests the link between impaired cognition and aberrant inflammatory response. Severity of symptoms might be linked to individual genetic predispositions and single-nucleotide polymorphisms (SNPs) in genes encoding interleukins and their receptors. Current genetic association studies include anti-inflammatory interleukins, such as IL10. Functional polymorphisms of IL10 (rs1800871, rs18008729) have been indicated to affect information processing in schizophrenia.In this study, we analyzed the potential impact of 27 functional SNPs in 8 cytokine genes on cognitive parameters measured by Wisconsin card-sorting test (WCST) in schizophrenia group (n = 150) and healthy controls (n = 152).We found significant associations of two functional polymorphisms of IL10 (rs1800871, rs1800872) and WCST results. Allele A carriers in rs1800871 performed significantly better in Percent of Conceptual Level Responses (CLR%). Allele A carriers in rs1800871 and allele T carriers in rs1800872 obtained better results in Completed Categories (CC). The impact of illness duration was observed, with better performance of recent-onset patients.Results of this study indicate that genetic variants of inflammatory response are associated with cognitive deficits in schizophrenia. The role of cytokines in schizophrenia need to be investigated in the aspect of pro-/anti-inflammatory imbalance. Altered inflammatory response promote chronic mild inflammation in the brain and aberrant synaptic plasticity.

Cod (Gadus morhua), an important fish species in the Baltic Sea, is the paratenic host for many parasite species, including the zoonotic nematodes, Anisakis sp. and Contracaecum osculatum. We aimed to identify which invertebrate species (found in situ in the fish stomach) are responsible for infection of cod with zoonotic nematodes. We found that Crangon crangon and Gammarus sp., both invertebrate prey species of cod, were infected with Anisakis simplex and C. osculatum, respectively. These host–parasite systems are reported here for the first time, implicating C. crangon and Gammarus sp. as sources of infection of Baltic cod with zoonotic nematodes.

The consumption of raw or inadequately cooked marine fish can lead to several disorders caused by the ingestion of viable anisakid nematodes. Although anisakid larvae can be killed by subzero temperatures, making freezing an important control measure for this potential health hazard, these parasites can survive freezing under some conditions. Therefore, the aim of the present study was to experimentally evaluate the time-temperature conditions needed to kill Anisakis simplex and Pseudoterranova spp. The effectiveness of freezing was tested on two species of fish: cod, Gadus morhua from the North Atlantic, and herring, Clupea harengus membras from the southern Baltic Sea. Samples, which comprised skinless fillets of cod (n = 40) with visible parasites and whole herring (n = 240), were separately frozen at − 15, − 18, or − 20 °C for 24 h, or at − 20 °C for 48 h in the single-compressor freezer and at − 20, − 25, or − 35 °C for 24 h in the double-compressor freezer. After thawing, parasites were stained with malachite green and examined under the microscope for viability. All A. simplex and Pseudoterranova spp. larvae in cod fillets died at a temperature of − 15 °C or lower. However, freezing did not kill all the A. simplex larvae in whole herring: spontaneous movement of these parasites was observed in samples stored in the single-compressor freezer at − 15, − 18, and − 20 °C over 24 h. Our results demonstrate that the freezing procedure must consider both the capability of the freezing device and the nature of the fish product to ensure consumer safety.

Neurotrophin-3 (NTF3) and neurotrophin-4 (NTF4) play a crucial role in the neurodevelopment, differentiation, survival, and protection of neurons in different brain regions. Schizophrenia and depression are highly associated with metabolic abnormalities. Longitudinal and cross-sectional comparisons of NTF3 and NTF4 levels, as well as clinical and metabolic parameters, were studied in schizophrenia, first-episode depression, and control groups.Serum NTF3 and NTF4 levels, body mass index (BMI), fasting serum glucose and lipid profile: cholesterol, triglyceride, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were measured at baseline and week 8 in 133 women: 55 patients with schizophrenia (19 with first-episode and 36 chronic), 30 patients with a first-episode depression and 48 healthy controls. The severity of the symptoms was evaluated with the Positive and Negative Syndrome Scale, 17-item Hamilton Depression Rating Scale and the Beck Depression Inventory.Longitudinal and cross-sectional comparisons did not detect any differences in the serum levels of NTF3 and NTF4 between studied groups. NTF3 and NTF4 levels were strongly correlated. Correlation of NTF3 and HDL-C levels at baseline was observed. Significant changes in cholesterol and fasting serum glucose levels in first-episode depression patients during 8 weeks of treatment were detected. Significant differences in BMI and LDL-C levels between schizophrenia and first-episode depression patients were discovered.To our knowledge, this is the first research which correlates NTF3 and NTF4 with metabolic parameters. Our study does not support the theory that the peripheral levels of NTF3 and NTF4 are disturbed in schizophrenia or first-episode depression.

Due to the need of continual development, company managements must implement solutions supporting the company operation. The need for company enhancement leads to the implementation of developed management concepts aimed at improving product quality and increasing productivity while reducing prime costs at the same time. One of such concepts is TPM and its crucial component, Autonomous Maintenance. The paper describes the use of an application supporting machinery maintenance tasks carried out by the operators.

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of psychiatric disorders. Schizophrenia is associated with metabolic abnormalities and BDNF regulates energy homeostasis and glucose metabolism in peripheral tissues. The aim of this study was to examine serum levels of BDNF in schizophrenic women during 8 weeks of treatment and control group, and its correlation with clinical and metabolic parameters. The study was performed on a group of 96 women: 55 diagnosed with paranoid schizophrenia according to DSM-IV criteria, and 41 healthy controls. Positive and Negative Syndrome Scale (PANSS) was used to assess the severity of schizophrenia. BDNF serum levels and metabolic parameters: fasting serum glucose, total cholesterol, triglyceride (TG), high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C) were measured at baseline and week 8 of treatment. BDNF serum levels were significantly elevated in medicated patients with schizophrenia comparing to controls. After 8 weeks of antipsychotic treatment, BDNF levels did not significantly change. Increase in TG and TG/HDL-C ratio and a decrease in HDL-C was detected in medicated patients. Correlation between BDNF and lipid profile as well as symptoms severity was found. In our study we detected abnormalities in BDNF levels and lipid profile in medicated schizophrenic women in Polish population.

Melatonin is a neurohormone that maintains the circadian rhythms of the body. By regulating the secretion of other hormones and neurotransmitters, it acts as a pleiotropic modulator that affects, for example, reproductive, immune, cardiovascular, sleep, and wake systems and mood. Thus, synthetic melatonin has become an essential component in the treatment of depressive disorders. Although we know the pathway of melatonin action in the brain, we lack comprehensive cross-sectional studies on the periphery of depressed patients. This study aimed to comprehensively analyze the differences between healthy control subjects (n = 84) and unipolar and bipolar depression patients (n = 94), including an analysis of the melatonin pathway at the level of the genes and serum biomarkers. An innovative approach is a pilot study based on gene expression profiling carried out on clinical and cell culture models using agomelatine and melatonin. We confirmed the melatonin biosynthesis pathway's molecular regulation dysfunctions, with a specific pattern for unipolar and bipolar depression, at the AANAT gene, its polymorphisms (rs8150 and rs3760138), and examined the serum biomarkers (serotonin, AANAT, ASMT, and melatonin). The biological pathway analysis uncovered pathways and genes that were uniquely altered after agomelatine treatment in a clinical model and melatonin treatment in a cell culture model. In both models, we confirmed the immunomodulatory effect of melatonin agents in depression.

BackgroundStudying the phenotypic and genetic characteristics of age and polarity at onset (AAO, PAO) in bipolar disorder (BD) can provide new insights into disease pathology and facilitate the development of screening tools.AimsTo examine the genetic architecture of AAO and PAO and their association with BD disease characteristics.MethodsGenome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (N=12977) and PAO (N=6773) were conducted in BD patients of 34 cohorts and a replication sample (N=2237). The association of onset with disease characteristics was investigated in two of these cohorts.ResultsEarlier AAO was associated with an increased risk of psychotic symptoms, suicidality, and fewer episodes. A depressive onset correlated with lifetime suicidality and a manic onset with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in SNV-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased polygenic scores for autism spectrum disorder (β=-0.34 years, SE=0.08), major depression (β=-0.34 years, SE=0.08), schizophrenia (β=-0.39 years, SE=0.08), and educational attainment (β=-0.31 years, SE=0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO.ConclusionsAAO and PAO are associated with indicators of BD severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents, and phenotype definitions introduce significant heterogeneity, affecting analyses.RELEVANCE STATEMENTIn the largest study to systematically characterize age at onset (N=12977) and polarity at onset (N=6773) in bipolar disorder, we describe an association between illness onset characteristics and indicators of severity, confirming their clinical relevance. Our study shows that that early illness onset is associated with genetic liability for a broad range of psychiatric disorders. However, we also highlight systematic differences in age at onset across cohorts, continents, and phenotype definitions. This heterogeneity results in reduced heritability and affects genetic analyses, underscoring the need for the development of standardized phenotype definitions.

A significant challenge in psychiatry is the differential diagnosis of depressive episodes in the course of mood disorders. Gene expression profiling may provide an opportunity for such distinguishment.We studied differentially expressed genes in women with a depressive episode in the course of unipolar depression (UD) (Different types of depression varied in the number and type of up or down-regulated genes. The pathway analysis showed: in UD, up-regulated rheumatoid arthritis pathway (includingThis pilot study suggests a probability of differentiating depression in the course of UD, BDI, and II, based on transcriptomic profiling.

Lithium has been the most important mood stabilizer used for the treatment of bipolar disorder and prophylaxis of manic and depressive episodes. Despite long use in clinical practice, the exact molecular mechanisms of lithium are still not well identified. Previous experimental studies produced inconsistent results due to different duration of lithium treatment and using animals without manic-like or depressive-like symptoms. Therefore, we aimed to analyze the gene expression profile in three brain regions (amygdala, frontal cortex and hippocampus) in the rat model of mania and depression during chronic lithium administration (2 and 4 weeks). Behavioral changes were verified by the forced swim test, open field test and elevated maze test. After the experiment, nucleic acid was extracted from the frontal cortex, hippocampus and amygdala. Gene expression profile was done using SurePrint G3 Rat Gene Expression whole transcriptome microarrays. Data were analyzed using Gene Spring 14.9 software. We found that chronic lithium treatment significantly influenced gene expression profile in both mania and depression models. In manic rats, chronic lithium treatment significantly influenced the expression of the genes enriched in olfactory and taste transduction pathway and long non-coding RNAs in all three brain regions. We report here for the first time that genes regulating olfactory and taste receptor pathways and long non-coding RNAs may be targeted by chronic lithium treatment in the animal model of mania.

Mood disorders have been discussed as being in relation to glial pathology. S100B is a calcium-binding protein, and a marker of glial dysfunctions. Although alterations in the S100B expression may play a role in various central nervous system diseases, there are no studies on the potential role of S100B in mood disorders in adolescents and young adults . In a prospective two-year follow-up study, peripheral levels of S100B were investigated in 79 adolescent/young adult patients (aged 14–24 years), diagnosed with mood disorders and compared with 31 healthy control subjects. A comprehensive clinical interview was conducted which focused on clinical symptoms and diagnosis change. The diagnosis was established and verified at each control visit. Serum S100B concentrations were determined. We detected: lower S100B levels in medicated patients, compared with those who were drug-free, and healthy controls; higher S100B levels in a depressed group with a family history of affective disorder; correlations between age and medication status; sex-dependent differences in S100B levels; and lack a of correlation between the severity of depressive or hypo/manic symptoms. The results of our study indicate that S100B might be a trait-dependent rather than a state-dependent marker. Due to the lack of such studies in the youth population, further research should be performed. A relatively small sample size, a lack of exact age-matched control group, a high drop-out rate.

Due to current depression prevalence, it is crucial to make the correct diagnosis as soon as possible. The study aimed to identify commonly available, easy to apply, and quick to interpret tools allowing for a differential diagnosis between unipolar and bipolar disorder. The study group includes women with long duration of unipolar (UP, N = 34) and bipolar (BP, N = 43) affective disorder. The diagnosis was established according to the DSM criteria using SCID questionnaire. Additional questionnaires were used to differentiate between UP and BP. BP patients had an earlier age of onset, were hospitalized more times, and more often had a family history of psychiatric disorders than UP (p-value < 0.05). Moreover, BP achieved a higher impulsiveness score and more frequently had experienced severe problems with close individuals. To our knowledge, this is the first publication presenting results of numerous questionnaires applied simultaneously in patients on clinical group. Several of them suggest the direction of clinical assessment, such as: the age of onset, family psychiatric burdens, history of stressful life events, learning problems, social and job relations. Further studies are necessary to confirm the utility of this approach.

Objectives: In mood disorders chronic stress contributes to decreased glucocorticoid receptor signalling in the brain and resistance in the periphery. We hypothesised that aberrant glucocorticoid receptor function may result from genetic predisposition and that decreased GR signalling in the brain correlates with the expression of genes regulating GR complex formation. Methods: We performed the association analysis of 698 patients: 490 patients with bipolar disorder and 208 patients with major depressive disorder and 564 control subjects. We genotyped 11 variants using TaqMan assays. Gene expression in the brain tissue was done in male Wistar rats after chronic mild stress protocol. The SRSF5 serum concentration was performed using ELISA. Data were analysed in Statistica and GraphPad. Results: We found an association of STIP1 and SRSF5 variants with major depressive disorder and BAG1 variant with bipolar disorder. Gene expression analysis in a rat model of depression confirmed significant changes in the expression of SRSF5, BAG1, and FKBP4 in the brain. For SRSF5, we observed significantly increased expression in the serum of depressed females and male rats exposed to chronic stress. Conclusions: Our results indicate the involvement of genes associated with GR function, SRSF5, BAG1, and FKBP4 with susceptibility to mood disorders.