CASP3 gene expression and the role of caspase 3 in the pathogenesis of depressive disorders.

BACKGROUND: The aim of our study was to evaluate the expression of the CASP3 gene at both mRNA and protein levels in patients with depressive disorders and to determine the impact of caspase 3 in the pathogenesis of depression; METHODS: A total of 290 subjects, including 190 depressed patients and 100 healthy controls, participated in the study. Socio-demographic and clinical data were collected, and the severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Venous blood was collected and gene expression was evaluated using RT-PCR and ELISA at the mRNA and protein levels, respectively; RESULTS: The expression of the CASP3 gene was significantly lower in depressed patients compared to healthy controls at both the mRNA and protein levels. Additionally, a positive correlation was observed between CASP3 gene expression and disease duration as well as the number of depressive episodes; CONCLUSIONS: Further studies are needed to investigate the role of caspase 3 in depressive disorders.

Emotional control in selected somatic and psychiatric diseases.

THE AIM: was to assess the level of subjective control of emotional states among patients treated for dermatological and gastrointestinal somatic diseases compared to those with depressive and anxiety disorders. The results were related to the analyzed dimensions of emotion regulation in healthy subjects. MATERIALS AND METHODS: The reports of the conducted studies were compiled for a total of 310 people, including 120 patients diagnosed with a somatic disease (psoriasis, rosacea, irritable bowel syndrome, and gastroesophageal reflux), as well as 96 patients diagnosed with depressive disorders and 30 patients with anxiety disorders. The control group consisted of healthy subjects (64 individuals). To assess the psychological variables analyzed, the subjects completed the Emotion Regulation Questionnaire developed by J. Brzezinski. RESULTS: The study showed that the patients suffering from a chronic somatic symptom disorder, similarly to those treated for depression and anxiety disorders, differed from the healthy individuals in most aspects of emotional control. The patients with dermatological and gastrointestinal diseases differed statistically significantly from the patients with depression and the patients with anxiety disorders in relation to three dimensions of emotional control. Patients with a somatic disease are characterized by higher emotional and rational motivation, lower emotional resilience and lower emotional arousal. CONCLUSIONS: A chronic disease co-occurs with the emotional sphere of a person's daily functioning. Regardless of the diagnosis in terms of somatic disorders and mental illnesses, the way in which emotional states are controlled can be an important factor in the onset of the disease, coping with it as well as the treatment process.

Single-Nucleotide Polymorphisms in Genes Maintaining the Stability of Mitochondrial DNA Affect the Occurrence, Onset, Severity and Treatment of Major Depressive Disorder.

One of the key features of major depressive disorder (MDD, depression) is increased oxidative stress manifested by elevated levels of mtROS, a hallmark of mitochondrial dysfunction, which can arise from mitochondrial DNA (mtDNA) damage. Thus, the current study explores possibility that the single-nucleotide polymorphisms (SNPs) of genes encoding the three enzymes that are thought to be implicated in the replication, repair or degradation of mtDNA, i.e., POLG, ENDOG and EXOG, have an impact on the occurrence, onset, severity and treatment of MDD. Five SNPs were selected: EXOG c.-188T > G (rs9838614), EXOG c.*627G > A (rs1065800), POLG c.-1370T > A (rs1054875), ENDOG c.-394T > C (rs2977998) and ENDOG c.-220C > T (rs2997922), while genotyping was performed on 538 DNA samples (277 cases and 261 controls) using TaqMan probes. All SNPs of EXOG and ENDOG modulated the risk of depression, but the strongest effect was observed for rs1065800, while rs9838614 and rs2977998 indicate that they might influence the severity of symptoms, and, to a lesser extent, treatment effectiveness. Although the SNP located in POLG did not affect occurrence of the disease, the result suggests that it may influence the onset and treatment outcome. These findings further support the hypothesis that mtDNA damage and impairment in its metabolism play a crucial role not only in the development, but also in the treatment of depression.

Serum IL-5, POSTN and IL-33 levels in chronic rhinosinusitis with nasal polyposis correlate with clinical severity.

BACKGROUND: Chronic rhinosinusitis (CRS) is a group of heterogeneous diseases characterized by epithelial inflammation and tissue eosinophilic infiltration. IL-5, POSTN, and IL-33 are important factors that act as chemoattractants for eosinophils, and a tissue-remodeling protein positively correlated with eosinophils in blood and mediators of eosinophilic infiltration. The aim of the study was to determine the expression of IL-5, POSTN and IL-33, at the gene and protein levels, in eosinophilic CRS with nasal polyps (CRSwNP) and without nasal polyps (CRSsNP), and to correlate this expression with clinical severity. MATERIALS AND METHODS: The study included 40 CRSwNP patients and 53 CRSsNP patients and 40 control subjects. The expression of IL-5, POSTN and IL-33 mRNA was determined in sinonasal mucosal samples and in nasal polyp tissue by real-time PCR. Protein levels in the serum of CRSwNP patients were measured by ELISA. Computed tomography was evaluated according to Lund-Mackay scores, and visual analog scale scores were assessed. RESULTS: NP tissue demonstrated significantly higher IL-5 and POSTN mRNA expression than the sinonasal tissue in the CRSsNP and CRSwNP groups. CRS groups demonstrated elevated IL-33 mRNA expression in comparison to controls irrespective of the presence of NP. No correlation was found between IL-5, POSTN and IL-33 mRNA expression and disease severity. CRSwNP group demonstrated significantly higher serum IL-5, POSTN and IL-33 protein levels than controls, and this corresponds to disease severity. CONCLUSION: Serum IL-5, POSTN and IL-33 levels may be important markers for classification of eosinophilic CRSwNP patients, along with disease severity.

A Review of the Global Impact of the COVID-19 Pandemic on Public Mental Health, with a Comparison Between the USA, Australia, and Poland with Taiwan and Thailand.

Coronavirus may have a negative impact not only on physical, but also on mental wellbeing. Despite the different approaches of countries to stop the spread of the virus and different infection rates, the dynamically developing pandemic has already affected the entire world. The consequences of the coronavirus for our mental health can be divided into those related to strategies for the prevention of infection, like isolation, quarantine, limitation of social contacts, and remote work, and those related to the direct impact of infection on our nervous system. This review aims to highlight the global effects of the Coronavirus Disease 2019 (COVID-19) pandemic on public mental health following social restrictions, to identify how infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have direct neurophysiological effects and to compare the impact on public mental health between the USA, Australia, and Poland with Taiwan and Thailand.

Dopamine D2 receptor partial agonists in the treatment of schizophrenia -example of brexpiprazole. / Czesciowi agonisci receptora dopaminowego D2 w leczeniu schizofrenii -przyklad brekspiprazolu.

Since the 1950s, there have been rapid developments in psychiatric pharmacotherapy, resulting not only in more effective treatment of patients, but also in improvements in minimizing adverse effects of therapy. Modern third-generation antipsychotics, in addition to antagonism toward D2 receptors, also exhibit partial agonism toward dopamine receptors. Such a mechanism of action is intended to regulate dopaminergic transmission - inhibit (antagonism) it in pathways where it is excessive (excessive transmission in the mesolimbic pathway in psychotic patients, excessive transmission in the tuberoinfundibular pathway in patients with hyperprolactinemia) and stimulate (agonism) it in pathways where it is too low (mesocortical pathway). This has a beneficial effect on both the reduction of adverse symptoms and the negative, affective and cognitive symptoms of patients suffering from schizophrenia. The purpose of this review article is to present the most important clinical aspects of the use of dopamine D2 receptor partial agonists in the treatment of schizophrenia, using brexpiprazole as an example, and to define the profile of patients to whom this drug could be dedicated - based on recent studies.

The Power of Psychobiotics in Depression: A Modern Approach through the Microbiota-Gut-Brain Axis: A Literature Review.

The microbiota-gut-brain (MGB) axis is a complex communication network linking the gut, microbiota, and brain, influencing various aspects of health and disease. Dysbiosis, a disturbance in the gut microbiome equilibrium, can significantly impact the MGB axis, leading to alterations in microbial composition and function. Emerging evidence highlights the connection between microbiota alterations and neurological and psychiatric disorders, including depression. This review explores the potential of psychobiotics in managing depressive disorders, emphasizing their role in restoring microbial balance and influencing the MGB axis. Psychobiotics exhibit positive effects on the intestinal barrier, immune response, cortisol levels, and the hypothalamic-pituitary-adrenal (HPA) axis. Studies suggest that probiotics may serve as an adjunct therapy for depression, especially in treatment-resistant cases. This review discusses key findings from studies on psychobiotics interventions, emphasizing their impact on the gut-brain axis and mental health. The increasing acceptance of the expanded concept of the MGB axis underscores the importance of microorganisms in mental well-being. As our understanding of the microbiome's role in health and disease grows, probiotics emerge as promising agents for addressing mental health issues, providing new avenues for therapeutic interventions in depressive disorders.

Polish standard of treatment with racemic ketamine for patients with depressive disorders developed by a Working Group appointed by the National Consultant in the field of psychiatry. / Polski standard leczenia racemiczna ketamina pacjentów z zaburzeniami depresyjnymi opracowany przez zespól roboczy powolany przez Konsultanta Krajowegow dziedzinie psychiatrii.

The Polish standard of treatment with racemic ketamine for patients with depressive disorders was developed by a Working Group appointed by the National Consultant in the field of psychiatry. Despite the wide range of available medications, as many as one-third of depressed patients do not respond to standard antidepressant treatment, raising the need for an ongoing search for new effective and safe therapies. In recent years, the possible role of overactivity of the glutamatergic system in the etiopathogenesis of depression has again attracted the attention of many experts. The possibility of using substances with a modulating effect on the glutamatergic system in the treatment of depressive disorders has been postulated, among others, the long-known anesthetic ketamine, which is a noncompetitive NMDA receptor antagonist. This paper summarizes the results of studies on the efficacy and safety of racemic ketamine (administered intravenously) in the treatment of patients with depressive symptoms in the course of both unipolar and bipolar affective disorder, and, meeting the expectations of many practicing psychiatrists wishing to broaden the range of therapies offered to their patients, presents recommendations on indications, contraindications, precautions and the treatment regimen itself with intravenous ketamine for patients with mood disorders.

Psychiatric Treatment in Pregnancy: A Narrative Review.

Pregnancy, childbirth and the puerperium are a series of transformations and huge changes in a woman's life, which may also be accompanied by various mental problems. Very often, women experiencing mental disorders during this period and their doctors face a decision on safety of treatment. The purpose of the following review was to assess the safety of treatment during pregnancy. Internet scientific database PubMed was searched. There are groups of psychiatric medications contraindicated during pregnancy such as valproates as well as relatively safe ones such as selective serotonin reuptake inhibitors (SSRIs) or antipsychotics. However, in every clinical situation, a decision should be made with caution, based on individual characteristics of patient, severity of disorder and clinical picture.

Common pathomechanism of migraine and depression. / Wspólny patomechanizm migreny i depresji.

Migraine and depression often coexist and constitute an important clinical problem. Both disorders are associated with the necessity of chronic treatment, and their mutual coexistence contributes to the phenomenon of drug resistance. Influencing the functioning of patients, they also cause numerous social consequences - affecting the quality of life and achievement of personal goals of patients. This review presents factors that may explain the common pathomechanisms of depression and migraine. Structural and functional disturbances of the central nervous system (CNS), disturbances in the neurotransmitter systems, inflammatory theories, hormonal disturbances, as well as a possible genetic basis were taken into account. Due to the fact that both depression and migraine have a multifactorial etiology and at the present stage of scientific research it is difficult to clearly determine which factor is the most important, such a broad overview has been presented. It is also difficult to determine which of the above-mentioned factors, well documented in international studies, only coexist, and which of them may have a cause-and-effect relationship in the described disorders. Further research into the comorbidity and causes of migraine and depression seems to be worth considering.

Experiencing Violence among Children and Adolescents with Depression in the Aspect of Polish Law.

Violence is not uncommon in the contemporary world. The consequences of harmful experiences in childhood are often educational problems, difficult behavior, failure to cope in adulthood, duplication of learned, negative behavior patterns and disorders in various spheres/areas of life. The experience of childhood violence is associated with the occurrence of about half of mental disorders with onset in childhood and one third of disorders that appear later in life. Various emotional and behavioral disorders are mentioned among the psychological effects of violence against a child, including depressive disorders. Regarding experiences of violence, there is strong evidence that exposure to sexual or physical violence is a predictor of depressive episodes and depressive symptoms in adolescents. Among adolescents, the impact of violence on depression has been shown to be sustained. Accordingly, evidence suggests that elevated depressive symptoms and episodes of depression may even persist for up to two years after experiencing cases of violence. Due to the destructive consequences of such behavior, international and national law devote much attention to the protection of children's rights. Under Polish law, there are regulations describing measures of reaction within the family, as well as provisions sanctioning violent behavior. Therefore, the study discusses the family and criminal law aspects of violence against minors. The whole study is imbued with considerations of the so-called the obligation to denounce, i.e., to notify about the disclosure of a prohibited act committed to the detriment of minors. This issue was presented in the context of medical secrets and its type-psychiatric discretion.

Expression of p11 in Patients with Depression.

(1) Background: Some studies suggest that the p11 protein, belonging to the so-called S100 family and located, i.a., in the nucleus accumbens of the brain, is responsible for the occurrence of depression. This protein is encoded by the S100A10 gene. The aim of our study was to evaluate the expression of the S100A10 gene at the mRNA and protein levels in patients with depressive disorders and to determine the impact of p11 in the etiopathogenesis of depression; (2) Methods: A total of 290 people (190 depressed patients, 100 healthy controls) participated in the study. Socio-demographic and clinical data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Venous blood was collected from all participants. RT-PCR was used to evaluate gene expression at the mRNA level, while enzyme-linked immunosorbent assay (ELISA) was used to evaluate gene expression at the protein level; (3) Results: The results indicate slightly increased S100A10 gene expression (both at the protein and mRNA levels) in patients with depression, but these values do not reach statistical significance; (4) Conclusions: Due to the fact that the study was limited by the participation of patients already undergoing antidepressant treatment, its results may confirm that pharmacological treatment affecting serotonin neurotransmission is effective in upregulation of p11 in patients with depression.

Expression of PON1, PON2, PON3 and MPO Genes in Patients with Depressive Disorders.

Background: Taking into account the role of oxidative stress in neurodegeneration, we sought to evaluate the expression of genes for select enzymes with antioxidant properties (paraoxonases PON1, PON2 and PON3 and myeloperoxidase MPO) at the mRNA and protein levels in patients with depressive disorders. We further sought to determine the impact of oxidative stress in the etiopathogenesis of this group of mood disorders. Methods: A total of 290 subjects (190 depressed patients, 100 healthy controls) took part in the study. Sociodemographic and clinical data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Venous blood was collected. RT-PCR was used to assess gene expression at the mRNA level, while enzyme-linked immunosorbent assay (ELISA) was used to assess gene expression at the protein level. Results: The expression of the PON2 and PON3 genes at the protein level was significantly higher in depressive patients than in healthy controls. mRNA expression of the PON1, PON2 and PON3 genes was slightly higher in patients with depressive disorders than in the control group, however, this relationship was not statistically significant. On the other hand, the expression of the MPO gene at both mRNA and protein levels was significantly lower in patients with depressive disorder than in the control group. Conclusions: Our results are not in agreement with many studies on enzymes involved in maintaining oxidative balance. Our findings may not support the utility of paraoxonases (PON) or myeloperoxidase (MPO) as promising biomarker candidates of depression pending larger and well controlled studies.

Ways of Coping with Stress among Patients with Depressive Disorders.

BACKGROUND: Experiencing stressful life events and ways of coping with them can predispose to the onset of depressive mood disorders, while depression itself can be responsible for severe stress and can weaken resilience to stressors. Thus, variables relevant to the onset of depressive episodes and the course of depression have significant relationships with coping strategies to stressors. The aim of this research was to evaluate the most commonly used stress-coping strategies in patients treated for depression compared to patients with anxiety disorders and to healthy subjects. METHODS: The multidimensional coping inventory (COPE Inventory) by C. S. Carver, M. F. Scheier, and J. K. Weintraub, covering 15 stress response strategies included in more general and overarching coping styles, was used in the study. RESULTS: Patients with depression differed from the healthy subjects in a statistically significant way. Statistical analysis showed that people with depression are less likely than healthy subjects to use Active Coping, Planning, Seeking of Instrumental and Emotional Social Support, Suppression of Competing Activities, and Positive Reinterpretation. In contrast, they are more likely to use Denial, Mental Disengagement, and Behavioral Disengagement compared to those not treated for mental disorders. The patients with depressive disorders, compared to the group of patients with anxiety disorders, scored significantly differently on stress coping strategies in only two types of actions taken in stressful situations. CONCLUSION: The patients with depression differed from the healthy subjects in terms of the highest number of the stress coping strategies assessed. Compared to the healthy individuals, a tendency toward an avoidant behavior style was prevalent among the depressed patients. There was no statistically significant difference between the patients with the first episode of the disease and recurrent depressive disorders in terms of stress coping strategies.

Is the JAK-STAT Signaling Pathway Involved in the Pathogenesis of Depression?

(1) Background: Only 60-70% of depressed patients respond to standard antidepressant treatments. Hence, it is essential to search for new, effective and safe therapies for unmet clinical needs of treatment-resistant depression (TRD). Agents targeting the components of the JAK-STAT signaling pathway have been shown to be relevant in immunology and are commonly used in the treatment of many hematological, rheumatological and dermatological diseases. The aim of this study was to investigate the role of elements of the JAK-STAT signaling pathway in the etiopathogenesis of depressive disorders. (2) Methods: A total of 290 subjects took part in the study (190 depressed patients, 100 healthy controls). Sociodemographic data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). The gene expression at the mRNA protein levels of JAK (JAK1-JAK3) and STAT (STAT1-STAT5) was assessed by using RT-PCR and ELISA. (3) Results: Increased expression of JAK3 and decreased expression of STAT1 were observed in the group of depressed patients. (4) Conclusions: Further studies are necessary to determine whether moderation of the JAK-STAT signaling pathways is involved in the treatment of depression.

Treatment-resistant depression - recommendations of the National Consultant in the field of psychiatry. / Depresja oporna na leczenie ­ zalecenia Konsultanta Krajowego w dziedzinie psychiatrii.

Depression is one of the most common mental disorders, it affects about 5-17% of the population. Depressive disorders are a serious economic and social problem. Depression has a significant impact on the employment status, financial success and interpersonal relationships. It is the reason for the greatest number of days of absence from work among all diseases. Patients who do not respond to standard antidepressant treatment cost twice as much as patients who do respond to treatment (response to standard antidepressant treatment occurs only in 60-70% of patients suffering fromdepressivedisorder). According to epidemiological data, even one-third of patients may have treatment-resistant depression, which is defined as depressive disorder in adults who have not responded to at least two different antidepressants (used at the right dose for the appropriate period) in the current episode of moderate to severe depression. The purpose of this publication is to present the problem of drug resistance in depression and to present strategies for dealing with treatment-resistant depression.

Neuroimmunology and (Epi)Genetics in Depressive Disorders.

Depression causes individual suffering, loss of productivity, increased health care costs and high suicide risk [...].

Expression of Selected Genes Involved in Neurogenesis in the Etiopathogenesis of Depressive Disorders.

(1) Background: The neurogenic theory suggests that impaired neurogenesis within the dentate gyrus of the hippocampus is one of the factors causing depression. Immunology also has an impact on neurotrophic factors. The aim of the study was to assess the importance of selected genes involved in the process of neurogenesis i.e., nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF) and neuron-restrictive silencer factor (REST gene) in the etiopathogenesis of depressive disorders. (2) Methods: A total of 189 subjects took part in the study (95 depressed patients, 94 healthy controls). Sociodemographic data were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). RT-PCR was used to assess gene expression at the mRNA levels, while Enzyme-Linked Immunosorbent Assay (ELISA) was used to assess gene expression at the protein level. (3) Results: Expression of NGF, BDNF, REST genes is lower in depressed patients than in the control group, whereas the expression of GDNF gene is higher in patients with depressive disorders than in the group of healthy volunteers. (4) Conclusions: The expression of selected genes might serve as a biomarker of depression.

Update on the neurodevelopmental theory of depression: is there any 'unconscious code'?

Depression is currently one of the most common psychiatric disorders and the number of patients receiving antidepressant treatment is increasing every year. Therefore, it is essential to understand the underlying mechanisms that are associated with higher prevalence of depression. The main component leading to the change in functioning, in the form of apathy, anhedonia, lack of motivation and sleep disturbances, is stress. This is the factor that in recent decades-due to the civilization speed, dynamic technological development as well as competitiveness and competition in relationships-significantly affects the psychophysical condition, which results in an increase in the prevalence of civilization diseases, including depression. To understand the mechanism of susceptibility to this disease, one should consider the significant role of the interaction between immune and nervous systems. Their joint development from the moment of conception is a matrix of later predispositions, both associated with the mobilization of the proinflammatory pathways (TNFα, IL-1ß, IL-6) and associated with psychological coping with stress. Such an early development period is associated with epigenetic processes that are strongly marked in prenatal development up to 1 year of age and determinate the characteristic phenotype for various forms of pathology, including depression. Regarding the inflammatory hypothesis of depression, interleukin 17 (IL-17), among other proinflammatory cytokines, might play an important role in the development of depressive disorders. It is secreted by Th17 cells, crossed the placental barrier and acts on the brain structures of the fetus by increasing IL-17 receptor levels and affecting the intensity of its signaling in the brain.

Inflammatory versus Anti-inflammatory Profiles in Major Depressive Disorders-The Role of IL-17, IL-21, IL-23, IL-35 and Foxp3.

BACKGROUND: The authors of this research study intended to verify whether there are any changes in gene expression in depressed patients without coexisting inflammatory diseases for selected immune-inflammatory factors that are particularly important in autoimmune disease pathogenesis (IL-17, IL-21, IL-23, IL-35, Foxp3). METHODS: The study was carried out on a group of 190 patients with depression and 100 healthy volunteers. The severity of depressive symptoms was assessed using the Hamilton Depression Scale. RT-PCR was used to evaluate mRNA expression and ELISA was used to measure protein expression of these genes. RESULTS: The level of gene expression for IL-17, IL-21, IL-23, and IL-35 was substantially higher in the group of patients with depression compared to the control group. The mean mRNA expression of Foxp3 was considerably reduced in patients suffering from depressive disorders. There was a statistically significant correlation between the number of hospitalizations and the expression of specific inflammatory factors. CONCLUSIONS: Expression of specific inflammatory genes may be a factor in the etiopathogenesis of depressive disorders. The duration of the disease seems to be more important for the expression of the genes in question than the severity of depression. These cytokines may affect the metabolism of neurotransmitters and neuroendocrine functions in the brain as well as be a marker and a new potential therapeutic target for recurrent depressive disorders.