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.

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.

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.

Pharmacogenetics and Schizophrenia-Can Genomics Improve the Treatment with Second-Generation Antipsychotics?

Schizophrenia (SCZ) is a complex psychiatric disorder of multifactorial origin, in which both genetic and environmental factors have an impact on its onset, course, and outcome. Large variability in response and tolerability of medication among individuals makes it difficult to predict the efficacy of a chosen therapeutic method and create universal and precise guidelines for treatment. Pharmacogenetic research allows for the identification of genetic polymorphisms associated with response to a chosen antipsychotic, thus allowing for a more effective and personal approach to treatment. This review focuses on three frequently prescribed second-generation antipsychotics (SGAs), risperidone, olanzapine, and aripiprazole, and aims to analyze the current state and future perspectives in research dedicated to identifying genetic factors associated with antipsychotic response. Multiple alleles of genes involved in pharmacokinetics (particularly isoenzymes of cytochrome P450), as well as variants of genes involved in dopamine, serotonin, and glutamate neurotransmission, have already been identified as ones of significant impact on antipsychotic response. It must, however, be noted that although currently obtained results are promising, trials with bigger study groups and unified protocols are crucial for standardizing methods and determining objective antipsychotic response status.

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.

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.

Is Interleukin 17 (IL-17) Expression A Common Point in the Pathogenesis of Depression and Obesity?

(1) Background: Activated immune-inflammatory pathways play an important role in the pathogenesis of depression and pathological obesity. Obesity might promote production of cytokine interleukin 17, which plays a significant role in neuro-immune reactions. The study aimed at assessing the relationship between Body Mass Index (BMI) and IL-17 expression, taking into account the clinical psychiatric variables in patients with depression. (2) Methods: A total of 125 participants took part in the study (95 depressed patients, 30 healthy controls). Data concerning the course of depressive disorders and BMI were collected. The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Reverse transcription polymerase chain reaction (RT-PCR) was used to assess IL-17 gene expression at the mRNA levels, while enzyme-linked immunosorbent assay (ELISA) was used to assess IL-17 expression at the protein level. (3) Results: Patients with more hospitalizations showed significantly higher IL-17 mRNA expression levels and higher BMI. However, no correlation between BMI and IL-17 expression was found in depressed patients. (4) Conclusions: Our study revealed that BMI does not affect IL-17 expression in patients with depression. However, further studies should be conducted to evaluate the effects of IL-17 inhibition on adipose tissue and vice versa.