The pathogenesis of depression is complex and heterogeneous, and the management of this disease remains unsatisfactory, so mechanisms and therapeutic strategies are constantly being sought. This study aimed to determine the potential role of estrogen metabolites in the pathogenesis of treatment-resistant depression (TRD) based on the determination of concentrations of estrogens and their metabolites and hydrogen peroxide (H202) in the biological material of patients with TRD. In this study, we observed for the first time an association between unbalanced estrogen metabolism and elevated H202 levels in TRD patients. Reduced concentrations of 2-methoxyestradiol (2-ME2), 17α-estradiol (α-E2) and 17β-estradiol (β-E2) may be due to abnormal estrogen metabolism toward neurotoxic semiquinones and quinones which are a potential as yet undescribed mechanism responsible for generating oxidative stress (OS) in TRD.

Depression is underpinned by a complex pathogenesis that involves the hippocampus and dorsal raphe nucleus (DRN) of the central nervous system. Although electroacupuncture (EA) is proven to be safe and effective for alleviating depression symptoms and causes minimal side effects, its underlying therapeutic mechanism remains unclear. In this study, we performed targeted metabolomics to identify metabolite alterations in the hippocampus and DRN of Wistar Kyoto (WKY) rats and elucidate the role and potential mechanism of action of EA. Our results indicated that 3 weeks of consecutive EA significantly ameliorated depression-like behaviors in WKY rats. Targeted metabolomics revealed 42 differentially expressed metabolites (DEMs) in the hippocampus and 97 DEMs in the DRN between Wistar and WKY rats. In addition, we observed 19 hippocampal DEMs and 41 DRN DEMs between WKY and EA-treated rats. Subsequent pathway analyses indicated that these DEMs were primarily enriched in amino acid-related metabolic pathways. Moreover, six DEMs were found to be significantly associated with at least one depression-like behavior, indicating their involvement in the pathogenesis of depression. EA intervention modulated the levels of 1-methylhistidine, 3-methylhistidine, carnosine, and riboflavin in depressed rats. Collectively, these findings demonstrate that disturbances in cerebral metabolites, especially amino acids, may be one of the causes underlying depression in WKY rats, and the therapeutic effect of EA is potentially mediated through the modulation of the levels of these metabolites.

Neuroinflammation plays a pivotal role in the pathogenesis of depression. G protein-coupled receptor 35 (GPR35) is expressed in the brain and plays a role in regulating inflammatory processes. However, its specific role in depression remains unclear. Herein, we investigate the role of GPR35 in depressive behaviors induced by lipopolysaccharide (LPS) in mice.

We employed an LPS-induced depression mouse model and conducted behavioral tests, molecular analyses, and morphological assessments, along with chemogenetic techniques, to investigate the role of GPR35 in depression.

Our results showed a significant increase in GPR35 expression in the brain of LPS-treated mice. Both pharmacological inhibition and genetic knockdown of GPR35 alleviated LPS-induced depressive-like behaviors by mitigating neuroinflammation, oxidative stress, synaptic plasticity deficits, and TLR4/NF-κB signaling in mice. Conversely, pharmacological activation of GPR35 notably exacerbated LPS-induced depressive-like behaviors in mice. Additionally, the GPR35 antagonist ML-145 effectively prevented LPS-induced inflammation responses in BV-2 microglia cells. Moreover, fluoxetine treatment effectively mitigated the upregulation of hippocampal GPR35 expression induced by LPS in mice. However, administration of the GPR35 agonist zaprinast reversed the antidepressant effects of fluoxetine. Chemogenetic activation of hippocampal glutamatergic neurons attenuated LPS-induced depression-like behaviors, accompanied by decreased GPR35 expression.

Hippocampal GPR35 is closely associated with depressive behaviors in the inflammatory model, highlighting its potential as a therapeutic target for antidepressant drug development.

The impact of weather on mental illness is widely debated, but the mechanism of this relationship remains unclear. The immunoseasonal theory suggests that in winter, a T-helper 1 (Th1) response predominates, impairing Prefrontal Cortex (PFC) control, which exacerbates symptoms of depression, while after it, in summer, a Th2 response predominates in immunologically prone individuals, activating cortical and mesolimbic centers, which can exacerbate symptoms of psychosis. In this paper, we aim to describe the validity of this theory through a narrative review of data related to weather and immunology in psychiatry. This review extends existing literature by integrating immunological findings with psychiatric seasonality research, offering a mechanistic perspective that links Th1/Th2 shifts to specific symptom exacerbations. Winter Th1 severity may worsen depression and anxiety, while summer Th2 dominance appears to be associated with exacerbations of schizophrenia, mania, impulsivity, and suicide risk. It is possible that the mechanism of Th1 response potentiation and deterioration of PFC function is common to most psychiatric entities and is nonspecific. This suggests that seasonal immune dysregulation may play a broader role in psychiatric disorders than previously recognized, challenging the idea that seasonality impacts only selected conditions. Characteristic dysfunctions within an individual determine further differences in clinical manifestations. The mechanism of Th2 potentiation may not be limited to mania and psychosis but may also be associated with increased impulsivity and suicide risk. If the immunoseasonal theory is confirmed, selected immunological markers could be used not only in the diagnosis of psychiatric exacerbations but also in predicting symptom fluctuations and tailoring treatment strategies. This could enable more personalized interventions, such as seasonally adjusted medication dosing or targeted anti-inflammatory therapies. While this mechanism seems plausible, further research, especially analyzing markers of inflammatory and anti-inflammatory responses, is needed to better understand and confirm it.

Depression is one of the most common psychological disorders, and due to its high prevalence and mortality rates, it imposes a significant disease burden. Contemporary treatments for depression involve various synthetic drugs, which have limitations such as side effects, single targets, and slow onset of action. Unlike synthetic medications, phytochemicals offer the benefits of a multi-target and multi-pathway mode of treatment for depression. In this literature review, we describe the pharmacological actions, experimental models, and clinical trials of the antidepressant effects of various phytochemicals. Additionally, we summarize the potential mechanisms by which these phytochemicals prevent depression, including regulating neurotransmitters and their receptors, the HPA axis, inflammatory responses, managing oxidative stress, neuroplasticity, and the gut microbiome. Phytochemicals exert therapeutic effects through multiple pathways and targets, making traditional Chinese medicine (TCM) a promising adjunctive antidepressant for the prevention, alleviation, and treatment of depression. Therefore, this review aims to provide robust evidence for subsequent research into developing phytochemical resources as effective antidepressant agents.

Depression is presented as a multi-factorial bio-psycho-social expression that has evolved primarily as an effect of stressors related to the motivational/emotional systems that regulate the BrainMind in our relationship with conspecifics. These stressors may be caused by two sources of threat, firstly, the loss of bonding with the caregiver and later with a partner and/or group which relates to the SEPARATION (PANIC/GRIEF) system, secondly, social defeat as an expression of the social competition and social dominance. The sexual maturity drives the individual to social competition and social dominance, even if the latter often occurs before sexual maturity, e.g., chickens, dogs, non-human primates, and humans. Depression is an evolutionarily conserved mechanism in mammals to terminate both separation anxiety, so as to protect the vulnerable social brain from the consequences of prolonged separation anxiety, and the stress of social competition when social defeat is predictable. Adolescence and Young adulthood are particularly susceptible to these two types of threat because of human developmental characteristics that are summarized by the term neoteny. This refers to the slowing down of growth and development, resulting in both a prolonged period of dependence on a caring/protective adult and the persistence of juvenile characteristics throughout life. Therefore, neoteny makes the transition from childhood to sexual maturity more dramatic, making the integration of the SEPARATION (PANIC/GRIEF) system with the dynamics of social competition and dominance more stressful and a source of depression. Stress is an expression of the HPA-Hypothalamic-Pituitary-Adrenal axis that articulates with other systems, mainly the autonomic nervous system and the immune-inflammatory system. The latter is believed to be one of the most significant components in the dynamics of depressive processes, connected to the prodromes of its activation in childhood, under the pressure of environmental and relational stressors which can lead to learned helplessness. The recurrence of stressors makes it easier for the immune-inflammatory system to be activated in later life, which could make a significant contribution to the establishment of a depressive disease. The possible contribution of children's identification processes with their parents' depressive personalities through observational learning is considered.

In the present study, we wanted to check whether TCS OX2 29 (TCS), a potent selective antagonist of OX2 receptors, would have positive effects in an animal model of detrusor overactivity co-existed with the depression-like state in Wistar male rats.

The forced swim test with the measurement of spontaneous locomotor activity, conscious cystometry, determination of c-Fos expression in central micturition areas, and a set of biochemical analyses (with the use of urine, hippocampus, bladder urothelium, and detrusor muscle of tested animals) were carried out.

The outcomes showed that a 7-day administration of TCS (3 mg/kg/day, subcutaneously) normalizes the cystometric parameters corresponding to overactivity of the detrusor and reverses the pro-depressive response. Furthermore, the antagonism of OX2 receptors restored the abnormal levels of overactive bladder markers (i.e., ATP, CGRP, OCT3, TRPV1, ROCK1, and VAChT), diminished neuronal overactivity in central micturition areas (i.e., pontine micturition center, ventrolateral periaqueductal gray, and medial preoptic area) as well as restored the altered hippocampal levels of CRF, cytokines (IL-1β, IL-6, IL-10, and TNF-α), and growth factors (BDNF and NGF) that reflected biochemical disturbances detected in depressed people.

It seems that our findings open new perspectives regarding the implication of the orexin system in the functioning of the urinary bladder and in the pathophysiology of depression.

Several clinical neuroimaging studies have reported structural and functional brain abnormalities associated with peripheral inflammatory cytokines or kynurenine pathway metabolites in patients with depression. However, it is not clear whether the abnormal findings are changes that are intrinsic to depression or whether they are caused by confounding factors such as age, illness duration, or medication.

To exclude confounding factors, we used chronic unpredictable mild stress (CUMS) rat model and magnetic resonance T1/T2 mapping to investigate the microstructural characteristics of the prefrontal cortex (PFC), hippocampus and corpus callosum and further explored the association between peripheral blood depression-related indicators and microstructural characteristics.

The results revealed that the T2 relaxation time of the corpus callosum was significantly decreased in the CUMS model compared to the control group. Additionally, positive correlations were found between the levels of inflammatory cytokines (interleukin (IL)-1 and IL-6) and the T1 relaxation time of the corpus callosum and between the level of IL-6 and the T1 relaxation time of the PFC.

Our study demonstrates that the microstructural abnormality of the corpus callosum is an intrinsic change that accompanies depression and also provides robust evidence that the microstructural characteristics of the corpus callosum and PFC associated with inflammatory cytokines in peripheral blood play an important role in the fundamental pathophysiological mechanism of depression.

Depression, a widespread mental disorder, presents significant risks to both physical and mental health due to its high rates of recurrence and suicide. Currently, single-target antidepressants typically alleviate depressive symptoms or delay the progression of depression rather than cure it. Ginsenoside Rg1 is one of the main ginsenosides found in Panax ginseng roots. It improves depressive symptoms through various mechanisms, suggesting its potential as a treatment for depression.

We evaluated preclinical studies to comprehensively discuss the antidepressant mechanism of ginsenoside Rg1 and review its toxicity and medicinal value. Additionally, pharmacological network and molecular docking analyses were performed to further validate the antidepressant effects of ginsenoside Rg1.

The antidepressant mechanism of ginsenoside Rg1 may involve various pharmacological mechanisms and pathways, such as inhibiting neuroinflammation and over-activation of microglia, preserving nerve synapse structure, promoting neurogenesis, regulating monoamine neurotransmitter levels, inhibiting hyperfunction of the hypothalamic-pituitary-adrenal axis, and combatting antioxidative stress. Moreover, ginsenoside Rg1 preserves astrocyte gap junction function by regulating connexin43 protein biosynthesis and degradation, contributing to its antidepressant effect. Pharmacological network and molecular docking studies identified five targets (AKT1, STAT3, EGFR, PPARG, and HSP90AA1) as potential molecular regulatory sites of ginsenoside Rg1.

Ginsenoside Rg1 may exert its antidepressant effects via various pharmacological mechanisms. In addition, multicenter clinical case-control and molecular targeted studies are required to confirm both the clinical efficacy of ginsenoside Rg1 and its potential direct targets.

High Mobility Group Box Protein-1 (HMGB1), which has proinflammatory properties, is known to be involved in psychiatric disorders as far as we know, there are only one clinical studies investigating the role of HMGB1 in major depressive disorder (MDD). In this study, we aimed to investigate the role of HMGB1 in the etiopathogenesis of MDD and whether HMGB1 can be used as a biomarker in MDD by measuring the serum HMGB1 levels of depressed patients in the episode and remission periods. This study included 30 patients diagnosed with MDD in episode, 30 patients in remission and 30 healthy controls. Each group comprised 20 female and 10 male participants. In this study, serum HMGB1 levels were found to be lower in the patient group in the episode compared to the patient group in the remission period and the healthy control group. There was no significant difference between the patient group in remission and the healthy control group in terms of serum HMGB1 levels. The fact that serum HMGB1 levels were lower in the patient group in the episode compared to the patient group in the remission period and the control group may be related to the neuroprotective effects of HMGB1. HMGB1 may be used as a biomarker for MDD.

Randomised controlled trials have demonstrated the benefit of diet modification to improve diet quality in the treatment of adult major depressive disorder (MDD). However, research examining nutritional interventions for adolescents with MDD is sparse. This pilot study examined the feasibility of a personalised nutrition intervention for adolescents with MDD. Ten adolescents with MDD and their parents recruited from a tertiary care setting participated in an 8-week, single-arm mixed-methods study. Feasibility was assessed using five criteria (demand, acceptability, implementation, adaptation and limited efficacy testing) alongside qualitative interviews. The intervention involved four bi-weekly virtual nutrition counselling sessions with a stepped approach to dietary change, menu planning, grocery delivery and educational eHealth messages. Study participants sought positive changes in diet, health and lifestyle for adolescents and family-wide benefits. Recruitment challenges included concerns about managing mood fluctuations, anticipated dietary restrictions and the potential time and effort required for diet adherence. Feedback based on interviews emphasised moderate to high acceptability, satisfaction with menu planning and counselling and recognition of the benefits of trying new foods and sustaining positive dietary changes beyond the study. Improvements in depression symptoms (Cohen's d = 0·36, 95 % CI (-0·24, 3·36)), parent food modeling (Cohen's d = 0·24, 95 % CI (-0·43, 1·16) and the family food environment (Cohen's d = 0·61, 95 % CI (-0·04, 2·61)) were observed. This nutrition intervention was feasible for adolescents with MDD and was acceptable to both parents and depressed adolescents. These preliminary data suggest that further examination of the intervention and its potential benefits on depression symptoms and family food dynamics are warranted.

To analyze the cytokine profile in cerebrospinal fluid (CSF), as well as mood, anxiety, and cognition profiles in patients with CC.

One hundred and nine individuals were evaluated, 37 controls, 18 CWC, and 54 CC patients. Assessments included BDI, HADS, Digit Span, FAS-verbal, Animals/WMS-R, Matrix Reasoning and Vocabulary (WASI), and QLQ-C30.

The CC group exhibited 62.96% depression and probable anxiety/depression, with 75.92% showing attention deficits. The CC and CWC groups demonstrated significant cognitive impairment on the WASI-Vocabulary test (CWC: 13.4 ± 2.2; CC: 15.9 ± 1.1) compared to the control group (Ct: 22.8 ± 1.6; p = 0.0002). In the QLQ-C30 scores, the CC group reported a greater perceived loss of quality of life and health deterioration (score of 17.5 ± 2.6) and lower scores on the Functional Scale (49.8 ± 4.5). The CC group had 18.52% illiteracy, 18.52% incomplete higher education, and 22.22% complete elementary education. The CC group also had lower weight (Ct: 67.8 ± 1.4; CWC: 61.7 ± 3.1; CC: 59.6 ± 1.7; p = 0.0023) and BMI (CC: 21.5 [18.3; 24.8]; Ct: 24.9 [23; 25.8]; p = 0.0021) compared to controls. Cytokines detected in the CSF were MCP-1, VEGF, IL-8, IP-10, and MIP-1β. Higher concentrations of MCP-1 were found in cancer patients (CSC: 571.2 ± 105.8; CC: 399.5 ± 65.9; Ct: 1477 ± 0.1; p < 0.0001), along with lower levels of MIP-1β (CC: 4345 [3060; 7353]) and VEGF (CC: 48.3 ± 2.0; CWC: 49.8 ± 3.8; Ct: 64.8 ± 3.2; p < 0.0001).

The level of mental impairment (mood, anxiety, and cognitive deficits) correlated with cancer-associated and cachexia-associated inflammation, weight loss, low BMI, elevated C-reactive protein (CRP), leukocytosis, lymphopenia, anemia, hypoalbuminemia, and low scores on the QLQ-C30 questionnaire (Global Health Status, Functional Scale, Symptom Scale). The CC group exhibited a higher prevalence of depression/anxiety, a stronger correlation between depression and inflammation, and greater cognitive impairment in attention, reasoning, and language, alongside lower average educational attainment. The low concentration of certain cytokines in the CSF combined with elevated systemic CRP in cancer and cachexia, associated with mental disorders, presents a paradox that requires further investigation. Higher concentrations of the cytokine MCP-1 in cancer patient groups indicated a positive correlation with the preservation of language abilities in these patients.

Depression is a serious medical illness characterized by persistent feelings of sadness, hopelessness, and lack of interest in daily activities. It can interfere with daily functioning and quality of life. Despite decades of research, the pathophysiology of depression remains incompletely understood. The correlation between depression and inflammation has recently attracted considerable attention. This study investigated the potential antidepressant effect of etanercept, a tumor necrosis factor-alpha (TNF-α) inhibitor, utilizing a chronic mild stress (CMS) model in rats. Male Wistar rats were divided into two groups; one following a non-stressed protocol and the other a stressed protocol for 5 weeks. From the beginning of the third week, rats were treated either with saline daily or with etanercept twice a week (0.3 mg/kg, i.p.) or with fluoxetine daily (10 mg/kg, i.p) as a reference. Etanercept exhibited comparable effects to those of fluoxetine in counteracting CMS-induced behavioral manifestation in the forced swimming and splash tests. Etanercept also restored serotonin and norepinephrine levels to control values in the prefrontal cortex (PFC). Moreover, the current study verified the antioxidant and anti-inflammatory effects of etanercept. Interestingly, etanercept halted the expression of both norepinephrine and serotonin transporters in stressed rats. This could be attributed to abrogation of the p38 mitogen-activated protein kinase (p38 MAPK) and signal transducer and activator of transcription 3 (STAT-3) pathways in the PFC. The findings of the present study contribute to the understanding of the potential of etanercept as an antidepressant and provide insights into the neurobiological mechanisms underlying its therapeutic effects.

Inflammation and neuroinflammation are integral to the progression and severity of many diseases and are strongly associated with cardiovascular disease, cancer, autoimmune disorders, neurodegenerative disease, and neuropsychiatric disorders. These diseases can be difficult to treat without addressing the underlying inflammation, and, as such, a growing need has arisen for pharmaceutical treatments that target inflammatory mediators and signaling pathways. Our lab has investigated the therapeutic potential of the irreversible µ-opioid antagonist β-funaltrexamine (β-FNA) and discovered that acute treatment ameliorates inflammation in astrocytes in vitro and inhibits central and peripheral inflammation and reduces anxiety- and sickness-like behavior in male C57BL/6J mice. Now, our investigation has expanded to investigate the chronic pre-treatment effects of β-FNA on lipopolysaccharide (LPS)-induced inflammation and behavior in male C57BL/6J mice.

Micro-osmotic drug pumps were surgically inserted into the subcutaneous intrascapular space of male C57BL/6J mice. β-FNA or saline vehicle was continuously administered for seven days. On the sixth day, mice were given intraperitoneal injections of LPS or saline. An elevated plus maze test, followed by a forced swim test, were administered 24 h post-injection to measure sickness-, anxiety- and depressive-like behavior. Immediately after testing, frontal cortex, hippocampus, spleen, and plasma were collected. Levels of inflammatory chemokines C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 10 (CXCL10) were measured in tissues by enzyme-linked immunosorbent assay (ELISA). Quantitative reverse transcription polymerase chain reaction (RT-qPCR) was used to assess expression of the enzyme indoleamine 2, 3-dioxygenase 1 (IDO1) and the NLR family pyrin domain-containing protein 3 (NRLP3) inflammasome in frontal cortex and spleen tissues. Chronic pre-treatment robustly decreased inflammation in the hippocampus, frontal cortex, and spleen and reduced or abolished anxiety- and sickness-like behavior (e.g., increased time spent motionless, increased time spent in a contracted position, and reduced distance moved). However, treatment with β-FNA alone increased both inflammation in the frontal cortex and anxiety-like behavior.

These findings provide novel insights into the anti-inflammatory and behavior-modifying effects of chronic β-FNA pre-treatment and continue to support the therapeutic potential of β-FNA under inflammatory conditions.

Currently, 280 million people worldwide experience depression, ranking it third in the global burden of disease. The incidence of depression has risen due to the COVID-19 pandemic, making it essential to examine evidence-based practices in reducing depressive symptoms during this unprecedented time. This systematic review and meta-analysis aim to analyze randomized controlled trials during the COVID-19 pandemic that evaluated the effect of mindfulness meditation on depressive symptoms in individuals with depression. Four databases (PubMed, Embase, Web of Science, and Scopus) were searched in November 2023 using search terms including meditation, mindfulness, depression, and depressive symptoms. The meta-analysis was conducted using Review Manager 5.4 software (Cochrane Collaboration). A random model and Standard Mean Difference analysis with 95% CIs were used for continuous variables. The systematic review included 26 RCT studies. The meta-analysis showed significant effects of mindfulness meditation interventions (SMD = - 1.14; 95% CI - 1.45 to - 0.83; P < 0.001) in reducing depressive symptoms compared to comparison groups. The findings suggest a positive effect of mindfulness meditation on depressive symptoms in individuals with depression during the COVID-19 pandemic.

The connection between chronic psychological stress and the onset of various diseases, including diabetes, HIV, cancer, and cardiovascular conditions, is well documented. This review synthesizes current research on the neurological, immune, hormonal, and genetic pathways through which stress influences disease progression, affecting multiple body systems: nervous, immune, cardiovascular, respiratory, reproductive, musculoskeletal, and integumentary. Central to this review is an evaluation of 16 Behavioral Stress Reduction Programs (BSRPs) across over 200 studies, assessing their effectiveness in mitigating stress-related health outcomes. While our findings suggest that BSRPs have the potential to enhance the effectiveness of medical therapies and reverse disease progression, the variability in study designs, sample sizes, and methodologies raises questions about the generalizability and robustness of these results. Future research should focus on long-term, large-scale studies with rigorous methodologies to validate the effectiveness of BSRPs.

The recent pandemic caused by the SARS-CoV-2 virus and the associated mental health complications have renewed scholarly interest in the relationship between viral infections and the development of mental illnesses, a topic that was extensively discussed in the previous century in the context of other viruses, such as influenza. The most probable and analyzable mechanism through which viruses influence the onset of mental illnesses is the inflammation they provoke. Both infections and mental illnesses share a common characteristic: an imbalance in inflammatory factors. In this study, we sought to analyze and compare cytokine profiles in individuals infected with viruses and those suffering from mental illnesses. The objective was to determine whether specific viral diseases can increase the risk of specific mental disorders and whether this risk can be predicted based on the cytokine profile of the viral disease. To this end, we reviewed existing literature, constructed cytokine profiles for various mental and viral diseases, and conducted comparative analyses. The collected data indicate that the risk of developing a specific mental illness cannot be determined solely based on cytokine profiles. However, it was observed that the combination of IL-8 and IL-10 is frequently associated with psychotic symptoms. Therefore, to assess the risk of mental disorders in infected patients, it is imperative to consider the type of virus, the mental complications commonly associated with it, the predominant cytokines to evaluate the risk of psychotic symptoms, and additional patient-specific risk factors.

Maintenance hemodialysis (MHD) patients suffer from enormous physical, mental stress and poor quality of life, so an increasing number of patients are in a long-term state of depression. A prominent feature of MHD patients is chronic persistent inflammation, which is also an important mechanism for the onset of depression. Therefore, finding economically convenient inflammatory markers to predict and diagnose the onset of depression in MHD patients is of great value. As a novel inflammatory marker, systemic immune inflammation index (SII) can more comprehensively reflect the inflammation and immunity level of patients. This study aims to explore the relationship between SII and depressive symptoms in MHD patients.

A cross-sectional study was conducted on 206 MHD patients from three dialysis centers. Based on the Hospital Anxiety and Depression Scale (HADS) scores, patients were divided into non-depression and depression groups. Inter group comparison and multivariate logistic regression analysis were performed to determine whether SII is an independent risk factor for depression in MHD patients. Receiver operating characteristic (ROC) curve was used to evaluate the predictive value of SII on depression symptoms in MHD patients.

According to the HADS scale score, 38.83% of the included patients were in a state of depression. After adjusting for all confounding factors, MHD patients with SII>963.93 had a 4.709 times higher risk of depression than those with SII ≤ 478.32 (OR=4.709, 95% CI 1.821-12.178, P<0.01). ROC analysis showed that SII>685.11 was the best cutoff value for MHD depression patients, and the area under the curve (AUC) was 0.681.

High SII is an independent risk factor for depressed MHD patients and an ideal inflammatory marker for predicting and identifying depression in MHD patients as assessed by the HADS scale.

Major Depressive Disorder (MDD) significantly impairs the quality of life for those affected. While the exact causes of MDD are not fully understood, the deficit of monoamines, especially serotonin and noradrenaline, is widely accepted. Resistance to long-term treatments and adverse effects are often observed, highlighting the need for new pharmacological therapies. Synthetic organic compounds containing selenium have exhibited pharmacological properties, including potential antidepressant effects.

To evaluate the antidepressant-like effect of N-(3-((3-(trifluoromethyl)phenyl)selenyl)prop-2-yn-1-yl) benzamide (CF3SePB) in mice and the involvement of the serotonergic and noradrenergic systems.

Male Swiss mice were treated with CF3SePB (1-50 mg/kg, i.g.) and 30 min later the forced swimming test (FST) or tail suspension test (TST) was performed. To investigate the involvement of the serotonergic and noradrenergic systems in the antidepressant-like effect of CF3SePB, mice were pre-treated with p-CPA (a 5-HT depletor, 100 mg/kg, i.p.) or the receptor antagonists WAY100635 (0.1 mg/kg, s.c., a 5-HT1A receptor antagonist), ketanserin (1 mg/kg, i.p., a 5-HT2A/2C receptor antagonist), ondansetron (1 mg/kg, i.p., a 5-HT3 receptor antagonist), GR110838 (0.1 mg/kg, i.p., a 5-HT4 receptor antagonist), prazosin (1 mg/kg, i.p., an α1-adrenergic receptor antagonist), yohimbine (1 mg/kg, i.p., an α2-adrenergic receptor antagonist) and propranolol (2 mg/kg, i.p., a non-selective beta-adrenergic receptor antagonist) at specific times before CF3SePB (50 mg/kg, i.g.), and after 30 min of CF3SePB administration the FST was performed.

CF3SePB showed an antidepressant-like effect in both FST and TST and this effect was related to the modulation of the serotonergic system, specially the 5-HT1A and 5-HT3 receptors. None of the noradrenergic antagonists prevented the antidepressant-like effect of CF3SePB. The compound exhibited a low potential for inducing acute toxicity in adult female Swiss mice.

This study pointed a new compound with antidepressant-like effect, and it could be considered for the development of new antidepressants.

Selenium binding protein 1 (SELENBP1) is involved in neurologic disorders, such as multiple sclerosis, spinal cord injury, Parkinson's disease, epilepsy, and schizophrenia. However, the role of SELENBP1 in the neurogenesis of depression, which is a neurologic disorder, and the underlying mechanisms of oxidative stress and inflammation in depression remain unknown. In this study, we evaluated the changes in the expression levels of SELENBP1 in the hippocampus of a mouse model of depression and in the serum of human patients with depression using the Gene Expression Omnibus database. These changes were validated using blood samples from human patients with depression and mouse models with chronic unpredictable mild stress (CUMS)-induced depressive-like behavior. We also investigated the effects of SELENBP1 knockout (KO) on inflammation, oxidative stress, and hippocampal neurogenesis in mice with CUMS-induced depression. Our results revealed that SELENBP1 levels was decreased in the blood of human patients with depression and in the hippocampus of mice with CUMS-induced depression. SELENBP1 KO increased CUMS-induced depressive behavior in mice and caused dysregulation of inflammatory cytokines and oxidative stress. This led to a decrease in the numbers of doublecortin- and Ki67-positive cells, which might aggravate CUMS-induced depressive symptoms. These findings suggest that SELENBP1 might be involved in the regulation of neurogenesis in mice with depression and could be served as a potential target for diagnosing and treating depression.

Major depressive disorder (MDD) is a mood disorder that has become a global health emergency according to the World Health Organization (WHO). It affects 280 million people worldwide and is a leading cause of disability and financial loss. Patients with MDD present immunoendocrine alterations like cortisol resistance and inflammation, which are associated with alterations in neurotransmitter metabolism. There are currently numerous therapeutic options for patients with MDD; however, some studies suggest a high rate of therapeutic failure. There are multiple hypotheses explaining the pathophysiological mechanisms of MDD, in which several systems are involved, including the neuroendocrine and immune systems. In recent years, inflammation has become an important target for the development of new therapeutic options. Extracellular monomeric ubiquitin (emUb) is a molecule that has been shown to have immunomodulatory properties through several mechanisms including cholinergic modulation and the generation of regulatory T cells. In this perspective article, we highlight the influence of the inflammatory response in MDD. In addition, we review and discuss the evidence for the use of emUb contained in Transferon as a concomitant treatment with selective serotonin reuptake inhibitors (SSRIs).

Depression and anxiety are recognized as the most common mental diseases worldwide. New approaches have considered different therapeutic targets, such as oxidative stress and the inflammation process, due to their close association with the establishment and progression of mental diseases. In the present study, we evaluated the antioxidant and anti-inflammatory activities of the methanolic extracts of the plant species Heteropterys brachiata and Heteropterys cotinifolia and their main compounds, chlorogenic acid and rutin, as potential complementary therapeutic tools for the treatment of anxiety and depression, since the antidepressant and anxiolytic activities of these methanolic extracts have been shown previously. Additionally, we also evaluated their inhibitory activity on the enzyme acetylcholinesterase (AChE). Our results revealed that both species exhibited potent antioxidant activity (>90%) through the TBARS assay, while by means of the DPPH assay, only H. cotinifolia exerted potent antioxidant activity (>90%); additionally, low metal chelating activity (<40%) was detected for all samples tested in the ferrozine assay. The methanolic extracts of H. brachiata and H. cotinifolia exhibited significant anti-inflammatory activities in the TPA-induced ear edema, while only H. cotinifolia exerted significant anti-inflammatory activities in the MPO assay (>45%) and also exhibited a higher percentage of inhibition on AChE of even twice (>80%) as high as the control in concentrations of 100 and 1000 µg/mL. Thus, the potent antioxidant and inflammatory properties and the inhibition of AChE may be involved in the antidepressant activities of the species H. cotinifolia, which would be positioned as a candidate for study in drug development as an alternative in the treatment of depression.

Depression is a common mental illness characterised by abnormal and depressed emotions. Total paeony glycoside (TPG) is a naturally active saponin extracted from the traditional Chinese medicine Radix Paeoniae rubra. However, the antidepressant and neuroinflammatory effects of TPG have not been thoroughly studied.

To study the therapeutic potential of TGP in depression caused by neuronal injury and neuroinflammation and to explore the mechanism of TGP and the relationship between the NLRP3 inflammasome, pyroptosis, and autophagy.

A chronic unpredictable mild stress (CUMS)-induced depression model and a cell model of corticosterone (CORT)-induced hippocampal neuron injury were established to evaluate the therapeutic effects of TPG.

The composition of TPG was analysed using high-performance liquid chromatography and mass spectrometry. The effects of TPG and fluoxetine on depression-like behaviour, neuronal injury, neuroinflammation, pyroptosis, and mitochondrial autophagy in the mice models were evaluated.

TGP alleviated depression-like behaviours in mice and inhibited hippocampal neuronal apoptosis. The secretion of inflammatory cytokines was significantly reduced in CORT-induced hippocampal neuron cells and in the serum of a mouse model of CUMS-induced depression. In addition, TGP treatment reduced the levels of NLRP3 family pyrin structural domains, including NLRP3, pro-caspase-1, caspase-1, and IL-1β, and the pyroptosis related proteins such as GSDMD-N. Importantly, TPG attenuated mitochondrial dysfunction, promoted the clearance of damaged mitochondria, and the activation of mitochondrial autophagy, which reduced ROS accumulation and NLRP3 inflammasome activation. An in-depth study observed that the regulatory effect of TPG on autophagy was attenuated by the autophagy inhibitor 3-methyladenine (3-MA) in vitro and in vivo. However, administration of the caspase-1 inhibitor Belnacasan (VX-765) successfully inhibited pyroptosis and showed a synergistic therapeutic effect with TPG.

These results indicate that TPG can repair neuronal damage by activating autophagy, restoring mitochondrial function, and reducing inflammation-mediated pyroptosis, thereby playing an important role in the alleviation of neuroinflammation and depression. This study suggests new potential drugs and treatment strategies for neuroinflammation-related diseases and depression.

Depressive disorders are a growing problem worldwide. They are also characterized by high comorbidity, including from the circle of dermatological diseases. Autoimmune diseases seem to be particularly correlated with depressive comorbidity, raising the question of their possible common pathomechanism. The PubMed database was searched, focusing on results published after 2016. A particular reciprocal correlation of depressive disorders with psoriasis, atopic dermatitis, alopecia areata, impetigo, lupus and systemic scleroderma was found. One possible explanation for the co-occurrence of the above diseases is that the inflammatory theory may be applicable to depression, the various elements of which also apply to autoimmune diseases.

Cafeteria diet (CD) model for in-vivo studies mimics the western diet having imbalanced nutritional value, high caloric-density and palatability. Uncontrolled eating leads to the development of childhood obesity, poor self-esteem and depression due to its effects on brain development. Herbal supplements are novel inclusion in the management of obesity and mental well-being. Pterostilbene (PTE) found in blueberries and Pterocarpus marsupium heartwood, is known to prevent obesity in invivo models. Adolescent Swiss albino male mice were fed on CD for 70 days and the development of obesity was assessed by gain in body weight, abdominal circumference. Forced swim and tail suspension test confirmed depression in CD fed mice. Obesity induced depressed (OID) mice were treated with PTE (10, 20, 40 mg/kg), standard antiobesity drug cetilistat (10 mg/kg), antidepressant fluoxetine (10 mg/kg) for 28 days. Post treatment, PTE-treated mice showed reduction in BW and depression-like behavior analysed using paradigms such as sucrose preference, open field, marble burying, and resident intruder test in comparison to the CD group. Insulin resistance, lipid profile, antioxidant enzyme, inflammatory cytokines (NF-κB, IL-6, TNF α) and cortisol levels were mitigated by PTE. It also restored normal cellular architecture of the brain and adipose tissue and increased the Silent mating type information regulation 2 homolog1 (SIRT1), leptin and ghrelin receptors gene expression in the brain. Thus, it can be concluded that PTE might have inhibited OID like behavior in mice via inhibition of IR, modulating neuroinflammation and hypothalamic-pituitary-adrenal axis dysfunction and upregulating SIRT1 mediated leptin-ghrelin signaling.

Major depressive disorder is a severe mood disorder associated with a marked decrease in quality of life and social functioning, accompanied by a risk of suicidal behavior. Therefore, seeking out and adhering to effective treatment is of great personal and society-wide importance. Weight changes associated with antidepressant therapy are often cited as the reason for treatment withdrawal and thus are an important topic of interest. There indeed exists a significant mechanistic overlap between depression, antidepressant treatment, and the regulation of appetite and body weight. The suggested pathomechanisms include the abnormal functioning of the homeostatic (mostly humoral) and hedonic (mostly dopaminergic) circuits of appetite regulation, as well as causing neuromorphological and neurophysiological changes underlying the development of depressive disorder. However, this issue is still extensively discussed. This review aims to summarize mechanisms linked to depression and antidepressant therapy in the context of weight change.

Celiac disease (CD) is an immune-mediated disease affecting the small intestine. The only treatment strategy for CD is the gluten-free diet (GFD). One of the more common mental disorders in CD patients is major depressive disorder (MDD). The influence of GFD on the occurrence of MDD symptoms in patients with CD will be evaluated. This diet often reduces nutritional deficiencies in these patients and also helps to reduce depressive symptoms. Both disease entities are often dominated by the same deficiencies of nutrients such as iron, zinc, selenium, iodine, or B and D vitamins. Deficiencies of particular components in CD can favor MDD and vice versa. Gluten can adversely affect the mental state of patients without CD. Also, intestinal microbiota may play an important role in the described process. This work aims to comprehensively assess the common factors involved in the pathomechanisms of MDD and CD, with particular emphasis on nutrient imbalances. Given the complexity of both disease entities, and the many common links, more research related to improving mental health in these patients and the implementation of a GFD would need to be conducted, but it appears to be a viable pathway to improving the quality of life and health of people struggling with CD and MDD. Therefore, probiotics, micronutrients, macronutrients, and vitamin supplements are recommended to reduce the risk of MDD, given that they may alleviate the symptoms of both these disease entities. In turn, in patients with MDD, it is worth considering testing for CD.

The new and evolving paradigms of psychiatric disorders pathogenesis are deeply inclined toward chronic inflammation that leads to disturbances in the neuronal networks of patients. A strong association has been established between the inflammation and neurobiology of depression which is mediated by different toll-like receptors (TLRs). TLRs and associated signalling pathways are identified as key immune regulators to stress and infections in neurobiology. They are a special class of transmembrane proteins, which are one of the broadly studied members of the Pattern Recognition Patterns family. This review focuses on summarizing the important findings on the role of TLRs associated with psychotic disorders and acquired epilepsy. This review also shows the promising potential of TLRs in immune response mediated through antidepressant therapies and TLRs polymorphism associated with various psychotic disorders. Moreover, this also sheds light on future directions to further target TLRs as a therapeutic approach for psychiatric disorders.

Persistent stress increases the probability for developing depression significantly thereafter. Repeated social defeat stress is a widely used model to investigate depressive-like behavior in preclinical models. Hence, the repeated social defeat stress model provided an ideal animal model, through which the hypotheses of prevention and treatment can be investigated. We have successfully induced depressive-like behavior for male C57BL/6J mice with this model. Here, we reported that certain level of during-stress social interactions with single female or multiple male peer(s) exerted a positive role in preventing the development of depressive-like behavior induced by repeated social defeat stress. Our data suggested that the stress-susceptible mice may benefit from positive social interaction, which reduces the chance for depressive-like behavior development. Since numerous studies indicate that the metabotropic glutamate receptor 5 (mGluR5) plays an important role in various cognitive functions, we further investigate the treatment effect of 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) on the depressive-like behavior induced by repeated social defeat stress. Most importantly, robust anti-depressant effects have been achieved through modulating the mGluR5 function. We found that single oral dose administration of CDPPB (20 mg/kg), to some extent, alleviated the social avoidance behaviors for the stress-susceptible mice. Our data implies that the CDPPB, a positive allosteric modulator of mGluR5, is a promising anti-depressant candidate with limited side effect.

The Dietary Inflammatory Index (DII) is a composite nutritional index that has gained significant attention in the past decade due to its association with physical and mental well-being. To accurately assess the precise effects of DII on health outcomes, the effects of nutrients and foods need to be adjusted. This study aimed to investigate the association between DII and mental disorders (depression, anxiety, and stress) using multilevel modeling to minimize the bias of the previous methods.

This cross-sectional analytical study was conducted using data from the initial phase of the Tehran University of Medical Sciences Employees' Cohort Study (TEC). Nutritional information was obtained through a dish-based semi-quantitative food frequency questionnaire (DFQ), while psychological data were collected using the depression, anxiety and stress scale (DASS-42). The acquired data were analyzed using multilevel modeling in three levels (foods, nutrients, and DII, respectively) through GLIMMIX in the SAS software.

A total of 3,501 individuals participated in this study. The results of the multilevel model demonstrated a significant statistical association between DII and mental disorders after adjusting for baseline characteristics, nutrients and foods. For each unit increase in DII, the mean scores for stress, anxiety, and depression increased by 3.55, 4.26, and 3.02, respectively (p < 0.001).

Based on the multilevel model's findings, it is recommended to minimize the use of pro-inflammatory nutrients and foods to increase the mental health. Multilevel data analysis has also been recommended in nutritional studies involving nested data to obtain more accurate and plausible estimates.

Both depression and rheumatoid arthritis (RA) have a very high comorbidity rate. A bilateral association is estimated to increase the mutual risk and the common denominator is inflammation being observed in both diseases. Previous studies have mainly focused on assessing peripheral blood's inflammatory and pro-inflammatory cytokines levels. We aimed to extend insights into the molecular mechanisms of depression based on hub RA genes. To do so, we prioritized RA-related genes using in-silico tools. We then investigated whether RA-related genes undergo altered expression in patients with unipolar and bipolar depression without a concurrent RA diagnosis and any exponents of active inflammation. In addition, we selected a homogeneous group of patients treated with lithium (Li), which has immunomodulatory properties. The study was performed on patients with bipolar depression (BD, n = 45; Li, n = 20), unipolar depression (UD, n = 27), and healthy controls (HC, n = 22) of both sexes. To identify DEGs in peripheral blood mononuclear cells (PBMCs), we used the SurePrint G3 Microarray and GeneSpring software. We selected a list of 180 hub genes whose altered expression we analyzed using the expression microarray results. In the entire study group, we identified altered expression of 93 of the 180 genes, including 35 down-regulated (OPRM1 gene with highest FC > 3) and 58 up-regulated (TLR4 gene with highest FC > 3). In UD patients, we observed maximally up-regulated expression of the TEK gene (FC > 3), and in BD of the CXCL8 gene (FC > 5). On the other hand, in lithium-treated patients, the gene with the most reduced expression was the TRPV1 gene. The study proved that depression and RA are produced by a partially shared "inflammatory interactome" in which the opioid and angiogenesis pathways are important.

The translational defect has emerged as a common feature of neurological disorders. Studies have suggested that alterations between opposing and balanced synaptic protein synthesis and turnover processes could lead to synaptic abnormalities, followed by depressive symptoms. Further studies link this phenomenon with eIF4E and TrkB/BDNF signaling. However, the interplay between the eIF4E and TrkB/BDNF signaling in the presence of neuroinflammation is yet to be explored. To illuminate the role of eIF4E activities within LPS-induced neuroinflammation and depression symptomology, we applied animal behavioral, biochemical, and pharmacological approaches. In addition, we sought to determine whether eIF4E dysregulated activities correlate with synaptic protein loss via the TrkB/BDNF pathway. Our results showed that LPS administration induced depressive-like behaviors, accompanied by neuroinflammation, reduced spine numbers, and synaptic protein dysregulation. Concurrently, LPS treatment enhanced eIF4E phosphorylation and TrkB/BDNF signaling defects. However, eFT508 treatment rescued the LPS-elicited neuroinflammation and depressive behaviors, as well as altered eIF4E phosphorylation, synaptic protein expression, and TrkB/BDNF signaling. The causal relation of eIF4E with BDNF signaling was further explored with TrkB antagonist K252a, which could reverse the effects of eFT508, validating the interplay between the eIF4E and TrkB/BDNF signaling in regulating depressive behaviors associated with neuroinflammation via synaptic protein translational regulation. In conclusion, our results support the involvement of eIF4E-associated translational dysregulation in synaptic protein loss via TrkB/BDNF signaling, eventually leading to depressiven-like behaviors upon inflammation-linked stress.

Inflammation is an important component of the etiopathology of depression that uses oxidative and nitrosative stress (O&NS) and elevated inflammatory markers. SARS-CoV-2 infection is also associated with abnormal inflammatory processes, which may impair effective treatment of depression in COVID-19 survivors. In the presented study, thirty-three hospitalized patients with major depressive disorder (MDD) were started on antidepressant treatment, and twenty-one were re-evaluated after 4-6 weeks. The control group consisted of thirty healthy volunteers. All participants underwent neuropsychiatric evaluation, biochemical blood and urine analyses. The results of the research demonstrated positive correlations of the Hamilton Depression Rating Scale (HAM-D) scores with serum catalase (CAT) and urinary S-Nitrosothiols levels, and the Beck Depression Inventory (BDI) scores with serum reduced glutathione (GSH) and superoxide dismutase (SOD) levels. Depressed patients with a history of COVID-19 prior to the treatment had higher urinary nitric oxide (NO) levels and lower serum glutathione peroxidase (GPx) levels. In the control group, COVID-19 survivors had higher levels of urinary N-formylkynurenine (NFK). Our results suggest that the antidepressant treatment has a modulating effect on O&NS, reduces depressive symptoms and improves cognitive functions The present study does not indicate that clinical response to antidepressant treatment is associated with COVID-19 history and baseline SARS-CoV-2 antibody levels. Nevertheless, further research in this area is needed to systematize antidepressant treatment in COVID-19 survivors.

The involvement of the peripheral immune system in the etiology of neurodegenerative diseases has recently been emphasized. Genome-wide association studies (GWAS) have recently identified several candidate immune genes linked to development of both Alzheimer's disease (AD) and depression. TBX21 (T-bet) which drives the Th1 immune response, is linked to the major depressive disorder (MDD) phenotype. This study investigated the association between the TBX21 immune gene and the possibility of late-onset Alzheimer's disease (LOAD) incidence in 194 LOAD and 200 control subjects using the real-time qPCR and the Tetra-ARMS-PCR methods. We also used an in silico approach to analyze the potential effects imparted by TBX21 rs17244587 and rs41515744 polymorphisms in LOAD pathogenesis.

We found that the TBX21 "immune gene" had significantly elevated mRNA expression levels in the leukocytes of peripheral blood in patients with LOAD (P < 0.0001). We also found an upward trend in TBX21 expression with increasing age in LOAD patients compared to the control group (P < 0.05; CI = 95%). We noticed that the TT genotype of rs41515744 plays a protective role in LOAD incidence, as it attenuates the expression of TBX21 in the control group. We observed that the dominant model of rs41515744 represented a substantial association with LOAD (P = 0.019).

Our results show for the first time the likely impact of the TBX21 (T-bet) immune gene in LOAD development and that the elevated TBX21 mRNAs in the WBCs of LOAD patients may represent a new easy diagnostic test for Alzheimer's disease.

Applying machine-based learning and synthetic cognition, commonly referred to as artificial intelligence (AI), to medicine intimates prescient knowledge. The ability of these algorithms to potentially unlock secrets held within vast data sets makes them invaluable to healthcare. Complex computer algorithms are routinely used to enhance diagnoses in fields like oncology, cardiology, and neurology. These algorithms have found utility in making healthcare decisions that are often complicated by seemingly endless relationships between exogenous and endogenous variables. They have also found utility in the allocation of limited healthcare resources and the management of end-of-life issues. With the increase in computing power and the ability to test a virtually unlimited number of relationships, scientists and engineers have the unprecedented ability to increase the prognostic confidence that comes from complex data analysis. While these systems present exciting opportunities for the democratization and precision of healthcare, their use raises important moral and ethical considerations around Christian concepts of autonomy and hope. The purpose of this essay is to explore some of the practical limitations associated with AI in medicine and discuss some of the potential theological implications that machine-generated diagnoses may present. Specifically, this article examines how these systems may disrupt the patient and healthcare provider relationship emblematic of Christ's healing mission. Finally, this article seeks to offer insights that might help in the development of a more robust ethical framework for the application of these systems in the future.

In recent years, there has been a significant increase in depression, which is related to, among other things, the COVID-19 pandemic. Depression can be fatal if not treated or if treated inappropriately. Depression is the leading cause of suicide attempts. The disease is multifactorial, and pharmacotherapy often fails to bring satisfactory results. Therefore, increasingly more importance is attached to the natural healing substances and nutrients in food, which can significantly affect the therapy process and prevention of depressive disorders. A proper diet is vital to preventing depression and can be a valuable addition to psychological and pharmacologic treatment. An inadequate diet may reduce the effectiveness of antidepressants or increase their side effects, leading to life-threatening symptoms. This study aimed to review the literature on the pathogenesis of the development and treatment of depression, with particular emphasis on dietary supplements and the role of nutrition in the prevention and treatment of depressive disorders.

The pathogenesis of depression is related to immune inflammatory response. Atherogenic coefficient (AC) is an important indicator of lipid abnormalities, which can lead to immune inflammatory responses. However, no study has investigated the relationship between AC and depression in adult Americans. Therefore, we investigated this relationship.

This study used a cross-sectional design.

The National Health and Nutrition Examination Survey (2005-2018) data were used for this study.

A total of 32 502 participants aged 20 years or older who had complete information for AC and depression were included in this study.

Depressive symptoms were assessed using the nine-item version of the Patient Health Questionnaire (PHQ-9), with a cut-off point of 9/10 indicating likely depression cases. Weighted logistic regression analyses and the smooth curve fittings were performed to explore the association between AC and depression.

After adjusting for potential confounders, a single unit increase in AC was associated with a 3% increase in the prevalence of depression (HR=1.03, 95% CI=1.00 to 1.06, p=0.039). The relationship between AC and depression was more obvious in females.

The AC is positively associated with depression.

Postpartum depression (PPD) is a disorder that impairs the formation of the relationship between mother and child, and reduces the quality of life for affected women to a functionally significant degree. Studying markers associated with PPD can help in early detection, prevention, or monitoring treatment. The purpose of this paper is to review biomarkers linked to PPD and to present selected theories on the pathogenesis of the disease based on data from biomarker studies. The complex etiology of the disorder reduces the specificity and sensitivity of markers, but they remain a valuable source of information to help clinicians. The biggest challenge of the future will be to translate high-tech methods for detecting markers associated with postpartum depression into more readily available and less costly ones. Population-based studies are needed to test the utility of potential PPD markers.

Polycystic ovary syndrome (PCOS) is an endocrine disorder with a broad spectrum of clinical symptoms. Some of the serious complications of PCOS are mental disorders including depression. Therefore, the aim of the meta-analysis was to determine the prevalence, mean level, standardized mean difference and probability of depression based on the research conducted with the Hospital Anxiety and Depression Scale (HADS). A systematic literature search was performed using the following databases: PubMed, EMBASE, Scopus, ClinicalTrials.gov and Google for research published until January 2023. The meta-analysis was conducted on a group of 4002 patients obtained from 19 studies, which met the inclusion criteria (adult pre-menopausal women diagnosed with PCOS, papers on the prevalence of depression or the HADS scoring). According to the research performed, the mean prevalence of depression was 31% (I2 = 93%; p < 0.001), whereas the mean HADS depression score in patients with PCOS was 6.31 (I2 = 93%; p < 0.001). The standardized difference of mean depression scores was SMD = 0.421 (95% confidence interval = 0.17-0.68, I2 = 67%). The overall probability of depression in PCOS patients was more than 2.5-fold higher than in healthy women ((RR: 2.58), confidence interval [1.38-4.85]; I2 = 90%, p < 0.001). The research results imply an increased risk of depressive symptoms in women with PCOS.

This study aims to investigate the association between the systemic immune-inflammatory index (SII) and suicide attempt (SA) in children and adolescents with first-episode, drug-naïve Major Depressive Disorder (MDD) during the COVID-19 pandemic.

A retrospective study was conducted on 263 MDD patients hospitalized at the Third Hospital of Fuyang City between 2020 and 2022. Patients were categorized into two groups based on the presence of previous SA. The study compared the differences in SII and clinical characteristics between the two groups and used the receiver operating characteristic (ROC) curve to determine the optimal critical value of SII and the area under the curve. Binary logistic regression was used to analyze the independent risk factors for SA.

Compared with the patients without SA history, the patients with a personal history of SA had a higher mean HDRS scores (Z=-2.369, p=0.018), higher mean neutrophil count (Z=-2.870, p=0.004), higher mean platelet count (Z=-2.155, p=0.031), and higher mean SII (Z=-3.170, p=0.002). The optimal critical SII determined by the ROC curve was 548.15 (sensitivity = 63.2%, specificity = 83.1%), and the area under the curve was 0.661. After adjusting for gender, age, BMI, illness duration and HDRS score, the risk of total SA in patients with high SII was 8.296 times higher than in those with low SII (OR = 8.296, 95% CI: 3.803-18.095, P < 0.001), The risk of recent SA was 13.922 times higher in patients with high SII than in those with low SII (OR = 13.922, 95% CI: 5.587-34.693, p < 0.001). However, high SII was not a risk factor for past SA (OR = 0.547, 95% CI: 0.062-4.842, P=0.587).

SII may be an inexpensive, easily accessible strategy that can assist in determining suicide risk in adolescents with MDD.

Some new mothers have been shown to suffer from anxiety and depression associated with insomnia during the postpartum period. Our study assessed the impact of demographic, psychopathological, and biochemical factors on the incidence of depression in women during the early postpartum period.

A total of 119 women were evaluated at 24-48 h postpartum with the following psychometric scales: Hamilton Depression Rating Scale (HDRS), Edinburgh Postnatal Depression Scale (EPDS), Hamilton Anxiety Rating Scale (HARS) and Athens Insomnia Scale (AIS). In addition, blood was drawn to assay interleukin 6 (IL-6) and interleukin 10 (IL-10).

The factors that had the greatest impact on the risk of postpartum depression detected with the HDRS were high HARS scores and evidence of insomnia in the AIS. There were no significant differences in IL-6 or IL-10 levels in women with and without depression (based on either HDRS or EPDS scores) and insomnia (based on AIS) after childbirth. Considering demographic factors, divorced and single women were shown to be at higher risk of postpartum depression (based on EPDS scores).

Small sample size and short observation span.

This study highlights the relationship between postpartum depression and both anxiety and insomnia and emphasises the importance to assess symptoms of anxiety and sleep quality as part of screening in women at risk of postpartum depression.

One of the current challenges in psychiatry is the search for answers on how to effectively manage drug-resistant depression. The occurrence of drug resistance in patients is an indication for the use of electroconvulsive therapy (ECT). This method is highly effective and usually results in relatively quick health improvement. Despite the knowledge of how ECT works, not all of the biological pathways activated during its use have been identified. Hence, based on the neuroinflammatory hypothesis of depression, we investigated the concentration of two opposite-acting adipokines (anti-inflammatory adiponectin and proinflammatory resistin) and BDNF in antidepressant-resistant patients undergoing ECT.

The study group comprised 52 patients hospitalized due to episodes of depression in the course of unipolar and bipolar affective disorder. The serum concentration of adipokines and BDNF was determined before and after the therapeutic intervention using an ELISA method. In the analyses, we also included comparisons considering the type of depression, sex, and achieving remission.

Adiponectin, resistin, and BDNF concentrations change after ECT treatment. These changes are correlated with an improvement in the severity of depressive symptoms and are more or less pronounced depending on the type of depression.

Although not all observed changes reach statistical significance, adipokines in particular remain exciting candidates for biomarkers in assessing the course of the disease and response to ECT treatment.