Etiology Of Depression Research Articles

Multiple risk markers for increases in depression symptoms across two years: Evidence from the Reward Positivity and the Error-Related Negativity

BackgroundBoth a blunted Reward Positivity (RewP) and Error-Related Negativity (ERN) have been associated with depression. Associations between these neural markers and depression have been observed cross-sectionally, but evidence that they can prospectively predict the development of, or increases in, symptoms of depression is more limited. MethodIn this study, we collected EEG data from 157 young adults at a baseline visit (T1), using the Doors and Flanker Tasks to elicit the RewP and the ERN respectively. Participants also reported on symptoms of depression at T1, and multiple times across two academic years (T2 – T8). ResultsUsing a multilevel model with the RewP and the ERN as predictors, we found that the RewP predicted future symptoms of depression, while controlling for symptoms of depression at T1, such that a blunted RewP at baseline predicted higher depressive symptoms later. In our data, however, the ERN was not a significant predictor of increases in depression symptoms. ConclusionsThese findings replicate previous work showing the RewP prospectively predicted increases in depression, and further suggest the specificity of this association. Results support the utility of the RewP as a neurophysiological marker that can help clarify the etiology of depression and inform treatment planning.

Hippocampal Synaptic Plasticity Reduction Leads to Decreased Resilience to Depression and Anxiety in the ASCL-Mouse Model

A substantial body of research has been conducted with the objective of elucidating the role of synaptic plasticity in the aetiology of depression and anxiety. Despite the fact that numerous existing tests have demonstrated a correlation between neuroplasticity and depression, the precise role of synaptic plasticity remains unclear. The objective of this experiment is to elucidate the impact of hippocampal synaptic plasticity on resilience to depression and anxiety. The experiment comprises a preliminary test and a series of main experiments. The preliminary tests are conducted to eliminate the potential effects of apoptosis caused by the BAX gene. The main experiments then assess anxiety and cognitive levels by dividing subjects into multiple groups and administering a battery of tests. In a 40-week period, the mice will be modified and will experience major depression as a result of an 8-week UCMS treatment.

Fahr syndrome: linking late onset depression and cognitive decline

Fahr syndrome, a rare neurological disorder characterized by bilateral calcifications of the basal ganglia and other brain regions, has been associated with various neuropsychiatric symptoms. This case report highlights the correlation between late-onset depression and cognitive decline in a patient diagnosed with Fahr syndrome. A 45-year-old female patient presented with progressive cognitive impairment and depressive symptoms over a period of 2 years. Neuroimaging revealed extensive calcifications in the basal ganglia and frontal lobes consistent with Fahr syndrome. Neuropsychological assessment confirmed significant deficits in memory, attention, and executive function. Pharmacological intervention for depression resulted in partial improvement in mood but limited effect on cognitive symptoms. This case underscores the importance of recognizing Fahr syndrome as a potential etiology for late-onset depression and cognitive decline, necessitating comprehensive neurological evaluation and management.

Investigating the genetic relationship of intracranial and subcortical brain volumes with depression and other psychiatric disorders

Abstract Depression is one of the most common mental health disorders worldwide, yet its neurobiological mechanisms remain poorly understood. Structural brain differences in subcortical limbic regions are thought to be implicated in the pathology of depression. We leveraged genome-wide association studies (GWAS) summary-level data to explore the molecular pathways underlying the relationship between genetic risk for depression and intracranial and subcortical brain volumes measured via magnetic resonance imaging. At the whole-genome level, we identified a negative genetic correlation (rG) between depression and the volume of the ventral diencephalon (rG = -0.08), which remained significant after adjusting for multiple testing. We observed nominal (P < 0.05) positive genetic correlations between depression and the volumes of the caudate nucleus (rG = 0.06) and the putamen (rG = 0.06), while hippocampal volume displayed a negative genetic correlation (rG = -0.06) with depression. Pairwise GWAS analyses uncovered 104 genome segments with genetic variants influencing the aetiology of depression and at least one brain volume at the local genetic level. Gene association analyses of these genomic segments suggest putative links with dopamine neurotransmission, mesocorticolimbic functional connectivity, GABAergic transmission, and the insulin signalling pathway. Sensitivity analyses showed that the volume of the ventral diencephalon is also negatively correlated with bipolar disorder and schizophrenia; however, most of the genes associated with depression and brain volumes are specific for depression and do not replicate when investigating bipolar disorder or schizophrenia with brain volumes. We observed negative phenotypic correlations between depression and intracranial and subcortical brain volumes. Overall, our findings contribute to our understanding of the neurobiology of depression and suggest that, besides the known role of the hippocampus, other subcortical structures might also play essential roles in the aetiology of depression.

Association of Biomarkers with the Severity of Depression

Background: The pathogenesis of depression remains elusive and uncertain. The literature suggests that low-grade systemic inflammation might contribute to the etiology of depression. Other markers that are studied are serum magnesium and serum cortisol. The association between these factors might help understand the etiology. Methods: This was a cross-sectional study conducted on a sample of 40 participants. Socio-demographic data was noted, and the Hamilton depression rating scale was applied to rate the severity of depression. Blood samples were drawn at 8 a.m. to record a complete blood picture (to derive the neutrophil–lymphocyte ratio (NLR)), C-reactive protein, serum magnesium, and serum cortisol. Results: In this study, conducted on a sample size of 40, inflammatory markers such as C-reactive protein (CRP: mg/dl) and NLR were significantly increased to 15.52 ± 13.10 and 6.46 ± 2.92, respectively, showing an underlying inflammatory pathology. Serum cortisol (µg/dl) was also raised to 22.30 ± 5.46, and there was a fall in serum magnesium. Also, it is noteworthy that all these markers were significantly associated with the severity of depression, as the Pearson correlation between the Hamilton depression rating scale-21 item (HAM-D-21) score and CRP, NLR, and serum cortisol was positive and statistically significant ( r = 0.55, p < .01; r = 0.51, p = .01; r = 0.46, p = .002). The Pearson correlation between the HAM-D score and serum magnesium was negative and statistically significant ( r = -0.82, p < .01) Conclusion: There is a state of systemic inflammation, hypercortisolemia, and hypomagnesemia in depressive disorders.

Factors Associated with the Development of Depression and the Influence of Obesity on Depressive Disorders: A Narrative Review.

Depression affects several aspects of life, including socioeconomic status, relationships, behavior, emotions, and overall health. The etiology of depression is complex and influenced by various factors, with obesity emerging as a significant contributor. This narrative review aims to investigate the factors associated with the development of depression, with a particular focus on the role of obesity. The literature search was conducted on PubMed, Embase, and PsycINFO from May to July 2024. The review highlights the impact of environmental and socioeconomic conditions; lifestyle choices, including physical activity and dietary habits; stress; traumatic experiences; neurotransmitter imbalances; medical and psychological conditions; hormone fluctuations; and epigenetic factors on depression. A key emphasis is placed on the inflammatory processes linked to obesity, which may drive the bidirectional relationship between obesity and depression. The findings suggest that obesity is associated with an increased risk of depression, potentially due to chronic inflammation, neurochemical dysregulation, and the emotional and social challenges related to weight stigma and obesity management. Understanding these interconnected factors is important for developing targeted interventions to address both obesity and depression, leading to improved quality of life for those affected.

Microbiome‐gut‐brain axis as a novel hotspot in depression

AbstractAs a prevalent psychiatric disorder, the etiology of depression remains largely elusive, necessitating further investigation into its pathophysiological underpinnings. Notably, the comorbidity of depression with other mental health conditions and chronic diseases often presents alongside gastrointestinal symptoms. Research on the microbiome‐gut‐brain axis (MGBA) has emerged as a promising avenue for elucidating the pathophysiology of depression. In this study, bibliometric analysis tools, including HistCite, VOSviewer, CiteSpace, and the bibliometrix R package, were employed to comprehensively explore the MGBA‐depression connection. A comprehensive survey identified 980 relevant publications concerning the MGBA‐depression relationship, with a significant increase in research output observed since 2014. This analysis pinpointed five key factors within the MGBA‐depression domain: cytokines, maternal separation, neuroinflammation, probiotics, and the vagus nerve. The insights presented herein offer valuable perspectives on prevailing research models that investigate the intricate interplay among the microbiome, gastrointestinal system, and brain within the context of depression. Based on these findings, future investigations should prioritize developing microbial‐based interventions and innovative therapeutic modalities aimed at alleviating depression. By leveraging interdisciplinary collaboration and enhancing our understanding of MGBA–depression connections, we can pave pathways toward more effective treatments. Furthermore, improving outcomes for individuals with depression may be achieved by deepening our comprehension of the complex relationships between depression itself, the gut‐brain axis, and gastrointestinal microbiota.

The Role of Inflammation in Depression and Beyond: A Primer for Clinicians.

We evaluate available evidence for the role of inflammation in depression. We reappraise literature involving systemic inflammation, neuroinflammation and neurotransmission and their association with depression. We review the connection between depression, autoimmunity and infectious diseases. We revise anti-inflammatory treatments used in depression. Peripheral inflammatory markers are present in a subset of patients with depression and can alter common neurotransmitters in this population but there is no clear causality between depression and systemic inflammation. Infectious conditions and autoimmune illnesses do not have a clear correlation with depression. Certain medications have positive evidence as adjunctive treatments in depression but studies are heterogenic, hence they are sparsely used in clinical settings. The current evidence does not fully support inflammation, infections or autoimmunity as possible etiologies of depression. The available studies have numerous confounders that obscure the findings. Anti-inflammatory agents may have potential for treatment of depression, but further research is needed to clarify their usefulness in routine clinical practice.

Clinical and sociodemographic features of the Texas resilience against depression (T-RAD) study: Findings from the initial cohort

ObjectiveThe burden of major depressive disorder is compounded by a limited understanding of its risk factors, the limited efficacy of treatments, and the lack of precision approaches to guide treatment selection. The Texas Resilience Against Depression (T-RAD) study was designed to explore the etiology of depression by collecting comprehensive socio-demographic, clinical, behavioral, neurophysiological/neuroimaging, and biological data from depressed individuals (D2K) and youth at risk for depression (RAD). MethodsThis report details the baseline sociodemographic, clinical, and functional features from the initial cohort (D2K N = 1040, RAD N = 365). ResultsOf the total T-RAD sample, n = 1078 (76.73 %) attended ≥2 in-person visits, and n = 845 (60.14 %) attended ≥4 in-person visits. Most D2K (84.82 %) had a primary diagnosis of any depressive disorder, with a bipolar disorder diagnosis being prevalent (13.49 %). RAD participants (75.89 %) did not have a psychiatric diagnosis, but other non-depressive diagnoses were present. D2K participants had 9-item Patient Health Questionnaire scores at or near the moderate range (10.58 ± 6.42 > 24 yrs.; 9.73 ± 6.12 10–24 yrs). RAD participants were in the non-depressed range (2.19 ± 2.65). While the age ranges in D2K and RAD differ, the potential to conduct analyses that compare at-risk and depressed youth is a strength of the study. The opportunity to examine the trajectory of depressive symptoms in the D2K cohort over the lifespan is unique. LimitationsAs a longitudinal study, missing data were common. ConclusionT-RAD will allow data to be collected from multiple modalities on a clinically well-characterized sample. These data will drive important discoveries on diagnosis, treatment, and prevention of depression.

Behavioral Animal Models and Neural-Circuit Framework of Depressive Disorder.

Depressive disorder is a chronic, recurring, and potentially life-endangering neuropsychiatric disease. According to a report by the World Health Organization, the global population suffering from depression is experiencing a significant annual increase. Despite its prevalence and considerable impact on people, little is known about its pathogenesis. One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression. Furthermore, the neural circuit mechanism of depression induced by various factors is particularly complex. Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression, a comparison between the neural circuits of depression induced by various factors is essential for its treatment. In this review, we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression, aiming to provide a theoretical basis for depression prevention.

Peer Social Genetic Effects and the Etiology of Substance Use Disorders, Major Depression, and Anxiety Disorder in a Swedish National Sample.

There is growing interest in how peers' genotypes may influence health (i.e., peer social genetic effects). The authors sought to clarify the nature of peer social genetic effects on risk for drug use disorder, alcohol use disorder (AUD), major depression, and anxiety disorder. Cox models were used with data from a population-based Swedish cohort (N=655,327). Outcomes were drug use disorder, AUD, major depression, and anxiety disorder registrations between ages 17 and 30 from medical, criminal, and pharmacy registries. The authors indexed peer social genetic effects with peers' family genetic risk scores (FGRSs) for the same disorders, which are personalized measures of genetic risk inferred from diagnoses in first- to fifth-degree relatives. Across disorders, peer FGRSs predicted increased risks of proband registration (hazard ratio range, 1.01-1.59), with stronger effects for drug use disorder and AUD than for major depression and anxiety disorder. Peer social genetic effects were stronger for school classmates than for geographically proximal peers, and for peers from upper secondary school (ages 16-19) versus peers from lower secondary school (ages 7-16). Peer social genetic effects remained significant following statistical control for sociodemographic confounders, whether peers were affected, and peers' FGRS for educational attainment. Peer social genetic effects were more pronounced for probands at higher genetic risk. The genetic makeup of adolescents' peers has long-reaching consequences on risks for drug use disorder, AUD, major depression, and anxiety disorder. Individuals at high genetic risk are more sensitive to social genetic effects. Alternative hypotheses such as sociodemographic stratification, exposure to affected peers, and genetic predispositions for educational attainment did not explain the risk associated with peer social genetic effects for substance use and psychiatric disorders.

Rasd2 regulates depression-like behaviors via DRD2 neurons in the prelimbic cortex afferent to nucleus accumbens core circuit.

Depressive symptoms, such as anhedonia, decreased social interaction, and lack of motivation, implicate brain reward systems in the pathophysiology of depression. Exposure to chronic stress impairs the function of brain reward circuits and is well-known to be involved in the etiology of depression. A transcriptomic analysis found that stress alters the expression of Rasd2 in mice prefrontal cortex (PFC). Similarly, in our previous study, acute fasting decreased Rasd2 expression in mice PFC, and RASD2 modulated dopamine D2 receptor (DRD2)-mediated antidepressant-like effects in ovariectomized mice. This research suggests the role of RASD2 in stress-induced depression and its underlying neural mechanisms that require further investigation. Here, we show that 5-day unpredictable mild stress (5-d UMS) exposure reduces RASD2 expression in both the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) of mice, while overexpression (but not knock-down) of Rasd2 in the NAc core (NAcc) alleviates 5-d UMS-induced depression-like behaviors and activates the DRD2-cAMP-PKA-DARPP-32 signaling pathway. Further studies investigated neuronal projections between the mPFC (Cg1, PrL, and IL) and NAcc, labeled by the retrograde tracer Fluorogold. Depression-like behaviors induced by 5-d UMS were only related to inhibition of the PrL-NAcc circuit. DREADD (Designer receptors exclusively activated by designer drug) analysis found that the activation of PrL-NAcc glutaminergic projection alleviated depression-like behaviors and increased DRD2- and RASD2-positive neurons in the NAcc. Using Drd2-cre transgenic mice, we constructed mice with Rasd2 overexpression in DRD2PrL-NAcc neurons, finding that Rasd2 overexpression ameliorated 5-d UMS-induced depression-like behaviors. These findings demonstrate a critical role for RASD2 modulation of DRD2PrL-NAcc neurons in 5-d UMS-induced depression-like behaviors. In addition, the study identifies a new potential strategy for precision medical treatment of depression.

Neurotrophic Hypothesis of Development of Depression

Currently, depression is a widespread mental disorder in modern society and is associated with significant impairments in the quality of life of patients. The review examines the main representatives of neurotrophic factors belonging to various families, in particular nerve growth factor, transforming growth factor beta, neurokines and non-neuronal factors. Neurotrophins, being large polypeptides, play an integrative role, fulfilling the signaling mission of intermediaries in a wide range of physiological processes. At the moment, a large number of studies have been carried out in order to understand the interaction between factors of various directions, including biological, psychological and environmental factors that determine the etiopathogenesis of this pathology. Based on the data obtained, one of the main hypotheses for the development of depression is considered - neurotrophic, which most fully explains the emerging pathogenetic changes. According to this hypothesis, the leading role in the etiology of depression is played by neurotrophic factors that ensure the maintenance of normal neuron-glial interaction, the processes of neurogenesis, angiogenesis, and synaptic plasticity. Neurotrophins have a high physiological activity due to the presence of several binding groups for different cell receptors and the regulatory ability to express other signaling molecules, the ability to penetrate the blood-brain barrier, showing trophic, anti-inflammatory, growth, mediator and effector properties. To date, the mechanisms of the onset of depression, despite the widespread prevalence of this pathology, remain largely unclear, hindering a directed search for targets for the development of effective therapy. The revealed disorders of neurotrophic factors in depression make it reasonable to consider neurotrophins as therapeutic agents in a multitarget approach to the treatment of depressive disorders.

Associations of methylmalonic acid and depressive symptoms with mortality: a population-based study

Methylmalonic acid (MMA), a biomarker of mitochondrial dysfunction, has been reported to be associated with depression in specific populations (i.e., older adults and postpartum women). Our study aimed to investigate to what extent MMA was associated with depressive symptoms and mortality in the general population, and assess whether depressive symptoms mediate the relationship between MMA and mortality. We analyzed cross-sectional data from 8343 participants from the US National Health and Nutrition Examination Survey. MMA was measured by liquid chromatography-tandem mass spectrometry, while depressive symptoms were measured by the Patient Health Questionnaire-9. Mortality data were obtained through linkage with National Death Index records. Linear regression models were performed to assess the association between MMA and depressive symptoms. The Cox proportional hazard regression model was utilized to assess the association of MMA and depressive symptoms with mortality. Mediation analysis was conducted within the counterfactual framework. In this general population, each SD (around 0.49 μmol/L) increase in MMA was associated with a 0.03 SD (approximately 0.15 score) increase in depressive symptoms (β = 0.033, 95% CI: 0.010, 0.055, p = 0.005). Notably, this association was more pronounced in men and participants over 60 years old. Higher levels of MMA and having more depressive symptoms were associated with a higher risk of mortality. However, depressive symptoms do not mediate the relationship between MMA and mortality. Elevated MMA levels were associated with depressive symptoms and an increased risk of mortality. These findings suggest that mitochondrial dysfunction may contribute to the multifactorial etiology of depression.

Beta activity in human anterior cingulate cortex mediates reward biases

The rewards that we get from our choices and actions can have a major influence on our future behavior. Understanding how reward biasing of behavior is implemented in the brain is important for many reasons, including the fact that diminution in reward biasing is a hallmark of clinical depression. We hypothesized that reward biasing is mediated by the anterior cingulate cortex (ACC), a cortical hub region associated with the integration of reward and executive control and with the etiology of depression. To test this hypothesis, we recorded neural activity during a biased judgment task in patients undergoing intracranial monitoring for either epilepsy or major depressive disorder. We found that beta (12–30 Hz) oscillations in the ACC predicted both associated reward and the size of the choice bias, and also tracked reward receipt, thereby predicting bias on future trials. We found reduced magnitude of bias in depressed patients, in whom the beta-specific effects were correspondingly reduced. Our findings suggest that ACC beta oscillations may orchestrate the learning of reward information to guide adaptive choice, and, more broadly, suggest a potential biomarker for anhedonia and point to future development of interventions to enhance reward impact for therapeutic benefit.

The Relationship Between Gestational Diabetes and Postpartum Depression: A Systematic Review.

This study aims to examine the relationship between gestational diabetes mellitus (GDM) and the likelihood of postpartum depression (PPD) symptoms. PubMed, Scopus, Web of Science, ScienceDirect, and the Wiley Online Library were systematically searched for relevant literature. Our results included eight studies with a total of 4,209 women diagnosed with GDM and/or PPD. The prevalence of PPD in women diagnosed with GDM ranged from 6.5% to 48.4%. The included studies demonstrated that PPD was more likely to strike women with GDM. One study reported that the most severe type of GDM is more likely to occur in those with a history of depression. Perinatal depression during pregnancy can be strongly predicted by age, BMI, and a personal history of depression. The findings imply that GDM and the likelihood of depression during the postpartum phase are related. It was also found that there was a positive correlation between depression and the chance of having GDM. This emphasizes how the association between GDM and depression appears to be reciprocal. However, the association does not imply causation, and the data at hand do not allow for the establishment of causality. Subsequent studies ought to endeavor to show causative connections between GDM and depression as well as pinpoint shared underlying endocrine variables that may play a role in the genesis of both conditions. The available information that is now available is limited due to the complexity of the etiology of both GD and depression in pregnant women; nonetheless, prevention of both conditions depends on a better understanding of the link between GD and depression. The risk of bias in the included studies was moderate to high.

The Etiology, Pathogenesis and Clinical Treatment of Depression Were Analyzed from the Perspective of Traditional Chinese Medicine

As the pace of life quickens, the prevalence of depression rises. Due to the incomplete understanding of depression and various causes, it is still unable to fully effective prevention and treatment in clinical practice. Western medicine treatment of depression has high cost and side effects, while Chinese medicine treatment has advantages, according to different syndromes, different treatment means and Chinese medicine drugs can be used, efficient and targeted. Traditional Chinese medicine believes that the cause of depression lies in the poor operation of Qi and blood, which leads to the dysfunction of multiple viscera, and the symptoms such as emotional depression appear in the light, and the serious phenomena such as loss of survival motivation appear. This article will discuss the causes and treatment methods of depression from the perspective of traditional Chinese medicine, and provide new ideas for clinical treatment.

Analysis of hippocampal synaptic function in a rodent model of early life stress.

Early life stress (ELS) is an important risk factor in the aetiology of depression. Developmental glucocorticoid exposure impacts multiple brain regions with the hippocampus being particularly vulnerable. Hippocampal mediated behaviours are dependent upon the ability of neurones to undergo long-term potentiation (LTP), an N-methyl-D-aspartate receptor (NMDAR) mediated process. In this study we investigated the effect of ELS upon hippocampal NMDAR function. Hooded Long-Evans rat pups (n=82) were either undisturbed or maternally separated for 180 minutes per day (MS180) between post-natal day (PND) 1 and PND14. Model validation consisted of sucrose preference (n=18) and novelty supressed feeding (NSFT, n=34) tests alongside assessment of corticosterone (CORT) and paraventricular nucleus (PVN) cFos reactivity to stress and hippocampal neurogenesis (all n=18). AMPA/NMDA ratios (n=19), miniEPSC currents (n=19) and LTP (n=15) were assessed in whole-cell patch clamp experiments in CA1 pyramidal neurones. MS180 animals showed increased feeding latency in the NSFT alongside increased overall CORT in the restraint stress experiment and increased PVN cFos expression in males but no changes in neurogenesis or sucrose preference. MS180 was associated with a lower AMPA/NMDA ratio with no change in miniEPSC amplitude or area. There was no difference in short- or long-term potentiation between MS180 and control animals nor were there any changes during the induction protocol. The MS180 model showed a behavioural phenotype consistent with previous work. MS180 animals showed increased NMDAR function with preliminary evidence suggesting that this was not concurrent with an increase in LTP.

Comparison of Monocyte to Lymphocyte and Platelet to Lymphocyte Ratio between Patients with Depression according to Severity of Disease

Background: Depression is one of the most common psychiatric disorders with global public health concern that is linked to systemic inflammation. The monocyte to lymphocyte (MLR) and platelet to lymphocyte ratio (PLR) are partially new markers which may be evaluated with simple blood test and which are shown to be highly informative in showing chronic low grade inflammation associated with pathophysiology of depressive disorder. Objective: To evaluate the relation of MLR and PLR between patients with depression according to severity of disease. Methods: This observational study was conducted in the Department of Psychiatry of Jahurul Islam Medical College Hospital (JIMCH), Bajitpur, Kishoregonj between November 2012 and April 2013. Subjects between the age group of 25 and 55 were included in the study that involved 253 subjects with diagnosed depressive disorder according to the criteria of Diagnostic and Statistical Manual of Mental Disorders, Revised Text (DSM IV-TR) who received no pharmacological therapy of depression within the past 01 month. A sociodemographic information form and the Hamilton Rating Scale for depression (HAM-D) were administered. Patients were classified into four groups according to their HAM-D score such as mild, moderate, severe, and very severe depression. Blood sample were taken for biochemical analysis and complete blood parameters were evaluated in the hematology laboratory of JIMCH. All data were expressed as mean±SD. For statistical analysis, Chi-square test (χ2) was used to compare categorical variables, frequencies, and ratios. An independent sample ‘t’ test was used to compare normally distributed variables between two groups. Results: In the present study, it was found significant differences in the MLR, PLR, monocyte, leukocyte values of the patient group with depression according to severity of disease. Severe and very severe depression had significantly higher MLR levels compared to patients with mild and moderate depression. On the other hand, mild and moderate depression. On the other hand, mild and moderate depression had significantly higher PLR levels compared to patients with severe and very severe depression. Conclusion: In summary, the findings of the study reveal that higher HAM-D scores are associated with higher MLR and lower PLR levels in patients with depressive illness compared to patients with lower HAM-D scores. Moreover, a high MLR values supports the view that inflammation is a critical factor in the etiology of depression. JAFMC Bangladesh, Vol 19, No 2 (December) 2023:12-15.

Therapeutic potential of Erxian decoction and its special chemical markers in depression: a review of clinical and preclinical studies.

The increasing prevalence of depression is a major societal burden. The etiology of depression involves multiple mechanisms. Thus, the outcomes of the currently used treatment for depression are suboptimal. The anti-depression effects of traditional Chinese medicine (TCM) formulations have piqued the interest of the scientific community owing to their multi-ingredient, multi-target, and multi-link characteristics. According to the TCM theory, the functioning of the kidney is intricately linked to that of the brain. Clinical observations have indicated the therapeutic potential of the kidney-tonifying formula Erxian Decoction (EXD) in depression. This review aimed to comprehensively search various databases to summarize the anti-depression effects of EXD, explore the underlying material basis and mechanisms, and offer new suggestions and methods for the clinical treatment of depression. The clinical and preclinical studies published before 31 August 2023, were searched in PubMed, Google Scholar, China National Knowledge Infrastructure, and Wanfang Database. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Clinical studies have demonstrated that EXD exhibits therapeutic properties in patients with menopausal depression, postpartum depression, and maintenance hemodialysis-associated depression. Meanwhile, preclinical studies have reported that EXD and its special chemical markers exert anti-depression effects by modulating monoamine neurotransmitter levels, inhibiting neuroinflammation, augmenting synaptic plasticity, exerting neuroprotective effects, regulating the hypothalamic-pituitary-adrenal axis, promoting neurogenesis, and altering cerebrospinal fluid composition. Thus, the anti-depression effects of EXD are mediated through multiple ingredients, targets, and links. However, further clinical and animal studies are needed to investigate the anti-depression effects of EXD and the underlying mechanisms and offer additional evidence and recommendations for its clinical application. Moreover, strategies must be developed to improve the quality control of EXD. This review provides an overview of EXD and guidance for future research direction.