Challenges in Diagnosing and Managing Severe Hypernatremia in Patients With Major Depressive Disorder: A Case Report.

Hypernatremia, characterized by a plasma sodium concentration above 145 mmol/L, is frequently observed in critically ill patients, often due to factors such as gastrointestinal losses, dehydration, and diabetes insipidus. Psychiatric patients, particularly those with major depressive disorder, are also at risk of developing hypernatremia due to abnormalities in thirst sensation, mineralocorticoid excess, or medication side effects. Severe hypernatremia in psychiatric patients is associated with a high mortality rate, presenting challenges in diagnosis and management. The treatment of chronic hypernatremia (>48 hours) typically involves administering isotonic saline to hypovolemic patients until normalization of vital signs, followed by dextrose 5% in water (D5W) based on water deficit and losses. The goal is to decrease plasma sodium by 8-10 mmol/day. Acute hypernatremia (<48 hours) is corrected with a plasma sodium reduction of 1 mmol/L/hour in the first six to eight hours. While there are no clear guidelines for sodium correction in severe hypernatremia, the literature suggests a safe correction rate of 8-10 mmol/day for chronic hypernatremia and 1 mmol/L/hour for acute cases. In a specific case, a 51-year-old female with severe depression and reduced oral intake was admitted. She exhibited signs of dehydration and was found to have severe hypernatremia (191 mmol/L) with acute kidney injury. Treatment involved D5W, followed by D5W/half-normal saline at 150 mL/hr. Within 24 hours, her plasma sodium decreased to 178 mmol/L and gradually normalized to 143 mmol/L without neurological complications. This case highlights the challenges and underscores the importance of early recognition and management of severe hypernatremia in psychiatric patients. The primary treatment approach addresses water deficits and losses and administers D5W. Recent findings suggest that rapid correction of the condition is acceptable.

Combination of Transcranial Magnetic Stimulation and Ketamine in Treatment-Resistant Depression: A Systematic Review.

Treatment-resistant depression (TRD) is a significant challenge in psychiatric practice, affecting a substantial proportion of patients with major depressive disorder (MDD). Traditional treatment modalities often fall short, necessitating the exploration of alternative therapies. This literature review examines the combined use of Transcranial Magnetic Stimulation (TMS) and ketamine in treating TRD. The objective of this study is to evaluate the efficacy, safety, and potential synergies of combining TMS and ketamine in the treatment of TRD. A comprehensive literature search was conducted using PubMed and Google Scholar databases from 2014 to 2024. The search terms included combinations of "Transcranial Magnetic Stimulation," "Ketamine," "Depression," "Major Depressive Disorder," "Treatment-Resistant Depression," and "Combination." After screening for relevance and applying inclusion and exclusion criteria, six studies were selected for review, including three case reports, a retrospective study, a pilot study, and a review study. The selected studies demonstrated that the combination of TMS and ketamine resulted in substantial and sustained improvement in depressive symptoms for patients with TRD. Case reports and retrospective studies highlighted significant reductions in depression severity and improvements in psychosocial functioning. The combination therapy showed a higher efficacy compared to monotherapies of either TMS or ketamine alone. Notably, adverse effects were generally mild and transient, with no severe adverse events reported in most studies. In conclusion, the combination of TMS and ketamine presents a promising treatment modality for patients with TRD, offering significant improvements in depressive symptoms and better outcomes compared to traditional monotherapies. However, the heterogeneity in study designs and small sample sizes underline the need for larger, randomized controlled trials to establish standardized protocols and further validate these findings.

Applying neural ordinary differential equations for analysis of hormone dynamics in Trier Social Stress Tests.

Introduction: This study explores using Neural Ordinary Differential Equations (NODEs) to analyze hormone dynamics in the hypothalamicpituitary-adrenal (HPA) axis during Trier Social Stress Tests (TSST) to classify patients with Major Depressive Disorder (MDD). Methods: Data from TSST were used, measuring plasma ACTH and cortisol concentrations. NODE models replicated hormone changes without prior knowledge of the stressor. The derived vector fields from NODEs were input into a Convolutional Neural Network (CNN) for patient classification, validated through cross-validation (CV) procedures. Results: NODE models effectively captured system dynamics, embedding stress effects in the vector fields. The classification procedure yielded promising results, with the 1x1 CV achieving an AUROC score that correctly identified 83% of Atypical MDD patients and 53% of healthy controls. The 2x2 CV produced similar outcomes, supporting model robustness. Discussion: Our results demonstrate the potential of combining NODEs and CNNs to classify patients based on disease state, providing a preliminary step towards further research using the HPA axis stress response as an objective biomarker for MDD.

Evaluating cognitive assessment tools for patients with major depressive disorder receiving electroconvulsive therapy: A systematic review and meta-analysis.

BACKGROUND: Major Depressive Disorder (MDD) affects 350 million people worldwide. Electroconvulsive therapy (ECT) is effective, yet research on cognitive assessments post-treatment is lacking. This study systematically reviews and meta-analyzes the effectiveness of cognitive assessment tools post-ECT to optimize MDD treatment. METHODS: Following PRISMA guidelines, this review was pre-registered on PROSPERO (CRD42023470318). Searches were conducted across nine databases up to November 12, 2023. Quality assessment for Randomized Controlled Trials (RCTs) and quasi-experimental studies was performed using the Cochrane risk of bias tool, JBI critical appraisal tools, and the Jadad scale. Meta-analyses for short-term and long-term cognitive function involved 24 and 18 tools, respectively. FINDINGS: Thirty studies (20 RCTs and 10 quasi-experimental) involving 2462 MDD patients were evaluated. Results indicated no significant differences in overall short-term and long-term cognitive functions post-ECT. Short-term analysis showed impairments in memory, learning, and verbal abilities but improvements in attention and processing speed. Long-term analysis revealed enhancements in memory, learning, verbal, and visuospatial abilities compared to baseline. Based on GRADE classification, we recommend 11 tools for assessing acute cognitive function and 10 tools for chronic cognitive impairment. These tools demonstrated high reliability and validity, supporting their clinical use. INTERPRETATION: These findings provide critical evidence for future ECT clinical guidelines in managing MDD. The recommended tools can aid clinicians in adjusting ECT regimens, identifying early cognitive changes, and improving therapeutic outcomes in MDD treatment.

Neural substrates of predicting anhedonia symptoms in major depressive disorder via connectome-based modeling.

MAIN PROBLEM: Anhedonia is a critical diagnostic symptom of major depressive disorder (MDD), being associated with poor prognosis. Understanding the neural mechanisms underlying anhedonia is of great significance for individuals with MDD, and it encourages the search for objective indicators that can reliably identify anhedonia. METHODS: A predictive model used connectome-based predictive modeling (CPM) for anhedonia symptoms was developed by utilizing pre-treatment functional connectivity (FC) data from 59 patients with MDD. Node-based FC analysis was employed to compare differences in FC patterns between melancholic and non-melancholic MDD patients. The support vector machines (SVM) method was then applied for classifying these two subtypes of MDD patients. RESULTS: CPM could successfully predict anhedonia symptoms in MDD patients (positive network: r = 0.4719, p < 0.0020, mean squared error = 23.5125, 5000 iterations). Compared to non-melancholic MDD patients, melancholic MDD patients showed decreased FC between the left cingulate gyrus and the right parahippocampus gyrus (p_bonferroni = 0.0303). This distinct FC pattern effectively discriminated between melancholic and non-melancholic MDD patients, achieving a sensitivity of 93.54%, specificity of 67.86%, and an overall accuracy of 81.36% using the SVM method. CONCLUSIONS: This study successfully established a network model for predicting anhedonia symptoms in MDD based on FC, as well as a classification model to differentiate between melancholic and non-melancholic MDD patients. These findings provide guidance for clinical treatment.

Profiling the combination of bupropion and dextromethorphan as a treatment option for major depressive disorder.

INTRODUCTION: Major Depressive Disorder (MDD) is a common mental health disorder marked by sadness, hopelessness, and anhedonia. Various therapies exist, but their effectiveness is limited. Dextromethorphan hydrobromide combined with bupropion hydrochloride (Auvelity®) is a recently approved alternative for treating this condition in adults. AREAS COVERED: This review summarizes the neurobiology of major depression and delves into the pharmacology, efficacy, safety, and tolerability of dextromethorphan plus bupropion in adult patients. It is based on observational studies, clinical trials, and other secondary studies obtained through systematic literature searches. EXPERT OPINION: The combination of bupropion and dextromethorphan as a new pharmacotherapy for mental health is an interesting addition to the treatment options that can be used for MDD. The combination can be used in a range of scenarios, including as a first line therapy, as a second option when a patient has failed to achieve remission with a serotonin targeting agent, and for treatment resistant depression. Further research for other indications, including addiction disorders, may provide exciting results. Although a new combination, clinicians will be very familiar with both agents, increasing their acceptability. This pharmacotherapy also may bring increased impetus for discovering other combinations that may have beneficial synergistic effects.

Insulin resistance, clinical presentation and resistance to selective serotonin and noradrenaline reuptake inhibitors in major depressive disorder.

BACKGROUND: The understanding of mechanisms underlying non-response to antidepressants is limited. The latest data highlights the role of insulin resistance (IR) in major depressive disorder (MDD) pathophysiology, presentation, and treatment efficacy. This work aimed to assess IR in MDD and explore the relationships between IR, MDD presentation and non-response to selective serotonin and noradrenaline reuptake inhibitors (SNRI). METHODS: 67 MDD individuals: 36 responsive (MDD T[+]), 31 non-responsive (MDD T[-]) to SNRI and 30 healthy controls were recruited. The treatment response criteria were: Clinical Global Impression Scale-Improvement score of 1 or 2 after ≥ 8 weeks of treatment. Participants were assessed by physician and self-report tools measuring depression, anhedonia, anxiety, bipolarity, sleep quality. Blood samples were collected to assess fasting glucose and insulin levels and calculate HOMA-IR (homeostasis model assessment of insulin resistance). RESULTS: MDD T[-] vs. MDD T[+] had significantly higher body mass index, insulin levels, and HOMA-IR. MDD T[-] presented higher levels of depressed mood, appetite/weight changes, loss of interest, energy, overall depressive symptoms, and sleep impairment; some evaluations suggested higher anhedonia and anxiety in MDD T[-] vs. MDD T[+]. Insulin and IR were weakly but significantly correlated with the severity of psychomotor symptoms, energy level, thoughts of death/suicide, self-criticism, appetite/weight, depressed mood symptoms, sleep problems. IR was weakly but significantly correlated with anhedonia. CONCLUSION: IR appears to be linked to depressive symptoms characteristic of the "metabolic" MDD subtype, such as psychomotor changes, energy level, anhedonia, sleep problems, appetite/weight changes, state and trait anxiety, sleep quality, and non-response to SNRI.

Bioinformatics and systems biology approach to identify the pathogenetic link of neurological pain and major depressive disorder.

Neurological pain (NP) is always accompanied by symptoms of depression, which seriously affects physical and mental health. In this study, we identified the common hub genes (Co-hub genes) and related immune cells of NP and major depressive disorder (MDD) to determine whether they have common pathological and molecular mechanisms. NP and MDD expression data was downloaded from the Gene Expression Omnibus (GEO) database. Common differentially expressed genes (Co-DEGs) for NP and MDD were extracted and the hub genes and hub nodes were mined. Co-DEGs, hub genes, and hub nodes were analyzed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, the hub nodes, and genes were analyzed to obtain Co-hub genes. We plotted Receiver operating characteristic (ROC) curves to evaluate the diagnostic impact of the Co-hub genes on MDD and NP. We also identified the immune-infiltrating cell component by ssGSEA and analyzed the relationship. For the GO and KEGG enrichment analyses, 93 Co-DEGs were associated with biological processes (BP), such as fibrinolysis, cell composition (CC), such as tertiary granules, and pathways, such as complement, and coagulation cascades. A differential gene expression analysis revealed significant differences between the Co-hub genes ANGPT2, MMP9, PLAU, and TIMP2. There was some accuracy in the diagnosis of NP based on the expression of ANGPT2 and MMP9. Analysis of differences in the immune cell components indicated an abundance of activated dendritic cells, effector memory CD8+ T cells, memory B cells, and regulatory T cells in both groups, which were statistically significant. In summary, we identified 6 Co-hub genes and 4 immune cell types related to NP and MDD. Further studies are needed to determine the role of these genes and immune cells as potential diagnostic markers or therapeutic targets in NP and MDD.

Microglial circ-UBE2K exacerbates depression by regulating parental gene UBE2K via targeting HNRNPU.

Background: Knowledge about the pathogenesis of depression and treatments for this disease are lacking. Epigenetics-related circRNAs are likely involved in the mechanism of depression and have great potential as treatment targets, but their mechanism of action is still unclear. Methods: Circular RNA UBE2K (circ-UBE2K) was screened from peripheral blood of patients with major depressive disorder (MDD) and brain of depression model mice through high-throughput sequencing. Microinjection of circ-UBE2K overexpression lentivirus and adeno-associated virus for interfering with microglial circ-UBE2K into the mouse hippocampus was used to observe the role of circ-UBE2K in MDD. Sucrose preference, forced swim, tail suspension and open filed tests were performed to evaluate the depressive-like behaviors of mice. Immunofluorescence and Western blotting analysis of the effects of circ-UBE2K on microglial activation and immune inflammation. Pull-down-mass spectrometry assay, RNA immunoprecipitation (RIP) test and fluorescence in situ hybridization (FISH) were used to identify downstream targets of circ-UBE2K/ HNRNPU (heterogeneous nuclear ribonucleoprotein U) axis. Results: In this study, through high-throughput sequencing and large-scale screening, we found that circ-UBE2K levels were significantly elevated both in the peripheral blood of patients with MDD and in the brains of depression model mice. Functionally, circ-UBE2K-overexpressing mice exhibited worsened depression-like symptoms, elevated brain inflammatory factor levels, and abnormal microglial activation. Knocking down circ-UBE2K mitigated these changes. Mechanistically, we found that circ-UBE2K binds to heterogeneous nuclear ribonucleoprotein U (HNRNPU) to form a complex that upregulates the expression of the parental gene ubiquitin conjugating enzyme E2 K (UBE2K), leading to abnormal microglial activation and neuroinflammation and promoting the occurrence and development of depression. Conclusions: The findings of the present study revealed that the expression of circUBE2K, which combines with HNRNPU to form the circUBE2K/HNRNPU complex, is increased in microglia after external stress, thus regulating the expression of the parental gene UBE2K and mediating the abnormal activation of microglia to induce neuroinflammation, promoting the development of MDD. These results indicate that circ-UBE2K plays a newly discovered role in the pathogenesis of depression.

Assessing the Relationship Between Vitiligo and Major Depressive Disorder Severity: Cross-Sectional Study.

BACKGROUND: Vitiligo, a common dermatological disorder in Saudi Arabia, is associated with significant psychological impacts. This study explores the relationship between vitiligo and the severity of major depressive disorder (MDD), highlighting the broader implications on mental health among affected individuals. OBJECTIVE: We aim to assess the prevalence and predictors of depression among adult patients with vitiligo, and to examine the relationship between MDD severity and vitiligo. METHODS: Using a cross-sectional design, the research used the vitiligo area severity index and the Patient Health Questionnaire-9 to measure the extent of vitiligo and depression severity, respectively. This study involved 340 diagnosed patients with vitiligo from various health care settings. Logistic and ordinal regression analysis were applied to evaluate the impact of sociodemographic variables and vitiligo types on MDD severity. RESULTS: The prevalence of MDD was 58.8% (200/340) of participants. Depression severity varied notably: 18.2% (62/340) of patients experienced mild depression, 17.9% (61/340) moderate, 11.8% (40/340) moderately severe, and 10.9% (37/340) severe depression. Female patients had higher odds of severe depression than male patients (adjusted odds ratio [aOR] 3.14, 95% CI 1.93-5.1; P<.001). Age was inversely related to depression severity, with patients aged older than 60 years showing significantly lower odds (aOR 0.1, 95% CI 0.03-0.39; P<.001). Lower income was associated with higher depression severity (aOR 10.2, 95% CI 3.25-31.8; P<.001). Vitiligo types also influenced depression severity; vulgaris (aOR 5.3, 95% CI 2.6-10.9; P<.001) and acrofacial vitiligo (aOR 2.8, 95% CI 1.5-5.1; P<.001) were significantly associated with higher depression levels compared to focal vitiligo. CONCLUSIONS: The findings suggest that vitiligo contributes to an increased risk of severe depression, highlighting the need for integrated dermatological and psychological treatment approaches to address both the physical and mental health aspects of the disease.

Exploring the potential of drug repurposing for treating depression.

Researchers are interested in drug repurposing or drug repositioning of existing pharmaceuticals because of rising costs and slower rates of new medication development. Other investigations that authorized these treatments used data from experimental research and off-label drug use. More research into the causes of depression could lead to more effective pharmaceutical repurposing efforts. In addition to the loss of neurotransmitters like serotonin and adrenaline, inflammation, inadequate blood flow, and neurotoxins are now thought to be plausible mechanisms. Because of these other mechanisms, repurposing drugs has resulted for treatment-resistant depression. This chapter focuses on therapeutic alternatives and their effectiveness in drug repositioning. Atypical antipsychotics, central nervous system stimulants, and neurotransmitter antagonists have investigated for possible repurposing. Nonetheless, extensive research is required to ensure their formulation, effectiveness, and regulatory compliance.

Assessing the associations of 1,400 blood metabolites with major depressive disorder: a Mendelian randomization study.

Background and objectives: Major Depressive Disorder (MDD) is one of the most prevalent and debilitating health conditions worldwide. Previous studies have reported a link between metabolic dysregulation and MDD. However, evidence for a causal relationship between blood metabolites and MDD is lacking. Methods: Using a two-sample bidirectional Mendelian randomization analysis (MR), we assessed the causal relationship between 1,400 serum metabolites and Major Depressive Disorder (MDD). The Inverse Variance Weighted method (IVW) was employed to estimate the causal association between exposures and outcomes. Additionally, MR-Egger regression, weighted median, simple mode, and weighted mode methods were used as supplementary approaches for a comprehensive appraisal of the causality between blood metabolites and MDD. Pleiotropy and heterogeneity tests were also conducted. Lastly, the relevant metabolites were subjected to metabolite function analysis, and a reverse MR was implemented to explore the potential influence of MDD on these metabolites. Results: After rigorous screening, we identified 34 known metabolites, 13 unknown metabolites, and 18 metabolite ratios associated with Major Depressive Disorder (MDD). Among all metabolites, 33 were found to have positive associations, and 32 had negative associations. The top five metabolites that increased the risk of MDD were the Arachidonate (20:4n6) to linoleate (18:2n6) ratio, LysoPE(18:0/0:0), N-acetyl-beta-alanine levels, Arachidonate (20:4n6) to oleate to vaccenate (18:1) ratio, Glutaminylglutamine, and Threonine to pyruvate ratio. Conversely, the top five metabolites that decreased the risk of MDD were N6-Acetyl-L-lysine, Oleoyl-linoleoyl-glycerol (18:1 to 18:2) [2] to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) [2] ratio, Methionine to phosphate ratio, Pregnanediol 3-O-glucuronide, and 6-Oxopiperidine-2-carboxylic acid. Metabolite function enrichment was primarily concentrated in pathways such as Bile Acid Biosynthesis (FDR=0.177), Glutathione Metabolism (FDR=0.177), Threonine, and 2-Oxobutanoate Degradation (FDR=0.177). In addition, enrichment was noted in pathways like Valine, Leucine, and Isoleucine Biosynthesis (p=0.04), as well as Ascorbate and Aldarate Metabolism (p=0.04). Discussion: Within a pool of 1,400 blood metabolites, we identified 34 known metabolites and 13 unknown metabolites, as well as 18 metabolite ratios associated with Major Depressive Disorder (MDD). Additionally, three functionally enriched groups and two metabolic pathways were selected. The integration of genomics and metabolomics has provided significant insights for the screening and prevention of MDD.

Subjective and objective cognitive functioning in untreated late-life depression: An exploration centered on comorbid generalized anxiety disorder.

BACKGROUND: Late-Life Depression (LLD) is a prevalent mental health disorder that is often accompanied by cognitive impairments. The objective of this study is to investigate the influence of coexisting Generalized Anxiety Disorder (GAD) on both subjective and objective cognitive abilities in untreated LLD individuals. METHODS: A total of 77 participants aged 60 years and above were recruited for this study, comprising 31 individuals with Major Depressive Disorder (LLD group), 46 with MDD and coexisting Generalized Anxiety Disorder (LLDA group), and 54 healthy controls (HC). Prior to the study, all patients had abstained from psychotropic medication for a minimum of two weeks. Comprehensive neuropsychological assessments were administered to all participants. RESULTS: The LLDA group exhibited substantial disparities in memory, attention, processing speed,executive function,overall cognitive functioning, and subjective cognitive functioning when compared to the HC group. The LLD group displayed deficits in memory, SCWT-W in attention, SCWT-C in processing speed,overall cognitive functioning, and subjective cognitive functioning in comparison to the healthy controls. Although the LLD group achieved lower average scores in executive function, TMTA in processing speed, and DSST in attention than the HC group, no significant distinctions were identified between these groups in these domains. Linear regression analysis unveiled that anxiety symptoms had a significant impact on subjective cognitive deficits among MDD patients, but exhibited a milder influence on objective cognitive performance. After adjusting for the severity of depression, anxiety symptoms were found to affect TMTA in processing speed and subjective cognitive functioning in LLD patients. CONCLUSION: Late-Life Depression (LLD) exhibits pervasive cognitive impairments, particularly in individuals with generalized anxiety disorder, presenting a crucial target for future therapeutic interventions. Among elderly individuals with depression, anxiety symptoms significantly impact subjective cognitive functioning, suggesting its potential utility in distinguishing between depression-associated cognitive decline and pre-dementia conditions.

An association study of m6A methylation with major depressive disorder.

OBJECTIVE: To find the relationship between N6-methyladenosine (m6A) genes and Major Depressive Disorder (MDD). METHODS: Differential expression of m6A associated genes between normal and MDD samples was initially identified. Subsequent analysis was conducted on the functions of these genes and the pathways they may affect. A diagnostic model was constructed using the expression matrix of these differential genes, and visualized using a nomogram. Simultaneously, an unsupervised classification method was employed to classify all patients based on the expression of these m6A associated genes. Following this, common differential genes among different clusters were computed. By analyzing the functions of the common differential expressed genes among clusters, the role of m6A-related genes in the pathogenesis of MDD patients was elucidated. RESULTS: Differential expression was observed in ELAVL1 and YTHDC2 between the MDD group and the control group. ELAVL1 was associated with comorbid anxiety in MDD patients. A linear regression model based on these two genes could accurately predict whether patients in the GSE98793 dataset had MDD and could provide a net benefit for clinical decision-making. Based on the expression matrix of ELAVL1 and YTHDC2, MDD patients were classified into three clusters. Among these clusters, there were 937 common differential genes. Enrichment analysis was also performed on these genes. The ssGSEA method was applied to predict the content of 23 immune cells in the GSE98793 dataset samples. The relationship between these immune cells and ELAVL1, YTHDC2, and different clusters was analyzed. CONCLUSION: Among all the m6A genes, ELAVL1 and YTHDC2 are closely associated with MDD, ELAVL1 is related to comorbid anxiety in MDD. ELAVL1 and YTHDC2 have opposite associations with immune cells in MDD.

Higher levels of plasma Adrenocorticotropic hormone (ACTH) are associated with lower suicidal ideation in depressed patients compared to controls and suicide attempters, independently from depression severity.

Introduction: Suicidal ideation, an important risk factor for suicide attempts, has an unclear neurobiological basis and is potentially linked to the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and immune-inflammatory systems. While inflammatory markers have been associated with suicide attempts and, to a lower extent suicidal ideation, the data on the role of a stress-response system is less robust, with most studies carried out with cortisol showing inconsistent results. The present study extends on the previous studies implicating stress-response and immune-inflammatory systems in suicidal thoughts and behaviours, focusing on the associations of several stress-response (adrenocorticotropic hormone (ACTH), cortisol, and dehydroepiandrosterone (DHEA)) and immune-inflammatory (C-reactive protein (CRP),interle ukin-6 (IL-6), and tumour necrosis factor-alpha (TNF-alpha)) with suicidal ideation severity in recent suicide attempters, patients with major depressive disorder, and non-psychiatric controls. Methods: This observational study included 156 adults from three Vilnius hospitals, recruited into one of the three groups in equal parts: recent suicide attempters, patients with major depressive disorder in current depressive episode, and non-psychiatric controls. Measures included the Hamilton Depression Rating Scale (HDRS-17) and the Beck Scale for Suicide Ideation/Suicide Severity Index (BSS/SSI), alongside sociodemographic data, alcohol, tobacco use, and morning blood samples, measuring plasma ACTH, cortisol, DHEA, CRP, and IL-6. Data were analysed with non-parametric tests, Kendall's tau correlation, and multivariate linear regression adjusted for confounders. Results: We found a negative correlation between the plasma ACTH levels and suicidal ideation severity (tau = -0.130, p = 0.033), which was driven by the patients with major depressive disorder (tau = -0.237, p = 0.031). Suicidal ideation severity was also negatively correlated with TNF-alpha (tau = -0.231; p < 0.001), positively correlated with IL-6 (tau = 0.154, p = 0.015), and CRP levels (tau = 0.153, p = 0.015), but no differences were observed in group-stratified analyses. The association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder remained robust to adjustment for major confounders (adjusted for age, sex, education years, body mass index, smoking status, plasma CRP and PEth concentration (measuring chronic alcohol exposure), and antidepressant use) in the linear regression model (t = -2.71, p = 0.011), as well as additionally adjusting for depression severity (t = -2.99, p = 0.006). Discussion: The present study shows an association between plasma ACTH levels and suicidal ideation severity in patients with major depressive disorder, robust to adjustment for antidepressant use and depression severity. This finding highlights the potential role of ACTH, in elucidating the effects of stress and mental health disorders. Our findings underscore the importance of the HPA axis in the diagnosis and treatment of suicidal ideation in major depressive disorder and invite further research on interventions targeting this pathway.

Optimally combining transcranial magnetic stimulation with antidepressants in major depressive disorder: A systematic review and Meta-analysis.

There is a critical knowledge gap in optimally combining transcranial magnetic stimulation (TMS) and antidepressants to treat patients with major depressive disorder (MDD). TMS is effective in treating MDD in patients who have failed at least one antidepressant trial, with accelerated protocols showing faster remission in treatment-resistant depression (TRD). Although clinicians routinely augment antidepressants with TMS, there is a knowledge gap in stopping versus continuing antidepressants or the dosing strategies when starting or tapering TMS. These considerations are important when considering maintenance TMS (delivered alone or in combination with suitable antidepressants) to maintain remission in MDD after the index course of TMS. As the first step towards filling this knowledge gap, we reviewed randomized controlled trials (RCTs) and open-label trials from 2 databases (PubMed/Medline and EMBASE) that compared active TMS combined with a pre-specified antidepressant dosed in the same manner for adults with MDD versus sham TMS combined with the same antidepressant as in the active arm. All studies were published between January 1, 2000, and December 31, 2023. We excluded case reports, case series, and clinical studies that augmented TMS with antidepressants and vice versa. We found 10 RCTs (n = 654 participants) and performed a meta-analysis. This showed active TMS combined with pre-specified antidepressants had greater efficacy for MDD treatment than sham TMS combined with the same antidepressants as in the active arm (Hedge's g = 1; 95 % CI [0.27, 1.73]). The review and meta-analysis indicate greater short-term efficacy in combining antidepressants with TMS from the get-go in MDD. Given the increasing role of accelerated TMS protocols in expediting remission in MDD and the results of our meta-analysis, we advocate for RCTs examining the short-term and long-term effects of various antidepressant classes on these TMS protocols in MDD. This can also optimize and individualize maintenance TMS protocols to prevent relapse in MDD.

Diagnosis support of major depressive disorder using event-related potentials during affective priming tasks.

Major Depressive Disorder (MDD) is a global problem. Currently, the most common diagnosis is based on criteria susceptible to the subjectivity of the patient and the clinician. A possible solution to this problem is to look for diagnostic biomarkers that can accurately and early detect this mental condition. Some researchers have focused on electroencephalogram (EEG) analysis to identify biomarkers. In this study we used a dataset composed of EEG recordings from 24 subjects with MDD and 29 healthy controls (HC), during the execution of affective priming tasks with three different emotional stimuli (images): fear, sadness, and happiness. We investigated abnormalities in depressed patients using a novel technique, by directly comparing Event-Related Potential (ERP) waveforms to find statistically significant differences between the MMD and HC groups. Compared to the control group (healthy subjects), we found out that for the emotions fear and happiness there is a decrease in cortical activity at temporal regions in MDD patients. Just the opposite, for the emotion sadness, an increase in MDD brain activity occurs in frontal and occipital regions. Our findings suggest that emotions regulate the attentional control of cognitive processing and are promising for clinical application in diagnosing patients with MDD more objectively.

Enhanced neuronal survival and BDNF elevation via long-term co-activation of galanin 2 (GALR2) and neuropeptide Y1 receptors (NPY1R): potential therapeutic targets for major depressive disorder.

BACKGROUND: Major Depressive Disorder (MDD) is a prevalent and debilitating condition, necessitating novel therapeutic strategies due to the limited efficacy and adverse effects of current treatments. We explored how galanin receptor 2 (GALR2) and Neuropeptide Y1 Receptor (NPYY1R) agonists, working together, can boost brain cell growth and increase antidepressant-like effects in rats. This suggests new ways to treat Major Depressive Disorder (MDD). RESEARCH DESIGN AND METHODS: In a controlled laboratory setting, adult naive Sprague-Dawley rats were administered directly into the brain's ventricles, a method known as intracerebroventricular (ICV) administration, with GALR2 agonist (M1145), NPYY1R agonist, both, or in combination with a GALR2 antagonist (M871). Main outcome measures included long-term neuronal survival, differentiation, and behavioral. RESULTS: Co-administration of M1145 and NPYY1R agonist significantly enhanced neuronal survival and maturation in the ventral dentate gyrus, with a notable increase in Brain-Derived Neurotrophic Factor (BDNF) expression. This neurogenic effect was associated with an antidepressant-like effect, an outcome partially reversed by M871. CONCLUSIONS: GALR2 and NPYY1R agonists jointly promote hippocampal neurogenesis and exert antidepressant-like effects in rats without adverse outcomes, highlighting their therapeutic potential for MDD. The study's reliance on an animal model and intracerebroventricular delivery warrants further clinical exploration to confirm these promising results.

Evaluating the prevalence and risk factors for depression in patients with temporal lobe epilepsy with hippocampal sclerosis: A cross-sectional multicenter study.

BACKGROUND: Epilepsy frequently accompanies Major Depressive Disorder (MDD). Notably, people with temporal lobe epilepsy and hippocampal sclerosis may face an increased susceptibility to MDD, as evidence indicates the involvement of the limbic system in the development of emotional symptoms. OBJECTIVES: To determine the prevalence and predictors of depression in temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and compare them to those of other epilepsy types. METHODS: A sample of 293 epilepsy patients, including 159 non-TLE-HS and 134 TLE-HS, were recruited from three hospitals. Of these, 215 completed a two-section electronic survey. The first section collected demographic and epilepsy data, while the second used the Arabic version of the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E). RESULTS: Of 215 patients, 104 (48%) had TLE-HS-38 with right TLE-HS (37%), 56 with left TLE-HS (54%), and 10 with bilateral TLE-HS (10%). The prevalence and severity of depression was assessed with an NDDI-E score of 15 or higher identified 35 patients (16%) with MDD. Valproic acid and lamotrigine were associated with higher NDDI-E scores. No such associations were found for levetiracetam or carbamazepine. Polytherapy in TLE-HS showed a significant correlation with daily poor concentration. CONCLUSION: We explored the differences in depression prevalence between TLE-HS and other epilepsy types and concluded they are minimal but slightly higher in TLE-HS. Predictors of depression such as seizure frequency and disease duration influenced MDD prevalence in TLE-HS. Lamotrigine and valproate were linked to higher NDDI-E scores.

Exploring the Effects of Major Depressive Disorder on Daily Occupations and the Impact of Psychotherapy: A Literature Review.

Major depressive disorder (MDD) is a prevalent psychological mood disorder that can disrupt one's functioning and result in decreased engagement in daily activities. Psychotherapy, in different approaches, is a common approach for individuals experiencing MDD. Nevertheless, a literature review of the research supporting the effectiveness of psychotherapeutic interventions in patients with MDD-impacted areas of their daily occupations, such as back to work, cognitive deficits, and well-being, has not been conducted. A literature review was carried out to evaluate the effectiveness of psychotherapy on daily occupations for individuals diagnosed with MDD. Due to variations in study design and outcome measures, a best evidence synthesis was carried out instead of a meta-analysis. Forty-one identified articles were fully assessed in total. These studies were conducted in various countries so that a global approach could be considered comprehensive. The findings showed strong evidence supporting the effectiveness of psychotherapy on return-to-work interventions in improving depressive symptoms. There was limited evidence for the effectiveness of psychotherapy on lifestyle interventions in reducing anxiety and suicidal ideation, as well as limited evidence for enhancing work participation. Notably, there were no studies evaluating individualized client-centered psychotherapy interactions with occupations, revealing a research gap. Challenges such as incomplete reporting within studies and study heterogeneity prevented a meta-analysis. While the overall evidence base for the effectiveness of psychotherapy for MDD in treating functionality is limited, the findings provide strong support for the efficacy of occupational therapy return-to-work interventions. This is particularly important given the economic costs associated with mental health issues and work-related absences. Further research is required to strengthen the existing evidence base.