Hamilton Depression Rating Scale Scores Research Articles

Metabolic Effects of Antidepressants: Results of a Randomized Study's Interim Analysis.

Individuals with major depressive disorder exhibit a dysregulated metabolic profile. There are few studies on how vilazodone, escitalopram, and vortioxetine alter metabolic parameters. Our study aimed to determine the change in plasma glucose, HbA1c, serum cholesterol, triglyceride, and creatinine at 12 weeks. An ongoing randomized, open-label, three-arm study's interim analysis is portrayed here. The participants were assessed at baseline, 4, 8, and 12 weeks after receiving oral tablets of either vilazodone (20-40mg/d), escitalopram (10-20mg/d), or vortioxetine (5-20mg/d). This study is CTRI-registered (2022/07/043808). Of 71 recruited participants, 49 (69%) completed the 12-week visit. The median Hamilton Depression Rating Scale (HDRS) scores of the participants in vilazodone, escitalopram, and vortioxetine groups were 30.0, 29.5, and 29.0 at baseline (p=0.76) and 19.5, 19.5, and 18.0 (p=0.18) at 12 weeks, respectively. The median fasting blood sugar (FBS) values were 98.5, 105.5, and 98.0 at baseline (p=0.07) and 94.0, 99.5, and 96.0 (p=0.19) at 12 weeks, for vilazodone, escitalopram, and vortioxetine groups, respectively.The post hoc analysis did not yield statistically significant differences regarding any parameters. According to this interim study, the HDRS scores declined after 12 weeks of therapy. The subjects' metabolic parameters did not significantly change. It is essential to perform further investigation regarding these impacts.

Association of Neurofilament Light Chain With the Antidepressant Effects of Low-Dose Ketamine Infusion Among Patients With Treatment-Resistant Depression.

The role of neurofilament light chain (NFL) in treatment-resistant depression (TRD) is unclear. Whether baseline NFL concentrations are associated with the antidepressant effects of low-dose ketamine infusion has not been determined. The NFL concentrations of 71 patients with TRD and 17 healthy controls were assessed. Patients with TRD were randomly administered a single infusion of 0.5mg/kg ketamine, 0.2mg/kg ketamine, or normal saline. Depressive symptoms were assessed prior to infusion and sequentially at postinfusion timepoints (after 240min and 2-7 and 14 days after infusion) using the Hamilton Depression Rating Scale (HDRS). After adjustment for age, sex, and body mass index, patients with TRD were more likely to have higher concentrations of NFL than healthy controls (p < 0.001). A generalized estimating equation model with adjustments for infusion group, age, sex, body mass index, and baseline HDRS scores showed that baseline NFL concentrations were positively associated with subsequent HDRS scores following low-dose ketamine infusion (p = 0.038). Higher concentrations of NFL were observed among patients with TRD compared with healthy controls. Baseline NFL concentrations may predict the antidepressant effects of low-dose ketamine infusion.

Reward Behavior Disengagement, a Neuroeconomic Model-Based Objective Measure of Reward Pathology in Depression: Findings from the EMBARC Trial.

The probabilistic reward task (PRT) has identified reward learning impairments in those with major depressive disorder (MDD), as well as anhedonia-specific reward learning impairments. However, attempts to validate the anhedonia-specific impairments have produced inconsistent findings. Thus, we seek to determine whether the Reward Behavior Disengagement (RBD), our proposed economic augmentation of PRT, differs between MDD participants and controls, and whether there is a level at which RBD is high enough for depressed participants to be considered objectively disengaged. Data were gathered as part of the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study, a double-blind, placebo-controlled clinical trial of antidepressant response. Participants included 195 individuals with moderate to severe MDD (Quick Inventory of Depressive Symptomatology (QIDS-SR) score ≥ 15), not in treatment for depression, and with complete PRT data. Healthy controls (n = 40) had no history of psychiatric illness, a QIDS-SR score < 8, and complete PRT data. Participants with MDD were treated with sertraline or placebo for 8 weeks (stage I of the EMBARC trial). RBD was applied to PRT data using discriminant analysis, and classified MDD participants as reward task engaged (n = 137) or reward task disengaged (n = 58), relative to controls. Reward task engaged/disengaged groups were compared on sociodemographic features, reward-behavior, and sertraline/placebo response (Hamilton Depression Rating Scale scores). Reward task disengaged MDD participants responded only to sertraline, whereas those who were reward task engaged responded to sertraline and placebo (F(1293) = 4.33, p = 0.038). Reward task engaged/disengaged groups did not differ otherwise. RBD was predictive of reward impairment in depressed patients and may have clinical utility in identifying patients who will benefit from antidepressants.

Endocan: A novel biomarker of endothelial dysfunction in depression?

Endocan is a proteoglycan secreted from endothelium upon endothelial damage. Since depression is associated with higher inflammation and oxidative stress to the vascular endothelium, endothelial dysfunction is prevalent and it is one of the responsible mechanisms for increased cardiovascular morbidity and mortality in depressive disorders. This study aimed to investigate endocan levels in patients with depression (either bipolar or unipolar) and healthy controls to evaluate the projected endothelial injury. We included nonsmoker patients without comorbid inflammatory conditions: 31 with Bipolar Disorder Depression (BDD), 30 with Major Depressive Disorder (MDD) and 25 healthy controls (HC). The severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS). Ultimately, serum endocan levels were significantly higher in patients with BDD than in patients with MDD (p < .000) and HCs (p < .000). Also, patients with MDD had significantly higher endocan levels than HCs (p < .000). The AUC value for the endocan to differentiate patients with depression from controls was 0.990 (95% CI: 0.971–1.000; p < .001) with sensitivity and specificity of 98.4 and 100%, respectively, and an optimal cut-off value of 316.92 ng/L. Serum endocan levels showed a mild positive correlation with HDRS scores (r = 0.372, p = .039) in the BDD group but not in the MDD group (r = −0.242, p = .20). Patients with BDD had higher endocan levels than MDD; this finding, while preliminary, could be an implication of higher endothelial dysfunction in BDD.

Serum alkaline phosphatase was independently associated with depression in patients with cerebrovascular disease.

Blood markers have important value in the diagnosis of depressive disorders. Serum alkaline phosphatase (ALP) not only predicts stroke recurrence and poor functional prognosis in cerebrovascular disease (CVD) patients but also increases significantly in middle-aged women with depression. Thus, it has not been reported whether serum ALP is associated with the development of depression and/or vascular depression (VDe) in CVD patients. This was a cross-sectional study of 353 CVD patients (stroke patients, n = 291; cerebral small vessel disease (CSVD) patients, n = 62). Baseline demographic information, fasting blood markers (such as blood counts, liver function, kidney function and lipids), and brain CT/MRI scans were collected. CVD patients were divided into non-depression, suspected vascular depression (SVD), and positive vascular depression (PVD) groups according to their Hamilton Rating Scale for Depression (HAMD) scores. Univariate analysis of baseline data, blood markers, and the prevalence of lesions (> 1.5 cm) was performed. Subsequently, the diagnostic performance of the univariate and combined variables for SVD and PVD was analyzed using binary logistic regression. The diagnostic value of the multivariate model for VDe was analyzed by ordinal logistic regression. (1) Serum ALP (p = 0.003) and hypersensitive C-reactive protein (hs-CRP, p = 0.001) concentrations increased as HAMD scores increased, and the prevalence of brain atrophy (p = 0.016) and lesions in the basal ganglia (p = 0.001) and parietal (p = 0.001), temporal (p = 0.002), and frontal lobes (p = 0.003) also increased, whereas the concentrations of hemoglobin (Hb, p = 0.003), cholinesterase (ChE, p = 0.001), and high-density lipoprotein cholesterol (HDL-C, p = 0.005) declined. Among these variables, hs-CRP (r = 0.218, p < 0.001) had a weak positively association with HAMD scores, and ChE (r = -0.226, p < 0.001) had a weak negative association. (2) The combination of Hb, hs-CRP, ChE, ALP, and HDL-C improved diagnostic performance for VDe [AUC = 0.775, 95% CI (0.706, 0.844), p < 0.001]. (3) Hb (OR = 0.986, p = 0.049), ChE (OR = 0.999, p = 0.020), ALP (OR = 1.017, p = 0.003), and basal ganglia lesions (OR = 2.197, p < 0.001) were important factors impacting VDe development. After adjusting for Hb, hs-CRP, ChE, HDL-C, lesions in the above mentioned four locations, sex, age and the prevalence of CSVD and brain atrophy, ALP [OR = 1.016, 95% CI (1.005, 1.027), p = 0.004] was independently associated with VDe. Hb, hs-CRP, ChE, ALP, and HDL-C concentrations are potential blood markers of depression in CVD patients and, when combined, may improve diagnostic performance for VDe. Serum ALP was independently associated with VDe in patients with CVD.

What are the treatment remission, response and extent of improvement rates after up to four trials of antidepressant therapies in real-world depressed patients? A reanalysis of the STAR*D study’s patient-level data with fidelity to the original research protocol

ObjectiveReanalyse the patient-level data set of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study with fidelity to the original research protocol and related publications.DesignThe study was open label and...

Altered beta band spatial-temporal interactions during negative emotional processing in major depressive disorder: An MEG study

BackgroundThe mood-concordance bias is a key feature of major depressive disorder (MDD), but the spatiotemporal neural activity associated with emotional processing in MDD remains unclear. Understanding the dysregulated connectivity patterns during emotional processing and their relationship with clinical symptoms could provide insights into MDD neuropathology. MethodsWe enrolled 108 MDD patients and 64 healthy controls (HCs) who performed an emotion recognition task during magnetoencephalography recording. Network-based statistics (NBS) was used to analyze whole-brain functional connectivity (FC) across different frequency ranges during distinct temporal periods. The relationship between the aberrant FC and affective symptoms was explored. ResultsMDD patients exhibited decreased FC strength in the beta band (13–30 Hz) compared to HCs. During the early stage of emotional processing (0-100 ms), reduced FC was observed between the left parahippocampal gyrus and the left cuneus. In the late stage (250-400 ms), aberrant FC was primarily found in the cortex-limbic-striatum systems. Moreover, the FC strength between the right fusiform gyrus and left thalamus, and between the left calcarine fissure and left inferior temporal gyrus were negatively associated with Hamilton Depression Rating Scale (HAMD) scores. LimitationsMedication information was not involved. ConclusionMDD patients exhibited abnormal temporal-spatial neural interactions in the beta band, ranging from early sensory to later cognitive processing stages. These aberrant interactions involve the cortex-limbic-striatum circuit. Notably, aberrant FC in may serve as a potential biomarker for assessing depression severity.

Tau deposition in the locus coeruleus and depression in cognitively unimpaired older adults

AbstractBackgroundDepression is a common manifestation of Alzheimer’s disease (AD) and frequently observed at the early phase of the disease. Several postmortem studies demonstrated that tau deposition was found at the brainstem nuclei including the locus coeruleus (LC) and dossal raphe nucleus (DRN) (3, 4), even before early Braak stages of neurofibrillary tangle pathology. Given the disturbance of monoaminergic system is related to depression in general, tau deposition in the LC or DRN may underlie depression in late‐life, as suggested in a couple of postmortem studies. In this context, we tried to examine the hypothetical association between in vivo tau depostion at the brain stem monoaminergic nuclei and depression in cognitively unimpaired older adults.MethodA total of 69 cognitively unimpaired older adults from the Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer’s Disease (KBASE) were included. All participants underwent comprehensive clinical assessment including the Hamilton Rating Scale for Depression (HRSD) and [18F] AV‐1451 positron emission tomography. Tau deposition in the LC and DRN was measured using the Harvard Ascending Arousal Network Atlas (AAN). Tau deposition in the pons was also assessed as a non‐monoaminergic control for comparison. Age, education, sex, and apolipoprotein E ε4 positivity were controlled as covariates in the analyses for the association between brain stem tau and HRSD score.ResultTau deposition in the LC was significantly associated with HRSD total score (β = 3.861, P = .009). In contrast, there was no significant association between tau deposition in the DRN and HRSD score (β = 2.229, P = .090). Tau deposition in the pons was also not related to HRSD score (β = 1.632, P = .207).ConclusionThe findings support the possibility that alteration of the noradrenergic neurons in the LC by tau pathology may underlie depressive manifestation in cognitively unimpaired older individuals.

Severe Depressive Episode with Psychotic Symptoms: A Homoeopathic Case Study

Abstract Background Global burden of depression has increased in the recent years with reduction in productivity, reduced quality of life, increased morbidity and mortality. Although there is an evidence base for effectiveness of homoeopathy in depression, severe depressive episode (SDE) with psychotic symptoms is challenging for homoeopaths to treat. Case Summary A 27-year-old female patient presented with dullness, easy fatiguability, withdrawn nature with loathing of life, lack of interest in daily and pleasurable activities. She believed that her body was disfigured and was suspicious that someone was spying on her. The case was diagnosed as SDE with psychotic symptoms (F-32.3 according to International Classification of Diseases, 10th revision). Natrum muriaticum 30 was given as the first prescription and repeated as necessary in the follow-up visits. Carcinosinum 200 was given as intercurrent on the basis of past history of thyroid malignancy. This case presents an example for Hahnemann's concept of Somato-psychic disorder mentioned in §216 of Organon of Medicine. Results Hamilton Depression Rating Scale score at baseline which was 42 turned to 0 at the end of 6 months and remained the same over a 3 year observation period. Conclusion Homoeopathic medicines are effective in the management of SDE with psychotic symptoms. Effectiveness of Natrum muriaticum in reducing depressive symptoms and its effect on neurotransmitters is the arena of future research.

Med Check: Zuranolone for Depression, Uzedy for Schizophrenia, and More

Back to table of contents Previous article Next article Med CheckFull AccessMed Check: Zuranolone for Depression, Uzedy for Schizophrenia, and MoreTerri D’ArrigoTerri D’ArrigoSearch for more papers by this authorPublished Online:25 May 2023https://doi.org/10.1176/appi.pn.2023.06.6.1Zuranolone Found to Quickly Reduce Major Depression SymptomsAdults with major depressive disorder may experience mood improvements within days of taking zuranolone (50 mg/day), a study published in May in The American Journal of Psychiatry (AJP) suggests. Zuranolone is an oral, once-daily neuroactive steroid that acts on GABA-A receptors.The phase 3 trial included patients who were between the ages of 18 and 64 years, had received a diagnosis of major depressive disorder, had been experiencing symptoms of depression for a least four weeks, and had a Hamilton Depression Rating Scale (HAM-D) score of at least 24 at screening and before they started taking the assigned study medication.The researchers randomized 534 participants to take either 14 days of treatment with zuranolone 50 mg/day or placebo in the evening. The researchers evaluated the participants 10 times over the course of the 42-day trial using such assessments as the HAM-D, the Columbia–Suicide Severity Rating Scale, the Clinical Global Impressions severity score, and more.Compared with patients who took placebo, those who took zuranolone demonstrated a statistically significant improvement in depressive symptoms at day 15. “Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM-D score, −9.8 vs. −6.8), which were sustained at all visits throughout the treatment and follow-up periods of the study,” the researchers wrote.FDA Approves Uzedy for Treating SchizophreniaIn April the U.S. Food and Drug Administration (FDA) approved Uzedy (risperidone extended-release injectable suspension) for the treatment of schizophrenia in adults, Teva and MedinCell announced. Uzedy is a long-acting subcutaneous antipsychotic that may be given in one- or two-month dosing intervals.In the phase 3 RISE trial, 544 patients aged 13 to 65 years with schizophrenia were randomized to receive a subcutaneous injection of Uzedy (either once per month or once every two months) or placebo. Those who received Uzedy once per month or once every two months had a reduction of 80.0% and 62.5% in the risk to relapse compared with those who received placebo, respectively. Results were similar in the phase 3 SHINE trial, which examined the long-term safety of the drug for up to 56 weeks in 336 patients aged 13 to 65 years with schizophrenia.A companion survey of participants in the SHINE trial found that 89% of patients and 92% of health professionals rated administration of Uzedy as easy when asked how easy or difficult it was to receive or administer the medication in its current form. Further, 70% of patients reported that Uzedy provided a better injection experience than their previous long-acting injectables (LAIs).Abilify Asimtufii Approved for Schizophrenia, Bipolar I TreatmentAbilify Asimtufii (aripiprazole extended release injectable suspension) has been approved by the FDA for the treatment of schizophrenia in adults and as a monotherapy treatment of bipolar I disorder in adults, Otsuka and Lundbeck announced in April. Abilify Asimtufii is a long-acting subcutaneous atypical antipsychotic that may be given every two months.The approval was based on safety and efficacy data from trials of Abilify Maintena, which is for once monthly dosing, and on the results of a phase 1-2 study. In the phase 1-2 study, 266 adults with schizophrenia or bipolar I disorder were randomly assigned to receive either Abilify Asimtufii 960 mg every 56 days, for a total of four injections or Abilify Maintena 400 mg administered every 28 days for a total of eight injections. Treatment with Abilify Asimtufii resulted in similar aripiprazole plasma concentrations and efficacy to Abilify Maintena. ■ ISSUES NewArchived

Kullback-Leibler Divergence of Sleep-Wake Patterns Related with Depressive Severity in Patients with Epilepsy.

(1) Objective: Whether abnormal sleep-wake rhythms were associated with depressive symptoms in patents with epilepsy had remained unclear. Our study aimed to establish relative entropy for the assessment of sleep-wake patterns and to explore the relationship between this index and the severity of depressive symptoms in patients with epilepsy. (2) Methods: We recorded long-term scalp electroencephalograms (EEGs) and Hamilton Depression Rating Scale-17 (HAMD-17) questionnaire scores from 64 patients with epilepsy. Patients with HAMD-17 scores of 0-7 points were defined as the non-depressive group, while patients with scores of 8 or higher were defined as the depression group. Sleep stages were firstly classified based on EEG data. We then quantified sleep-wake rhythm variations in brain activity using the Kullback-Leibler divergence (KLD) of daytime wakefulness and nighttime sleep. The KLD at different frequency bands in each brain region was analyzed between the depression and non-depression groups. (3) Results: Of the 64 patients with epilepsy included in our study, 32 had depressive symptoms. It was found that patients with depression had significantly decreased KLD for high-frequency oscillations in most brain areas, especially the frontal lobe. A detailed analysis was conducted in the right frontal region (F4) because of the significant difference in the high-frequency band. We found that the KLDs at the gamma bands were significantly decreased in the depression groups compared to the non-depression group (KLDD = 0.35 ± 0.05, KLDND = 0.57 ± 0.05, p = 0.009). A negative correlation was displayed between the KLD of gamma band oscillation and HAMD-17 score (r = -0.29, p = 0.02). (4) Conclusions: Sleep-wake rhythms can be assessed using the KLD index calculated from long-term scalp EEGs. Moreover, the KLD of high-frequency bands had a negative correlation with HAMD-17 scores in patients with epilepsy, which indicates a close relationship between abnormal sleep-wake patterns and depressive symptoms in patients with epilepsy.

Association between metabolic syndrome components and impulse control disorders in Parkinson's disease.

Current evidence on management of impulse control disorders (ICDs) in Parkinson's disease (PD) remains scarce, and exploring modifiable risk factors is crucial. We evaluated the profiles of ICDs in PD patients and aimed to determine the associations between ICDs, metabolic syndrome components and other clinical features. We enrolled patients diagnosed with PD in this study and conducted comprehensive clinical assessments. We recruited 39 PD patients with ICDs and 66 PD patients without ICDs. Out of the 39 patients with ICDs, 19 (48.7%) had one impulse control disorder, while 20 (51.3%) had two or more. The most commonly reported symptom of ICDs was compulsive eating (48.7%). Significant differences were observed between the PD patients with and without ICDs in terms of their HbA1c levels, history of diabetes mellitus, dopamine agonist use, levodopa equivalent dose of dopamine agonists (LED DA), and Hamilton Depression Rating Scale (HAMD) scores. HbA1c levels were significantly higher in the PD patients with compulsive eating. Stepwise logistic regression analyses were performed with the dependent variables of ICDs (yes/no) and compulsive eating (yes/no). Among the 105 PD patients, those with ICDs exhibited higher levels of HbA1c, HAMD score and LED DA than those without ICDs (p < 0.01). Among 39 PD patients with ICDs, those with compulsive eating exhibited higher levels of HbA1c (OR = 2.148, 95% CI = 1.004-4.594, p < 0.05). Among 105 PD patients, those with compulsive eating exhibited higher levels of HbA1c, LED DA and HAMD score (p < 0.05). This study provides insights into the profiles of ICDs in PD patients and their associations with various clinical features. Compulsive eating was the most common ICDs symptom reported. Notably, HbA1c levels were found to be higher in patients with compulsive eating, indicating that poor blood glucose control may be a potential risk factor for ICDs in PD. However, it should be noted that the higher HbA1c levels could also be a consequence of compulsive eating rather than a causal factor for ICDs in PD. Further research is needed to confirm the modifiable risk factors for ICDs in PD.

Suprachiasmatic nucleus functional connectivity related to insomnia symptoms in adolescents with major depressive disorder.

Insomnia is a commonly seen symptom in adolescents with major depressive disorder (MDD). The suprachiasmatic nucleus (SCN), which is the circadian rhythm regulation center, plays a crucial role in the regulation of sleep-wake circulation. Nevertheless, how SCN function contributes to the exact neural mechanisms underlying the associations between insomnia and depressive symptoms has not been explored in adolescents. In the current study, we aimed to explore the relationship between SCN functional connectivity (FC) and insomnia symptoms in adolescents with MDD using a seed-based FC method. In the current study, we recruited sixty-eight first-episode drug-naïve adolescents with MDD and classified them into high insomnia (MDD-HI) and low insomnia (MDD-LI) groups according to the sleep disturbance subscale of the Hamilton Depression Rating Scale (HAMD-S). Forty-three age/gender-matched healthy controls (HCs) were also recruited. SCN FC maps were generally for all subjects and compared among three groups using one-way ANOVA with age, gender and adjusted HAMD score as covariates. We used partial correlations to explore associations between altered FC and clinical symptoms, including sleep quality scores. Adolescents with MDD showed worse sleep quality, which positively correlated with the severity of depression. Compared to MDD-LI and HCs, MDD-HI adolescents demonstrated significantly decreased FC between the right SCN and bilateral precuneus, and there was no significant difference between the MDD-LI and HC groups. The HAMD-S scores were negatively correlated with bilateral SCN-precuneus connectivity, and the retardation factor score of HAMD was negatively correlated with right SCN-precuneus connectivity. The altered FC between the SCN and precuneus may underline the neural mechanism of sleep-related symptoms in depressive adolescents and provide potential targets for personalized treatment strategies.

New treatment found to quickly reduce major depression symptoms

Adults with major depressive disorder may experience mood improvements within days of taking zuranolone (50 mg/day), a study in The American Journal of Psychiatry suggests. Zuranolone is an oral, once‐daily neuroactive steroid that acts on GABAA receptors. “Patients receiving zuranolone 50 mg/day demonstrated significantly greater improvements in depressive symptoms at day 15 compared with those receiving placebo,” wrote Anita H. Clayton, M.D., of the University of Virginia School of Medicine and colleagues. The study “supports the potential role for a 14‐day therapy with oral zuranolone 50 mg/day in adults with MDD [major depressive disorder], with rapid improvements in depressive symptoms observed at the day 3 visit that were sustained through day 42, relatively high response and remission rates, and a favorable safety profile.” The phase 3 trial included patients who were between the ages of 18 and 64 years, had received a diagnosis of MDD (according to Diagnostic and Statistical Manual of Mental Disorders criteria), had been experiencing symptoms of depression for a least four weeks, and had a Hamilton Depression Rating Scale (HAM‐D) score of at least 24 at screening and before they started taking the assigned study medication. A total of 534 patients (266 in the zuranolone group; 268 in the placebo group) were included in the final analysis. The patients in both groups (who were predominantly white and female) had experienced MDD for a mean of approximately 11 years. Compared with patients who took placebo, those who took zuranolone demonstrated a statistically significant improvement in depressive symptoms at day 15. “Numerically greater improvements in depressive symptoms for zuranolone versus placebo were observed by day 3 (least squares mean change from baseline HAM‐D score, −9.8 vs. −6.8), which were sustained at all visits throughout the treatment and follow‐up periods of the study,” Clayton and colleagues wrote.

Aberrant Histone Modification of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 in Major Depressive Disorder.

Activated toll-like receptor (TLR) signaling has been well investigated in major depressive disorder (MDD). We previously reported that TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 play important roles in regulating the toll-like receptor 4 (TLR4) signaling pathway and may serve as novel targets in the pathogenesis of MDD. Recently, aberrant histone modification has been implicated in several psychiatric disorders, including schizophrenia and mood disorder; the most thoroughly studied modification is histone 3 lysine 4 tri-methylation (H3K4me3). In this work, we aimed to explore H3K4me3 differences in the promotors of genes encoding the abovementioned factors in patients with MDD, and whether they were altered after antidepressant treatment. A total of 30 MDD patients and 28 healthy controls were recruited. Peripheral blood mononuclear cells (PBMCs) were collected. The levels of H3K4me3 in the promoters of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 were measured through chromatin immunoprecipitation (ChIP) followed by DNA methylation assay. Analysis of covariance was used to evaluate between-group differences after adjusting for age, sex, BMI, and smoking. In comparison with healthy controls, patients with MDD showed significantly lower H3K4me3 levels in the promoters of TNFAIP3, TLR4, TNIP2, miR-146a, and miR-155 in PBMCs. These levels were not significantly altered after completion of a 4-week antidepressant treatment. To explore the association between depression severity and H3K4me3 levels, a multiple linear regression model was generated. The results revealed that levels of H3K4me3 in the TNIP2 promoters a negative correlation with the 17-item Hamilton Depression Rating Scale (HAND-17) score, whereas that of TLR4 had a positive correlation with this score. The present results suggest that decreased H3K4me3 levels in the promoters of the genes encoding TNFAIP3, TLR4, miR-146a, miR-155, and TNIP2 are involved in psychopathology of major depressive disorder.

Association between depressive symptoms and socioeconomic status in head and neck cancer patients attending rural tertiary health care center.

To study the association between depressive symptoms and socio-economic status (SES) in patients with head and neck cancer (HNC). Histopathology-proven non-metastatic and non-recurrent HNC patients attending radiation oncology services in February and June 2021 who consented to the study were evaluated with an interview. Hamilton Depression Rating Scale (HDRS) and modified BG Prasad classification were used to assess depressive symptoms and SES, respectively. Statistical analysis was done using SYSTAT version 12 (by Crane's software, Bangalore). The study cohort comprised 100 patients. The median age was 55 years (minimum: 28, maximum: 86) with a male-to-female ratio of 2.57:1. The majority of patients were educated beyond middle-school level (44%), of middle SES (47%), oral cavity subsite (68%), stage IVA (36%) disease, and were on treatment (79%). HDRS scores showed absent, moderate, and severe depressive symptoms in 21, 63, and 16 patients, respectively, that is, the prevalence of depressive symptoms was 79%. Lower socioeconomic strata showed a significantly higher prevalence of severe depressive symptoms (P-value = 0.01). HDRS score was significantly higher in females (P-value = 0.024) and in patients who were illiterate or were educated less than middle-school level (P-value = 0.010). No statistically significant difference was found between HDRS score and age of patient, stage and site of disease, and on treatment or follow-up status. Depressive symptoms are common in patients with head and neck cancer. Low socioeconomic status (SES), female gender, and education less than middle school are associated with severe depressive symptoms. Psycho-oncological and psychotherapeutic interventions are the need of the hour.

Effect of milnacipran on brain‑derived neurotrophic factor and oxidative stress biomarkers in patients of major depressive disorder.

Emerging hypotheses in the pathophysiology of major depressive disorder (MDD) suggest important role of neurotrophic factors and oxidative stress. This study assessed the effect of milnacipran (a dual serotonin‑noradrenaline reuptake inhibitor) on brain‑derived neurotrophic factor (BDNF) and oxidative stress biomarkers i.e., malondialdehyde (MDA), glutathione‑s‑ transferase (GST) and glutathione reductase (GR) in patients of MDD. Thirty patients (aged 18 to 60 years) with MDD diagnosed by DSM‑IV criteria, with Hamilton Depression Rating scale (HAM‑D) score ≥ 14 were included in the study. Patients were given milnacipran in the doses of 50‑100 mg once daily. Patients were followed up for 12 weeks. HAM‑D score at the start of treatment was 17.8±1.7 which significantly reduced to 8.9±3.1 at 12 weeks of treatment. In responders, the plasma BDNF levels increased significantly at 12 weeks post treatment. There was no significant change in the pre‑ and post‑treatment values of oxidative stress parameters (MDA, GST and GR) after 12 week treatment. Milnacipran is effective and well tolerated in MDD patients, and its therapeutic response is associated with an increase in plasma BDNF levels. However, milnacipran did not affect oxidative stress biomarkers.

Childhood trauma and its influence on the clinical features of bipolar disorder

BackgroundChildhood trauma is an environmental risk factor for bipolar disorder (BD), But its influence on the clinical features of BD has not been examined sufficiently. ObjectiveWe compared the childhood trauma between patients with BD and healthy controls (HCs) and determined how childhood trauma impacts clinical features, such as severity, mood episodes, and disease duration. Participants and settingThe study population comprised patients with BD (in a state of euthymia or depression, n = 90) and HCs (n = 94). MethodsThe Structured Clinical Interview for DSM-IV Axis I Disorders was used to diagnose BD and ascertain its clinical features. The Childhood Trauma Questionnaire (CTQ) was used to assess childhood trauma. ResultsThe total CTQ score and scores for the CTQ subscales emotional abuse, sexual abuse, emotional neglect, and physical neglect, significantly differed between the BD and HC groups. Emotional abuse was correlated with higher Hamilton Anxiety Rating Scale (HARS) score and more frequent mood episodes; emotional neglect was correlated with higher HARS score, longer disease duration, and more mood episodes; and total CTQ score was positively correlated with HARS score, disease duration, and mood episodes. Regression analysis showed that emotional neglect significantly predicted HARS score, Hamilton Depression Rating Scale score, and disease duration in the BD group (P < 0.05). ConclusionsPatients with BD have more serious childhood trauma. General childhood trauma, emotional abuse, and emotional neglect negatively affect the clinical features of BD.

Association of plasma cytokines and antidepressant response following mild-intensity whole-body hyperthermia in major depressive disorder

Whole-body hyperthermia (WBH) shows promise for the treatment of major depressive disorder (MDD). Because MDD is associated with increased inflammation, and anti-inflammatory agents show some promise as antidepressants, the current study sought to identify the acute and longer-term immune effects of WBH in participants with MDD and to explore whether these effects associate with the procedure’s antidepressant properties. Thirty participants who met DSM-IV-TR criteria for MDD were randomized to receive a single session of WBH (n = 16) or sham treatment (n = 14). Hamilton Depression Rating Scale (HDRS) scores were assessed at baseline and 1, 2, 4, and 6 weeks post-treatment (WBH vs. sham), and plasma cytokine concentrations were assessed at baseline, immediately post-treatment, and 1 and 4 weeks post-treatment. As previously reported, WBH produced a rapid and sustained antidepressant effect. When compared to sham, WBH increased plasma interleukin (IL)-6 immediately post-treatment (time by treatment: χ2(3, N=108) = 47.33, p < 0.001), while having no effect on other cytokines acutely and no impact on IL-6, or any other cytokine, at 1 or 4 weeks post treatment. In the study sample as a whole, increased IL-6 post-treatment was associated with reduced HDRS depression scores over the 6 weeks of follow-up (F(1, 102.3) = 6.74, p = 0.01). These results suggest a hitherto unrecognized relationship between hyperthermia, the immune system, and depression, and may point to WBH as a novel modality for exploring behavioral effects of IL-6 when the cytokine is activated in isolation from the inflammatory mediators with which it frequently travels.

An Interim Analysis of a Randomized, Open-Label Study of Vilazodone, Escitalopram, or Vortioxetine for Major Depressive Disorder.

The troubling issues of conventional antidepressants are inadequate disease remission and potential adverse effects. There is a dearth of research findings comparing vilazodone, escitalopram, and vortioxetine. The objective of this analysis is to determinechanges in the Hamilton Depression Rating Scale (HDRS) and Montgomery-Åsberg Depression Rating Scale (MADRS) scoresand the incidence of adverse events at 12 weeks. This is an exploratory interim analysis of a randomized, three-arm, open-label ongoing study. The participants were randomly assigned in a 1:1:1 ratio to receive either vilazodone(20-40 mg/d), escitalopram (10-20 mg/d), or vortioxetine (5-20 mg/d). Efficacy and safety assessments were done at baseline, four weeks, eight weeks, and 12 weeks. Forty-nine(69%) of the 71 enrolled participants (mean age 43.9±12.2 years; 37 men (52%)) completed the 12-week follow-up. At baseline, the three groups' median HDRS scores were 30.0, 29.5, and 29.0 (p=0.76), respectively, and at 12 weeks, they amounted to 19.5, 19.5, and 18.0 (p=0.18), respectively. At baseline, group-wise median MADRS scores were 36, 36, and 36, respectively (p=0.79); at 12 weeks, they were 24, 24, and 23, respectively (p=0.03). In the post-hoc analysis, the inter-group comparison of the change in HDRS (p = 0.02) and MADRS (p = 0.06) scores from baseline did not reach statistical significance. No participants experienced serious adverse events. In this initial assessment of a continuing study, vortioxetine exhibited a clinically (not statistically) significant drop in HDRS and MADRS scores, compared tovilazodone and escitalopram. The antidepressant effects need to be investigated further.