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Background and Aims: There is limited research on the impact of COVID-19 pandemic on caregivers of patients with severe mental illness (SMI) during its late phase when sufficient and widespread knowledge about management and preventive aspects existed. We aimed to assess the impact of COVID-19 pandemic on caregivers of patients with SMI during Omicron wave. Methodology: We assessed 100 caregivers of patients with preexisting SMI diagnosed on the Diagnostic and Statistical Manual of Mental Disorders-5, 50 each of schizophrenia and related psychotic disorders (SCZ) and bipolar disorder (BD) from December 14, 2021, to February 9, 2022. We assessed symptoms of depression, anxiety, stress, and family burden in caregivers and their coping strategies by the Depression, Anxiety, and Stress Scale-21 Hindi version, Family Burden Interview Schedule (FBIS), and Brief-Coping Orientation to Problem Experienced, respectively. Results: Caregivers of SMI experienced symptoms of depression (51%), anxiety (72%), and stress (13%), with significantly more symptoms of depression (P = 0.002) and anxiety (P = 0.025) in caregivers of SCZ. High caregiver burden (score: 25.76, > half of the total score on FBIS) was found with no significant difference in the two groups. Caregivers of SCZ used a greater number of emotion-focused coping strategies, whereas those with BD used more problem-focused coping, but the difference was not significant. A significant association was seen between coping strategies of substance use and depressed symptoms (P = 0.003), substance use and anxiety symptoms (P = 0.007); anxiety symptoms with denial (P = 0.001) anxiety symptoms and venting (P = 0.008) in caregivers of BD. Conclusion: Caregivers of patients with preexisting SMI experienced depression, anxiety, and high family burden during Omicron wave. They used both emotion- and problem-focused coping strategies. [ABSTRACT FROM AUTHOR]

Background The clinical heterogeneity in major depressive disorder (MDD), variable treatment response, and conflicting findings limit the ability of genomics toward the discovery of evidence-based diagnosis and treatment regimen. This study attempts to curate all genetic association findings to evaluate potential variants for clinical translation. Methods We systematically reviewed all candidates and genome-wide association studies for both MDD susceptibility and antidepressant response, independently, using MEDLINE, particularly to identify replicated findings. These variants were evaluated for functional consequences using different in silico tools and further estimated their diagnostic predictability by calculating positive predictive values. Results A total of 217 significantly associated studies comprising 1200 variants across 545 genes and 128 studies including 921 variants across 412 genes were included with MDD susceptibility and antidepressant response, respectively. Although the majority of associations were confirmed by a single study, we identified 31 and 18 replicated variants (in at least 2 studies) for MDD and antidepressant response. Functional annotation of these 31 variants predicted 20% coding variants as deleterious/damaging and 80.6% variants with regulatory effect. Similarly, the response-related 18 variants revealed 25% coding variant as damaging and 88.2% with substantial regulatory potential. Finally, we could calculate the diagnostic predictability of 19 and 5 variants whose positive predictive values ranges from 0.49 to 0.66 for MDD and 0.36 to 0.66 for response. Conclusions The replicated variants presented in our data are promising for disease diagnosis and improved response outcomes. Although these quantitative assessment measures are solely directive of available observational evidence, robust homogenous validation studies are required to strengthen these variants for molecular diagnostic application. [ABSTRACT FROM AUTHOR]

Serotonin‐dopamine activity modulators (SDAMs) have been approved as an adjunctive treatment to antidepressants in patients with inadequate response. These drugs have been proposed to have a beneficial effect on cognition, sleep‐related problems, and other affective symptoms in patients with depression. Previous studies have shown inconsistent evidence and have not reported a pooled effect of the 2 drugs of this class: aripiprazole and brexpiprazole. This meta‐analysis evaluated the effect of augmentation with SDAM drugs in patients with major depression. The meta‐analysis protocol was made as per Preferred Reporting Items for Systematic Reviews and Meta‐Analysis Protocol guidelines and registered in the International Prospective Register of Ongoing Systematic Reviews. The PubMed/MEDLINE, Cochrane Clinical Trial registry, and EudraCT databases were searched with prespecified search terms. A random‐effects meta‐analysis was performed using the meta package in R software. Fifteen studies were included in this meta‐analysis. The random‐effects model analysis observed a pooled effect of 1.55 (95%CI, 1.32‐1.84; prediction interval, 0.95‐2.55, z = 5.19 [P <.0001]) for remission between the SDAM and placebo groups. A pooled effect of 1.58 (95%CI, 1.37‐1.83; prediction interval, 1.00–2.51, z = 6.34 [P <.0001]) for adverse events and 0.72 (95%CI, 0.48‐1.08; prediction interval, 0.46‐1.12; z = −1.58 [P =.113]) for serious adverse events was observed. No significant publication bias was noticed. The quality of the evidence was rated as high. Adjunct SDAM increased remission in patients and had no significant effect on serious adverse events compared to placebo. Therefore, we conclude that SDAM drugs can be an effective and safe antidepressant augmentation strategy in patients with major depressive disorder. [ABSTRACT FROM AUTHOR]

Background: Non-surgical factors have been found to have significant impact on outcome following Total Knee Arthroplasty (TKA). The study was conducted to know the independent effect of each of the four interacting psychological factors: anxiety, depression, pain catastrophizing and kinesiophobia on early outcome following TKA in an Indian population. Materials and Methods: 104 consecutive patients undergoing TKA were included in the study and followed up at 6 weeks, 6 months and one year. Preoperatively, Hospital Anxiety and Depression Scale was used to diagnose and quantify anxiety and depression, pain catastrophizing and kinesiophobia were assessed using Pain Catastrophizing Scale and Tampa Scale for Kinesiophobia, respectively. Outcome was assessed on the basis of Knee Society Score and Knee Injury and Osteoarthritis Outcome Score. Regression analysis was done to know independent effect of each factor on outcome scores. Results: Nine (8.7%) patients were found to have undiagnosed psychopathology. The patients with psychopathologies were found to have significantly worse knee outcome scores on follow-up, although the rate of improvement in knee symptoms and function was not significantly different from those without psychopathology. The degree of Anxiety correlated with worse knee pain and stiffness up to 6 months while it correlated with poor knee function for a longer duration. The degree of depression and pain catastrophizing correlated with worse knee pain, stiffness and function at all visits while kinesiophobia didn't show correlation independent other factors. Conclusion: Psychopathology was found to be associated poor knee outcome scores with degree of preoperative depression and pain catastrophizing as significant independent predictors as poor outcome, whereas the effect of degree of anxiety on knee pain and stiffness was found to wane over time. Kinesiophobia didn't show any independent correlation. [ABSTRACT FROM AUTHOR]

Despite numerous studies on major depressive disorder (MDD) susceptibility, the precise underlying molecular mechanism has not been elucidated which restricts the development of etiology-based disease-modifying drug. Major depressive disorder treatment is still symptomatic and is the leading cause of (~30%) failure of the current antidepressant therapy. Here we comprehended the probable genes and pathways commonly associated with antidepressant response and MDD. A systematic review was conducted, and candidate genes/pathways associated with antidepressant response and MDD were identified using an integrative genetics approach. Initially, single nucleotide polymorphisms (SNPs)/genes found to be significantly associated with antidepressant response were systematically reviewed and retrieved from the candidate studies and genome-wide association studies (GWAS). Also, significant variations concerning MDD susceptibility were extracted from GWAS only. We found 245 (Set A) and 800 (Set B) significantly associated genes with antidepressant response and MDD, respectively. Further, gene set enrichment analysis revealed the top five co-occurring molecular pathways (p ≤ 0.05) among the two sets of genes: Cushing syndrome, Axon guidance, cAMP signaling pathway, Insulin secretion, and Glutamatergic synapse, wherein all show a very close relation to synaptic plasticity. Integrative analyses of candidate gene and genome-wide association studies would enable us to investigate the putative targets for the development of disease etiology-based antidepressant that might be more promising than current ones. [ABSTRACT FROM AUTHOR]

Background & objectives: Genetic factors have potential of predicting response to antidepressants in patients with major depressive disorder (MDD). In this study, an attempt was made to find an association between response to escitalopram in patients with MDD, and serotonin transporter (SLC6A4) and receptor (5HTR1A, 5HTR2A) polymorphisms. Methods: Fifty five patients diagnosed as suffering from MDD, were selected for the study. The patients were treated with escitalopram over a period of 6-8 wk. Severity of depression, response to treatment and side effects were assessed using standardised instruments. Genetic variations from HTR1A (rs6295), HTR2A (rs6311 andrs6313) and SLC6A4 (44 base-pair insertion/deletion at 5-HTTLPR) were genotyped. The genetic data of the responders and non-responders were compared to assess the role of genetic variants in therapeutic outcome. Results: Thirty six (65.5%) patients responded to treatment, and 19 (34.5%) had complete remission. No association was observed for genotype and allelic frequencies of single nucleotide polymorphisms (SNPs) among remitter/non-remitter and responder/non-responder groups, and six most common side-effects, except memory loss which was significantly associated with rs6311 (P=0.03). Interpretation & conclusions: No significant association was found between the SNPs analysed and response to escitalopram in patients with MDD though a significant association was seen between the side effect of memory loss and rs6311. Studies with larger sample are required to find out genetic basis of antidepressant response in Indian patients. [ABSTRACT FROM AUTHOR]

Identifying biomarkers for diagnosing Major Depressive Disorder (MDD), assessing its severity, and guiding treatment is crucial. We conducted whole genome transcriptomic study in North Indian population, and analyzed biochemical parameters. Our longitudinal study investigated gene-expression profiles from 72 drug-free MDD patients and 50 healthy controls(HCs) at baseline and 24 patients after 12-weeks of treatment. Gene expression analyses identified differentially expressed genes(DEGs) associated with MDD susceptibility, symptom severity and treatment response, independently validated by qPCR. Hierarchical clustering revealed distinct expression patterns between MDD and HCs, also between mild and severe cases. Enrichment analyses of significant DEGs revealed inflammatory, apoptosis, and immune-related pathways in MDD susceptibility, severity, and treatment response. Simultaneously, we assessed thirty biochemical parameters in the same cohort, showed significant differences between MDD and HCs in 13 parameters with monocytes, eosinophils, creatinine, SGPT, and total protein remained independent predictors of MDD in a multivariate-regression model. Our study supports the role of altered immune/inflammatory signaling in MDD pathophysiology, offering clinically relevant biochemical parameters and insights into transcriptomic gene regulation in MDD pathogenesis and treatment response. • Transcriptomic and biochemical profiling of 72 drug-free MDD patients and 50 healthy controls. • Hierarchical clustering using significant DEGs clearly differentiate cases from healthy controls and severe from mild cases. • Inflammatory, apoptotic, and immune pathways involvement in MDD susceptibility, severity and drug response. • Differentially expressed genes shape neuroplasticity via 'TNF-α - NF-κB – IL8' interplay. • Monocytes, eosinophils, creatinine, SGPT, and total protein as independent predictors of MDD. [ABSTRACT FROM AUTHOR]

• Early detection of depression in persons with epilepsy (PWE) is highly desirable. • Using MINI, NDDI-E, HAM-D and PHQ-9 nearly 42.4 (40.1–45.4)% PWE had depression. • Polytherapy and gender were associated with risk of depression in PWE. • Mini International Neuropsychiatric Interview and HAM-D are appropriate for diagnosis and assessment of severity of depression. • Neurological Disorders Depression Inventory for Epilepsy and PHQ-9 may be used for screening in tertiary and primary care settings. Depression is an important co-morbidity in persons with epilepsy (PWE) and its timely identification is essential. The aim of the study was to assess and compare the psychometric properties of potentially suitable screening tools of depression in PWE in a tertiary care setting in India. After ethical clearance, 449 PWE above 18 years of age, on anti-seizure drugs (ASDs), attending epilepsy clinic in neurology outpatient department (OPD) of All India Institute of Medical Sciences, New Delhi, India, were recruited and evaluated for depression using different tools namely: Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), Patient Health Questionnaire (PHQ-9) and Hamilton Depression Rating Scale (HAM-D). Mini International Neuropsychiatric Interview (MINI: Module A, version 6.0.0) was used as reference standard. The association if any of depression with PWE variables was also determined. A variable percentage of PWE were positive for depression– 40.1% with MINI, 40.5% with NDDI-E, 44.3% with HAM-D and 45.4% with PHQ-9. Suicidal ideation was present in 4.5% of PWE. The sensitivity and specificity of scales using MINI as a reference standard were found to be maximal at scores ≥5, ≥8 and >11 for PHQ-9, HAM-D, and NDDI-E, respectively. The ROC analysis revealed a statistically significant difference among NDDI-E and PHQ-9 (p = 0.0268). Polytherapy in PWE had significant association with risk of depression (p < 0.01) and female PWE had 1.5 times the odds of depression as compared with males (95% CI, 1.02–2.2). All the tools used in this study were found to be appropriate for use in PWE if cut-off points are validated. The choice of tool can be based on the clinical setting. [ABSTRACT FROM AUTHOR]

• COVID-19 pandemic has significantly compromised care for persons with epilepsy (PWE). • Epilepsy is associated with multiple comorbidities like depression which require attention. • During pandemic while seizure frequency varied, reduction in prevalence of depression was seen. • Increased seizure frequency correlated with polytherapy, altered use of medicines, depression. • Depression/seizure correlated with non-adherence due to financial, access, and interest issues. COVID-19 pandemic has disrupted healthcare services for chronic disorders such as epilepsy. In this study, the impact of COVID-19 pandemic on persons with epilepsy (PWE) with regard to their seizure control, depression status, and medication adherence was assessed. After ethical clearance, 449 PWE who had been previously evaluated for depression at All India Institute of Medical Sciences (AIIMS), New Delhi, India, were telephonically revaluated using Mini International Neuropsychiatric Interview and surveyed for source of medication and medication adherence over past 6 months. The prevalence and the association of depression, suicidality, and seizures during pandemic with different PWE variables were determined. Out of 449 PWE, 70.6% responded. 19.9% were diagnosed positive for depression as per MINI while suicidal ideation was observed in 5.4%. Seventy six (23.9%) PWE reported seizures during pandemic. The incidence was greater in females, unemployed, previously uncontrolled epilepsy, polytherapy, altered use of medications, and depressed PWE. Seizure during pandemic, increased seizure frequency, previous history of depression, and altered use of medications were all significantly associated with depression during COVID-19 pandemic (2.6–95%CI, 1.45–4.73; 1.9–95%CI, 1.01–3.57; 8.8–95%CI, 4.54–17.21; 2.9–95%CI, 1.19–7.24), and polytherapy (2.9–95%CI, 0.92–9.04), seizures during pandemic (3.9–95%CI, 1.45–10.53) and previous history of depression and suicidality, were related with suicidal ideation. COVID-19 pandemic-induced disruptions can be detrimental for PWE, and restoring services to the precovid levels as well as putting appropriate continuity plans in place for care of PWE should be a priority. [ABSTRACT FROM AUTHOR]