Genome-wide transcriptomic and biochemical profiling of major depressive disorder: Unravelling association with susceptibility, severity, and antidepressant response.

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.

Genetic Landscape of Major Depressive Disorder: Assessment of Potential Diagnostic and Antidepressant Response Markers.

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.

Assessment of psychological distress pattern & its correlates among people receiving COVID-19 vaccination during the COVID-19 pandemic: A cross-sectional study.

Background & objectives: There is a possibility that vaccinated people may experience lesser psychological distress due to the sense of safety felt by them against getting the COVID-19 infection as compared to those who are not vaccinated. However, there is a paucity of research examining the mental health status of this important sub-group of population. Thus, the present study was aimed to examine the pattern of psychological distress and its correlates among people receiving COVID-19 vaccine. Methods: This cross-sectional study assessed individuals receiving COVID-19 vaccine at a tertiary care hospital. Psychological distress and COVID-19-related anxiety were assessed using the Depression Anxiety Stress Scale (DASS-21) and the COVID-19 Anxiety Scale-7, respectively. Results: The study comprised 728 individuals with a mean age of 44.8 yr. Moderate levels of depression, anxiety and stress were reported by about 50, six and 15 per cent of the participants, respectively, as assessed on DASS-21. Generalized linear model and quantile regression analyses revealed COVID-19-related anxiety, and being a healthcare worker or front-line worker as significant correlates of psychological distress. Interpretation & conclusions: About half of the study participants receiving COVID-19 vaccine reported moderate to severe symptoms of depression. Strategies focusing on alleviation of COVID-19-related fear and anxiety might be effective in improving the symptoms of psychological distress.

Learning from telepsychiatry during COVID-19 pandemic in India: Boon for public mental health in low- & middle-income countries.

Novel coronavirus disease (COVID-19) pandemic has affected the mental well-being of the population and posed many challenges in availing mental healthcare. Telepsychiatry has been proven to be an effective route for the delivery of mental healthcare. We share our experience of using the telemedicine approach in providing mental health services at a tertiarycare hospital in India during the COVID-19 pandemic, following the break in routine outpatient services during the national lockdown. The telepsychiatry approach helped in ensuring the maintenance of mental healthcare. The utility of telepsychiatry as an option for such future situations and for its use in routine follow up care in indicated cases, have also been discussed.

Chronic Noncancer Pain and Opioid Addiction: Diagnostic and Management Challenges.

Chronic pain is associated with higher rates of psychiatric comorbidity, including substance use disorders. Patients with chronic pain often require opioids for their pain relief. Often, clinicians are reluctant to prescribe opioids to patients with chronic pain due to fear of patients becoming dependent on opioids. Diagnosing opioid addiction in chronic pain with comorbid prescription opioid use is challenging, as some of the symptoms of addiction overlap with those of physical dependence. A 28-year-old female presented with a history of recurrent abdominal pain beginning at the age of 16 years. The patient was diagnosed with chronic pancreatitis and was prescribed tramadol orally or injections for pain. The patient started experiencing craving with repeated administration of tramadol. She started using it daily and increased her dose to about 6-7 ampoules per day. She also developed complications due to injections. She was not able to work due to her pain, as well as injection use. She would go to multiple chemist shops for getting herself injected with tramadol injections. She also developed depressive symptoms in this period. Due to abdominal pain, the patient was admitted in the gastroenterology ward, from where she was shifted to the psychiatry ward for the management of opioid misuse and depressive symptoms. The patient was diagnosed to be suffering from opioid dependence syndrome with depressive episodes, for which she was provided tablet buprenorphine 14 mg/day dose along with tablet sertraline 150 mg/day. The case demonstrates several challenges in the diagnosis and management of opioid dependence and chronic pain when they occur simultaneously.

Systems Approach to Identify Common Genes and Pathways Associated with Response to Selective Serotonin Reuptake Inhibitors and Major Depression Risk.

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.

The Effect of Low-Frequency Repetitive Transcranial Magnetic Stimulation at Orbitofrontal Cortex in the Treatment of Patients With Medication-Refractory Obsessive-Compulsive Disorder: A Retrospective Open Study.

OBJECTIVE: Obsessive-compulsive disorder (OCD) is a chronic debilitating psychiatric disorder, with significant proportion of patients failing to respond with current first-line treatments. The present study assesses the safety and effectiveness of low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) over left-orbitofrontal cortex (Lt-OFC) as a potential augmentation strategy in treatment of patients with medication-refractory OCD in real-world clinical setting. The present report also aims to examine the factors affecting response to rTMS and the durability of effects produced by rTMS over 1 month of follow-up period. METHODS: Retrospective review and analysis of clinical case files of 25 patients with medication-refractory OCD, all of whom had received 20 sessions of LF-rTMS over Lt-OFC as part of routine clinical care. A reduction of 25% and 35% in Yale-Brown Obsessive Compulsive Scale scores was used to determine the proportion of partial and complete responders, respectively. RESULTS: There was a significant decrease in mean Yale-Brown Obsessive Compulsive Scale score at the end of 20 sessions of rTMS compared with baseline (7.04 ± 5.07; P < 0.001), with no further significant change during the subsequent 1-month follow-up period (0.20 ± 1.38; P = 0.47). Thirteen patients (52%) met criteria for partial response, of which 11 patients (44%) showed complete response. Furthermore, higher number of failed medication trials was found to be significantly associated with greater chances of nonresponse to rTMS treatment. CONCLUSIONS: There is a role of applying LF-rTMS over Lt-OFC as an augmentation strategy in ameliorating clinical symptoms among patients with medication-refractory OCD.

Pattern and Type of Aggressive Behavior in Patients with Severe Mental Illness as Perceived by the Caregivers and the Coping Strategies Used by Them in a Tertiary Care Hospital.

Aggressive behavior by patients with severe mental illness is a major problem needing intervention. This descriptive cross sectional study examined the perception and coping strategies of caregivers with a sample of 100 toward aggressive behavior by patients with severe mental illness in the outpatient and inpatient unit of the department of psychiatry in a tertiary care hospital. The data were collected by a semistructured interview using Revised Overt Aggression Scale-modified, Aggressive Behavior and Intervention Checklist, Ways of Coping Checklist-Hindi Adaptation and Impact of Patient Aggression on Carers Scale-Adapted. The caregivers perceived aggression in varying extent from the patients. Majority used problem-focused coping to deal with aggressive behavior. Most of the caregivers perceived insisting to take medicines and talking about patient's illness as the triggers for aggressive behavior which was managed by talking to the patient calmly, lovingly and by leaving the patient alone. The findings strongly suggest aggressive behavior as a frequent problem faced by family members of patient with severe mental illness. Nursing interventions should focus on counseling and psycho education for empowering caregivers to utilize strategies to reduce occurrence of aggressive behavior from patient and ways to effectively cope with the situation.

Challenges for setting up psychiatric services in a trauma centre in India.

Psychiatric sequelae may occur following traumatic injury irrespective of whether an insult has been caused to the brain. A range of psychiatric illnesses have been either causative of or associated with road traffic accidents and traumatic injuries, including depression, anxiety, post-traumatic stress disorder, substance use disorder and attention-deficit hyperactivity disorder. Despite literature on such associations, psychiatric intervention in the treatment of patients following traumatic injury is limited. The authors share their experience of challenges in addressing mental health problems in a tertiary care trauma centre located in North India. Steps in overcoming those challenges included: developing a semi-structured form to be completed for referrals and consultations, a psychiatrist attending weekly rounds with the surgeons, and initiating a psychiatry out-patient clinic for patients discharged from the trauma centre. It may be worthwhile in the future to set up a trauma psychiatry unit at the centre, involving a clinical psychologist, a psychiatric social worker and an occupational therapist for the comprehensive care of patients.

Pattern of adult psychiatric emergencies at a tertiary care center before and after the onset of the COVID-19 pandemic.

A gap exists in published data on psychiatric emergencies presenting to Indian centers over the entire pandemic. We assessed 2,048 consecutive adult psychiatric emergencies for the period April 2019-September 2021 to compare 18 months following the onset of the pandemic, with the pre pandemic year as the control. Mean age was 33.8 ± 13.6 years, with 55% females. The proportion with ICD-10 schizophrenia and related psychotic disorders (18.9% vs 15.3%; P = 0.031), mood disorders (21.8% vs 18.1%; P = 0.038), and personality disorders (3.8% vs 2%; P = 0.018) showed a significant increase during a pandemic, while those with no diagnosable illness reduced (28.6% vs 34.3%; P = 0.006). Suicidality was the reason for referral in 43%, comparable to pre pandemic year. Those with stay ≥24 hours increased (14% vs 11%; P = 0.034). Benzodiazepines remained the commonly prescribed medication, but a notable rise was seen in mood stabilizer prescriptions.

An analysis of financial hardship faced by patients with First Episode Psychosis, and their families, in an Indian setting.

BACKGROUND: The economic burden of psychotic disorders is not well documented in LMICs like India, due to several bottlenecks present in Indian healthcare system like lack of adequate resources, low budget for mental health services and inequity in accessibility of treatment. Hence, a large proportion of health expenditure is paid out of pocket by the households. OBJECTIVE: To evaluate the direct and indirect costs incurred by patients with First Episode Psychosis and their families in a North Indian setting. METHOD: Direct and Indirect costs were estimated for 87 patients diagnosed at AIIMS, New Delhi with first-episode psychosis (nonaffective) in the first- and sixth month following diagnosis, and the six months before diagnosis, using a bespoke questionnaire. Indirect costs were valued using the Human Capital Approach. RESULTS: Mean total costs in month one were INR 7991 ($107.5). Indirect costs were 78.3% of this total. Productivity losses was a major component of the indirect cost. Transportation was a key component of direct costs. Costs fell substantially at six months (INR 2732, Indirect Costs 61%). Respondents incurred substantial costs pre-diagnosis, related to formal and informal care seeking and loss of income. CONCLUSION: Families suffered substantial productivity loss. Care models and financial protection that address this could substantially reduce the financial burden of mental illness. Measures to address disruption to work and education during FEP are likely to have significant long-term benefits. Families also suffered prolonged income loss pre-diagnosis, highlighting the benefits of early and effective diagnosis.

Changes in Psychosocial Variables Among Caregivers of Patients With Schizophrenia: A Short-Term Follow-Up Study.

BACKGROUND AND AIMS: Caring for a person with schizophrenia entails considerable effort. The caregiving experience while caring for a person with schizophrenia has been described as both stressful and enriching. The literature on changes in caregiving experience with time has been fairly limited. The present analysis looks at the change in the caregiving experience of caregivers of patients with schizophrenia. METHOD: This study had a sample of 50 caregivers of patients with schizophrenia who were followed up after a period of 6 to 10 months. Caregiving experience, knowledge of the mental illness, family functioning, coping, social support, psychological distress, quality of life, and spiritual, religious, and personal beliefs were assessed at the two time points. RESULTS: Among the negative caregiving experiences, caregivers' need for back-up and patient dependency reduced significantly at follow-up as compared to baseline, though total negative or positive experiences of caregiving did not show a significant difference. Knowledge about mental illness did not significantly increase at follow-up, though issues related to poor communication and affective involvement in family functioning reduced over the period of time. Coping and social support remained largely the same, while psychological distress was reduced. All domains of quality of life improved over the follow-up period, while the hope, optimism, and inner peace aspects of spiritual, religious, and personal beliefs improved with time. CONCLUSION: Some aspects of caregiving experiences may change with time. As caregivers become more adjusted to caregiving roles, their distress may reduce, and their quality of life may improve.

Psychosocial Correlates of the Experience of Caregiving Among Caregivers of Patients With Schizophrenia.

BACKGROUND: Family caregivers provide essential support to their loved ones with schizophrenia with profound outcomes for themselves. The caregiver burden fails to consider the entire caregiving experience, which also incorporates positive aspects of caring. Many potentially significant variables are associated with this. AIM: To examine the correlates of the experience of caregiving in caregivers of patients with schizophrenia. The specific objectives were to examine the socio-demographic variables of the patients and caregivers, clinical variables of the patient, caregivers' knowledge of illness, caregivers' perspectives of family functioning, caregiver coping, their social support, psychological distress, quality of life, and their spirituality, religiosity and personal beliefs and the associations of these variables with the caregivers' experience of caregiving. METHODS: This cross-sectional observational study was conducted between August 2018 and January 2021 at All India Institute of Medical Sciences, New Delhi, India. One hundred and fifty-eight dyads of patients with schizophrenia and their family caregivers were recruited using purposive sampling. Experience of Caregiving Inventory was used to evaluate the caregiving experience. The caregivers were also assessed on socio-demographics, knowledge of illness, family functioning, coping, social support, general mental health, quality of life, and spiritual, religious, and personal beliefs. Patient socio-demographics and clinical variables were also assessed. RESULTS: A negative experience of caregiving was reported by caregivers of patients who had higher positive or negative symptoms of schizophrenia. Impaired Communication, Roles, Affective Responsiveness, Affective Involvement, and General Functioning aspects of family functioning were associated with a negative experience of caregiving. Denial/blame and seeking social support as coping were also associated with a negative experience of caregiving. A negative experience of caregiving was significantly positively correlated with greater psychological distress and poorer quality of life. Greater inner peace was associated with a less negative experience of caregiving. Spiritual strength was associated with a more positive experience of caregiving. Knowledge of mental illness and caregiver social support were not significantly associated with the experience of caregiving. CONCLUSION: Experience of caregiving is a relevant construct, the understanding of which can help inform caregiver-directed interventions in the future. Specifically, family-based interventions, which include ameliorating patient symptomatology, improving the family environment, strengthening caregivers' coping strategies, attending to caregiver distress, and encouraging spirituality among caregivers, may lead to a less negative and more positive experience of caregiving; and a better quality of life for caregivers.

Qualitative study to explore the perspectives and mental health experiences of first episode psychosis patients and their caregivers in North India.

BACKGROUND: The onset of psychosis brings unfamiliar experiences that can be disturbing for patients and their caregivers. Few studies from India (only one from North India) have examined these experiences from the perspective of the patient and caregiver. We explored experiences of first episode psychosis (FEP) patients and their caregivers within a North Indian context. METHOD: Semi-structured interviews were conducted in 2019 with ten FEP patients and their caregivers (total n=20) receiving out-patient care in a tertiary care centre. Topic guides focused on concerns/complaints, symptoms, help-seeking, and barriers and facilitators to treatment. Interviews were audio recorded, transcribed, and analysed using qualitative content analysis. RESULTS: Main categories of responses from patients and caregivers included: initial complaints for seeking help, initial emotional response, barriers to seeking treatment, perceived dysfunction and improvement, experienced stigma, understanding about illness, early follow-up, preventive measures and awareness programs. Caregivers undergo myriad of emotional reactions including anger, anxiety, guilt, and confusion. Symptoms other than psychotic symptoms were the primary complaint upon seeking help, and there was lack of understanding about the psychosocial model of care (role of medications acknowledged with little awareness regarding psychosocial interventions in recovery). Persisting occupational dysfunction despite perceived symptomatic improvement was described by both patients and caregivers. CONCLUSION: North Indian patients with FEP lack awareness of symptoms. Therefore, onus for seeking help often falls on their caregivers. Psychoeducation from first contact with services and increasing awareness about psychotic illness within the community might help address lack of awareness about symptoms, mental health services, early signs of relapse, and importance of psychosocial interventions in achieving functional recovery.

Pilot study to test the feasibility and clinical efficacy of a psychosocial care programme for patients with psychosis in low-resource settings.

BACKGROUND: Home-based psychosocial care has the potential to improving outcomes in patients with schizophrenia and related disorders (SCZ). There is lack of India data for such care in early psychosis. We developed the "Saksham" programme, a bespoke self-managed home-based psychosocial care model, available in two formats: manual-based and mobile-application based. With the anticipated success of recruitment of early psychosis cases in our setting, we plan to test the such intervention in this population in future trials. AIM: To assess the feasibility of the Saksham programme intervention in people with SCZ and its clinical efficacy as an adjunct to treatment as usual. METHODS: Seventy-five patient-caregiver pairs (total n=150) were recruited. Patients received either: treatment-as-usual (TAU) (n=25), manual-based Saksham intervention+TAU (n=25), or app-based Saksham intervention+TAU (n=25). Feasibility (i.e. acceptability, practicality, demand, implementation and integration) was assessed at three-months. Participants were assessed for psychopathology, illness-severity, cognition, functioning, disability, and caregiver-coping at baseline, one-month, and three-month. The percentage changes over time were compared across three groups. RESULTS: More found the mobile application-based intervention acceptable and easy-to-use than the manual-based intervention (92 % vs 68 %, and 76 % vs 68 %, respectively). Psychopathology and caregiver-burden improved significantly in all three groups (p<0.05). Cognition, disability, functioning, and caregiver burden improved significantly in the two Saksham intervention groups, with greater improvement in the Saksham app group (p<0.05). CONCLUSION: Home-based intervention is feasible and acceptable in a low-resource setting, with preliminary evidence for effectiveness. These findings need corroboration with randomised controlled trials in early psychosis to ameliorate course of illness.

Development and validation of home-based psychosocial self-management interventions in schizophrenia and related disorders in low-resource settings: A mixed methods approach.

Background: Psychosocial interventions, crucial for recovery in patients with schizophrenia, have often been developed and tested in high income countries. We aimed at developing and validating home-based a booklet based psycho-social intervention with inputs from stakeholders: patients, families, and mental health professionals (MHP) for patients with schizophrenia and related disorders in low resource settings. Methods: We developed a preliminary version of psychosocial intervention booklets based on six themes derived from focus group discussions conducted with patients, families, and MHP. Initially, quantitative assessment of content validity was done by MHP on overall and Content Validity Index of individual items of the specific booklets, followed by in-depth interviews about their views. The booklets were modified based on their inputs. Further, pilot testing of manuals was done on the users - nine pairs of patients and caregivers followed by development of a final version of psycho-social intervention. Results: The percentage content validity of individual modules and overall booklets was ≥78.5% indicating good validity. Most MHP reported that the manuals were relevant and easy to use but were text-heavy, and lengthy. On pilot testing of modified manuals with patients and their family caregivers, majority (77.8%) of them found booklets useful and suggested that there should be separate booklets for both patients and caregivers for providing information and entering separate response for the activities, integrating helpful tips. Language should be simple. Finally, two sets of booklets ("info book" and "workbook") named 'Saksham' (meaning empowered) were created with specific modules (viz., 'Medicine adherence', 'Daily routine', 'Eating right', 'Physical activity', 'Physical health monitoring', 'Self-reliance', and 'Psychoeducation') for patients and caregivers each, in two languages (Hindi and English). Conclusion: Booklets with modules for psychosocial interventions for patients with schizophrenia and their caregivers were developed after establishing content validity and pilot testing.