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.

Polysubstance use in South Asia.

PURPOSE OF REVIEW: Polysubstance use is very common in the world, but there has been limited research in this area. South Asia is sandwiched between two of the world's largest heroin producing areas: the Golden Crescent and the Golden Triangle. The burden and prevalence of polysubstance use have not been estimated in this region of the world. We review the research findings on polysubstance use in different South Asian countries. The review also comments on the gaps in knowledge regarding polysubstance use in this region of the world. RECENT FINDINGS: The available literature on polysubstance use from South Asia suggests its widespread presence in the region, ranging from 20 to 90%, more commonly among illicit opioid drug users and injection drug users. Most of the available data is from epidemiological studies. There are few studies on the adverse effects of polysubstance use, but the limited data clearly suggests an elevated risk of comorbid psychopathology and health problems. SUMMARY: Polysubstance use still lacks a consensus definition. There is a need of more research on its prevalence, effects on health, and prevention and treatment.

Pattern of Psychiatric Emergencies in Children and Adolescents at a Tertiary Care Centre After Onset of COVID-19 Pandemic.

OBJECTIVES: To assess changes in profile of psychiatric emergencies in children and adolescents (aged <19 year) during the coronavirus disease 2019 (COVID-19) pandemic compared to pre-pandemic period. METHODS: The psychiatric emergency records were analyzed for the period of April, 2019 - September, 2021 to assess the pattern and profile of mental health emergencies in children and adolescents in the period before and after the onset of the pandemic lockdown (i.e., 23 March, 2020). RESULTS: 379 consecutive child and adolescent psychiatric emergencies were identified, of which 219 were seen after the onset of pandemic. Commonest reason for referral in the pandemic group was attempted self-harm (44.3%). The ICD-10 neurotic, stress-related and somatoform disorders constituted the commonest diagnostic category, similar to pre-pandemic period. A significantly higher proportion (44% vs 28%) of children was prescribed benzodiazepines in the pandemic period, compared to the pre-pandemic period. CONCLUSION: The average monthly psychiatric emergencies in children and adolescents showed no increase during the pandemic period. Self-harm was the commonest cause of psychiatric referral in emergency services mental health crisis in the younger population.

Negative Emotions, Triggers, and Coping Strategies Among Postpartum Indian Women During Second Wave of COVID-19 Pandemic: Lessons for the Subsequent Waves and Beyond.

Introduction: The study aimed to evaluate COVID-19 associated psychological distress among pregnant and postpartum women during the second wave of COVID-19 in India. Methods: A cross-sectional survey was done using a pre-validated tool involving 491 participants attending a tertiary-care hospital during the second wave of COVID-19 in India. Results: Three-fourths of participants experienced negative emotions such as fear and various features of depression. Participants (75%) reported COVID-related news on TV/Radio/Newspapers including social media as the major trigger for these negative emotions. Loss of social support mainly affected postpartum women (p < 0.001) and working women (p < 0.001). Inability to access healthcare services had negative associations with age (p < 0.001), education (p < 0.001), and socioeconomic class (p < 0.001). Various coping strategies being followed by participants included watching TV/Videos or reading books (93%), resorting to social media (77%), spending more time praying and meditating (86%), and engaging in hobbies (56%). Conclusion: During the second wave, the COVID-19 pandemic had a significantly high negative impact on the psychological and social well-being of pregnant and postpartum women. Hence, it is important to initiate appropriate preventive and corrective steps by the policymakers for any future waves of the pandemic.

Reasons for leaving treatment among patients with opioid dependence: A 3-month prospective follow-up study.

OBJECTIVE: This study aimed to ascertain the reasons why patients with opioid dependence leave treatment. DESIGN: Prospective follow-up observational study. SETTING: This study was carried out at a tertiary care substance use treatment facility in north India with both outpatient and inpatient services. The facility is a public-funded institution. PARTICIPANTS: One hundred and twenty opioid-dependent male patients with age 18 years or more who were willing to provide a valid telephone number for followup and willing to consent for the study were included. MAIN OUTCOME MEASURE(S): Enquiries were made using the Reasons to Leave Treatment Questionnaire (RLTQ) and an open-ended question about why the patient left treatment. RESULTS: As per the RLTQ, the most common reasons for patients with opioid dependence leaving treatment were in the domains of external influence, motivational inconsistencies, and problem severity. Logistic problem was another issue that was highlighted by the patients. On open-ended question, the most common reason for leaving treatment pertained to feeling that one has improved and does not need treatment. Baseline characteristics that predicted patients leaving treatment were not being prescribed buprenorphine at discharge, not being formally educated, and living alone or in a nuclear family. CONCLUSION: Several factors may lead to patients with opioid dependence leaving treatment prematurely after receiving inpatient care. Addressing these reasons might help to better retain patients in treatment and improve their outcomes.

Understanding needs of stakeholders and outcomes desired from a home-based intervention program for "difficult to treat" schizophrenia and related disorders: A qualitative study.

Background: We aimed to understand the needs of service users - families and patients with schizophrenia and related disorders, and mental health professionals (MHPs) and expectations from a home-based psychosocial intervention program in Indian setting. Materials and Methods: We conducted four focus group discussions (FGDs) with families, patients with schizophrenia and related disorders and MHPs. Two FGDs were conducted with families and one each with the patients and MHPs. Participants in families and MHP group were asked about their primary concerns in caring for the patients, perceived needs of patients and the areas that can be targeted through a home-based psychosocial intervention program. All FGDs were audio-recorded and verbatim transcribed. Content analysis of the data was done to obtain a final list of needs and expected outcomes from a psychosocial intervention supported by families. Results: Six key priority needs were identified for intervention: medication adherence, activities of daily living, promoting physical health, engagement in meaningful work, building of social and support networks and information about all aspects of illness. Priority outcomes identified by MHPs were mostly clinical like symptom reduction, fewer rehospitalisation while families and patients focused more on psychosocial outcomes, such as improvement of wellbeing, having relationships, engagement in meaningful activities, better organization of the day, increased self-respect, reduced stress, lesser interference, and critical comments. All groups suggested that book or mobile app or video could be used. Conclusion: This qualitative study shows that while both clinicians and service users consider recovery from schizophrenia and related disorders to be important, they differ on what they prioritise.

The Telepsychiatry Operational Guidelines 2020 in India: a welcome step.

The release of the Telepsychiatry Operational Guidelines 2020 in India, during the COVID-19 pandemic, is a relief for both clinicians and patients. These guidelines embark on initiating and executing naive and recently started telepsychiatry services in India. The document is aligned with other ethical regulations, policies, laws and the 2020 Telemedicine Practice Guidelines in India. This paper discusses a few points about the broader applicability of the guideline for the benefit of humankind in the prevailing healthcare crisis. The guidelines may be extrapolated in policy-making for telepsychiatry services in other low- and middle-income countries sharing a similar socioeconomic, cultural and political milieu.

Audit of requests for disability certification of adults received at a tertiary care general hospital psychiatry unit.

BACKGROUND: Persons with disability (PwD) are entitled to certain benefits from the State on grounds of being disabled. With the recent enactment of the Rights of PwD Act, 2016, and increased efforts to provide assistance to persons with certifiable disabilities, data pertaining to disability requests can be useful to understand the way in which services are utilized. MATERIALS AND METHODS: This study is an audit of the disability certificates issued to all subjects with age ≥18 years between 2016 and 2019 at a tertiary care general hospital psychiatry unit, and discusses the pattern and profile of the certificates. RESULTS: A total of 356 patients were issued disability certificates (2016-2019). The mean age of the subjects was 32.8 (±11.2) years and about 30% of them were females. Intellectual disability (58.3%) was the most common diagnosis, followed by schizophrenia and related disorders (31%), while all other disorders constituted a smaller proportion (11%) of the sample. About 60% of the subjects had moderate disability, 37.4% had severe disability, and 1.7% had profound disability. CONCLUSION: A large majority of the certificates were issued to subjects with intellectual disability. Patients with severe mental illnesses are probably not accessing the disability benefits optimally. This audit also points to under-representation of women as well as an overall underutilization of services by individuals with mental disability.

Hospital Based Psychosocial Support Program for Children with ALL and their Families: A Comprehensive Triad's Perspective.

OBJECTIVES: To elucidate potential target areas of intervention and mechanisms for implementation of intervention for children with cancer during the treatment phase. METHODS: Focused group discussion (FGDs) served as a primary source of providing phenomenal perspectives to explore the key objective. Eight focus groups of 45-60 min each were held with 5-9 members in each discussion. The participants were either patients, their caregivers or health care providers. The focus group audio recordings were professionally transcribed after all identifiers were removed. Employing a constructivist paradigm with a phenomenological approach, also known as emergent-systematic focus group design the study reported on families' experiences of childhood cancer as construction of objective reality. Investigator triangulation method was adopted to ensure trustworthiness. RESULTS: Using constant comparison analysis, multistage process analysis was done which resulted in 849 codes, 32 subthemes, 20 themes and 5 domains. A total of 64 participants participated: 4 FGDs with parents of children with ALL (n = 31); 1 FGD with professionals working in the field of cancer (n = 10) and 3 FGDs with children with ALL (n = 23). Participant's mean age at the time of study was 10 y (+3.3) for children; 37 y (+4.93) for caregivers and 35 y (+3.5) for professionals. The number of participants and their age range at study varied slightly between the eight focus groups. CONCLUSIONS: Caregivers presented care burden and compromised aspects of Quality of life (QOL). An effective and culturally sensitive psychosocial support for patients and their families during and post treatment, in addition to medical therapy, is strongly recommended.