Childhood adversities characterize the heterogeneity in the brain pattern of individuals during neurodevelopment.

BACKGROUND: Several factors shape the neurodevelopmental trajectory. A key area of focus in neurodevelopmental research is to estimate the factors that have maximal influence on the brain and can tip the balance from typical to atypical development. METHODS: Utilizing a dissimilarity maximization algorithm on the dynamic mode decomposition (DMD) of the resting state functional MRI data, we classified subjects from the cVEDA neurodevelopmental cohort (n = 987, aged 6-23 years) into homogeneously patterned DMD (representing typical development in 809 subjects) and heterogeneously patterned DMD (indicative of atypical development in 178 subjects). RESULTS: Significant DMD differences were primarily identified in the default mode network (DMN) regions across these groups (p < 0.05, Bonferroni corrected). While the groups were comparable in cognitive performance, the atypical group had more frequent exposure to adversities and faced higher abuses (p < 0.05, Bonferroni corrected). Upon evaluating brain-behavior correlations, we found that correlation patterns between adversity and DMN dynamic modes exhibited age-dependent variations for atypical subjects, hinting at differential utilization of the DMN due to chronic adversities. CONCLUSION: Adversities (particularly abuse) maximally influence the DMN during neurodevelopment and lead to the failure in the development of a coherent DMN system. While DMN's integrity is preserved in typical development, the age-dependent variability in atypically developing individuals is contrasting. The flexibility of DMN might be a compensatory mechanism to protect an individual in an abusive environment. However, such adaptability might deprive the neural system of the faculties of normal functioning and may incur long-term effects on the psyche.

Risk clustering and psychopathology from a multi-center cohort of Indian children, adolescents, and young adults.

Developmental adversities early in life are associated with later psychopathology. Clustering may be a useful approach to group multiple diverse risks together and study their relation with psychopathology. To generate risk clusters of children, adolescents, and young adults, based on adverse environmental exposure and developmental characteristics, and to examine the association of risk clusters with manifest psychopathology. Participants (n = 8300) between 6 and 23 years were recruited from seven sites in India. We administered questionnaires to elicit history of previous exposure to adverse childhood environments, family history of psychiatric disorders in first-degree relatives, and a range of antenatal and postnatal adversities. We used these variables to generate risk clusters. Mini-International Neuropsychiatric Interview-5 was administered to evaluate manifest psychopathology. Two-step cluster analysis revealed two clusters designated as high-risk cluster (HRC) and low-risk cluster (LRC), comprising 4197 (50.5%) and 4103 (49.5%) participants, respectively. HRC had higher frequencies of family history of mental illness, antenatal and neonatal risk factors, developmental delays, history of migration, and exposure to adverse childhood experiences than LRC. There were significantly higher risks of any psychiatric disorder [Relative Risk (RR) = 2.0, 95% CI 1.8-2.3], externalizing (RR = 4.8, 95% CI 3.6-6.4) and internalizing disorders (RR = 2.6, 95% CI 2.2-2.9), and suicidality (2.3, 95% CI 1.8-2.8) in HRC. Social-environmental and developmental factors could classify Indian children, adolescents and young adults into homogeneous clusters at high or low risk of psychopathology. These biopsychosocial determinants of mental health may have practice, policy and research implications for people in low- and middle-income countries.

Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA): A developmental cohort study protocol.

BACKGROUND: Low and middle-income countries like India with a large youth population experience a different environment from that of high-income countries. The Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), based in India, aims to examine environmental influences on genomic variations, neurodevelopmental trajectories and vulnerability to psychopathology, with a focus on externalizing disorders. METHODS: cVEDA is a longitudinal cohort study, with planned missingness design for yearly follow-up. Participants have been recruited from multi-site tertiary care mental health settings, local communities, schools and colleges. 10,000 individuals between 6 and 23 years of age, of all genders, representing five geographically, ethnically, and socio-culturally distinct regions in India, and exposures to variations in early life adversity (psychosocial, nutritional, toxic exposures, slum-habitats, socio-political conflicts, urban/rural living, mental illness in the family) have been assessed using age-appropriate instruments to capture socio-demographic information, temperament, environmental exposures, parenting, psychiatric morbidity, and neuropsychological functioning. Blood/saliva and urine samples have been collected for genetic, epigenetic and toxicological (heavy metals, volatile organic compounds) studies. Structural (T1, T2, DTI) and functional (resting state fMRI) MRI brain scans have been performed on approximately 15% of the individuals. All data and biological samples are maintained in a databank and biobank, respectively. DISCUSSION: The cVEDA has established the largest neurodevelopmental database in India, comparable to global datasets, with detailed environmental characterization. This should permit identification of environmental and genetic vulnerabilities to psychopathology within a developmental framework. Neuroimaging and neuropsychological data from this study are already yielding insights on brain growth and maturation patterns.

The pharmaceutical company-healthcare relationship: much ado about something.

The relationship between the pharmaceutical companies and the healthcare profession, especially doctors, has always been fraught with conflicts of interest (COI). The publication of the influential The Diagnostic and Statistical Manual for Mental Disorders, Fifth edition, Text Revision (DSM-5-TR), by the American Psychiatric Society (APA) raised concerns that the financial relationships between pharma and members responsible for DSM could result in bias. This resulted in calls for stricter enforcement of controls on financial conflict of interest (FCOI) [1, 2], which could influence the formulation of diagnostic criteria (resulting in more people being "diagnosable as mentally ill"), creating a larger pool of "patients" who "need" pharmaceutical drugs. Knowingly or unknowingly, they would end up serving the pharmaceutical companies' agenda to sell more drugs and drive up profits [2] .

Growth trajectories for executive and social cognitive abilities in an Indian population sample: Impact of demographic and psychosocial determinants.

Cognitive abilities are markers of brain development and psychopathology. Abilities, across executive, and social domains need better characterization over development, including factors that influence developmental change. This study is based on the cVEDA [Consortium on Vulnerability to Externalizing Disorders and Addictions] study, an Indian population based developmental cohort. Verbal working memory, visuo-spatial working memory, response inhibition, set-shifting, and social cognition (faux pas recognition and emotion recognition) were cross-sectionally assessed in > 8000 individuals over the ages 6-23 years. There was adequate representation across sex, urban-rural background, psychosocial risk (psychopathology, childhood adversity and wealth index, i.e. socio-economic status). Quantile regression was used to model developmental change. Age-based trajectories were generated, along with examination of the impact of determinants (sex, childhood adversity, and wealth index). Development in both executive and social cognitive abilities continued into adulthood. Maturation and stabilization occurred in increasing order of complexity, from working memory to inhibitory control to cognitive flexibility. Age related change was more pronounced for low quantiles in response inhibition (ß∼4 versus  -1 versus -0.25 for lower quantiles). Wealth index had the largest influence on developmental change across cognitive abilities. Sex differences were prominent in response inhibition, set-shifting and emotion recognition. Childhood adversity had a negative influence on cognitive development. These findings add to the limited literature on patterns and determinants of cognitive development. They have implications for understanding developmental vulnerabilities in young persons, and the need for providing conducive socio-economic environments.

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India.

Importance: Arsenic, a contaminant of groundwater and irrigated crops, is a global public health hazard. Exposure to low levels of arsenic through food extends well beyond the areas with high arsenic content in water. Objective: To identify cognitive impairments following commonly prevalent low-level arsenic exposure and characterize their underlying brain mechanisms. Design, Setting, and Participants: This multicenter population-based cohort study analyzed cross-sectional data of the Indian Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA) cohort, recruited between November 4, 2016, and May 4, 2019. Participants aged 6 to 23 years were characterized using deep phenotyping measures of behavior, neuropsychology, psychopathology, brain neuroimaging, and exposure to developmental adversities and environmental neurotoxins. All analyses were performed between June 1, 2020, and December 31, 2021. Exposure: Arsenic levels were measured in urine as an index of exposure. Main Outcomes and Measures: Executive function measured using the cVEDA neuropsychological battery, gray matter volume (GMV) from T1-weighted magnetic resonance imaging, and functional network connectivity measures from resting state functional magnetic resonance imaging. Results: A total of 1014 participants aged 6 to 23 years (589 male [58.1%]; mean [SD] age, 14.86 [4.79] years) were included from 5 geographic locations. Sparse-partial least squares analysis was used to describe a negative association of arsenic exposure with executive function (r = -0.12 [P = 5.4 × 10-4]), brain structure (r = -0.20 [P = 1.8 × 10-8]), and functional connectivity (within network, r = -0.12 [P = 7.5 × 10-4]; between network, r = -0.23 [P = 1.8 × 10-10]). Alterations in executive function were partially mediated by GMV (b = -0.004 [95% CI, -0.007 to -0.002]) and within-network functional connectivity (b = -0.004 [95% CI, -0.008 to -0.002]). Socioeconomic status and body mass index moderated the association between arsenic and GMV, such that the association was strongest in participants with lower socioeconomic status and body mass index. Conclusions and Relevance: The findings of this cross-sectional study suggest that low-level arsenic exposure was associated with alterations in executive functioning and underlying brain correlates. These results indicate potential detrimental consequences of arsenic exposure that are below the currently recommended guidelines and may extend beyond endemic risk areas. Precision medicine approaches to study global mental health vulnerabilities highlight widespread but potentially modifiable risk factors and a mechanistic understanding of the impact of low-level arsenic exposure on brain development.

Federated Analysis in COINSTAC Reveals Functional Network Connectivity and Spectral Links to Smoking and Alcohol Consumption in Nearly 2,000 Adolescent Brains.

With the growth of decentralized/federated analysis approaches in neuroimaging, the opportunities to study brain disorders using data from multiple sites has grown multi-fold. One such initiative is the Neuromark, a fully automated spatially constrained independent component analysis (ICA) that is used to link brain network abnormalities among different datasets, studies, and disorders while leveraging subject-specific networks. In this study, we implement the neuromark pipeline in COINSTAC, an open-source neuroimaging framework for collaborative/decentralized analysis. Decentralized exploratory analysis of nearly 2000 resting-state functional magnetic resonance imaging datasets collected at different sites across two cohorts and co-located in different countries was performed to study the resting brain functional network connectivity changes in adolescents who smoke and consume alcohol. Results showed hypoconnectivity across the majority of networks including sensory, default mode, and subcortical domains, more for alcohol than smoking, and decreased low frequency power. These findings suggest that global reduced synchronization is associated with both tobacco and alcohol use. This proof-of-concept work demonstrates the utility and incentives associated with large-scale decentralized collaborations spanning multiple sites.

Effective and innovative teaching methods in psychiatry for the medical undergraduates in South India: An exploratory study of teachers' and students' perspectives.

Background: Effective teaching methods are important in psychiatry. Previous studies have focused on the assessment of students about the effective teaching methods but not on a self-assessment by teachers. Aims: Primary objective is to evaluate the teachers' and students' perspectives of effective teaching methods in psychiatry for medical undergraduates. Secondary objectives include assessment of the concordance of each item and exploring innovative teaching methods. Settings and Design: A cross-sectional study design used in teachers and medical students from St. John's Medical College, Bangalore (India). Methods and Material: A modified teachers and medical students perspectives of effective psychiatry teaching methods were used. Statistical Analysis: Differences in continuous variable assessed with independent sample-test and categorical variables with Chi-square test. The Domain scores were divided into tertiles and the highest and lowest tertiles were analyzed. Results: Both students and teachers had high perspectives on most of the teaching methods. Differences were found in items such as "using multimedia slide effectively," "good sense of humor while teaching," "presentation summarizes the key points," and "presentation links ideas effectively." Role play-based and live/simulated patient-based teachings were reported most frequently by both. Significantly, a higher proportion of the 6th term students and a lesser proportion of teachers were associated with the lowest tertiles for Domain 1, 2, and 3. Significantly, increased number of 8th term students were found in the higher tertiles in Domain 3. Conclusions: These findings have practical implications in identifying the gaps in effective teaching methods by the teachers. Teachers can improve their teaching methods by upgrading their presentation skills, employing new and innovative teaching skills.

Readings from a book by Victoria Sweet: A novel medical ethics learning experience.

As part of the postgraduate ethics sensitisation programme at St. John's Medical College, the faculty and students read excerpts from the book "God's Hotel" by Dr. Victoria Sweet. The reading was followed by personal reflection by the speaker and the session concluded with a discussion among the audience. Summarised below are the passages from the book and the reflections from each speaker, with feedback from the audience. The stories explore various dimensions of the doctor-patient relationship, respecting the wishes of patients, care of the terminally ill, coping with colleagues, and dilemmas in patient management.

Ethics in psychosocial interventions.

It is important for health professionals to have an ethical framework to help take decisions regarding psychosocial interventions in patients with addictive disorders. As patients with addictive disorders are vulnerable to unethical actions in the name of treatment, therapists need to aware of their role in delivering ethical care - not just in their own clinical practice but in the setting in which they deliver the interventions. This article aims to sensitize the health professional to the various arenas in which ethical challenges may arise.

Health for all in an unequal world: Obligations of global bioethics.

The theme of the joint 14th World Congress of Bioethics and 7th National Bioethics Conference Congress "Health for all in an unequal world: Obligations of global bioethics" is of critical relevance in the present global context. Although the world is better off in terms of improved health status of people by many measures than before, there exist colossal gaps across and within populations. Much needs to be done to respond to the lack of access to healthcare, poor quality of living and working conditions, and deteriorating quality of overall environment which affects more adversely the already deprived. We take this opportunity to make a few observations about the current status of affairs on this front, and offer brief analytical insights into the complex origins of the global health scenario characterised by disparities. We revisit the original conception of bioethics and suggest that it is well placed to respond to the current global crisis of inexorably widening disparities in health and wealth, and that global bioethics has an obligation to engage with this crisis.

IJME Fifth National Bioethics Conference: a summary report.

The Fifth National Bioethics Conference (NBC) was co-hosted by St John's National Academy of Health Sciences (SJNAHS), Bangalore; Society for Community Health Research Awareness and Action (SOCHARA), Bangalore; and Forum for Medical Ethics Society (FMES), Mumbai, which publishes the Indian Journal of Medical Ethics (IJME). The conference was held at the St John's campus, Bangalore from December 11 to 13, 2014. The theme of the Fifth NBC was "Integrity in medical care, public health, and health research".

Waist circumference correlates better with body mass index than waist-to-hip ratio in Asian Indians.

BACKGROUND: Waist circumference has been reported to be a better index of android (abdominal) obesity than waist-to-hip ratio. It is likely that the cut-off values that denote medical risk in the Caucasian population cannot be extrapolated to Asian Indians. METHODS: This was a hospital-based, cross-sectional study. Anthropometric measurements were taken in 285 subjects (207 men, mean age 37 years, range 18-76 years; and 78 women, mean age 31.5 years, range 18-69 years). The subjects comprised patients under psychiatric care as well as normal individuals. The correlation of waist circumference, hip circumference and waist-to-hip ratio with body mass Index was studied. The prevalence of abdominal obesity using waist circumference was compared to the prevalence of abdominal obesity using waist-to-hip ratio. (Both the standard and the new recommended cut-offs for Asians were used.) RESULTS: Waist circumference correlated better with body mass index than waist-to-hip ratio (in men r = 0.821 and 0.341, and in women r = 0.729 and 0.113; p < or = 0.01 ). Forty-seven per cent of overweight men and 73% of overweight women had abdominal obesity as defined by the standard waist circumference cut-offs compared to none of the men and 47% of overweight women using the waist-to-hip ratio. CONCLUSION: Waist circumference correlates better with body mass index than waist-to-hip ratio. The prevalence of abdominal obesity using waist circumference is higher than that with waist-to-hip ratio. This is especially so in Asian Indians as the new recommendations of both body mass index and waist circumference cut-offs to detect subjects at medical risk are lower in them than in Caucasians.

All about elephants in rooms and dogs that do not bark in the night: boundary violations and the health professional in India.

Sexual and non-sexual boundary violations occur in the health professional-patient relationship all over the world as well as in India. However, the issue is rarely, if ever, discussed here in a frank and rational manner. This paper discusses the challenges faced by all health professionals and particularly mental health professionals in handling this problem in India. Health professionals can now either let things remain as they are or try to change things for the better, despite the inherent risks in attempting the latter. Since knowledge about boundary issues is essential for effective healthcare, prevention of boundary violations by oneself and reducing harm to patients should a violation occur by another professional, it is important that all health professionals are aware of the issues involved.

Is there an elephant in the room? Boundary violations in the doctor-patient relationship in India.

An anonymous postal survey on the awareness of the occurrence of nonsexual and sexual boundary violations (NSBV and SBV) in the doctor-patient relationship in India was conducted with psychiatrists and psychologists working in the state of Karnataka in India (n=51). Though this was not designed to be a prevalence study on violations, the results suggest that both NSBV and SBVdo occur and, more importantly, respondents felt that this is an area which needs urgent attention in India. There was disagreement on whether some behaviours in certain situations could be construed as NSBV in the Indian culture. Though several respondents agreed that there was a need to develop guidelines on this issue in India, there was a perception that the problem was not in the availability of guidelines but in their implementation. The ethical implications of the study are discussed.

Psychiatric presentations of vitamin B 12 deficiency.

Vitamin B12 deficiency has been implicated in various psychiatric conditions for a long time. The association could be primary, secondary to the psychiatric disorder, or even just coincidental. However, left untreated, the deficiency can delay or preclude recovery. Hence early recognition is important, especially when the traditional manifestations of B12 deficiency like anaemia, macrocytosis or spinal cord symptoms are not prominent. Three cases are presented here where vitamin B12 deficiency and psychiatric symptomatology were coexistent, and the patients recovered only on a combination of B12 supplementation and psychiatric medication.