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.

Pharmacogenomics-assisted treatment versus standard of care in schizophrenia: a systematic review and meta-analysis.

BACKGROUND: Pharmacogenomic (PGx) factors significantly influence how patients respond to antipsychotic medications This systematic review was performed to synthesize the clinical utility of PGx-assisted treatment versus standard of care in schizophrenia. METHODS: PubMed, Embase, and Cochrane CENTRAL databases were searched for randomized controlled trials (RCTs) from inception till June 2024 that had compared the clinical utility of PGx-assisted intervention as compared to the standard of care in schizophrenia. The primary outcome was safety, and the secondary outcomes were efficacy and medication adherence. Pooled standardized mean differences (SMD) along with a 95% confidence interval (CI) were calculated (random-effects model) wherever feasible. RESULTS: A total of 18,821 studies were screened, and five were included for review. All the RCTs had a high risk of bias. Four studies included the commonly used antipsychotics. Three studies reported negative outcomes (safety, efficacy, and medication adherence) and two reported positive outcomes (safety) using different scales. In the meta-analysis, there were significant differences in the total Udvalg for Kliniske Undersogelser Side-Effect Rating scale score [SMD 0.95 (95% CI: 0.76-1.13), p < 0.001); I2 = 0%] and the total Positive and Negative Syndrome Scale score [SMD 10.65 (95% CI: 2.37-18.93), p = 0.01); I2 = 100%] between the PGx-assisted treatment and standard of care arms. However, the results were inconsistent, and the certainty of evidence (GRADE criteria) was very low. CONCLUSION: Current evidence on the clinical utility of PGx-assisted treatment in schizophrenia is limited and inconsistent and further evidence is required in this regard.

High prevalence of alcohol use disorder & psychiatric comorbidity among coal mine workers: Observations from a cross-sectional study in West Bengal.

Background & objectives Tobacco (30%), alcohol (21.4%) and cannabis (3%) are the three most commonly abused substances in India. Tobacco and alcohol abuse have higher prevalence rates among different occupational groups as compared to that in general population in the country. Both tobacco and alcohol lead to significant occupational harm in terms of absenteeism, injuries, sickness and lost productivity. This study estimated the patterns of substance use and associated common psychiatric comorbidity in a sample of coal mine workers. Methods Coal mine workers at the age of 18 yr or above engaged in mining activities (skilled/semi-skilled/unskilled) were recruited from the Raniganj - Asansol coal mining areas of Eastern Coalfields Limited (ECL). Participants were screened to identify patterns of substance use and other common mental health problems. All participants were administered ASSIST (The Alcohol, Smoking and Substance Involvement Screening Test); GENACIS (Gender, Alcohol and Culture: An International Study) modified questionnaire; and Hospital Anxiety and Depression Scale (HADS) for primary screening for anxiety and depression. Results Out of 202 participants 69 per cent (n=140) were found with either 'hazardous and harmful' (moderate risk); or 'dependent' (high risk) patterns of use of either tobacco or alcohol or cannabis or of more than one substance. Only 31 per cent (n=62) were 'low-risk' for all substances. Almost 65 per cent (n=132) and 49 per cent (n=99) participants out of the whole sample (n=202) belonged to 'hazardous and harmful' (moderate risk) and 'dependent' (high risk) pattern of tobacco and alcohol consumption, respectively. About 28.8 per cent (n=38) and 23.7 per cent (n=31) of all participants had anxiety and depression, respectively. Combined moderate to high use of both alcohol and tobacco use was significantly associated with the risk of having anxiety [adjusted odds ratio (AOR)=4.896, P<0.015] and depression (AOR=5.335, P<0.012). Interpretation & conclusions Alcohol and tobacco are major substance abuse problems among coal mine workers. This population requires early community and primary care based brief intervention as well as additional community-based pharmacotherapy for substance dependence problems as well as intervention for common mental health issues.

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.

Genotoxic Agents Produce Stressor-Specific Spectra of Spectinomycin Resistance Mutations Based on Mechanism of Action and Selection in Bacillus subtilis.

Mutagenesis is integral for bacterial evolution and the development of antibiotic resistance. Environmental toxins and stressors are known to elevate the rate of mutagenesis through direct DNA toxicity, known as stress-associated mutagenesis, or via a more general stress-induced process that relies on intrinsic bacterial pathways. Here, we characterize the spectra of mutations induced by an array of different stressors using high-throughput sequencing to profile thousands of spectinomycin-resistant colonies of Bacillus subtilis. We found 69 unique mutations in the rpsE and rpsB genes, and that each stressor leads to a unique and specific spectrum of antibiotic-resistance mutations. While some mutations clearly reflected the DNA damage mechanism of the stress, others were likely the result of a more general stress-induced mechanism. To determine the relative fitness of these mutants under a range of antibiotic selection pressures, we used multistrain competitive fitness experiments and found an additional landscape of fitness and resistance. The data presented here support the idea that the environment in which the selection is applied (mutagenic stressors that are present), as well as changes in local drug concentration, can significantly alter the path to spectinomycin resistance in B. subtilis.

The Consortium on Vulnerability to Externalizing Disorders and Addictions (c-VEDA): an accelerated longitudinal cohort of children and adolescents in India.

The global burden of disease attributable to externalizing disorders such as alcohol misuse calls urgently for effective prevention and intervention. As our current knowledge is mainly derived from high-income countries such in Europe and North-America, it is difficult to address the wider socio-cultural, psychosocial context, and genetic factors in which risk and resilience are embedded in low- and medium-income countries. c-VEDA was established as the first and largest India-based multi-site cohort investigating the vulnerabilities for the development of externalizing disorders, addictions, and other mental health problems. Using a harmonised data collection plan coordinated with multiple cohorts in China, USA, and Europe, baseline data were collected from seven study sites between November 2016 and May 2019. Nine thousand and ten participants between the ages of 6 and 23 were assessed during this time, amongst which 1278 participants underwent more intensive assessments including MRI scans. Both waves of follow-ups have started according to the accelerated cohort structure with planned missingness design. Here, we present descriptive statistics on several key domains of assessments, and the full baseline dataset will be made accessible for researchers outside the consortium in September 2019. More details can be found on our website [cveda.org].

A series of five population-specific Indian brain templates and atlases spanning ages 6-60 years.

Anatomical brain templates are commonly used as references in neurological MRI studies, for bringing data into a common space for group-level statistics and coordinate reporting. Given the inherent variability in brain morphology across age and geography, it is important to have templates that are as representative as possible for both age and population. A representative-template increases the accuracy of alignment, decreases distortions as well as potential biases in final coordinate reports. In this study, we developed and validated a new set of T1w Indian brain templates (IBT) from a large number of brain scans (total n = 466) acquired across different locations and multiple 3T MRI scanners in India. A new tool in AFNI, make_template_dask.py, was created to efficiently make five age-specific IBTs (ages 6-60 years) as well as maximum probability map (MPM) atlases for each template; for each age-group's template-atlas pair, there is both a "population-average" and a "typical" version. Validation experiments on an independent Indian structural and functional-MRI dataset show the appropriateness of IBTs for spatial normalization of Indian brains. The results indicate significant structural differences when comparing the IBTs and MNI template, with these differences being maximal along the Anterior-Posterior and Inferior-Superior axes, but minimal Left-Right. For each age-group, the MPM brain atlases provide reasonably good representation of the native-space volumes in the IBT space, except in a few regions with high intersubject variability. These findings provide evidence to support the use of age and population-specific templates in human brain mapping studies.

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.

Impact of regulatory spin of pioglitazone on prescription of antidiabetic drugs among physicians in India: A multicentre questionnaire-based observational study.

Background & objectives: Pioglitazone was suspended for manufacture and sale by the Indian drug regulator in June 2013 due to its association with urinary bladder carcinoma, which was revoked within a short period (July 2013). The present questionnaire-based nationwide study was conducted to assess its impact on prescribing behaviour of physicians in India. Methods: Between December 2013 and March 2014, a validated questionnaire was administered to physicians practicing diabetes across 25 centres in India. Seven hundred and forty questionnaires fulfilling the minimum quality criteria were included in the final analysis. Results: Four hundred and sixteen (56.2%) physicians prescribed pioglitazone. Of these, 281 used it in less than the recommended dose of 15 mg/day. Most physicians (94.3%) were aware of recent regulatory events. However, only 333 (44.8%) changed their prescribing pattern. Seventeen of the 416 (4.1%) physicians who prescribed pioglitazone admitted having come across at least one type 2 diabetes mellitus patient (T2DM) who had urinary bladder carcinoma, and of these 13 said that it was in patients who took pioglitazone for a duration of more than two years. Only 7.8 per cent of physicians (n=58) categorically advocated banning pioglitazone, and the rest opined for its continuation or generating more evidence before decision could be taken regarding its use in T2DM. Interpretation & conclusions: Majority of the physicians though were aware of the regulatory changes with regard to pioglitazone, but their prescribing patterns were not changed for this drug. However, it was being used at lower than the recommended dose. There is a need for generating more evidence through improved pharmacovigilance activities and large-scale population-based prospective studies regarding the safety issues of pioglitazone, so as to make effectual risk-benefit analysis for its continual use in T2DM.

Outbreaks of unexplained neurologic illness - Muzaffarpur, India, 2013-2014.

Outbreaks of an unexplained acute neurologic illness affecting young children and associated with high case-fatality rates have been reported in the Muzaffarpur district of Bihar state in India since 1995. The outbreaks generally peak in June and decline weeks later with the onset of monsoon rains. There have been multiple epidemiologic and laboratory investigations of this syndrome, leading to a wide spectrum of proposed causes for the illness, including infectious encephalitis and exposure to pesticides. An association between illness and litchi fruit has been postulated because Muzaffarpur is a litchi fruit-producing region. To better characterize clinical and epidemiologic features of the illness that might suggest its cause and how it can be prevented, the Indian National Centre for Disease Control (NCDC) and CDC investigated outbreaks in 2013 and 2014. Clinical and laboratory findings in 2013 suggested a noninflammatory encephalopathy, possibly caused by a toxin. A common laboratory finding was low blood glucose (<70 mg/dL) on admission, a finding associated with a poorer outcome; 44% of all cases were fatal. An ongoing 2014 investigation has found no evidence of any infectious etiology and supports the possibility that exposure to a toxin might be the cause. The outbreak period coincides with the month-long litchi harvesting season in Muzaffarpur. Although a specific etiology has not yet been determined, the 2014 investigation has identified the illness as a hypoglycemic encephalopathy and confirmed the importance of ongoing laboratory evaluation of environmental toxins to identify a potential causative agent, including markers for methylenecyclopropylglycine (MCPG), a compound found in litchi seeds known to cause hypoglycemia in animal studies. Current public health recommendations are focused on reducing mortality by urging affected families to seek prompt medical care, and ensuring rapid assessment and correction of hypoglycemia in ill children.

Correlates of problematic unrecorded alcohol consumption in Sikkim, Northeast India - Results from a cross-sectional pilot survey.

The magnitude and consequences of unrecorded alcohol consumption, defined as home brewed or clandestinely produced illicit liquor or surrogate alcoholic beverage has been little investigated in India. A significant portion of all alcohol consumed globally is unrecorded, therefore these consumers constitute a significant population. Sikkim, a province in Northeast India, lies in the foothills of the Himalayas. Unrecorded alcohol use is traditionally prevalent, with more than ten types available. This study investigated correlates of problematic unrecorded alcohol consumption in rural and urban communities of Sikkim. A cross-sectional, community-based pilot survey was conducted. Intensive case-finding recruited current heavy users (at least 3 days/week) of unrecorded alcohol of either sex above 16 years of age. On enrolment, participants responded to a socio-demographic instrument including 12 questions on their pattern of alcohol consumption and a 4-item CAGE questionnaire. Alcohol problems exist significantly among the young adult population. Although consumption of unrecorded alcohol is traditional in Sikkim, it has emerged as an important public health problem, with alarmingly high rates of problematic consumption. This is also expected to have significant economic costs. Therefore, prevention and treatment measures are an urgent need as well as policy decisions on production and sales of unrecorded alcohol.

Ocular rhinosporidiosis presenting as recurrent chalazion.

Rhinosporidiosis, a granulomatous disease caused by Rhinosporidium seeberi, is widely prevalent in Sri Lanka and southern parts of India. Besides the eye, the lacrimal passage and nasal cavity are affected. The most common ocular involvement is a subconjunctival bleeding mass. Our case, a 9-year-old girl from a rural background with a history of pond water bathing, presented with a marginal chalazion involving the left lower lid. She had a history of chalazion involving the same site three months earlier which was managed by incision and curettage. A decision of surgical exploration was made and the evacuated mass was examined histologically showing evidence of rhinosporidiosis. This type of clinical presentation for ocular rhinosporidiosis (as recurrent chalazion) has not been reported earlier in the literature. This case emphasises that the clinicians from this part of the world must consider ocular rhinosporidiosis as differential diagnosis in cases with recurrent chalazion especially in a rural background with a habit of pond water bathing.

Mental health burden following extreme weather events in South-east Asia: A systematic review and meta-analysis.

Background: Exposure to extreme weatherly events potentially develops mental disorders among affected individuals. Aim: To synthesize the burden of mental disorders following impact of extreme weather events in South-east Asian (SEA) countries. Methods: Proposal was registered in PROSPERO register [CRD42023469788] and reported as per PRISMA-2020 guidelines. Studies reporting prevalence of mental health disorders following extreme weather events from SEA countries during 1990 and 2023 were searched on Embase, PubMed, and Scopus databases. Study quality was assessed using Appraisal tool for Cross-Sectional Studies. Overall pooled prevalence was computed using DerSimonian-Laird method for random-effects model and reported as 95% confidence intervals. Results: On screening 12,046 records, we included 155 studies (2,04,474 participants) for analysis. Overall burden of mental disorders was 35.31% (95%CI: 30.42%-40.21%). In subgroup analysis, studies on cyclones, India, local residents, children and adolescents, rural settings, and community settings reported higher burden of mental disorders. Depression (28.58%; 95%CI: 24.05%-33.1%) and PTSD (29.36%; 95%CI: 26.26%-32.46%) had similar prevalence. Visiting tourists to SEA region experienced fear, fear of recurrence of tsunami, nightmares, and sense of helplessness. Mental health outcomes were relatively higher in studies conducted within 1 year of events. Heterogeneity and possibility of publication bias exists among the reported studies. Conclusion: With the significant rise in episodes of extreme weather events in SEA region over the last three decades, mental disorders are documented in different proportions. We suggest prioritizing well-informed policies to formulate inclusive and resilient strategies on effectively identifying and treating mental health concerns among victims of extreme weather events.

Pharmacogenomics-assisted schizophrenia management: A hybrid type 2 effectiveness-implementation study protocol to compare the clinical utility, cost-effectiveness, and barriers.

OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).

Current analgesic use predicts low emotional quality of life in youth: a cross-sectional survey among university students in Sikkim, North East India.

BACKGROUND & OBJECTIVES: Occurrence of chronic physical pain is increasingly identified among youth, and medically unsupervised analgesic use is a possible risk factor for opioid dependence and other mental diseases in later life. Therefore, the present study was carried out in young student population in Sikkim, India, to explore predictors (including current chronic pain and current analgesic use) of low QoL in youth to identify a subset of population vulnerable to substance use and mental diseases in later life. METHODS: The study was conducted in a health university setting in Sikkim, North East India. In this cross-sectional study, 156 participants were enrolled with almost equal number of males and females. Generic instruments for demographics and current analgesic use and SF - 36, for assessment of quality of life (QoL), were used. QoL was measured in general, physical and emotional domains. Presence of chronic physical pain during past four weeks was captured using SF - 36. RESULTS: Almost two-third participants reported presence of current physical pain (69%, n=108); and (14%, n=22) reported current analgesic use for pain. In logistic regression model controlled for age, ethnicity, gender and residence, higher body mass index (BMI) (ß=-0.16, P=0.02) and current analgesic use (ß=1.6, P=0.006) predicted low QoL in emotional domain (less accomplishment due to emotional problem). Current analgesic use also predicted low QoL in another measure of emotional domain (depressed ß=2.0, P=0.001). INTERPRETATION & CONCLUSIONS: This study identified a subset of participants in their youth with low QoL in emotional domain predicted by current analgesic use and possible overweight problem. Low QoL in more than one emotional domain also identifies possibility of later psychiatric impairment. However, chronic pain did not emerge as a significant predictor of low QoL in emotional domain.

Burden of mental health disorders and synthesis of community-based mental health intervention measures among adolescents during COVID-19 pandemic in low middle-income countries: A systematic review and meta-analysis.

BACKGROUND: COVID-19 pandemic and the resultant lockdown could have negatively impacted adolescent mental health. The synthesised burden of mental health illness among adolescents during or after the pandemic is unknown in Low Middle-Income Countries (LMICs). The objective was to ascertain the pooled prevalence of mental health disorders among adolescents aged 10 - 19 years and to systematically review & conduct a descriptive synthesis of community-based mental health intervention measures in addressing adolescent mental health disorders during the COVID-19 pandemic in LMICs. METHODS: The literature was searched in Embase, PubMed, and Scopus and selected the relevant studies. The data was extracted from the selected studies, and its quality was assessed using adapted Newcastle-Ottawa Quality Assessment Scales. Meta-analysis was performed using random effects model to pool the prevalence of mental health disorders. Statistical heterogeneity was evaluated through Cochran's Q test & I2 statistic. RESULTS: Thirty-five studies were selected out of 7955 identified studies. Most of the studies (n = 7, each) were from India and Iran. The majority of research works were community-based (n = 18), conducted in 2020 (23 articles), and participant interviews were conducted through online mode (n = 21). Varied instruments were used to measure the burden of mental health in different settings. Pooled prevalence (95% confidence intervals) of anxiety, depression and stress was found to be 43.69 (18.58-68.80)%, 47.02 (31.72-62.32)% and 39.97 (30.53-49.40)%, respectively, with high heterogeneity between the studies. No studies reported community-based mental health interventions. CONCLUSION: There has been a higher prevalence of anxiety, depression, stress, and other mental health illnesses, among adolescents in LMICs during the COVID-19 pandemic. It is important to note that no existing literature directly addresses community-based interventions for these common mental health illnesses. It is imperative to prepare the health system for early identification and management of common mental health illness among the adolescent age group in the event of any future disaster.

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.

Solubility of gold nanoparticles as a function of ligand shell and alkane solvent.

The solubility of ca. 5.0 nm gold nanoparticles was studied systematically as a function of ligand shell and solvent. The ligands were octane-, decane-, dodecane- and hexadecanethiols; the solvents were the n-alkanes from hexane to hexadecane and toluene. Supernatant concentrations in equilibrium with precipitated superclusters of nanoparticles were measured at room temperature (23 °C) with UV-Vis spectrophotometry. The solubility of nanoparticles ligated with decane- and dodecanethiol was greatest in n-decane and n-dodecane, respectively. In contrast, the solubility of nanoparticles ligated with octane- and hexadecanethiol showed decreasing solubility with increasing solvent chain length. In addition the solubility of the octanethiol ligated system showed a nonmonotonic solvent carbon number functionality with even numbered solvents being better solvents than neighboring odd numbered solvents.