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

Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA); Nilakshi Vaidya; Bharath Holla; Jon Heron; Eesha Sharma; Yuning Zhang; Gwen Fernandes; Udita Iyengar; Alex Spiers; Anupa Yadav; Surajit Das; Sanjit Roy; Chirag K Ahuja; Gareth J Barker; Debasish Basu; Rose Dawn Bharath; Matthew Hickman; Sanjeev Jain; Kartik Kalyanram; Kamakshi Kartik; Murali Krishna; Ghattu Krishnaveni; Kalyanaraman Kumaran; Rebecca Kuriyan; Pratima Murthy; Dimitri Papadopoulos Orfanos; Meera Purushottam; Sunita Simon Kurpad; Lenin Singh; Roshan Singh; B N Subodh; Mireille Toledano; Henrik Walter; Sylvane Desrivières; Amit Chakrabarti; Vivek Benegal; Gunter Schumann

doi:10.1001/jamanetworkopen.2023.12810

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

Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), Nilakshi Vaidya, Bharath Holla, Jon Heron, Eesha Sharma, Yuning Zhang, Gwen Fernandes, Udita Iyengar, Alex Spiers, Anupa Yadav, Surajit Das, Sanjit Roy, Chirag K Ahuja, Gareth J Barker, Debasish Basu, Rose Dawn Bharath, Matthew Hickman, Sanjeev Jain, Kartik Kalyanram, Kamakshi KartikMurali Krishna, Ghattu Krishnaveni, Kalyanaraman Kumaran, Rebecca Kuriyan, Pratima Murthy, Dimitri Papadopoulos Orfanos, Meera Purushottam, Sunita Simon Kurpad, Lenin Singh, Roshan Singh, B N Subodh, Mireille Toledano, Henrik Walter, Sylvane Desrivières, Amit Chakrabarti, Vivek Benegal, Gunter Schumann

Research output: Contribution to journal › Article › peer-review

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58 Downloads (Pure)

Abstract

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.

Original language	English
Pages (from-to)	e2312810
Journal	JAMA Network open
Volume	6
Issue number	5
DOIs	https://doi.org/10.1001/jamanetworkopen.2023.12810
Publication status	Published - 12 May 2023

Keywords

Humans
Male
Child
Adolescent
Young Adult
Executive Function
Arsenic
Cross-Sectional Studies
Cohort Studies
Brain/pathology
Brain Diseases

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Neurocognitive Analysis of Low-level A_VAIDYA_2023_GOLD VoR (CC BY)
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2023 Vaidya N et al. JAMA Network Open.
Final published version, 1.34 MBLicence: CC BY

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Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), Vaidya, N., Holla, B., Heron, J., Sharma, E., Zhang, Y., Fernandes, G., Iyengar, U., Spiers, A., Yadav, A., Das, S., Roy, S., Ahuja, C. K., Barker, G. J., Basu, D., Bharath, R. D., Hickman, M., Jain, S., Kalyanram, K., ... Schumann, G. (2023). Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India. JAMA Network open, 6(5), e2312810. https://doi.org/10.1001/jamanetworkopen.2023.12810

@article{a7f72c45bcea4444b1c778140081e73d,

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

abstract = "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.",

keywords = "Humans, Male, Child, Adolescent, Young Adult, Executive Function, Arsenic, Cross-Sectional Studies, Cohort Studies, Brain/pathology, Brain Diseases",

author = "{Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA)} and Nilakshi Vaidya and Bharath Holla and Jon Heron and Eesha Sharma and Yuning Zhang and Gwen Fernandes and Udita Iyengar and Alex Spiers and Anupa Yadav and Surajit Das and Sanjit Roy and Ahuja, {Chirag K} and Barker, {Gareth J} and Debasish Basu and Bharath, {Rose Dawn} and Matthew Hickman and Sanjeev Jain and Kartik Kalyanram and Kamakshi Kartik and Murali Krishna and Ghattu Krishnaveni and Kalyanaraman Kumaran and Rebecca Kuriyan and Pratima Murthy and {Papadopoulos Orfanos}, Dimitri and Meera Purushottam and Kurpad, {Sunita Simon} and Lenin Singh and Roshan Singh and Subodh, {B N} and Mireille Toledano and Henrik Walter and Sylvane Desrivi{\`e}res and Amit Chakrabarti and Vivek Benegal and Gunter Schumann",

year = "2023",

month = may,

day = "12",

doi = "10.1001/jamanetworkopen.2023.12810",

language = "English",

volume = "6",

pages = "e2312810",

journal = "JAMA Network open",

issn = "2574-3805",

publisher = "American Medical Association",

number = "5",

}

Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), Vaidya, N, Holla, B, Heron, J, Sharma, E, Zhang, Y, Fernandes, G, Iyengar, U, Spiers, A, Yadav, A, Das, S, Roy, S, Ahuja, CK, Barker, GJ, Basu, D, Bharath, RD, Hickman, M, Jain, S, Kalyanram, K, Kartik, K, Krishna, M, Krishnaveni, G, Kumaran, K, Kuriyan, R, Murthy, P, Papadopoulos Orfanos, D, Purushottam, M, Kurpad, SS, Singh, L, Singh, R, Subodh, BN, Toledano, M, Walter, H, Desrivières, S, Chakrabarti, A, Benegal, V & Schumann, G 2023, 'Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India', JAMA Network open, vol. 6, no. 5, pp. e2312810. https://doi.org/10.1001/jamanetworkopen.2023.12810

Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India. / Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA); Vaidya, Nilakshi; Holla, Bharath et al.
In: JAMA Network open, Vol. 6, No. 5, 12.05.2023, p. e2312810.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India

AU - Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA)

AU - Vaidya, Nilakshi

AU - Holla, Bharath

AU - Heron, Jon

AU - Sharma, Eesha

AU - Zhang, Yuning

AU - Fernandes, Gwen

AU - Iyengar, Udita

AU - Spiers, Alex

AU - Yadav, Anupa

AU - Das, Surajit

AU - Roy, Sanjit

AU - Ahuja, Chirag K

AU - Barker, Gareth J

AU - Basu, Debasish

AU - Bharath, Rose Dawn

AU - Hickman, Matthew

AU - Jain, Sanjeev

AU - Kalyanram, Kartik

AU - Kartik, Kamakshi

AU - Krishna, Murali

AU - Krishnaveni, Ghattu

AU - Kumaran, Kalyanaraman

AU - Kuriyan, Rebecca

AU - Murthy, Pratima

AU - Papadopoulos Orfanos, Dimitri

AU - Purushottam, Meera

AU - Kurpad, Sunita Simon

AU - Singh, Lenin

AU - Singh, Roshan

AU - Subodh, B N

AU - Toledano, Mireille

AU - Walter, Henrik

AU - Desrivières, Sylvane

AU - Chakrabarti, Amit

AU - Benegal, Vivek

AU - Schumann, Gunter

PY - 2023/5/12

Y1 - 2023/5/12

N2 - 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.

AB - 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.

KW - Humans

KW - Male

KW - Child

KW - Adolescent

KW - Young Adult

KW - Executive Function

KW - Arsenic

KW - Cross-Sectional Studies

KW - Cohort Studies

KW - Brain/pathology

KW - Brain Diseases

UR - http://www.scopus.com/inward/record.url?scp=85159257624&partnerID=8YFLogxK

U2 - 10.1001/jamanetworkopen.2023.12810

DO - 10.1001/jamanetworkopen.2023.12810

M3 - Article

C2 - 37171822

SN - 2574-3805

VL - 6

SP - e2312810

JO - JAMA Network open

JF - JAMA Network open

IS - 5

ER -

Consortium on Vulnerability to Externalizing Disorders and Addictions (cVEDA), Vaidya N, Holla B, Heron J, Sharma E, Zhang Y et al. Neurocognitive Analysis of Low-level Arsenic Exposure and Executive Function Mediated by Brain Anomalies Among Children, Adolescents, and Young Adults in India. JAMA Network open. 2023 May 12;6(5):e2312810. doi: 10.1001/jamanetworkopen.2023.12810

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

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Keywords

UN SDGs

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