Orbitofrontal cortex thickness and substance use disorders in emerging adulthood: causal inferences from a co-twin control/discordant twin study

Jeremy Harper; Sylia Wilson; Stephen M. Malone; Ruskin H. Hunt; Kathleen M. Thomas; William G. Iacono

doi:10.1111/add.15447

Orbitofrontal cortex thickness and substance use disorders in emerging adulthood: causal inferences from a co-twin control/discordant twin study

Jeremy Harper, Sylia Wilson, Stephen M. Malone, Ruskin H. Hunt, Kathleen M. Thomas, William G. Iacono

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

5 Scopus citations

Abstract

Background/aims: Research linking orbitofrontal cortex (OFC) structure and substance use disorders (SUDs) is largely correlational and often implies a causal effect of addiction/substance exposure on the brain, but familial risk factors (e.g. genetic liability) may confound these associations. We tested whether associations between alcohol, cannabis and tobacco use disorders and OFC thickness reflected the potential causal effects of familial risk or SUDs-related consequences (e.g. substance exposure). Design: A co-twin control/discordant twin design separated familial risk confounding from SUD-related consequences. Setting/participants: A population-based sample of 436 24-year-old twins (62% monozygotic) from the Minnesota Twin Family Study, USA. Measurements: Alcohol, cannabis and tobacco use disorders were assessed using the Composite International Diagnostic Interview—Substance Abuse Module. Cortical thickness of the medial and lateral OFC (mOFC and lOFC, respectively) was assessed using magnetic resonance imaging (MRI). Findings: Lower mOFC (P-values ≤ 0.006) but not lOFC (P-values ≥ 0.190) thickness was observed in diagnosed individuals (n = 185) relative to non-SUD controls (n = 251). Co-twin control analyses offered evidence that mOFC associations were consistent with familial risk across SUDs (between-pair effect: P-values ≤ 0.047) and the independent consequences of having an alcohol or cannabis use disorder (within-pair effect: P-values ≤ 0.024). That is, within alcohol/cannabis discordant twin pairs, affected twins had significantly lower mOFC thickness compared with their unaffected co-twins. Conclusions: A confounder-adjusted analysis of the Minnesota Twin Family Study appeared to indicate that, beyond a substance use disorders general familial risk effect, the experience of an alcohol or cannabis use disorder in emerging adulthood reduces the thickness of the medial orbitofrontal cortex, a region associated with value-guided decision-making.

Original language	English (US)
Pages (from-to)	2548-2558
Number of pages	11
Journal	Addiction
Volume	116
Issue number	9
Early online date	Feb 23 2021
DOIs	https://doi.org/10.1111/add.15447
State	Published - Sep 2021

Bibliographical note

Funding Information:
This work was supported by National Institute on Drug Abuse grants R01DA036216 and K01DA037280 and National Institute on Alcohol Abuse and Alcoholism grants R21AA026632 and R21AA026919. J.H. was supported by National Institute on Drug Abuse grant T32DA037183, the University of Minnesota College of Liberal Arts Eva O. Miller Fellowship, and the National Science Foundation Graduate Research Fellowship under Grant no. 00039202. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors acknowledge the Minnesota Supercomputing Institute (MSI; http://www.msi.umn.edu) and the Center for Magnetic Resonance Research (supported by grants NIBIB P41 EB027061 and 1S10OD017974-01) at the University of Minnesota for providing resources that contributed to the research results reported within this paper.

Funding Information:
This work was supported by National Institute on Drug Abuse grants R01DA036216 and K01DA037280 and National Institute on Alcohol Abuse and Alcoholism grants R21AA026632 and R21AA026919. J.H. was supported by National Institute on Drug Abuse grant T32DA037183, the University of Minnesota College of Liberal Arts Eva O. Miller Fellowship, and the National Science Foundation Graduate Research Fellowship under Grant no. 00039202. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Funding Information:
The authors acknowledge the Minnesota Supercomputing Institute (MSI; http://www.msi.umn.edu ) and the Center for Magnetic Resonance Research (supported by grants NIBIB P41 EB027061 and 1S10OD017974‐01) at the University of Minnesota for providing resources that contributed to the research results reported within this paper.

Publisher Copyright:
© 2021 Society for the Study of Addiction

Keywords

Addiction
alcohol
cannabis
co-twin control analysis
discordant twin design
emerging adulthood
endophenotype
orbitofrontal cortex
substance use disorders
tobacco

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BFC
ANDI
DR

UN SDGs

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

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10.1111/add.15447

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title = "Orbitofrontal cortex thickness and substance use disorders in emerging adulthood: causal inferences from a co-twin control/discordant twin study",

abstract = "Background/aims: Research linking orbitofrontal cortex (OFC) structure and substance use disorders (SUDs) is largely correlational and often implies a causal effect of addiction/substance exposure on the brain, but familial risk factors (e.g. genetic liability) may confound these associations. We tested whether associations between alcohol, cannabis and tobacco use disorders and OFC thickness reflected the potential causal effects of familial risk or SUDs-related consequences (e.g. substance exposure). Design: A co-twin control/discordant twin design separated familial risk confounding from SUD-related consequences. Setting/participants: A population-based sample of 436 24-year-old twins (62% monozygotic) from the Minnesota Twin Family Study, USA. Measurements: Alcohol, cannabis and tobacco use disorders were assessed using the Composite International Diagnostic Interview—Substance Abuse Module. Cortical thickness of the medial and lateral OFC (mOFC and lOFC, respectively) was assessed using magnetic resonance imaging (MRI). Findings: Lower mOFC (P-values ≤ 0.006) but not lOFC (P-values ≥ 0.190) thickness was observed in diagnosed individuals (n = 185) relative to non-SUD controls (n = 251). Co-twin control analyses offered evidence that mOFC associations were consistent with familial risk across SUDs (between-pair effect: P-values ≤ 0.047) and the independent consequences of having an alcohol or cannabis use disorder (within-pair effect: P-values ≤ 0.024). That is, within alcohol/cannabis discordant twin pairs, affected twins had significantly lower mOFC thickness compared with their unaffected co-twins. Conclusions: A confounder-adjusted analysis of the Minnesota Twin Family Study appeared to indicate that, beyond a substance use disorders general familial risk effect, the experience of an alcohol or cannabis use disorder in emerging adulthood reduces the thickness of the medial orbitofrontal cortex, a region associated with value-guided decision-making.",

keywords = "Addiction, alcohol, cannabis, co-twin control analysis, discordant twin design, emerging adulthood, endophenotype, orbitofrontal cortex, substance use disorders, tobacco",

author = "Jeremy Harper and Sylia Wilson and Malone, {Stephen M.} and Hunt, {Ruskin H.} and Thomas, {Kathleen M.} and Iacono, {William G.}",

note = "Funding Information: This work was supported by National Institute on Drug Abuse grants R01DA036216 and K01DA037280 and National Institute on Alcohol Abuse and Alcoholism grants R21AA026632 and R21AA026919. J.H. was supported by National Institute on Drug Abuse grant T32DA037183, the University of Minnesota College of Liberal Arts Eva O. Miller Fellowship, and the National Science Foundation Graduate Research Fellowship under Grant no. 00039202. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors acknowledge the Minnesota Supercomputing Institute (MSI; http://www.msi.umn.edu) and the Center for Magnetic Resonance Research (supported by grants NIBIB P41 EB027061 and 1S10OD017974-01) at the University of Minnesota for providing resources that contributed to the research results reported within this paper. Funding Information: This work was supported by National Institute on Drug Abuse grants R01DA036216 and K01DA037280 and National Institute on Alcohol Abuse and Alcoholism grants R21AA026632 and R21AA026919. J.H. was supported by National Institute on Drug Abuse grant T32DA037183, the University of Minnesota College of Liberal Arts Eva O. Miller Fellowship, and the National Science Foundation Graduate Research Fellowship under Grant no. 00039202. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: The authors acknowledge the Minnesota Supercomputing Institute (MSI; http://www.msi.umn.edu ) and the Center for Magnetic Resonance Research (supported by grants NIBIB P41 EB027061 and 1S10OD017974‐01) at the University of Minnesota for providing resources that contributed to the research results reported within this paper. Publisher Copyright: {\textcopyright} 2021 Society for the Study of Addiction",

year = "2021",

month = sep,

doi = "10.1111/add.15447",

language = "English (US)",

volume = "116",

pages = "2548--2558",

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T1 - Orbitofrontal cortex thickness and substance use disorders in emerging adulthood

T2 - causal inferences from a co-twin control/discordant twin study

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AU - Wilson, Sylia

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AU - Hunt, Ruskin H.

AU - Thomas, Kathleen M.

AU - Iacono, William G.

N1 - Funding Information: This work was supported by National Institute on Drug Abuse grants R01DA036216 and K01DA037280 and National Institute on Alcohol Abuse and Alcoholism grants R21AA026632 and R21AA026919. J.H. was supported by National Institute on Drug Abuse grant T32DA037183, the University of Minnesota College of Liberal Arts Eva O. Miller Fellowship, and the National Science Foundation Graduate Research Fellowship under Grant no. 00039202. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors acknowledge the Minnesota Supercomputing Institute (MSI; http://www.msi.umn.edu) and the Center for Magnetic Resonance Research (supported by grants NIBIB P41 EB027061 and 1S10OD017974-01) at the University of Minnesota for providing resources that contributed to the research results reported within this paper. Funding Information: This work was supported by National Institute on Drug Abuse grants R01DA036216 and K01DA037280 and National Institute on Alcohol Abuse and Alcoholism grants R21AA026632 and R21AA026919. J.H. was supported by National Institute on Drug Abuse grant T32DA037183, the University of Minnesota College of Liberal Arts Eva O. Miller Fellowship, and the National Science Foundation Graduate Research Fellowship under Grant no. 00039202. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: The authors acknowledge the Minnesota Supercomputing Institute (MSI; http://www.msi.umn.edu ) and the Center for Magnetic Resonance Research (supported by grants NIBIB P41 EB027061 and 1S10OD017974‐01) at the University of Minnesota for providing resources that contributed to the research results reported within this paper. Publisher Copyright: © 2021 Society for the Study of Addiction

PY - 2021/9

Y1 - 2021/9

N2 - Background/aims: Research linking orbitofrontal cortex (OFC) structure and substance use disorders (SUDs) is largely correlational and often implies a causal effect of addiction/substance exposure on the brain, but familial risk factors (e.g. genetic liability) may confound these associations. We tested whether associations between alcohol, cannabis and tobacco use disorders and OFC thickness reflected the potential causal effects of familial risk or SUDs-related consequences (e.g. substance exposure). Design: A co-twin control/discordant twin design separated familial risk confounding from SUD-related consequences. Setting/participants: A population-based sample of 436 24-year-old twins (62% monozygotic) from the Minnesota Twin Family Study, USA. Measurements: Alcohol, cannabis and tobacco use disorders were assessed using the Composite International Diagnostic Interview—Substance Abuse Module. Cortical thickness of the medial and lateral OFC (mOFC and lOFC, respectively) was assessed using magnetic resonance imaging (MRI). Findings: Lower mOFC (P-values ≤ 0.006) but not lOFC (P-values ≥ 0.190) thickness was observed in diagnosed individuals (n = 185) relative to non-SUD controls (n = 251). Co-twin control analyses offered evidence that mOFC associations were consistent with familial risk across SUDs (between-pair effect: P-values ≤ 0.047) and the independent consequences of having an alcohol or cannabis use disorder (within-pair effect: P-values ≤ 0.024). That is, within alcohol/cannabis discordant twin pairs, affected twins had significantly lower mOFC thickness compared with their unaffected co-twins. Conclusions: A confounder-adjusted analysis of the Minnesota Twin Family Study appeared to indicate that, beyond a substance use disorders general familial risk effect, the experience of an alcohol or cannabis use disorder in emerging adulthood reduces the thickness of the medial orbitofrontal cortex, a region associated with value-guided decision-making.

AB - Background/aims: Research linking orbitofrontal cortex (OFC) structure and substance use disorders (SUDs) is largely correlational and often implies a causal effect of addiction/substance exposure on the brain, but familial risk factors (e.g. genetic liability) may confound these associations. We tested whether associations between alcohol, cannabis and tobacco use disorders and OFC thickness reflected the potential causal effects of familial risk or SUDs-related consequences (e.g. substance exposure). Design: A co-twin control/discordant twin design separated familial risk confounding from SUD-related consequences. Setting/participants: A population-based sample of 436 24-year-old twins (62% monozygotic) from the Minnesota Twin Family Study, USA. Measurements: Alcohol, cannabis and tobacco use disorders were assessed using the Composite International Diagnostic Interview—Substance Abuse Module. Cortical thickness of the medial and lateral OFC (mOFC and lOFC, respectively) was assessed using magnetic resonance imaging (MRI). Findings: Lower mOFC (P-values ≤ 0.006) but not lOFC (P-values ≥ 0.190) thickness was observed in diagnosed individuals (n = 185) relative to non-SUD controls (n = 251). Co-twin control analyses offered evidence that mOFC associations were consistent with familial risk across SUDs (between-pair effect: P-values ≤ 0.047) and the independent consequences of having an alcohol or cannabis use disorder (within-pair effect: P-values ≤ 0.024). That is, within alcohol/cannabis discordant twin pairs, affected twins had significantly lower mOFC thickness compared with their unaffected co-twins. Conclusions: A confounder-adjusted analysis of the Minnesota Twin Family Study appeared to indicate that, beyond a substance use disorders general familial risk effect, the experience of an alcohol or cannabis use disorder in emerging adulthood reduces the thickness of the medial orbitofrontal cortex, a region associated with value-guided decision-making.

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KW - endophenotype

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KW - substance use disorders

KW - tobacco

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Orbitofrontal cortex thickness and substance use disorders in emerging adulthood: causal inferences from a co-twin control/discordant twin study

Abstract

Bibliographical note

Keywords

Center for Magnetic Resonance Research (CMRR) tags

UN SDGs

Publisher link

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