Mega-analysis of gray matter volume in substance dependence: General and substance-specific regional effects

ENIGMA Addiction Working Group

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. Conclusions: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

Original languageEnglish (US)
Pages (from-to)119-128
Number of pages10
JournalAmerican Journal of Psychiatry
Volume176
Issue number2
DOIs
StatePublished - Feb 1 2019

Fingerprint

Substance-Related Disorders
Brain
Alcohols
Nicotine
Alcoholism
Biomarkers
Tobacco Use Disorder
Methamphetamine
Cannabis
Gray Matter
Prefrontal Cortex
Cocaine

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Mega-analysis of gray matter volume in substance dependence : General and substance-specific regional effects. / ENIGMA Addiction Working Group.

In: American Journal of Psychiatry, Vol. 176, No. 2, 01.02.2019, p. 119-128.

Research output: Contribution to journalArticle

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abstract = "Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. Conclusions: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.",
author = "{ENIGMA Addiction Working Group} and Scott Mackey and Nicholas Allgaier and Bader Chaarani and Philip Spechler and Catherine Orr and Janice Bunn and Allen, {Nicholas B.} and Nelly Alia-Klein and Albert Batalla and Sara Blaine and Samantha Brooks and Elisabeth Caparelli and Chye, {Yann Ying} and Janna Cousijn and Alain Dagher and Sylvane Desrivieres and {Feldstein Ewing}, Sarah and Foxe, {John J.} and Goldstein, {Rita Z.} and Goudriaan, {Anna E.} and Heitzeg, {Mary M.} and Robert Hester and Kent Hutchison and Ozlem Korucuoglu and Li, {Chiang Shan R.} and Edythe London and Valentina Lorenzetti and Maartje Luijten and Rocio Martin-Santos and April May and Reza Momenan and Angelica Morales and Paulus, {Martin P.} and Godfrey Pearlson and Rousseau, {Marc Etienne} and Salmeron, {Betty Jo} and Ren{\'e}e Schluter and Lianne Schmaal and Gunter Schumann and Zsuzsika Sjoerds and Stein, {Dan J.} and Stein, {Elliot A.} and Rajita Sinha and Nadia Solowij and Susan Tapert and Anne Uhlmann and Dick Veltman and {Van Holst}, Ruth and Sarah Whittle and Wright, {Margaret J.}",
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T1 - Mega-analysis of gray matter volume in substance dependence

T2 - General and substance-specific regional effects

AU - ENIGMA Addiction Working Group

AU - Mackey, Scott

AU - Allgaier, Nicholas

AU - Chaarani, Bader

AU - Spechler, Philip

AU - Orr, Catherine

AU - Bunn, Janice

AU - Allen, Nicholas B.

AU - Alia-Klein, Nelly

AU - Batalla, Albert

AU - Blaine, Sara

AU - Brooks, Samantha

AU - Caparelli, Elisabeth

AU - Chye, Yann Ying

AU - Cousijn, Janna

AU - Dagher, Alain

AU - Desrivieres, Sylvane

AU - Feldstein Ewing, Sarah

AU - Foxe, John J.

AU - Goldstein, Rita Z.

AU - Goudriaan, Anna E.

AU - Heitzeg, Mary M.

AU - Hester, Robert

AU - Hutchison, Kent

AU - Korucuoglu, Ozlem

AU - Li, Chiang Shan R.

AU - London, Edythe

AU - Lorenzetti, Valentina

AU - Luijten, Maartje

AU - Martin-Santos, Rocio

AU - May, April

AU - Momenan, Reza

AU - Morales, Angelica

AU - Paulus, Martin P.

AU - Pearlson, Godfrey

AU - Rousseau, Marc Etienne

AU - Salmeron, Betty Jo

AU - Schluter, Renée

AU - Schmaal, Lianne

AU - Schumann, Gunter

AU - Sjoerds, Zsuzsika

AU - Stein, Dan J.

AU - Stein, Elliot A.

AU - Sinha, Rajita

AU - Solowij, Nadia

AU - Tapert, Susan

AU - Uhlmann, Anne

AU - Veltman, Dick

AU - Van Holst, Ruth

AU - Whittle, Sarah

AU - Wright, Margaret J.

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N2 - Objective: Although lower brain volume has been routinely observed in individuals with substance dependence compared with nondependent control subjects, the brain regions exhibiting lower volume have not been consistent across studies. In addition, it is not clear whether a common set of regions are involved in substance dependence regardless of the substance used or whether some brain volume effects are substance specific. Resolution of these issues may contribute to the identification of clinically relevant imaging biomarkers. Using pooled data from 14 countries, the authors sought to identify general and substance-specific associations between dependence and regional brain volumes. Method: Brain structure was examined in a mega-analysis of previously published data pooled from 23 laboratories, including 3,240 individuals, 2,140 of whom had substance dependence on one of five substances: alcohol, nicotine, cocaine, methamphetamine, or cannabis. Subcortical volume and cortical thickness in regions defined by FreeSurfer were compared with nondependent control subjects when all sampled substance categories were combined, as well as separately, while controlling for age, sex, imaging site, and total intracranial volume. Because of extensive associations with alcohol dependence, a secondary contrast was also performed for dependence on all substances except alcohol. An optimized split-half strategy was used to assess the reliability of the findings. Results: Lower volume or thickness was observed in many brain regions in individuals with substance dependence. The greatest effects were associated with alcohol use disorder. A set of affected regions related to dependence in general, regardless of the substance, included the insula and the medial orbitofrontal cortex. Furthermore, a support vector machine multivariate classification of regional brain volumes successfully classified individuals with substance dependence on alcohol or nicotine relative to nondependent control subjects. Conclusions: The results indicate that dependence on a range of different substances shares a common neural substrate and that differential patterns of regional volume could serve as useful biomarkers of dependence on alcohol and nicotine.

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