Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects

Scott Mackey, Nicholas Allgaier, Bader Chaarani, Philip Spechler, Catherine Orr, Janice Bunn, Nicholas B. Allen, Nelly Alia-Klein, Albert Batalla, Sara Blaine, Samantha Brooks, Elisabeth Caparelli, Yann Ying Chye, Janna Cousijn, Alain Dagher, Sylvane Desrivieres, Sarah W. Feldstein-Ewing, John J Foxe, Rita Z. Goldstein, Anna E Goudriaan & 3 others Valentina Lorenzetti, Murat Yücel, ENIGMA Addiction Working Group

Research output: Contribution to journalArticleResearchpeer-review

7 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
Pages (from-to)119-128
Number of pages10
JournalAmerican Journal of Psychiatry
Volume176
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

Keywords

  • mega-analysis
  • structural MRI
  • substance-related disorders

Cite this

Mackey, S., Allgaier, N., Chaarani, B., Spechler, P., Orr, C., Bunn, J., ... ENIGMA Addiction Working Group (2019). Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects. American Journal of Psychiatry, 176(2), 119-128. https://doi.org/10.1176/appi.ajp.2018.17040415
Mackey, Scott ; Allgaier, Nicholas ; Chaarani, Bader ; Spechler, Philip ; Orr, Catherine ; Bunn, Janice ; Allen, Nicholas B. ; Alia-Klein, Nelly ; Batalla, Albert ; Blaine, Sara ; Brooks, Samantha ; Caparelli, Elisabeth ; Chye, Yann Ying ; Cousijn, Janna ; Dagher, Alain ; Desrivieres, Sylvane ; Feldstein-Ewing, Sarah W. ; Foxe, John J ; Goldstein, Rita Z. ; Goudriaan, Anna E ; Lorenzetti, Valentina ; Yücel, Murat ; ENIGMA Addiction Working Group. / Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects. In: American Journal of Psychiatry. 2019 ; Vol. 176, No. 2. pp. 119-128.
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title = "Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects",
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.",
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author = "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 W.} and Foxe, {John J} and Goldstein, {Rita Z.} and Goudriaan, {Anna E} and Valentina Lorenzetti and Murat Y{\"u}cel and {ENIGMA Addiction Working Group}",
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Mackey, S, Allgaier, N, Chaarani, B, Spechler, P, Orr, C, Bunn, J, Allen, NB, Alia-Klein, N, Batalla, A, Blaine, S, Brooks, S, Caparelli, E, Chye, YY, Cousijn, J, Dagher, A, Desrivieres, S, Feldstein-Ewing, SW, Foxe, JJ, Goldstein, RZ, Goudriaan, AE, Lorenzetti, V, Yücel, M & ENIGMA Addiction Working Group 2019, 'Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects', American Journal of Psychiatry, vol. 176, no. 2, pp. 119-128. https://doi.org/10.1176/appi.ajp.2018.17040415

Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects. / Mackey, Scott; Allgaier, Nicholas; Chaarani, Bader; Spechler, Philip; Orr, Catherine; Bunn, Janice; Allen, Nicholas B.; Alia-Klein, Nelly; Batalla, Albert; Blaine, Sara; Brooks, Samantha; Caparelli, Elisabeth; Chye, Yann Ying; Cousijn, Janna; Dagher, Alain; Desrivieres, Sylvane; Feldstein-Ewing, Sarah W.; Foxe, John J; Goldstein, Rita Z.; Goudriaan, Anna E; Lorenzetti, Valentina; Yücel, Murat; ENIGMA Addiction Working Group.

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

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Mega-Analysis of Gray Matter Volume in Substance Dependence: General and Substance-Specific Regional Effects

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 W.

AU - Foxe, John J

AU - Goldstein, Rita Z.

AU - Goudriaan, Anna E

AU - Lorenzetti, Valentina

AU - Yücel, Murat

AU - ENIGMA Addiction Working Group

PY - 2019/2/1

Y1 - 2019/2/1

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.

AB - 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.

KW - mega-analysis

KW - structural MRI

KW - substance-related disorders

U2 - 10.1176/appi.ajp.2018.17040415

DO - 10.1176/appi.ajp.2018.17040415

M3 - Article

VL - 176

SP - 119

EP - 128

JO - American Journal of Psychiatry

JF - American Journal of Psychiatry

SN - 0002-953X

IS - 2

ER -