Associations and heritability of auditory encoding, gray matter, and attention in schizophrenia

Yu Han Chen; Breannan Howell; J. Christopher Edgar; Mingxiong Huang; Peter Kochunov; Michael A. Hunter; Cassandra Wootton; Brett Y. Lu; Juan Bustillo; Joseph R. Sadek; Gregory A. Miller; José M. Cañive

doi:10.1093/schbul/sby111

Associations and heritability of auditory encoding, gray matter, and attention in schizophrenia

Yu Han Chen, Breannan Howell, J. Christopher Edgar, Mingxiong Huang, Peter Kochunov, Michael A. Hunter, Cassandra Wootton, Brett Y. Lu, Juan Bustillo, Joseph R. Sadek, Gregory A. Miller, José M. Cañive

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

8 Citations (Scopus)

Abstract

Background: Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). Methods: Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h²_r) were obtained for M100, CT at each group-difference region, and the attention measure. Results: SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function−structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. Conclusions: Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function−structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function−structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function−structure relationships in SZ.

Original language	English
Pages (from-to)	859-870
Number of pages	12
Journal	Schizophrenia Bulletin
Volume	45
Issue number	4
DOIs	https://doi.org/10.1093/schbul/sby111
Publication status	Published - Jun 18 2019
Externally published	Yes

Bibliographical note

Funding Information:
This research was supported by grants from the National Institute of Mental Health (R01 MH65304 to Dr Cañive, K01 MH108822 to Dr Chen, and K08 MH085100 to Dr Edgar), a VA Merit grant (VA Merit CSR&D: IIR-04-212-3 to Dr Cañive), and University of California at San Diego Merit Review Grant from the Department of Veterans Affairs to Dr Huang. The authors would like to thank the subjects who enrolled in this study; Megan Schendel, Kim Paulson, Cassandra Wootton, and Emerson Epstein, who helped with data collection; and Lawrence Calais, Gloria Fuldauer, and Nickolas Lemke for their help with subject recruitment and administrative support related to this project. The authors have declared that there are no conflicts of interest in relation to the subject of this study.

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

ASJC Scopus Subject Areas

Psychiatry and Mental health

UN SDGs

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

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10.1093/schbul/sby111

Cite this

@article{263fac498f1a411a8d4ebf9c7af9ae79,

title = "Associations and heritability of auditory encoding, gray matter, and attention in schizophrenia",

abstract = "Background: Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). Methods: Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure. Results: SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function−structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. Conclusions: Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function−structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function−structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function−structure relationships in SZ.",

author = "Chen, {Yu Han} and Breannan Howell and Edgar, {J. Christopher} and Mingxiong Huang and Peter Kochunov and Hunter, {Michael A.} and Cassandra Wootton and Lu, {Brett Y.} and Juan Bustillo and Sadek, {Joseph R.} and Miller, {Gregory A.} and Ca{\~n}ive, {Jos{\'e} M.}",

note = "Funding Information: This research was supported by grants from the National Institute of Mental Health (R01 MH65304 to Dr Ca{\~n}ive, K01 MH108822 to Dr Chen, and K08 MH085100 to Dr Edgar), a VA Merit grant (VA Merit CSR&D: IIR-04-212-3 to Dr Ca{\~n}ive), and University of California at San Diego Merit Review Grant from the Department of Veterans Affairs to Dr Huang. The authors would like to thank the subjects who enrolled in this study; Megan Schendel, Kim Paulson, Cassandra Wootton, and Emerson Epstein, who helped with data collection; and Lawrence Calais, Gloria Fuldauer, and Nickolas Lemke for their help with subject recruitment and administrative support related to this project. The authors have declared that there are no conflicts of interest in relation to the subject of this study. Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com",

year = "2019",

month = jun,

day = "18",

doi = "10.1093/schbul/sby111",

language = "English",

volume = "45",

pages = "859--870",

journal = "Schizophrenia Bulletin",

issn = "0586-7614",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Associations and heritability of auditory encoding, gray matter, and attention in schizophrenia

AU - Chen, Yu Han

AU - Howell, Breannan

AU - Edgar, J. Christopher

AU - Huang, Mingxiong

AU - Kochunov, Peter

AU - Hunter, Michael A.

AU - Wootton, Cassandra

AU - Lu, Brett Y.

AU - Bustillo, Juan

AU - Sadek, Joseph R.

AU - Miller, Gregory A.

AU - Cañive, José M.

N1 - Funding Information: This research was supported by grants from the National Institute of Mental Health (R01 MH65304 to Dr Cañive, K01 MH108822 to Dr Chen, and K08 MH085100 to Dr Edgar), a VA Merit grant (VA Merit CSR&D: IIR-04-212-3 to Dr Cañive), and University of California at San Diego Merit Review Grant from the Department of Veterans Affairs to Dr Huang. The authors would like to thank the subjects who enrolled in this study; Megan Schendel, Kim Paulson, Cassandra Wootton, and Emerson Epstein, who helped with data collection; and Lawrence Calais, Gloria Fuldauer, and Nickolas Lemke for their help with subject recruitment and administrative support related to this project. The authors have declared that there are no conflicts of interest in relation to the subject of this study. Publisher Copyright: © The Author(s) 2018. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com

PY - 2019/6/18

Y1 - 2019/6/18

N2 - Background: Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). Methods: Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure. Results: SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function−structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. Conclusions: Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function−structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function−structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function−structure relationships in SZ.

AB - Background: Auditory encoding abnormalities, gray-matter loss, and cognitive deficits are all candidate schizophrenia (SZ) endophenotypes. This study evaluated associations between and heritability of auditory network attributes (function and structure) and attention in healthy controls (HC), SZ patients, and unaffected relatives (UR). Methods: Whole-brain maps of M100 auditory activity from magnetoencephalography recordings, cortical thickness (CT), and a measure of attention were obtained from 70 HC, 69 SZ patients, and 35 UR. Heritability estimates (h2r) were obtained for M100, CT at each group-difference region, and the attention measure. Results: SZ patients had weaker bilateral superior temporal gyrus (STG) M100 responses than HC and a weaker right frontal M100 response than UR. Abnormally large M100 responses in left superior frontal gyrus were observed in UR and SZ patients. SZ patients showed smaller CT in bilateral STG and right frontal regions. Interrelatedness between 3 putative SZ endophenotypes was demonstrated, although in the left STG the M100 and CT function−structure associations observed in HC and UR were absent in SZ patients. Heritability analyses also showed that right frontal M100 and bilateral STG CT measures are significantly heritable. Conclusions: Present findings indicated that the 3 SZ endophenotypes examined are not isolated markers of pathology but instead are connected. The pattern of auditory encoding group differences and the pattern of brain function−structure associations differ as a function of brain region, indicating the need for regional specificity when studying these endophenotypes, and with the presence of left STG function−structure associations in HC and UR but not in SZ perhaps reflecting disease-associated damage to gray matter that disrupts function−structure relationships in SZ.

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Associations and heritability of auditory encoding, gray matter, and attention in schizophrenia

Abstract

Bibliographical note

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UN SDGs

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