Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

E. Walton; D. P. Hibar; Karolinska Schizophrenia Project Consortium (KaSP); T. G.M. Van Erp; S. G. Potkin; R. Roiz-Santiañez; B. Crespo-Facorro; P. Suarez-Pinilla; University Medical Utrecht; S. M.C. De Zwarte; R. S. Kahn; W. Cahn; N. T. Doan; K. N. Jorgensen; T. P. Gurholt; I. Agartz; O. A. Andreassen; L. T. Westlye; I. Melle; A. O. Berg; L. Morch-Johnsen; A. Færden; L. Flyckt; H. Fatouros-Bergman; E. G. Jönsson; R. Hashimoto; H. Yamamori; M. Fukunaga; N. Jahanshad; P. De Rossi; F. Piras; N. Banaj; G. Spalletta; R. E. Gur; R. C. Gur; D. H. Wolf; T. D. Satterthwaite; L. M. Beard; I. E. Sommer; S. Koops; O. Gruber; A. Richter; B. Krämer; S. Kelly; G. Donohoe; C. McDonald; D. M. Cannon; A. Corvin; M. Gill; A. Di Giorgio; J. A. Turner

doi:10.1017/S0033291717001283

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

E. Walton, D. P. Hibar, Karolinska Schizophrenia Project Consortium (KaSP), T. G.M. Van Erp, S. G. Potkin, R. Roiz-Santiañez, B. Crespo-Facorro, P. Suarez-Pinilla, University Medical Utrecht, S. M.C. De Zwarte, R. S. Kahn, W. Cahn, N. T. Doan, K. N. Jorgensen, T. P. Gurholt, I. Agartz, O. A. Andreassen, L. T. Westlye, I. Melle, A. O. BergL. Morch-Johnsen, A. Færden, L. Flyckt, H. Fatouros-Bergman, E. G. Jönsson, R. Hashimoto, H. Yamamori, M. Fukunaga, N. Jahanshad, P. De Rossi, F. Piras, N. Banaj, G. Spalletta, R. E. Gur, R. C. Gur, D. H. Wolf, T. D. Satterthwaite, L. M. Beard, I. E. Sommer, S. Koops, O. Gruber, A. Richter, B. Krämer, S. Kelly, G. Donohoe, C. McDonald, D. M. Cannon, A. Corvin, M. Gill, A. Di Giorgio, J. A. Turner

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

79 Citations (Scopus)

Abstract

Background Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. Methods This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). Results Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. Conclusions Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

Original language	English
Pages (from-to)	82-94
Number of pages	13
Journal	Psychological Medicine
Volume	48
Issue number	1
DOIs	https://doi.org/10.1017/S0033291717001283
Publication status	Published - 1 Jan 2018
Externally published	Yes

Bibliographical note

Funding Information:
ENIGMA was supported in part by a Consortium grant (U54 EB020403 to PMT) from the NIH Institutes contributing to the Big Data to Knowledge (BD2K) Initiative, including the NIBIB and NCI. The authors would also like to express their gratitude for the personal support from the Deutsche Forschungsgemeinschaft (Research Fellowship to E.W.; Wa 3635/1–1). For additional support, see online Supplementary Section 3.

Publisher Copyright:
© 2017 Cambridge University Press.

UN SDGs

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

Access to Document

10.1017/S0033291717001283

Cite this

Walton, E., Hibar, D. P., Karolinska Schizophrenia Project Consortium (KaSP), Van Erp, T. G. M., Potkin, S. G., Roiz-Santiañez, R., Crespo-Facorro, B., Suarez-Pinilla, P., Utrecht, U. M., De Zwarte, S. M. C., Kahn, R. S., Cahn, W., Doan, N. T., Jorgensen, K. N., Gurholt, T. P., Agartz, I., Andreassen, O. A., Westlye, L. T., Melle, I., ... Turner, J. A. (2018). Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium. Psychological Medicine, 48(1), 82-94. https://doi.org/10.1017/S0033291717001283

@article{bd7299f3eac5476292c12be2bbb01842,

title = "Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium",

abstract = "Background Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. Methods This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). Results Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. Conclusions Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.",

author = "E. Walton and Hibar, {D. P.} and {Karolinska Schizophrenia Project Consortium (KaSP)} and {Van Erp}, {T. G.M.} and Potkin, {S. G.} and R. Roiz-Santia{\~n}ez and B. Crespo-Facorro and P. Suarez-Pinilla and Utrecht, {University Medical} and {De Zwarte}, {S. M.C.} and Kahn, {R. S.} and W. Cahn and Doan, {N. T.} and Jorgensen, {K. N.} and Gurholt, {T. P.} and I. Agartz and Andreassen, {O. A.} and Westlye, {L. T.} and I. Melle and Berg, {A. O.} and L. Morch-Johnsen and A. F{\ae}rden and L. Flyckt and H. Fatouros-Bergman and J{\"o}nsson, {E. G.} and R. Hashimoto and H. Yamamori and M. Fukunaga and N. Jahanshad and {De Rossi}, P. and F. Piras and N. Banaj and G. Spalletta and Gur, {R. E.} and Gur, {R. C.} and Wolf, {D. H.} and Satterthwaite, {T. D.} and Beard, {L. M.} and Sommer, {I. E.} and S. Koops and O. Gruber and A. Richter and B. Kr{\"a}mer and S. Kelly and G. Donohoe and C. McDonald and Cannon, {D. M.} and A. Corvin and M. Gill and {Di Giorgio}, A. and Turner, {J. A.}",

note = "Funding Information: ENIGMA was supported in part by a Consortium grant (U54 EB020403 to PMT) from the NIH Institutes contributing to the Big Data to Knowledge (BD2K) Initiative, including the NIBIB and NCI. The authors would also like to express their gratitude for the personal support from the Deutsche Forschungsgemeinschaft (Research Fellowship to E.W.; Wa 3635/1–1). For additional support, see online Supplementary Section 3. Publisher Copyright: {\textcopyright} 2017 Cambridge University Press.",

year = "2018",

month = jan,

day = "1",

doi = "10.1017/S0033291717001283",

language = "English",

volume = "48",

pages = "82--94",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

number = "1",

}

Walton, E, Hibar, DP, Karolinska Schizophrenia Project Consortium (KaSP), Van Erp, TGM, Potkin, SG, Roiz-Santiañez, R, Crespo-Facorro, B, Suarez-Pinilla, P, Utrecht, UM, De Zwarte, SMC, Kahn, RS, Cahn, W, Doan, NT, Jorgensen, KN, Gurholt, TP, Agartz, I, Andreassen, OA, Westlye, LT, Melle, I, Berg, AO, Morch-Johnsen, L, Færden, A, Flyckt, L, Fatouros-Bergman, H, Jönsson, EG, Hashimoto, R, Yamamori, H, Fukunaga, M, Jahanshad, N, De Rossi, P, Piras, F, Banaj, N, Spalletta, G, Gur, RE, Gur, RC, Wolf, DH, Satterthwaite, TD, Beard, LM, Sommer, IE, Koops, S, Gruber, O, Richter, A, Krämer, B, Kelly, S, Donohoe, G, McDonald, C, Cannon, DM, Corvin, A, Gill, M, Di Giorgio, A & Turner, JA 2018, 'Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium', Psychological Medicine, vol. 48, no. 1, pp. 82-94. https://doi.org/10.1017/S0033291717001283

TY - JOUR

T1 - Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

AU - Walton, E.

AU - Hibar, D. P.

AU - Karolinska Schizophrenia Project Consortium (KaSP)

AU - Van Erp, T. G.M.

AU - Potkin, S. G.

AU - Roiz-Santiañez, R.

AU - Crespo-Facorro, B.

AU - Suarez-Pinilla, P.

AU - Utrecht, University Medical

AU - De Zwarte, S. M.C.

AU - Kahn, R. S.

AU - Cahn, W.

AU - Doan, N. T.

AU - Jorgensen, K. N.

AU - Gurholt, T. P.

AU - Agartz, I.

AU - Andreassen, O. A.

AU - Westlye, L. T.

AU - Melle, I.

AU - Berg, A. O.

AU - Morch-Johnsen, L.

AU - Færden, A.

AU - Flyckt, L.

AU - Fatouros-Bergman, H.

AU - Jönsson, E. G.

AU - Hashimoto, R.

AU - Yamamori, H.

AU - Fukunaga, M.

AU - Jahanshad, N.

AU - De Rossi, P.

AU - Piras, F.

AU - Banaj, N.

AU - Spalletta, G.

AU - Gur, R. E.

AU - Gur, R. C.

AU - Wolf, D. H.

AU - Satterthwaite, T. D.

AU - Beard, L. M.

AU - Sommer, I. E.

AU - Koops, S.

AU - Gruber, O.

AU - Richter, A.

AU - Krämer, B.

AU - Kelly, S.

AU - Donohoe, G.

AU - McDonald, C.

AU - Cannon, D. M.

AU - Corvin, A.

AU - Gill, M.

AU - Di Giorgio, A.

AU - Turner, J. A.

N1 - Funding Information: ENIGMA was supported in part by a Consortium grant (U54 EB020403 to PMT) from the NIH Institutes contributing to the Big Data to Knowledge (BD2K) Initiative, including the NIBIB and NCI. The authors would also like to express their gratitude for the personal support from the Deutsche Forschungsgemeinschaft (Research Fellowship to E.W.; Wa 3635/1–1). For additional support, see online Supplementary Section 3. Publisher Copyright: © 2017 Cambridge University Press.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. Methods This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). Results Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. Conclusions Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

AB - Background Our understanding of the complex relationship between schizophrenia symptomatology and etiological factors can be improved by studying brain-based correlates of schizophrenia. Research showed that impairments in value processing and executive functioning, which have been associated with prefrontal brain areas [particularly the medial orbitofrontal cortex (MOFC)], are linked to negative symptoms. Here we tested the hypothesis that MOFC thickness is associated with negative symptom severity. Methods This study included 1985 individuals with schizophrenia from 17 research groups around the world contributing to the ENIGMA Schizophrenia Working Group. Cortical thickness values were obtained from T1-weighted structural brain scans using FreeSurfer. A meta-analysis across sites was conducted over effect sizes from a model predicting cortical thickness by negative symptom score (harmonized Scale for the Assessment of Negative Symptoms or Positive and Negative Syndrome Scale scores). Results Meta-analytical results showed that left, but not right, MOFC thickness was significantly associated with negative symptom severity (β std = -0.075; p = 0.019) after accounting for age, gender, and site. This effect remained significant (p = 0.036) in a model including overall illness severity. Covarying for duration of illness, age of onset, antipsychotic medication or handedness weakened the association of negative symptoms with left MOFC thickness. As part of a secondary analysis including 10 other prefrontal regions further associations in the left lateral orbitofrontal gyrus and pars opercularis emerged. Conclusions Using an unusually large cohort and a meta-analytical approach, our findings point towards a link between prefrontal thinning and negative symptom severity in schizophrenia. This finding provides further insight into the relationship between structural brain abnormalities and negative symptoms in schizophrenia.

UR - http://www.scopus.com/inward/record.url?scp=85039994013&partnerID=8YFLogxK

U2 - 10.1017/S0033291717001283

DO - 10.1017/S0033291717001283

M3 - Article

C2 - 28545597

AN - SCOPUS:85039994013

VL - 48

SP - 82

EP - 94

JO - Psychological Medicine

JF - Psychological Medicine

SN - 0033-2917

IS - 1

ER -

Prefrontal cortical thinning links to negative symptoms in schizophrenia via the ENIGMA consortium

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this