Heritability of cerebral blood flow and the correlation to schizophrenia spectrum disorders: a pseudo-continuous arterial spin labeling twin study

C.S. Legind; B.V. Broberg; R. Brouwer; R.C.W. Mandl; B.H. Ebdrup; S.J. Anhøj; M.H. Jensen; R. Hilker; B. Fagerlund; H.E. Hulshoff Pol; B.Y. Glenthøj; E. Rostrup

doi:10.1093/schbul/sbz007

Heritability of cerebral blood flow and the correlation to schizophrenia spectrum disorders: a pseudo-continuous arterial spin labeling twin study

C.S. Legind, B.V. Broberg, R. Brouwer, R.C.W. Mandl, B.H. Ebdrup, S.J. Anhøj, M.H. Jensen, R. Hilker, B. Fagerlund, H.E. Hulshoff Pol, B.Y. Glenthøj, E. Rostrup

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

Abstract

© 2019 The Author(s) 2019.Whether aberrant cerebral blood flow (CBF) in schizophrenia is affected by genetic influences, and consequently a potential marker for genetic susceptibility, is unknown. Our aims were to determine the heritability of CBF in thalamic, frontal, and striatal areas, and to ascertain if associations with disease were under genetic influence. Monozygotic (MZ) twin pairs concordant (n = 2) or discordant (n = 20) for schizophrenia spectrum disorders (ICD-10 F2x.x), matched on sex and age with dizygotic (DZ; n = 20) and healthy control pairs (MZ: n = 27; DZ: n = 18; total: n = 181 individuals), were recruited via the National Danish Twin Register. CBF in thalamus, frontal lobes, and putamen was measured with pseudo-continuous arterial spin labeling on a 3 T magnetic resonance scanner. Twin statistics were performed with structural equation modeling. CBF in the frontal lobes was heritable (h2 = 0.44, 95% CI [0.22-0.60]) but not correlated to disease. CBF correlated to schizophrenia spectrum disorders in the left thalamus (r = 0.17, [0.03-0.31]; P = 0.02), as well as in the left putamen (r = 0.19, [0.05-0.32]; P = 0.007) and the right putamen (r = 0.18, [0.03-0.32]; P = 0.02). When restricting the sample to schizophrenia (F20.x) only, shared genetic influences between CBF in the left putamen and schizophrenia liability (phenotypic correlation = 0.44, [0.28-0.58], P < 0.001) were found. Our results provide heritability estimates of CBF in the frontal lobes, and we find CBF in thalamus and putamen to be altered in schizophrenia spectrum disorders. Furthermore, shared genetic factors influence schizophrenia liability and striatal perfusion. Specifically, higher perfusion in the left putamen may constitute a marker of genetic susceptibility for schizophrenia.

Original language	English
Pages (from-to)	1231-1241
Journal	Schizophrenia bulletin
Volume	45
Issue number	6
DOIs	https://doi.org/10.1093/schbul/sbz007
Publication status	Published - 24 Oct 2019
Externally published	Yes

Funding

Lundbeck Foundation (grant nos. 25-A2701 and R155-2013-16337). Christian Stefan Legind was supported by a grant from The Mental Health Services—Capital Region of Denmark. The authors would like to acknowledge the valuable contributions of Mikkel Erlang Sørensen and Helle Schæbel. Dr Ebdrup has received lecture fees and/or is part of Advisory Boards of Bristol-Myers Squibb, Eli Lilly and Company, Janssen-Cilag, Otsuka Pharma Scandinavia, and Takeda Pharmaceutical Company. Dr Glenthøj is the leader of a Lundbeck Foundation Centre of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), which is partially financed by an independent grant from the Lundbeck Foundation based on international review and partially financed by the Mental Health Services in the Capital Region of Denmark, the University of Copenhagen, and other foundations. Her group has also received a research grant from Lundbeck A/S for another independent investigator-initiated study. All grants are the property of the Mental Health Services in the Capital Region of Denmark and administrated by them. She has no other conflicts to disclose. All other authors report no conflicts of interest.

Funders	Funder number
Mental Health Services in the Capital Region of Denmark
Mental Health Services—Capital Region of Denmark
Københavns Universitet
Lundbeckfonden	R155-2013-16337, 25-A2701
H. Lundbeck A/S

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Legind, C. S., Broberg, B. V., Brouwer, R., Mandl, R. C. W., Ebdrup, B. H., Anhøj, S. J., Jensen, M. H., Hilker, R., Fagerlund, B., Hulshoff Pol, H. E., Glenthøj, B. Y., & Rostrup, E. (2019). Heritability of cerebral blood flow and the correlation to schizophrenia spectrum disorders: a pseudo-continuous arterial spin labeling twin study. Schizophrenia bulletin, 45(6), 1231-1241. https://doi.org/10.1093/schbul/sbz007

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title = "Heritability of cerebral blood flow and the correlation to schizophrenia spectrum disorders: a pseudo-continuous arterial spin labeling twin study",

abstract = "{\textcopyright} 2019 The Author(s) 2019.Whether aberrant cerebral blood flow (CBF) in schizophrenia is affected by genetic influences, and consequently a potential marker for genetic susceptibility, is unknown. Our aims were to determine the heritability of CBF in thalamic, frontal, and striatal areas, and to ascertain if associations with disease were under genetic influence. Monozygotic (MZ) twin pairs concordant (n = 2) or discordant (n = 20) for schizophrenia spectrum disorders (ICD-10 F2x.x), matched on sex and age with dizygotic (DZ; n = 20) and healthy control pairs (MZ: n = 27; DZ: n = 18; total: n = 181 individuals), were recruited via the National Danish Twin Register. CBF in thalamus, frontal lobes, and putamen was measured with pseudo-continuous arterial spin labeling on a 3 T magnetic resonance scanner. Twin statistics were performed with structural equation modeling. CBF in the frontal lobes was heritable (h2 = 0.44, 95% CI [0.22-0.60]) but not correlated to disease. CBF correlated to schizophrenia spectrum disorders in the left thalamus (r = 0.17, [0.03-0.31]; P = 0.02), as well as in the left putamen (r = 0.19, [0.05-0.32]; P = 0.007) and the right putamen (r = 0.18, [0.03-0.32]; P = 0.02). When restricting the sample to schizophrenia (F20.x) only, shared genetic influences between CBF in the left putamen and schizophrenia liability (phenotypic correlation = 0.44, [0.28-0.58], P < 0.001) were found. Our results provide heritability estimates of CBF in the frontal lobes, and we find CBF in thalamus and putamen to be altered in schizophrenia spectrum disorders. Furthermore, shared genetic factors influence schizophrenia liability and striatal perfusion. Specifically, higher perfusion in the left putamen may constitute a marker of genetic susceptibility for schizophrenia.",

author = "C.S. Legind and B.V. Broberg and R. Brouwer and R.C.W. Mandl and B.H. Ebdrup and S.J. Anh{\o}j and M.H. Jensen and R. Hilker and B. Fagerlund and {Hulshoff Pol}, H.E. and B.Y. Glenth{\o}j and E. Rostrup",

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Legind, CS, Broberg, BV, Brouwer, R, Mandl, RCW, Ebdrup, BH, Anhøj, SJ, Jensen, MH, Hilker, R, Fagerlund, B, Hulshoff Pol, HE, Glenthøj, BY & Rostrup, E 2019, 'Heritability of cerebral blood flow and the correlation to schizophrenia spectrum disorders: a pseudo-continuous arterial spin labeling twin study', Schizophrenia bulletin, vol. 45, no. 6, pp. 1231-1241. https://doi.org/10.1093/schbul/sbz007

TY - JOUR

T1 - Heritability of cerebral blood flow and the correlation to schizophrenia spectrum disorders

T2 - a pseudo-continuous arterial spin labeling twin study

AU - Legind, C.S.

AU - Broberg, B.V.

AU - Brouwer, R.

AU - Mandl, R.C.W.

AU - Ebdrup, B.H.

AU - Anhøj, S.J.

AU - Jensen, M.H.

AU - Hilker, R.

AU - Fagerlund, B.

AU - Hulshoff Pol, H.E.

AU - Glenthøj, B.Y.

AU - Rostrup, E.

PY - 2019/10/24

Y1 - 2019/10/24

N2 - © 2019 The Author(s) 2019.Whether aberrant cerebral blood flow (CBF) in schizophrenia is affected by genetic influences, and consequently a potential marker for genetic susceptibility, is unknown. Our aims were to determine the heritability of CBF in thalamic, frontal, and striatal areas, and to ascertain if associations with disease were under genetic influence. Monozygotic (MZ) twin pairs concordant (n = 2) or discordant (n = 20) for schizophrenia spectrum disorders (ICD-10 F2x.x), matched on sex and age with dizygotic (DZ; n = 20) and healthy control pairs (MZ: n = 27; DZ: n = 18; total: n = 181 individuals), were recruited via the National Danish Twin Register. CBF in thalamus, frontal lobes, and putamen was measured with pseudo-continuous arterial spin labeling on a 3 T magnetic resonance scanner. Twin statistics were performed with structural equation modeling. CBF in the frontal lobes was heritable (h2 = 0.44, 95% CI [0.22-0.60]) but not correlated to disease. CBF correlated to schizophrenia spectrum disorders in the left thalamus (r = 0.17, [0.03-0.31]; P = 0.02), as well as in the left putamen (r = 0.19, [0.05-0.32]; P = 0.007) and the right putamen (r = 0.18, [0.03-0.32]; P = 0.02). When restricting the sample to schizophrenia (F20.x) only, shared genetic influences between CBF in the left putamen and schizophrenia liability (phenotypic correlation = 0.44, [0.28-0.58], P < 0.001) were found. Our results provide heritability estimates of CBF in the frontal lobes, and we find CBF in thalamus and putamen to be altered in schizophrenia spectrum disorders. Furthermore, shared genetic factors influence schizophrenia liability and striatal perfusion. Specifically, higher perfusion in the left putamen may constitute a marker of genetic susceptibility for schizophrenia.

AB - © 2019 The Author(s) 2019.Whether aberrant cerebral blood flow (CBF) in schizophrenia is affected by genetic influences, and consequently a potential marker for genetic susceptibility, is unknown. Our aims were to determine the heritability of CBF in thalamic, frontal, and striatal areas, and to ascertain if associations with disease were under genetic influence. Monozygotic (MZ) twin pairs concordant (n = 2) or discordant (n = 20) for schizophrenia spectrum disorders (ICD-10 F2x.x), matched on sex and age with dizygotic (DZ; n = 20) and healthy control pairs (MZ: n = 27; DZ: n = 18; total: n = 181 individuals), were recruited via the National Danish Twin Register. CBF in thalamus, frontal lobes, and putamen was measured with pseudo-continuous arterial spin labeling on a 3 T magnetic resonance scanner. Twin statistics were performed with structural equation modeling. CBF in the frontal lobes was heritable (h2 = 0.44, 95% CI [0.22-0.60]) but not correlated to disease. CBF correlated to schizophrenia spectrum disorders in the left thalamus (r = 0.17, [0.03-0.31]; P = 0.02), as well as in the left putamen (r = 0.19, [0.05-0.32]; P = 0.007) and the right putamen (r = 0.18, [0.03-0.32]; P = 0.02). When restricting the sample to schizophrenia (F20.x) only, shared genetic influences between CBF in the left putamen and schizophrenia liability (phenotypic correlation = 0.44, [0.28-0.58], P < 0.001) were found. Our results provide heritability estimates of CBF in the frontal lobes, and we find CBF in thalamus and putamen to be altered in schizophrenia spectrum disorders. Furthermore, shared genetic factors influence schizophrenia liability and striatal perfusion. Specifically, higher perfusion in the left putamen may constitute a marker of genetic susceptibility for schizophrenia.

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DO - 10.1093/schbul/sbz007

M3 - Article

SN - 0586-7614

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JO - Schizophrenia bulletin

JF - Schizophrenia bulletin

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ER -

Heritability of cerebral blood flow and the correlation to schizophrenia spectrum disorders: a pseudo-continuous arterial spin labeling twin study

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