Heritability of Cerebral Blood Flow and the Correlation to Schizophrenia Spectrum Disorders: A Pseudo-continuous Arterial Spin Labeling Twin Study

Christian S. Legind; Brian V. Broberg; Rachel Brouwer; Rene C. W. Mandl; Bjorn H. Ebdrup; Simon J. Anhoj; Maria H. Jensen; Rikke Warming Hilker; Birgitte Fagerlund; Hilleke E. Hulshoff Pol; Birte Yding Glenthoj; Egill 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

Christian S. Legind, Brian V. Broberg, Rachel Brouwer, Rene C. W. Mandl, Bjorn H. Ebdrup, Simon J. Anhoj, Maria H. Jensen, Rikke Warming Hilker, Birgitte Fagerlund, Hilleke E. Hulshoff Pol, Birte Yding Glenthoj, Egill Rostrup

2 Citationer (Scopus)

Abstract

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.

Originalsprog	Engelsk
Tidsskrift	Schizophrenia Bulletin
Vol/bind	45
Udgave nummer	6
Sider (fra-til)	1231-1241
ISSN	0586-7614
DOI	https://doi.org/10.1093/schbul/sbz007
Status	Udgivet - 24 okt. 2019

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10.1093/schbul/sbz007

https://academic.oup.com/schizophreniabulletin/article-pdf/45/6/1231/30294817/sbz007.pdf

Citationsformater

Legind, C. S., Broberg, B. V., Brouwer, R., Mandl, R. C. W., Ebdrup, B. H., Anhoj, S. J., Jensen, M. H., Hilker, R. W., Fagerlund, B., Pol, H. E. H., Glenthoj, 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

Legind, CS, Broberg, BV, Brouwer, R, Mandl, RCW, Ebdrup, BH, Anhoj, SJ, Jensen, MH, Hilker, RW , Fagerlund, B, Pol, HEH, Glenthoj, 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, bind 45, nr. 6, s. 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 = "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.",

keywords = "pCASL, cerebral blood flow, relatives, twins, genes",

author = "Legind, {Christian S.} and Broberg, {Brian V.} and Rachel Brouwer and Mandl, {Rene C. W.} and Ebdrup, {Bjorn H.} and Anhoj, {Simon J.} and Jensen, {Maria H.} and Hilker, {Rikke Warming} and Birgitte Fagerlund and Pol, {Hilleke E. Hulshoff} and Glenthoj, {Birte Yding} and Egill Rostrup",

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doi = "10.1093/schbul/sbz007",

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AU - Legind, Christian S.

AU - Broberg, Brian V.

AU - Brouwer, Rachel

AU - Mandl, Rene C. W.

AU - Ebdrup, Bjorn H.

AU - Anhoj, Simon J.

AU - Jensen, Maria H.

AU - Hilker, Rikke Warming

AU - Fagerlund, Birgitte

AU - Pol, Hilleke E. Hulshoff

AU - Glenthoj, Birte Yding

AU - Rostrup, Egill

PY - 2019/10/24

Y1 - 2019/10/24

N2 - 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 - 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.

KW - pCASL

KW - cerebral blood flow

KW - relatives, twins

KW - genes

U2 - 10.1093/schbul/sbz007

DO - 10.1093/schbul/sbz007

M3 - Journal article

C2 - 30776063

SN - 0586-7614

VL - 45

SP - 1231

EP - 1241

JO - Schizophrenia Bulletin

JF - Schizophrenia Bulletin

IS - 6

ER -

Heritability of Cerebral Blood Flow and the Correlation to Schizophrenia Spectrum Disorders: A Pseudo-continuous Arterial Spin Labeling Twin Study

Abstract

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