Heritability of cerebral glutamate levels and their association with schizophrenia spectrum disorders: a 1[H]-spectroscopy twin study

Christian Stefan Legind; Brian Villumsen Broberg; René Christiaan William Mandl; Rachel Brouwer; Simon Jesper Anhøj; Rikke Hilker; Maria Høj Jensen; Philip McGuire; Hilleke Hulshoff Pol; Birgitte Fagerlund; Egill Rostrup; Birte Yding Glenthøj

doi:10.1038/s41386-018-0236-0

Heritability of cerebral glutamate levels and their association with schizophrenia spectrum disorders: a ¹[H]-spectroscopy twin study

Christian Stefan Legind, Brian Villumsen Broberg, René Christiaan William Mandl, Rachel Brouwer, Simon Jesper Anhøj, Rikke Hilker, Maria Høj Jensen, Philip McGuire, Hilleke Hulshoff Pol, Birgitte Fagerlund, Egill Rostrup, Birte Yding Glenthøj

Department of Clinical Medicine

12 Citations (Scopus)

Abstract

Research findings implicate cerebral glutamate in the pathophysiology of schizophrenia, including genetic studies reporting associations with glutamatergic neurotransmission. The extent to which aberrant glutamate levels can be explained by genetic factors is unknown, and if glutamate can serve as a marker of genetic susceptibility for schizophrenia remains to be established. We investigated the heritability of cerebral glutamate levels and whether a potential association with schizophrenia spectrum disorders could be explained by genetic factors. Twenty-three monozygotic (MZ) and 20 dizygotic (DZ) proband pairs con- or discordant for schizophrenia spectrum disorders, along with healthy control pairs (MZ = 28, DZ = 18) were recruited via the National Danish Twin Register and the Psychiatric Central Register (17 additional twins were scanned without their siblings). Glutamate levels in the left thalamus and the anterior cingulate cortex (ACC) were measured using 1[H]-magnetic resonance spectroscopy at 3 Tesla and analyzed by structural equation modeling. Glutamate levels in the left thalamus were heritable and positively correlated with liability for schizophrenia spectrum disorders (phenotypic correlation, 0.16, [0.02-0.29]; p = 0.010). The correlation was explained by common genes influencing both the levels of glutamate and liability for schizophrenia spectrum disorders. In the ACC, glutamate and glx levels were heritable, but not correlated to disease liability. Increases in thalamic glutamate levels found in schizophrenia spectrum disorders are explained by genetic influences related to the disease, and as such the measure could be a potential marker of genetic susceptibility, useful in early detection and stratification of patients with psychosis.

Original language	English
Journal	Neuropsychopharmacology
Volume	44
Pages (from-to)	581-589
ISSN	0893-133X
DOIs	https://doi.org/10.1038/s41386-018-0236-0
Publication status	Published - 1 Feb 2019

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Legind, C. S., Broberg, B. V., Mandl, R. C. W., Brouwer, R., Anhøj, S. J., Hilker, R., Jensen, M. H., McGuire, P., Pol, H. H., Fagerlund, B., Rostrup, E., & Glenthøj, B. Y. (2019). Heritability of cerebral glutamate levels and their association with schizophrenia spectrum disorders: a ¹[H]-spectroscopy twin study. Neuropsychopharmacology, 44, 581-589. https://doi.org/10.1038/s41386-018-0236-0

Heritability of cerebral glutamate levels and their association with schizophrenia spectrum disorders: a ¹[H]-spectroscopy twin study. / Legind, Christian Stefan; Broberg, Brian Villumsen; Mandl, René Christiaan William et al.
In: Neuropsychopharmacology, Vol. 44, 01.02.2019, p. 581-589.

Research output: Contribution to journal › Journal article › Research › peer-review

Legind, CS, Broberg, BV, Mandl, RCW, Brouwer, R, Anhøj, SJ, Hilker, R, Jensen, MH, McGuire, P, Pol, HH, Fagerlund, B, Rostrup, E & Glenthøj, BY 2019, 'Heritability of cerebral glutamate levels and their association with schizophrenia spectrum disorders: a ¹[H]-spectroscopy twin study', Neuropsychopharmacology, vol. 44, pp. 581-589. https://doi.org/10.1038/s41386-018-0236-0

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abstract = "Research findings implicate cerebral glutamate in the pathophysiology of schizophrenia, including genetic studies reporting associations with glutamatergic neurotransmission. The extent to which aberrant glutamate levels can be explained by genetic factors is unknown, and if glutamate can serve as a marker of genetic susceptibility for schizophrenia remains to be established. We investigated the heritability of cerebral glutamate levels and whether a potential association with schizophrenia spectrum disorders could be explained by genetic factors. Twenty-three monozygotic (MZ) and 20 dizygotic (DZ) proband pairs con- or discordant for schizophrenia spectrum disorders, along with healthy control pairs (MZ = 28, DZ = 18) were recruited via the National Danish Twin Register and the Psychiatric Central Register (17 additional twins were scanned without their siblings). Glutamate levels in the left thalamus and the anterior cingulate cortex (ACC) were measured using 1[H]-magnetic resonance spectroscopy at 3 Tesla and analyzed by structural equation modeling. Glutamate levels in the left thalamus were heritable and positively correlated with liability for schizophrenia spectrum disorders (phenotypic correlation, 0.16, [0.02-0.29]; p = 0.010). The correlation was explained by common genes influencing both the levels of glutamate and liability for schizophrenia spectrum disorders. In the ACC, glutamate and glx levels were heritable, but not correlated to disease liability. Increases in thalamic glutamate levels found in schizophrenia spectrum disorders are explained by genetic influences related to the disease, and as such the measure could be a potential marker of genetic susceptibility, useful in early detection and stratification of patients with psychosis.",

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AU - Broberg, Brian Villumsen

AU - Mandl, René Christiaan William

AU - Brouwer, Rachel

AU - Anhøj, Simon Jesper

AU - Hilker, Rikke

AU - Jensen, Maria Høj

AU - McGuire, Philip

AU - Pol, Hilleke Hulshoff

AU - Fagerlund, Birgitte

AU - Rostrup, Egill

AU - Glenthøj, Birte Yding

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N2 - Research findings implicate cerebral glutamate in the pathophysiology of schizophrenia, including genetic studies reporting associations with glutamatergic neurotransmission. The extent to which aberrant glutamate levels can be explained by genetic factors is unknown, and if glutamate can serve as a marker of genetic susceptibility for schizophrenia remains to be established. We investigated the heritability of cerebral glutamate levels and whether a potential association with schizophrenia spectrum disorders could be explained by genetic factors. Twenty-three monozygotic (MZ) and 20 dizygotic (DZ) proband pairs con- or discordant for schizophrenia spectrum disorders, along with healthy control pairs (MZ = 28, DZ = 18) were recruited via the National Danish Twin Register and the Psychiatric Central Register (17 additional twins were scanned without their siblings). Glutamate levels in the left thalamus and the anterior cingulate cortex (ACC) were measured using 1[H]-magnetic resonance spectroscopy at 3 Tesla and analyzed by structural equation modeling. Glutamate levels in the left thalamus were heritable and positively correlated with liability for schizophrenia spectrum disorders (phenotypic correlation, 0.16, [0.02-0.29]; p = 0.010). The correlation was explained by common genes influencing both the levels of glutamate and liability for schizophrenia spectrum disorders. In the ACC, glutamate and glx levels were heritable, but not correlated to disease liability. Increases in thalamic glutamate levels found in schizophrenia spectrum disorders are explained by genetic influences related to the disease, and as such the measure could be a potential marker of genetic susceptibility, useful in early detection and stratification of patients with psychosis.

AB - Research findings implicate cerebral glutamate in the pathophysiology of schizophrenia, including genetic studies reporting associations with glutamatergic neurotransmission. The extent to which aberrant glutamate levels can be explained by genetic factors is unknown, and if glutamate can serve as a marker of genetic susceptibility for schizophrenia remains to be established. We investigated the heritability of cerebral glutamate levels and whether a potential association with schizophrenia spectrum disorders could be explained by genetic factors. Twenty-three monozygotic (MZ) and 20 dizygotic (DZ) proband pairs con- or discordant for schizophrenia spectrum disorders, along with healthy control pairs (MZ = 28, DZ = 18) were recruited via the National Danish Twin Register and the Psychiatric Central Register (17 additional twins were scanned without their siblings). Glutamate levels in the left thalamus and the anterior cingulate cortex (ACC) were measured using 1[H]-magnetic resonance spectroscopy at 3 Tesla and analyzed by structural equation modeling. Glutamate levels in the left thalamus were heritable and positively correlated with liability for schizophrenia spectrum disorders (phenotypic correlation, 0.16, [0.02-0.29]; p = 0.010). The correlation was explained by common genes influencing both the levels of glutamate and liability for schizophrenia spectrum disorders. In the ACC, glutamate and glx levels were heritable, but not correlated to disease liability. Increases in thalamic glutamate levels found in schizophrenia spectrum disorders are explained by genetic influences related to the disease, and as such the measure could be a potential marker of genetic susceptibility, useful in early detection and stratification of patients with psychosis.

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DO - 10.1038/s41386-018-0236-0

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EP - 589

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

ER -

Heritability of cerebral glutamate levels and their association with schizophrenia spectrum disorders: a 1[H]-spectroscopy twin study

Abstract

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Heritability of cerebral glutamate levels and their association with schizophrenia spectrum disorders: a ¹[H]-spectroscopy twin study