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

Legind, CS; Broberg, BV; Mandl, RCW; Brouwer, R; Anhøj, SJ; Hilker, R; Jensen, MH; McGuire, P; Pol, HH; Fagerlund, B; Rostrup, E; Glenthøj, BY

Neuroscience & Neuroimaging Research Collection

Journal article

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

Abstract:: Dysfunction of glutamate neurotransmission has been implicated in the pathophysiology of schizophrenia and may be particularly relevant in severe, treatment-resistant symptoms. The underlying mechanism may involve hypofunction of the NMDA receptor. We investigated whether schizophrenia-related pathway polygenic scores, composed of genetic variants within NMDA receptor encoding genes, are associated with cortical glutamate in schizophrenia. Anterior cingulate cortex (ACC) glutamate was measured in 70 participants across 4 research sites using Proton Magnetic Resonance Spectroscopy (1H-MRS). Two NMDA receptor gene sets were sourced from the Molecular Signatories Database and NMDA receptor pathway polygenic scores were constructed using PRSet. The NMDA receptor pathway polygenic scores were weighted by single nucleotide polymorphism (SNP) associations with treatment-resistant schizophrenia, and associations with ACC glutamate were tested. We then tested whether NMDA receptor pathway polygenic scores with SNPs weighted by associations with non-treatment-resistant schizophrenia were associated with ACC glutamate. A higher NMDA receptor complex pathway polygenic score was significantly associated with lower ACC glutamate (β = −0.25, 95 % CI = −0.49, −0.02, competitive p = 0.03). When SNPs were weighted by associations with non-treatment-resistant schizophrenia, there was no association between the NMDA receptor complex pathway polygenic score and ACC glutamate (β = 0.05, 95 % CI = −0.18, 0.27, competitive p = 0.79). These results provide initial evidence of an association between common genetic variation implicated in NMDA receptor function and ACC glutamate levels in schizophrenia. This association was specific to when the NMDA receptor complex pathway polygenic score was weighted by SNP associations with treatment-resistant schizophrenia

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

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. (2018). Heritability of cerebral glutamate levels and their association with schizophrenia spectrum disorders: a 1[H]-spectroscopy twin study. Neuropsychopharmacology, 44(3), 581–589.

MLA Style

Legind, CS, et al. “Heritability of Cerebral Glutamate Levels and Their Association with Schizophrenia Spectrum Disorders: a 1[H]-Spectroscopy Twin Study.” Neuropsychopharmacology, vol. 44, no. 3, 2018, pp. 581–89.

Chicago Style

Legind, CS, BV Broberg, RCW Mandl, et al. 2018. “Heritability of Cerebral Glutamate Levels and Their Association with Schizophrenia Spectrum Disorders: a 1[H]-Spectroscopy Twin Study.” Neuropsychopharmacology 44 (3): 581–89.
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