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

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.

SUBMITTER: Legind CS

PROVIDER: S-EPMC6333786 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Legind Christian Stefan CS Broberg Brian Villumsen BV Mandl René Christiaan William RCW Brouwer Rachel R Anhøj Simon Jesper SJ Hilker Rikke R Jensen Maria Høj MH McGuire Philip P Pol Hilleke Hulshoff HH Fagerlund Birgitte B Rostrup Egill E Glenthøj Birte Yding BY

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20181009 3

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 spec ...[more]

PMID: 30301944

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Project description:BackgroundThe etiology of Autism Spectrum Disorder (ASD) has been recently debated due to emerging findings on the importance of shared environmental influences. However, two recent twin studies do not support this and instead re-affirm strong genetic effects on the liability to ASD, a finding consistent with previous reports. This study conducts a systematic review and meta-analysis of all twin studies of ASD published to date and explores the etiology along the continuum of a quantitative measure of ASD.MethodsA PubMed Central, Science Direct, Google Scholar, Web of Knowledge structured search conducted online, to identify all twin studies on ASD published to date. Thirteen primary twin studies were identified, seven were included in the meta-analysis by meeting Systematic Recruitment criterion; correction for selection and ascertainment strategies, and applied prevalences were assessed for these studies. In addition, a quantile DF extremes analysis was carried out on Childhood Autism Spectrum Test scores measured in a population sample of 6,413 twin pairs including affected twins.ResultsThe meta-analysis correlations for monozygotic twins (MZ) were almost perfect at .98 (95% Confidence Interval, .96-.99). The dizygotic (DZ) correlation, however, was .53 (95% CI .44-.60) when ASD prevalence rate was set at 5% (in line with the Broad Phenotype of ASD) and increased to .67 (95% CI .61-.72) when applying a prevalence rate of 1%. The meta-analytic heritability estimates were substantial: 64-91%. Shared environmental effects became significant as the prevalence rate decreased from 5-1%: 07-35%. The DF analyses show that for the most part, there is no departure from linearity in heritability.ConclusionsWe demonstrate that: (a) ASD is due to strong genetic effects; (b) shared environmental effects become significant as a function of lower prevalence rate; (c) previously reported significant shared environmental influences are likely a statistical artefact of overinclusion of concordant DZ twins.

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

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

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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