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Proton MRS in twin pairs discordant for schizophrenia

Molecular Psychiatry volume 15, pages 308–318 (2010)Cite this article

Abstract

Proton magnetic resonance spectroscopy (1H MRS) neurometabolite abnormalities have been detected widely in subjects with and at risk for schizophrenia. We hypothesized that such abnormalities would be present both in patients with schizophrenia and in their unaffected twin siblings. We acquired magnetic resonance spectra (TR/TE=3000/30 ms) at voxels in the mesial prefrontal gray matter, left prefrontal white matter and left hippocampus in 14 twin pairs discordant for schizophrenia (2 monozygotic, 12 dizygotic), 13 healthy twin pairs (4 monozygotic, 9 dizygotic) and 1 additional unaffected co-twin of a schizophrenia proband. In the mesial prefrontal gray matter voxel, N-acetylaspartate (NAA), creatine+phosphocreatine (Cr), glycerophosphocholine+phosphocholine (Cho) and myo-inositol (mI) did not differ significantly between patients with schizophrenia, their unaffected co-twins or healthy controls. However, glutamate (Glu) was significantly lower in patients with schizophrenia (31%, percent difference) and unaffected co-twins (21%) than in healthy controls (collapsed across twin pairs). In the left hippocampus voxel, levels of NAA (23%), Cr (22%) and Cho (36%) were higher in schizophrenia patients compared with controls. Hippocampal NAA (25%), Cr (22%) and Cho (37%) were also significantly higher in patients than in their unaffected co-twins. Region-to-region differences in metabolite levels were also notable within all three diagnosis groups. These findings suggest that 1H MRS neurometabolite abnormalities are present not only in patients with schizophrenia, but also in their unaffected co-twins. Thus, reduced mesial prefrontal cortical Glu and elevated hippocampal NAA, Cr and Cho may represent trait markers of schizophrenia risk and, when exacerbated, state markers of schizophrenia itself.

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Acknowledgements

This work was supported by a research grant from the National Institute of Mental Health (to TDC). From the Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland, we thank Ulla Mustonen, Tiia Pirkola, Pirjo Käki, Eila Voipio and Annamari Tuulio-Henriksson for their contributions to subject recruitment and assessment; Antti Tanksanen for his contributions to the register searches; Kauko Heikkilä for his contributions to data management of the Finnish Twin Cohort Study and Sami Heikkinen for his work in setting up the protocol. We also thank Dr Provencher for providing the LCModel basis set. Finally, we thank the subjects, whose participation made this project possible.

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Authors and Affiliations

  1. Department of Neuroscience IDP, UCLA, Los Angeles, CA, USA

    E S Lutkenhoff

  2. Department of Psychology, UCLA, Los Angeles, CA, USA

    T G van Erp & T D Cannon

  3. Department of Radiological Sciences, UCLA, Los Angeles, CA, USA

    M A Thomas

  4. Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland

    S Therman, M Manninen, M O Huttunen, J Kaprio & J Lönnqvist

  5. Department of Public Health, University of Helsinki, Helsinki, Finland

    J Kaprio

  6. Division of Child and Adolescent Psychiatry, UCLA Semel Institute for Neuroscience, Los Angeles, CA, USA

    J O'Neill

  7. Department of Psychiatry, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

    J Lönnqvist

  8. Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, CA, USA

    T D Cannon

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  1. E S Lutkenhoff
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Lutkenhoff, E., van Erp, T., Thomas, M. et al. Proton MRS in twin pairs discordant for schizophrenia. Mol Psychiatry 15, 308–318 (2010). https://doi.org/10.1038/mp.2008.87

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