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Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia

  • Naoko Aoyama (a1), Jean Théberge (a2), Dick J. Drost (a3), Rahul Manchanda (a4), Sandra Northcott (a4), Richard W. J. Neufeld (a5), Ravi S. Menon (a6), Nagalingam Rajakumar (a7), William F. Pavlosky (a8), Maria Densmore (a9), Betsy Schaefer (a4) and Peter C. Williamson (a10)...

Abstract

Background

Thalamic glutamine loss and grey matter reduction suggest neurodegeneration in first-episode schizophrenia, but the duration is unknown.

Aims

To observe glutamine and glutamate levels, grey matter volumes and social functioning in patients with schizophrenia followed to 80 months after diagnosis.

Method

Grey matter volumes and proton magnetic resonance spectroscopy metabolites in left anterior cingulate and left thalamus were measured in 17 patients with schizophrenia before medication and 10 and 80 months after diagnosis. Social functioning was assessed with the Life Skills Profile Rating Scale (LSPRS) at 80 months.

Results

The sum of thalamic glutamate and glutamine levels decreased over 80 months, and correlated inversely with the LSPRS. Thalamic glutamine and grey matter loss were significantly correlated in frontal, parietal, temporal and limbic regions.

Conclusions

Brain metabolite loss is correlated with deteriorated social functioning and grey matter losses in schizophrenia, consistent with neurodegeneration.

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Copyright

Corresponding author

Peter C. Williamson, MD, Tanna Schulich Chair in Neuroscience and Mental Health, Department of Psychiatry, University Hospital, London Health Sciences Centre, 339 Windermere Road, London, Ontario, Canada, N6A 5A5. Email: williams@uwo.ca

Footnotes

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This work was supported by the Tanna Schulich Chair in Neuroscience and Mental Health and the Canadian Institutes of Health Research (Grant MT-12078)

Declaration of interest

None.

Footnotes

References

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Grey matter and social functioning correlates of glutamatergic metabolite loss in schizophrenia

  • Naoko Aoyama (a1), Jean Théberge (a2), Dick J. Drost (a3), Rahul Manchanda (a4), Sandra Northcott (a4), Richard W. J. Neufeld (a5), Ravi S. Menon (a6), Nagalingam Rajakumar (a7), William F. Pavlosky (a8), Maria Densmore (a9), Betsy Schaefer (a4) and Peter C. Williamson (a10)...
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eLetters

Grey matter and glutamate loss, social functioning and schizophrenia

John F Heffernan, Consultant Psychiatrist
21 July 2011

The study by Aoyama et al examines glutamine, glutamate levels and grey matter changes in subjects diagnosed with schizophrenia and compares changes with controls over a time period of 80 months.

The conclusion reached is that metabolite, grey matter loss and deteriorated social functioning is consistent with a process of neurodegeneration in schizophrenia.

Although the authors state a pre-specified aim of examining metabolite changes using magnetic resonance spectroscopy in the anterior cingulate and the thalamus, there was no pre-specified anatomical definition of what constitutes grey matter loss prior to analysis, even though various lobes were presented in the results section and subsequent analysis. Ioannidis(1), after finding excess significance bias in papers on brain volume changes, recommends using pre-specified protocols outlining specific anatomical areas prior to analysis to increase the reliability of brain volume studies.

The authors also do not present information on any of the subjects smoking levels, whether they were ever hospitalised and if they were for how long,

their level of social interaction during the study and their level of physical activity, presumably lower than the active volunteer controls. Similar volumetric follow up studies have presented data on smoking after initially not presenting smoking data in their original analysis.(2)

The use of MRI imaging to study volumetric brain changes have been conducted in many fields both medical and non medical. An increase in grey

matter volume (examining specifically the hippocampus) is documented in subjects with schizophrenia partaking in exercise programmes.(3) Healthy but sedentary older adults participating in an aerobic exercise programme show

increased grey matter volume over time versus controls.(4) In non-medical fields children who learn musical instruments versus those that don’t show

differences in structural brain changes and professional versus amateur musicians versus non-musicians have shown differences in motor, somatosensory and parietal areas associated with the degree of musician status.(5)

It is recognised that the brain, like other organs of the body, respond to changing physiological demands with corresponding anatomical changes which can be detected using imaging techniques. It is therefore reasonableto also conclude that an explanation for changes in grey matter volume, and presumably associated brain metabolite levels, may correlate with a reduction in both social interaction, physical activity and loss of social role in those diagnosed with schizophrenia with all the consequences this entails. Presumably similar changes may occur with someone who becomes unemployed and starts heavy smoking, or indeed any other change in psychosocial role that human beings undergo. The construction of a narrative in this paper that the changes reported are due to an independent disease mechanism, either through excitotoxicity or a specific neurodegenerative plasticity surely cannot be justified on the basis of what is presented. 1 Ioannidis JPA. Excess significance bias in the literature on brainvolume abnormalities. Archive of General Psychiatry 2011; April 4. Epub ahead of print.

2Van Haren NEM, Koolschijn PCMP, Cahn W, Schnack HG, Hulshoff Pol HE, Kahn RS. Cigarette smoking and progressive brain volume loss in schizophrenia. European Neuropsychopharmacology 2010; 20: 454–458.

3Pajonk F, Wobrock T, Gruber O, Scherk H, Berner D, Kaizl I, et al. Hippocampal Plasticity in Response to Exercise in Schizophrenia. Archive of General Psychiatry 2010; 67:133-143.

4Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E, et al. Aerobic Exercise Training Increases Brain Volume in Aging Humans. Journal of Gerontology 2006; 61A: 11, 1166–1170.

5Gaser C, Schlaug G. Brain Structures Differ between Musicians and Non-Musicians. The Journal of Neuroscience 2003; 23(27): 9240-9245.
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Conflict of interest: None Declared

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