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18 juillet 2011 1 18 /07 /juillet /2011 15:48

Neuropsychopharmacology (2011) 36, 1779–1780; doi:10.1038/npp.2011.83

Is there Evidence for Neurotoxicity in the Prodromal and Early Stages of Schizophrenia?

Adrienne C Lahti1 and Meredith A Reid1,2

  1.  1Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham, Birmingham, AL, USA
  2.  2Department of Biomedical Engineering, The University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence: Dr AC Lahti, Department of Psychiatry and Behavioral Neurobiology, The University of Alabama at Birmingham, 1530 3rd AVE S, Birmingham, AL 35294-0017, USA, Tel: +1 205 996 6776, Fax: +1 205 975 4879, E-mail: alahti@uab.edu

Received 19 April 2011; Accepted 19 April 2011


Retrospective and prospective studies in schizophrenia have identified a period of time, termed the prodromal period, that precedes the first episode of frank psychosis by a variable length of time (days–years) and is characterized by subthreshold psychotic symptoms. 

Importantly, both the prodromal phase and the early stages of the schizophrenia illness are associated with significant loss in social and intellectual abilities (Yung et al, 2005), as well as gray matter volume (Cahn et al, 2006; Pantelis et al, 2003).

Biol Psychiatry. 2009 Sep 15;66(6):533-9. Epub 2009 Jun 25.

Glutamate dysfunction in people with prodromal symptoms of psychosis: relationship to gray matter volume.

Stone JM, Day F, Tsagaraki H, Valli I, McLean MA, Lythgoe DJ, O'Gorman RL, Barker GJ, McGuire PK; OASIS.

Collaborators (8)



Institute of Psychiatry, King's College London, University College London, United Kingdom. james.stone@iop.kcl.ac.uk



The glutamate model of schizophrenia proposes that altered glutamatergic neurotransmission is fundamental to the development of the disorder. In addition, its potential to mediate neurotoxicity raises the possibility that glutamate dysfunction could underlie neuroanatomic changes in schizophrenia. Here we determine whether changes in brain glutamate are present in subjects at ultra high risk of developing psychosis and whether these changes are related to reductions in cortical gray matter volume.


Twenty-seven individuals with an at-risk mental state and a group of 27 healthy volunteers underwent proton magnetic resonance spectroscopy and volumetric proton magnetic resonance imaging using a 3-Tesla scanner. Glutamate and glutamine levels were measured in anterior cingulate, left hippocampus, and left thalamus. These measures were then related to cortical gray matter volume.


At-risk mental state (ARMS) subjects had significantly lower levels of glutamate than control subjects in the thalamus (p < .05) but higher glutamine in the anterior cingulate (p < .05). Within the ARMS group, the level of thalamic glutamate was directly correlated with gray matter volume in the medial temporal cortex and insula (p < .01).


This study provides the first evidence that brain glutamate function is perturbed in people with prodromal signs of schizophrenia and that glutamatergic dysfunction is associated with a reduction in gray matter volume in brain regions thought to be critical to the pathogenesis of the disorder. These findings support the hypothesis that drugs affecting the glutamate system may be of benefit in the early stages of psychotic illness.

Comment in

  1. Biol Psychiatry. 2009 Sep 15;66(6):530-2.

PMID: 19559402 [PubMed - indexed for MEDLINE]

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