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Positive and negative symptoms in schizophrenia: the NMDA receptor hypofunction hypothesis, neuregulin/ErbB4 and

Maxwell Bennett1

  • 1Brain and Mind Research Institute, University of Sydney, NSW, Australia. maxb@physiol.usyd.edu.au

The Australian and New Zealand Journal of Psychiatry
|July 25, 2009
PubMed

Insights

Schizophrenia symptoms may stem from impaired glutamate N-methyl-d-aspartate (NMDA) receptor function, leading to synaptic spine loss. Targeting neuregulin/ErbB4 pathways could restore NMDA receptor function and alleviate symptoms.

Area of Science:

  • Neuroscience
  • Psychiatry
  • Molecular Biology

Background:

  • Schizophrenia symptoms are linked to mesolimbic and mesocortical pathway dysfunction.
  • Glutamate N-methyl-d-aspartate (NMDA) receptor hypofunction is a proposed cause.
  • Synaptic spine loss, potentially stress-induced, is associated with positive symptoms.

Purpose of the Study:

  • To integrate hypotheses on schizophrenia pathogenesis.
  • To elucidate the molecular pathway linking neuregulin/ErbB4 to NMDA receptor function and synaptic spine morphology.
  • To identify therapeutic targets for NMDA receptor hypofunction.

Main Methods:

  • Review and synthesis of existing hypotheses.
  • Focus on molecular pathways involving neuregulin, ErbB4, and NMDA receptors.
  • Analysis of cytoskeletal changes in synaptic spines.

Main Results:

  • A unified scheme integrating neuregulin/ErbB4 signaling with NMDA receptor modulation and synaptic spine regression.
  • Identification of the pathway from neuregulin/ErbB4 to NMDA receptor hypofunction and spine loss.
  • Hypothesized role of stress in precipitating synaptic changes.

Conclusions:

  • The neuregulin/ErbB4 pathway is critical in modulating NMDA receptor function and synaptic integrity.
  • Understanding this pathway offers potential therapeutic strategies for schizophrenia.
  • Targeting molecular constituents may reverse NMDA receptor hypofunction and associated symptoms.

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