Glutamate and its role in psychiatric illness

Abstract

Glutamate, a dicarboxylic amino acid, is the most abundantly active neurotransmitter in the mammalian brain; it is also the principal excitatory neurotransmitter in the cerebral cortex. As our knowledge of this neurotransmitter deepens, it is increasingly being implicated in the pathophysiology of mental illness. This review begins by examining the physiology of glutamate and its receptors. Its role in memory, movement, perception and neuronal development is discussed. The development of the glutamate hypothesis of schizophrenia is traced, and the emerging lines of evidence for attenuated function of the N-methyl-D-aspartate receptor in schizophrenia are examined. For ease of discussion, these are divided into pharmacological, post-mortem, imaging, platelet and genetic studies. Interactions between glutamate and other neurotransmitters are discussed, as are possible mechanisms by which such altered receptor activity might result in the clinical expression of schizophrenia. The possible role of glutamate in major depression and bipolar disorder is explored. The review concludes by highlighting the importance of avoiding a reductionist approach to the pathophysiology of any mental illness. Copyright 2001 John Wiley & Sons, Ltd.

Molecular characterization of bipolar disorder by comparing gene expression profiles of postmortem brains of major mental disorders

“…The glutamatergic system is the main excitatory neurotransmitter system responsible for fundamental brain functions, and hypofunction of this system has been postulated in schizophrenia 19 and bipolar disorder. 20 The downregulation of two glutamate receptors, GRIK1 and GRM1, would be involved in the hypofunction of this system in bipolar disorder. In addition to GRIK1, HTR2C and NOTCH4 have been the candidate genes for association studies of schizophrenia and bipolar disorder, although consistent results have not been obtained.…”

Dysregulation of glutamate carboxypeptidase II in psychiatric disease

“…Although the neurobiological bases for such effects is not currently known, glutamatergic transmission is increasingly recognized as being dysregulated in depression (Belsham, 2001), (Choudary et al, 2005), with certain antiseizure agents known to decrease glutamate levels having a salutary effect in the disease (Abelli et al, 2005), and in bipolar disorders. That we demonstrated a similar trend in GCPII levels in PFC in patients with schizophrenia, depression and bipolar disorder is in keeping with the recent finding that these disorders may share common genetic mechanisms (Clapcote et al, 2007).…”

Glutamat Sistemi ve Şizofreni

“…Nöronlara ek olarak, astrositler glutamat prekürsörü olan glutamin için ana kaynaklardır (Dwivedi ve Pandey 2011). Sentezlenen glutamat vesiküler glutamat taşıyıcı ailesi (VGLUT1-3) tarafından sinaptik aralığa salınmak için vezikülle-re alınmaktadır (Belsham 2001, Dwivedi ve Pandey 2011, Shan ve ark. 2013, Hammond ve ark.…”

“…Şizofrenide glutamat hipotezi beyin omirilik sıvısında glutamat düzeylerinin azalmasına, ve şizofreni hastalarında hipokampus ve talamusta NMDA, AMPA reseptör expresyonlarının azalmasına dayanır (Fatemi 2008). Bu hipotez baş-langıçta yazarlar tarafından çok destek görmese de daha sonra bu teoriyi destekleyen birçok kanıt ortaya çıkmıştır (Ceylan ve Taşçı 1999, Belsham 2001, Gargiula ve Landa De Gargiulo 2014, Howes ve ark. 2015.…”