Magnetic resonance imaging in studying schizophrenia, negative symptoms and the glutamate system
Schizophrenia is characterized by positive, negative and cognitive symptoms. While positive symptoms occur periodically during psychotic exacerbations, negative and cognitive symptoms often emerge before the first psychotic episode and persist with low functional outcome and poor prognosis. This rev...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2014-04-01
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| Series: | Frontiers in Psychiatry |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fpsyt.2014.00032/full |
| _version_ | 1819267811331014656 |
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| author | Oliver eGruber Antonella eSantuccione Chadha Helmut eAach |
| author_facet | Oliver eGruber Antonella eSantuccione Chadha Helmut eAach |
| author_sort | Oliver eGruber |
| collection | DOAJ |
| description | Schizophrenia is characterized by positive, negative and cognitive symptoms. While positive symptoms occur periodically during psychotic exacerbations, negative and cognitive symptoms often emerge before the first psychotic episode and persist with low functional outcome and poor prognosis. This review article outlines the importance of modern functional magnetic resonance imaging (fMRI) techniques for developing a stratified therapy of schizophrenic disorders. Functional neuroimaging evidence on the neural correlates of positive and particularly negative symptoms and cognitive deficits in schizophrenic disorders is briefly reviewed. Acute dysregulation of dopaminergic neurotransmission is crucially involved in the occurrence of psychotic symptoms. However, increasing evidence also implicates glutamatergic pathomechanisms, in particular N-methyl-D-aspartate (NMDA) receptor dysfunction in the pathogenesis of schizophrenia and in the appearance of negative symptoms and cognitive dysfunctions. In line with this notion, several gene variants affecting the NMDA receptor’s pathway have been reported to increase susceptibility for schizophrenia, and have been investigated using the imaging genetics approach. In recent years, several attempts have been made to develop medications modulating the glutamatergic pathway with modest evidences for efficacy. The most successful approaches were those that aimed at influencing this pathway using compounds that enhance NMDA receptor function. The selective glycine reuptake inhibitor Bitopertin has been shown to improve NMDA receptor hypofunction by increasing glycine concentrations in the synaptic cleft. Further research is required to test whether pharmacological agents with effects on the glutamatergic system can help to improve the treatment of negative symptoms in schizophrenic disorders. |
| first_indexed | 2024-12-23T21:23:06Z |
| format | Article |
| id | doaj.art-debf91d8f0cc480fa231241c61e5f3c1 |
| institution | Directory Open Access Journal |
| issn | 1664-0640 |
| language | English |
| last_indexed | 2024-12-23T21:23:06Z |
| publishDate | 2014-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Psychiatry |
| spelling | doaj.art-debf91d8f0cc480fa231241c61e5f3c12022-12-21T17:30:42ZengFrontiers Media S.A.Frontiers in Psychiatry1664-06402014-04-01510.3389/fpsyt.2014.0003270609Magnetic resonance imaging in studying schizophrenia, negative symptoms and the glutamate systemOliver eGruber0Antonella eSantuccione Chadha1Helmut eAach2University Medical Center GöttingenRoche Pharma AGRoche Pharma AGSchizophrenia is characterized by positive, negative and cognitive symptoms. While positive symptoms occur periodically during psychotic exacerbations, negative and cognitive symptoms often emerge before the first psychotic episode and persist with low functional outcome and poor prognosis. This review article outlines the importance of modern functional magnetic resonance imaging (fMRI) techniques for developing a stratified therapy of schizophrenic disorders. Functional neuroimaging evidence on the neural correlates of positive and particularly negative symptoms and cognitive deficits in schizophrenic disorders is briefly reviewed. Acute dysregulation of dopaminergic neurotransmission is crucially involved in the occurrence of psychotic symptoms. However, increasing evidence also implicates glutamatergic pathomechanisms, in particular N-methyl-D-aspartate (NMDA) receptor dysfunction in the pathogenesis of schizophrenia and in the appearance of negative symptoms and cognitive dysfunctions. In line with this notion, several gene variants affecting the NMDA receptor’s pathway have been reported to increase susceptibility for schizophrenia, and have been investigated using the imaging genetics approach. In recent years, several attempts have been made to develop medications modulating the glutamatergic pathway with modest evidences for efficacy. The most successful approaches were those that aimed at influencing this pathway using compounds that enhance NMDA receptor function. The selective glycine reuptake inhibitor Bitopertin has been shown to improve NMDA receptor hypofunction by increasing glycine concentrations in the synaptic cleft. Further research is required to test whether pharmacological agents with effects on the glutamatergic system can help to improve the treatment of negative symptoms in schizophrenic disorders.http://journal.frontiersin.org/Journal/10.3389/fpsyt.2014.00032/fullGlutamatesSchizophrenianegative symptomscognitive deficitsPersonalized PsychiatryNeuroimaging Biomarkers |
| spellingShingle | Oliver eGruber Antonella eSantuccione Chadha Helmut eAach Magnetic resonance imaging in studying schizophrenia, negative symptoms and the glutamate system Frontiers in Psychiatry Glutamates Schizophrenia negative symptoms cognitive deficits Personalized Psychiatry Neuroimaging Biomarkers |
| title | Magnetic resonance imaging in studying schizophrenia, negative symptoms and the glutamate system |
| title_full | Magnetic resonance imaging in studying schizophrenia, negative symptoms and the glutamate system |
| title_fullStr | Magnetic resonance imaging in studying schizophrenia, negative symptoms and the glutamate system |
| title_full_unstemmed | Magnetic resonance imaging in studying schizophrenia, negative symptoms and the glutamate system |
| title_short | Magnetic resonance imaging in studying schizophrenia, negative symptoms and the glutamate system |
| title_sort | magnetic resonance imaging in studying schizophrenia negative symptoms and the glutamate system |
| topic | Glutamates Schizophrenia negative symptoms cognitive deficits Personalized Psychiatry Neuroimaging Biomarkers |
| url | http://journal.frontiersin.org/Journal/10.3389/fpsyt.2014.00032/full |
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