Stefan Smesny1, Alexander Gussew2, Natalie Joan Biesel3, Stephan Schack3, Mario Walther4, Reinhard Rzanny2, Berko Milleit5, Christian Gaser3, Thomas Sobanski6, Carl Christoph Schultz3, Paul Amminger7, Uta-Christina Hipler8, Heinrich Sauer3, Jürgen R Reichenbach2. 1. Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany. Electronic address: Stefan.Smesny@med.uni-jena.de. 2. Medical Physics Group, Department of Diagnostic and Interventional Radiology, Jena University Hospital, Philosophenweg 3, D-07740 Jena, Germany. 3. Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany. 4. Institute of Medical Statistics, Computer Sciences and Documentation (IMSID), Jena University Hospital, Friedrich-Schiller University Jena, Bachstraße 18, D-07743 Jena, Germany. 5. Department of Psychiatry, Jena University Hospital, Philosophenweg 3, D-07743 Jena, Germany; Department of Psychiatry, Thüringen-Kliniken "Georgius Agricola" GmbH Rainweg 68, D-07318 Saalfeld/Saale, Germany. 6. Department of Psychiatry, Thüringen-Kliniken "Georgius Agricola" GmbH Rainweg 68, D-07318 Saalfeld/Saale, Germany. 7. Department of Child and Adolescent Psychiatry, Medical University Vienna, Währingergürtel 18-20, A-1090 Vienna, Austria; Orygen Youth Health Research Centre, The University of Melbourne, Locked Bag 10, 35 Poplar Road Parkville, Victoria 3052, Melbourne, Australia. 8. Department of Dermatology, Jena University Hospital, Erfurter Straße 35, D-07743 Jena, Germany.
Abstract
BACKGROUND: Glutamatergic dysfunction and altered membrane lipid and energy metabolism have been repeatedly demonstrated in the frontal/prefrontal and anterior cingulate cortex (ACC) in schizophrenia. Though having been already studied in animals, the presumed link between glutamatergic function and structural plasticity has not been investigated directly in the human brain yet. We measured glutamate (Glu), focal energy metabolism, and membrane phospholipid turnover to investigate main pathologies in those key brain regions of schizophrenia. METHODS: (1)H- and (31)P-Chemical Shift Imaging (CSI) was combined in a single session to assess Glu and markers of energy (PCr, ATP) and membrane lipid (PME, PDE) metabolism in 31 neuroleptic-naïve first acute onset psychosis patients and 31 matched healthy controls. Multivariate analyses of covariance were used to assess disease effects on Glu and to investigate the impact of Glu alterations on phospholipid and energy metabolites. RESULTS: Glu levels of patients were increased in the frontal and prefrontal cortex bilaterally and in the ACC. Higher Glu was associated with increased left frontal/prefrontal PME and right frontal/prefrontal PDE in patients, which was not observed in healthy controls. In contrast, higher Glu levels were associated with lower PCr or ATP values in the frontal/prefrontal cortex bilaterally and in the right ACC of controls. This was not observed in the right ACC and left frontal/prefrontal cortex of patients. CONCLUSION: Frontal glutamatergic hyperactivity is disconnected from physiologically regulated energy metabolism and is associated with increased membrane breakdown in right and increased membrane restoration in left frontal and prefrontal cortical regions. As indicated by previous findings, this pathology is likely dynamic during the course of first acute illness and possibly associated with negative symptoms and cognitive impairment. Our findings underline the importance of further research on neuroprotective treatment options during the early acute or even better for the ultra-high risk state of psychotic illness.
BACKGROUND:Glutamatergic dysfunction and altered membrane lipid and energy metabolism have been repeatedly demonstrated in the frontal/prefrontal and anterior cingulate cortex (ACC) in schizophrenia. Though having been already studied in animals, the presumed link between glutamatergic function and structural plasticity has not been investigated directly in the human brain yet. We measured glutamate (Glu), focal energy metabolism, and membrane phospholipid turnover to investigate main pathologies in those key brain regions of schizophrenia. METHODS: (1)H- and (31)P-Chemical Shift Imaging (CSI) was combined in a single session to assess Glu and markers of energy (PCr, ATP) and membrane lipid (PME, PDE) metabolism in 31 neuroleptic-naïve first acute onset psychosispatients and 31 matched healthy controls. Multivariate analyses of covariance were used to assess disease effects on Glu and to investigate the impact of Glu alterations on phospholipid and energy metabolites. RESULTS:Glu levels of patients were increased in the frontal and prefrontal cortex bilaterally and in the ACC. Higher Glu was associated with increased left frontal/prefrontal PME and right frontal/prefrontal PDE in patients, which was not observed in healthy controls. In contrast, higher Glu levels were associated with lower PCr or ATP values in the frontal/prefrontal cortex bilaterally and in the right ACC of controls. This was not observed in the right ACC and left frontal/prefrontal cortex of patients. CONCLUSION: Frontal glutamatergic hyperactivity is disconnected from physiologically regulated energy metabolism and is associated with increased membrane breakdown in right and increased membrane restoration in left frontal and prefrontal cortical regions. As indicated by previous findings, this pathology is likely dynamic during the course of first acute illness and possibly associated with negative symptoms and cognitive impairment. Our findings underline the importance of further research on neuroprotective treatment options during the early acute or even better for the ultra-high risk state of psychotic illness.
Authors: Jennifer H Foss-Feig; Brendan D Adkinson; Jie Lisa Ji; Genevieve Yang; Vinod H Srihari; James C McPartland; John H Krystal; John D Murray; Alan Anticevic Journal: Biol Psychiatry Date: 2017-03-14 Impact factor: 13.382
Authors: Lisa A Bartolomeo; Andrew M Wright; Ruoyun E Ma; Tom A Hummer; Michael M Francis; Andrew C Visco; Nicole F Mehdiyoun; Amanda R Bolbecker; William P Hetrick; Ulrike Dydak; John Barnard; Brian F O'Donnell; Alan Breier Journal: Int J Psychophysiol Date: 2019-05-23 Impact factor: 2.997