Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans
Background Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in vivo in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic streng...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2022-04-01
|
| Series: | Chronic Stress |
| Online Access: | https://doi.org/10.1177/24705470221092734 |
| _version_ | 1811275081536503808 |
|---|---|
| author | Lynnette A. Averill Lihong Jiang Prerana Purohit Anastasia Coppoli Christopher L. Averill Jeremy Roscoe Benjamin Kelmendi Henk M. De Feyter Robin A de Graaf Ralitza Gueorguieva Gerard Sanacora John H. Krystal Douglas L. Rothman Graeme F. Mason Chadi G. Abdallah |
| author_facet | Lynnette A. Averill Lihong Jiang Prerana Purohit Anastasia Coppoli Christopher L. Averill Jeremy Roscoe Benjamin Kelmendi Henk M. De Feyter Robin A de Graaf Ralitza Gueorguieva Gerard Sanacora John H. Krystal Douglas L. Rothman Graeme F. Mason Chadi G. Abdallah |
| author_sort | Lynnette A. Averill |
| collection | DOAJ |
| description | Background Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in vivo in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC). Then, we used EPC to investigate the role of prefrontal neurotransmission in trauma-related psychopathology. Methods Healthy controls (n = 18) and patients with posttraumatic stress (PTSD; n = 16) completed 13 C-acetate magnetic resonance spectroscopy (MRS) scans to estimate prefrontal EPC, which is the ratio of neuronal energetic needs per glutamate neurotransmission cycle (V TCA /V Cycle ). Results Patients with PTSD were found to have 28% reduction in prefrontal EPC ( t = 3.0; df = 32, P = .005). There was no effect of sex on EPC, but age was negatively associated with prefrontal EPC across groups ( r = –0.46, n = 34, P = .006). Controlling for age did not affect the study results. Conclusion The feasibility and utility of estimating prefrontal EPC using 13 C-acetate MRS were established. Patients with PTSD were found to have reduced prefrontal glutamatergic synaptic strength. These findings suggest that reduced glutamatergic synaptic strength may contribute to the pathophysiology of PTSD and could be targeted by new treatments. |
| first_indexed | 2024-04-12T23:31:38Z |
| format | Article |
| id | doaj.art-9a7f7965ac9f4df9a4deec5793fd8086 |
| institution | Directory Open Access Journal |
| issn | 2470-5470 |
| language | English |
| last_indexed | 2024-04-12T23:31:38Z |
| publishDate | 2022-04-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Chronic Stress |
| spelling | doaj.art-9a7f7965ac9f4df9a4deec5793fd80862022-12-22T03:12:16ZengSAGE PublishingChronic Stress2470-54702022-04-01610.1177/24705470221092734Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in HumansLynnette A. Averill0Lihong Jiang1Prerana Purohit2Anastasia Coppoli3Christopher L. Averill4Jeremy Roscoe5Benjamin Kelmendi6Henk M. De Feyter7Robin A de Graaf8Ralitza Gueorguieva9Gerard Sanacora10John H. Krystal11Douglas L. Rothman12Graeme F. Mason13Chadi G. Abdallah14 Department of Psychiatry, , New Haven, CT, USA Yale Magnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, , New Haven, CT, USA Department of Psychiatry, , New Haven, CT, USA Yale Magnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, , New Haven, CT, USA Department of Psychiatry, , New Haven, CT, USA Department of Psychiatry, , New Haven, CT, USA Department of Psychiatry, , New Haven, CT, USA Yale Magnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, , New Haven, CT, USA Yale Magnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, , New Haven, CT, USA Department of Biostatistics, School of Public Health, , New Haven, CT, USA Department of Psychiatry, , New Haven, CT, USA Department of Psychiatry, , New Haven, CT, USA Yale Magnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, , New Haven, CT, USA Yale Magnetic Resonance Research Center, Department of Radiology and Biomedical Imaging, , New Haven, CT, USA Core for Advanced Magnetic Resonance Imaging (CAMRI), , Houston, TX, USABackground Trauma and chronic stress are believed to induce and exacerbate psychopathology by disrupting glutamate synaptic strength. However, in vivo in human methods to estimate synaptic strength are limited. In this study, we established a novel putative biomarker of glutamatergic synaptic strength, termed energy-per-cycle (EPC). Then, we used EPC to investigate the role of prefrontal neurotransmission in trauma-related psychopathology. Methods Healthy controls (n = 18) and patients with posttraumatic stress (PTSD; n = 16) completed 13 C-acetate magnetic resonance spectroscopy (MRS) scans to estimate prefrontal EPC, which is the ratio of neuronal energetic needs per glutamate neurotransmission cycle (V TCA /V Cycle ). Results Patients with PTSD were found to have 28% reduction in prefrontal EPC ( t = 3.0; df = 32, P = .005). There was no effect of sex on EPC, but age was negatively associated with prefrontal EPC across groups ( r = –0.46, n = 34, P = .006). Controlling for age did not affect the study results. Conclusion The feasibility and utility of estimating prefrontal EPC using 13 C-acetate MRS were established. Patients with PTSD were found to have reduced prefrontal glutamatergic synaptic strength. These findings suggest that reduced glutamatergic synaptic strength may contribute to the pathophysiology of PTSD and could be targeted by new treatments.https://doi.org/10.1177/24705470221092734 |
| spellingShingle | Lynnette A. Averill Lihong Jiang Prerana Purohit Anastasia Coppoli Christopher L. Averill Jeremy Roscoe Benjamin Kelmendi Henk M. De Feyter Robin A de Graaf Ralitza Gueorguieva Gerard Sanacora John H. Krystal Douglas L. Rothman Graeme F. Mason Chadi G. Abdallah Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans Chronic Stress |
| title | Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans |
| title_full | Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans |
| title_fullStr | Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans |
| title_full_unstemmed | Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans |
| title_short | Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans |
| title_sort | prefrontal glutamate neurotransmission in ptsd a novel approach to estimate synaptic strength in vivo in humans |
| url | https://doi.org/10.1177/24705470221092734 |
| work_keys_str_mv | AT lynnetteaaverill prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT lihongjiang prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT preranapurohit prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT anastasiacoppoli prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT christopherlaverill prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT jeremyroscoe prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT benjaminkelmendi prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT henkmdefeyter prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT robinadegraaf prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT ralitzagueorguieva prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT gerardsanacora prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT johnhkrystal prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT douglaslrothman prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT graemefmason prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans AT chadigabdallah prefrontalglutamateneurotransmissioninptsdanovelapproachtoestimatesynapticstrengthinvivoinhumans |