Prefrontal Glutamate Neurotransmission in PTSD: A Novel Approach to Estimate Synaptic Strength in Vivo in Humans
Year: 2022
Type: article
Study design: Observational Study
Abstract: ABSTRACT 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 psychopathology. Healthy control (n=18) and patients with posttraumatic stress (PTSD; n=16) completed 13 C-acetate magnetic resonance spectroscopy scans to estimate prefrontal EPC, which is the ratio of neuronal energetic needs per glutamate neurotransmission cycle (V TCA /V Cycle ). Patients with PTSD were found to have 28% reduction in prefrontal EPC ( t =3.0; df =32, p =0.005). There was no effect of sex on EPC, but age was negatively associated with prefrontal EPC across groups ( r =–0.46, n=34, p =0.006). Controlling for age did not affect the study results. The feasibility and utility of EPC 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. Highlights Glutamatergic synaptic strength is critical for brain function in health and disease. In vivo in human methods to estimate glutamatergic synaptic strength are limited. We here propose a new approach to estimate glutamatergic synaptic strength. The new method employs carbon-13 magnetic resonance spectroscopy ( 13 C MRS). The utility of the new approach was demonstrated in posttraumatic stress disorder (PTSD).
Source: Chronic Stress
Language: English
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $1,500
Funders: U.S. Department of Veterans Affairs, American Foundation for Suicide Prevention, Bristol-Myers Squibb, Eli Lilly and Company, AstraZeneca, Sanofi, Yale University, Gilead Sciences, Biogen, Teva Pharmaceutical Industries, National Alliance for Research on Schizophrenia and Depression, Valeant Pharmaceuticals International, Georgia Clinical and Translational Science Alliance, Vistagen Therapeutics, Servier, H. Lundbeck A/S, National Institutes of Health, Genentech, National Center for PTSD, U.S. Department of Veterans Affairs, National Institute on Alcohol Abuse and Alcoholism, National Institute of Mental Health, National Center for Research Resources, National Center for Advancing Translational Sciences, Yale Center for Clinical Investigation, Yale School of Medicine
Awards: G1041632141, G1044130170, G1621851408, Brain Acetate and Ethanol Metabolism in Alcohol Dependence and Abuse, G2454647661, G2794393058, G412534091, G4185277476, G4376220899, G582307518, Examining The Effect Of Ketamine On Glutamate/Glutamine Cycling, G7346014474, G7420383591, Yale University Clinical and Translational Science Award Program, Yale Clinical and Translational Science Award
OpenAlex ID: W4224307161