Reduced gamma-amino butyric acid (GABA) and glutamine in the anterior cingulate cortex (ACC) of veterans exposed to trauma

Sheth, Chandni; Prescot, Andrew P.; Legarreta, Margaret; Renshaw, Perry F.; McGlade, Erin; Yurgelun‐Todd, Deborah

doi:10.1016/j.jad.2019.01.037

Cited by 35 publications

(24 citation statements)

References 71 publications

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“…These findings further support the conclusions of a previous systematic review observing consistent decreases in hippocampal and anterior cingulate cortex NAA across the 1 H-MRS literature on PTSD. 46 In particular, our anterior cingulate cortex results also extend previous meta-analytic findings of decreased anterior cingulate NAA/Cr in PTSD relative to healthy controls and update three previously reviewed comparisons from two studies 71 , 75 underlying a significant effect of NAA in anterior cingulate cortex 45 with four more 63 , 69 , 74 , 77 that bring this metabolite result to non-significance. Similarly, reported reductions in left hippocampal NAA/Cr and NAA extend previously significant meta-analytic findings in both indices.…”

Section: Discussionsupporting

confidence: 84%

“…The anterior cingulate cortex (ACC) overlaps with portions of both ventromedial and dorsomedial prefrontal cortex, both of which have demonstrated structural and functional abnormality in PTSD. 13 It is thought that with roles in fear conditioning and extinction the dorsal ACC (dACC) in particular could contribute to PTSD vulnerability and/or pathogenesis, 69 with local functional abnormalities possibly contributing to disruptions in the salience network leading to hypervigilance. 88 …”

Section: Resultsmentioning

confidence: 99%

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Proton Magnetic Resonance Spectroscopy in Post-Traumatic Stress Disorder—Updated Systematic Review and Meta-Analysis

et al. 2022

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A stressor-related disorder wherein traumatic experience precipitates protracted disruptions to mood and cognition, post-traumatic stress disorder (PTSD) is associated with wide-ranging abnormalities across the body. While various methods have investigated these deviations, only proton magnetic resonance spectroscopy (1H MRS) enables noninvasive measurement of small-molecule metabolites in the living human. 1H MRS has correspondingly been employed to test hypotheses about the composition and function of multiple brain regions putatively involved in PTSD. Here we systematically review methodological considerations and reported findings, both positive and negative, of the current 1H-MRS literature in PTSD (N = 32 studies) to communicate the brain regional metabolite alterations heretofore observed, providing random-effects model meta-analyses for those most extensively studied. Our review suggests significant PTSD-associated decreases in N-acetyl aspartate in bilateral hippocampus and anterior cingulate cortex with less evident effect in other metabolites and regions. Model heterogeneities diverged widely by analysis (I2 < 0.01% to 90.1%) and suggested regional dependence on quantification reference (creatine or otherwise). While observed variabilities in methods and reported findings suggest that 1H-MRS explorations of PTSD could benefit from methodological standardization, informing this standardization by quantitative assessment of the existing literature is currently hampered by its small size and limited scope.

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Section: Discussionsupporting

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Proton Magnetic Resonance Spectroscopy in Post-Traumatic Stress Disorder—Updated Systematic Review and Meta-Analysis

et al. 2022

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“…Anxiety and fear, which are common symptoms observed in a wide range of psychiatric disorders, also correlate with the GABAergic system [15,16]. A decrease in GABA levels in the tissue or blood has been reported in anxiety disorder [5], post‐traumatic stress disorder [17,18], and mood disorders [19], suggesting that decreased GABA neurotransmission may underlie the neural basis of anxiety in these disorders. This is also consistent with the findings that benzodiazepines, which are stimulants of GABA A receptors, reduce anxiety [20].…”

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confidence: 99%

Genetic deletion of the 67‐kDa isoform of glutamate decarboxylase alters conditioned fear behavior in rats

et al. 2020

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The GABAergic system is thought to play an important role in the control of cognition and emotion, such as fear, and is related to the pathophysiology of psychiatric disorders. For example, the expression of the 67-kDa isoform of glutamate decarboxylase (GAD67), a GABA-producing enzyme, is downregulated in the postmortem brains of patients with major depressive disorder and schizophrenia. However, knocking out the Gad1 gene, which encodes GAD67, is lethal in mice, and thus, the association between Gad1 and cognitive/emotional functions is unclear. We recently developed Gad1 knockout rats and found that some of them can grow into adulthood. Here, we performed fear-conditioning tests in adult Gad1 knockout rats to assess the impact of the loss of Gad1 on fear-related behaviors and the formation of fear memory. In a protocol assessing both cued and contextual memory, Gad1 knockout rats showed a partial antiphase pattern of freezing during training and significantly excessive freezing during the contextual test compared with wild-type rats. However, Gad1 knockout rats did not show any synchronous increase in freezing with auditory tones in the cued test. On the other hand, in a contextual memory specialized protocol, Gad1 knockout rats exhibited comparable freezing behavior to wildtype rats, while their fear extinction was markedly impaired. These results suggest that GABA synthesis by GAD67 has differential roles in cued and contextual fear memory.

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“…As reported in Section 6.7, glutamatergic pyramidal neurons and GABAergic local interneuron in PFC play a pivotal role in driving the inhibitory control of memories. Alterations in glutamatergic and GABAergic transmissions have been reported in schizophrenia, depression, PTSD, and obsessive-compulsive disorder [237][238][239][240][241][242][243]. Moreover, studies on the role of these neurotransmitter systems in mental disorders seem to be promising for better understanding etiopathogenetic mechanisms, as well as for improving the effectiveness of pharmacological therapies [244][245][246][247][248][249][250].…”

Section: Discussionmentioning

confidence: 99%

Forgetting Unwanted Memories: Active Forgetting and Implications for the Development of Psychological Disorders

Costanzi

Cianfanelli

Santirocchi

et al. 2021

JPM

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Intrusive memories are a common feature of many psychopathologies, and suppression-induced forgetting of unwanted memories appears as a critical ability to preserve mental health. In recent years, biological and cognitive studies converged in revealing that forgetting is due to active processes. Recent neurobiological studies provide evidence on the active role of main neurotransmitter systems in forgetting, suggesting that the brain actively works to suppress retrieval of unwanted memories. On the cognitive side, there is evidence that voluntary and involuntary processes (here termed “intentional” and “incidental” forgetting, respectively) contribute to active forgetting. In intentional forgetting, an inhibitory control mechanism suppresses awareness of unwanted memories at encoding or retrieval. In incidental forgetting, retrieval practice of some memories involuntarily suppresses the retrieval of other related memories. In this review we describe recent findings on deficits in active forgetting observed in psychopathologies, like post-traumatic stress disorder, depression, schizophrenia, and obsessive-compulsive disorder. Moreover, we report studies in which the role of neurotransmitter systems, known to be involved in the pathogenesis of mental disorders, has been investigated in active forgetting paradigms. The possibility that biological and cognitive mechanisms of active forgetting could be considered as hallmarks of the early onset of psychopathologies is also discussed.

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Reduced gamma-amino butyric acid (GABA) and glutamine in the anterior cingulate cortex (ACC) of veterans exposed to trauma

Cited by 35 publications

References 71 publications

Proton Magnetic Resonance Spectroscopy in Post-Traumatic Stress Disorder—Updated Systematic Review and Meta-Analysis

Proton Magnetic Resonance Spectroscopy in Post-Traumatic Stress Disorder—Updated Systematic Review and Meta-Analysis

Genetic deletion of the 67‐kDa isoform of glutamate decarboxylase alters conditioned fear behavior in rats

Forgetting Unwanted Memories: Active Forgetting and Implications for the Development of Psychological Disorders

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