In Vivo Brain Glycine and Glutamate Concentrations in Patients With First-Episode Psychosis Measured by Echo Time–Averaged Proton Magnetic Resonance Spectroscopy at 4T

Kim, Sang-Young; Kaufman, Marc J.; Cohen, Bruce M.; Jensen, J. Eric; Coyle, Joseph T.; Du, Fei; Öngür, Döst

doi:10.1016/j.biopsych.2017.08.022

Cited by 35 publications

(23 citation statements)

References 47 publications

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“…Regarding inhibitory neurotransmission, a recent meta-analysis of 1 H-MRS studies investigating GABA levels across psychiatric conditions (Schur, et al 2016) report reduced GABA levels in symptomatic depressed patients and in patients with schizophrenia relative to healthy controls. These findings provide further support for E/I neurotransmitter imbalance in MDD and schizophrenia, supported by more recent studies which all report aberrant metabolite levels in schizophrenia and psychosis (Dwyer, et al 2018;Jelen, et al 2018;Psomiades, et al 2018;Reid, et al 2019;Kim, et al 2018;Singh, et al 2018). However, currently there is no evidence for differences in GABA levels between healthy controls and patients with bipolar or anxiety disorders (Schur, et al 2016 concentrations have also been shown to predict local activation during a word memory task, an association that appears to be absent in a CHR cohort ).…”

Section: Network Interactions and Excitatory/inhibitory Neurotransmitsupporting

confidence: 73%

Extrinsic and default mode networks in psychiatric conditions: Relationship to excitatory-inhibitory transmitter balance and early trauma

Allen

Sommer

Jardri

et al. 2019

Neuroscience & Biobehavioral Reviews

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Over the last three decades there has been an accumulation of Magnetic Resonance Imaging (MRI) studies reporting that aberrant functional networks may underlie cognitive deficits and other symptoms across a range of psychiatric diagnoses. The use of pharmacological MRI and 1H-Magnetic Resonance Spectroscopy (1H-MRS) has allowed researchers to investigate how changes in network dynamics are related to perturbed excitatory and inhibitory neurotransmission in individuals with psychiatric conditions. More recently, changes in functional network dynamics and excitatory/inhibitory (E/I) neurotransmission have been linked to early childhood trauma, a major antecedents for psychiatric illness in adulthood. Here we review studies investigating whether perturbed network dynamics seen across psychiatric conditions are related to changes in E/I neurotransmission, and whether such changes could be linked to childhood trauma.

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Section: Network Interactions and Excitatory/inhibitory Neurotransmitsupporting

confidence: 73%

Extrinsic and default mode networks in psychiatric conditions: Relationship to excitatory-inhibitory transmitter balance and early trauma

Allen

Sommer

Jardri

et al. 2019

Neuroscience & Biobehavioral Reviews

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“…This is consistent with the majority of findings from previous 1 H-MRS studies in minimally-medicated or antipsychoticnaïve first episode patients 14,18,[56][57][58][59][60] and a recent meta-analysis 61 although one study has reported greater ACC glutamate in patients than controls. 62 Glutamine and the glutamine/glutamate ratio may be elevated in first episode psychosis, 18,57,58 To our knowledge, this is the first published multi-centre 1 H-MRS study in schizophrenia.…”

Section: Discussionmentioning

confidence: 97%

Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels: a multicentre 1H-MRS study (OPTiMiSE)

et al. 2018

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Conventional antipsychotic medication is ineffective in around a third of patients with schizophrenia, and the nature of the therapeutic response is unpredictable. We investigated whether response to antipsychotics is related to brain glutamate levels prior to treatment. Proton magnetic resonance spectroscopy was used to measure glutamate levels (Glu/Cr) in the anterior cingulate cortex (ACC) and in the thalamus in antipsychotic-naive or minimally medicated patients with first episode psychosis (FEP, n = 71) and healthy volunteers (n = 60), at three sites. Following scanning, patients were treated with amisulpride for 4 weeks (n = 65), then H-MRS was repeated (n = 46). Remission status was defined in terms of Positive and Negative Syndrome Scale for Schizophrenia (PANSS) scores. Higher levels of Glu/Cr in the ACC were associated with more severe symptoms at presentation and a lower likelihood of being in remission at 4 weeks (P< 0.05). There were longitudinal reductions in Glu/Cr in both the ACC and thalamus over the treatment period (P < 0.05), but these changes were not associated with the therapeutic response. There were no differences in baseline Glu/Cr between patients and controls. These results extend previous evidence linking higher levels of ACC glutamate with a poor antipsychotic response by showing that the association is evident before the initiation of treatment.

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“…Thus, some patients may be genetically biased much more towards glutamatergic dysfunction than others. Second, sub‐grouping to enrich for patients with likely glutamatergic pathology could be accomplished through genotyping (polygenic scores) and assessment of other informative biomarkers, such as cortical glutamate measured by magnetic resonance . Third, additional strategies to reduce variance would be to: focus on clinics that have ‘real’ patients and not volunteers recruited by advertisements, reduce the number of sites with larger numbers of patients, and focus on the early stages of schizophrenia as chronic patients likely have a different pathology …”

Section: Treatment Based On Glutamate Hypothesismentioning

confidence: 99%

Glutamate hypothesis in schizophrenia

Uno

Coyle

2019

Psychiatry Clin Neurosci

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278

172

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Schizophrenia is a chronic and severe psychiatric disorder that has profound impact on an individual’s life and on society. Thus, developing more effective therapeutic interventions is essential. Over the past quarter‐century, an abundance of evidence from pharmacologic challenges, post‐mortem studies, brain imaging, and genetic studies supports the role of glutamatergic dysregulation in the pathophysiology of schizophrenia, and the results of recent randomized clinical trials based on this evidence have yielded promising results. In this article, we review the evidence that alterations in glutamatergic neurotransmission, especially focusing on the N‐methyl‐d‐aspartate receptor (NMDAR) function, may be a critical causative feature of schizophrenia, how this contributes to pathologic circuit function in the brain, and how these insights are revealing whole new avenues for treatment development that could reduce treatment‐resistant symptoms, which account for persistent disability.

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In Vivo Brain Glycine and Glutamate Concentrations in Patients With First-Episode Psychosis Measured by Echo Time–Averaged Proton Magnetic Resonance Spectroscopy at 4T

Cited by 35 publications

References 47 publications

Extrinsic and default mode networks in psychiatric conditions: Relationship to excitatory-inhibitory transmitter balance and early trauma

Extrinsic and default mode networks in psychiatric conditions: Relationship to excitatory-inhibitory transmitter balance and early trauma

Response to initial antipsychotic treatment in first episode psychosis is related to anterior cingulate glutamate levels: a multicentre 1H-MRS study (OPTiMiSE)

Glutamate hypothesis in schizophrenia

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