Effects of SSRI treatment on GABA and glutamate levels in an associative relearning paradigm

Spurny-Dworak, Benjamin; Vanicek, Thomas; Seiger, René; Reed, Murray Bruce; Klöbl, Manfred; Ritter, Vera; Unterholzner, Jakob; Godbersen, Godber Mathis; Silberbauer, Leo; Pacher, Daniel; Klug, Sebastian; Konadu, Melisande E.; Gryglewski, Gregor; Trattnig, Siegfried; Bogner, Wolfgang; Lanzenberger, Rupert

doi:10.1016/j.neuroimage.2021.117913

Cited by 25 publications

(31 citation statements)

References 111 publications

(136 reference statements)

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“…In a task-based fMRI analysis, neuronal activation was found to be decreased in the insula after relearning in subjects that were administered escitalopram (Reed et al, 2021). Further, we found a relationship between escitalopram and relearning when comparing glutamate levels in the hippocampus and thalamus before and after associative relearning (Spurny et al, 2021). These findings underline the effects of escitalopram and learning on various brain measures and we expected learning induced white matter changes.…”

Section: Discussionsupporting

confidence: 67%

“…Study participants were randomly assigned to one of four groups prior to study inclusion as follows: SSRI: 17 character-group, 16 faces-group; Placebo: 15 character-group, 23 faces-group. The design has been described in detail in previously published studies (Reed et al, 2021;Spurny et al, 2021). In brief, diffusion MRI scans were carried out before and after an associative learning period of 3 weeks as well as after a subsequent 3-week associative relearning under SSRI/placebo treatment.…”

Section: Subjects and Study Designmentioning

confidence: 99%

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Escitalopram Administration, Neuroplastic Effects and Relearning: A Diffusion Tensor Imaging Study in Healthy Individuals

Vanicek

Reed

Unterholzner

et al. 2021

Preprint

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Background: Neuroplastic processes are influenced by selective serotonergic reuptake inhibitors, while learning in conjunction with the administration of serotonergic agents alters white matter microstructure in humans. The goal of this double-blind, placebo-controlled imaging study was to investigate the influence of escitalopram on white matter plasticity during (re)learning. Methods: Seventy-one healthy individuals (age = 25.6+/-5.0, 43 females) underwent 3 diffusion magnetic resonance imaging sessions: at baseline, after 3-weeks of associative learning (emotional/non-emotional content) and after relearning shuffled associations for an additional 3 weeks. During the relearning phase, subjects received daily escitalopram 10 mg or placebo orally. Data were analyzed using the FMRIB Software Library (FSL) and the implemented Tract-Based Spatial Statistics (TBSS) approach. Results: The TBSS analysis revealed widespread decreases in fractional anisotropy metrics in subjects that received escitalopram. In addition, axial diffusivity decreases were mainly found in the corpus callosum and in areas within the internal capsule. In subjects receiving placebo, we did not find such effects, nor did our results show diffusivity changes related to learning or relearning. Conclusion: Diffusivity changes were found within several tracts in the escitalopram group, while we observed no changes in the placebo group. Although previous studies examining the effects of SSRIs on white matter tracts in humans are underrepresented, our results suggest a relationship between serotonergic agents and diffusivity parameters. The findings of this study implicate that escitalopram may directly or indirectly impact white matter microstructures in healthy subjects. Nevertheless, we did not find a relationship between serotonergic modulation, neuroplastic effects and relearning.

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Section: Discussionsupporting

confidence: 67%

Section: Subjects and Study Designmentioning

confidence: 99%

Escitalopram Administration, Neuroplastic Effects and Relearning: A Diffusion Tensor Imaging Study in Healthy Individuals

Vanicek

Reed

Unterholzner

et al. 2021

Preprint

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“…Animal studies revealed a relationship between sex hormone receptors and the regulation of depressive-like behavior via the GABAergic system (Selakovic, 2019). While previous studies showed an impact of antidepressant treatment on hippocampal neurotransmitter levels (Silberbauer, 2020;Spurny, 2021), GHT follows similar patterns in mediating hippocampal neurotransmitter levels. Thus, GHT shows properties to influence hippocampal neuronal networks that were shown to be involved in MDD and other psychiatric diseases on a molecular level via hormone receptors and changes in BDNF levels.…”

Section: Discussionmentioning

confidence: 95%

Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort

Spurny-Dworak

Handschuh

Spies

et al. 2022

Psychoneuroendocrinology

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“…Modifications of neurotransmitter systems are key aspects of the antidepressant actions of different interventions in order to restore GABAergic or glutamatergic function (Kalueff and Nutt, 2007 ; Sanacora et al, 2012 ). Several studies have shown SSRIs or ketamine to affect a variety of neurotransmitter systems including the serotonergic (Spindelegger et al, 2009 ; Hahn et al, 2010 ; Lanzenberger et al, 2012 ), GABAergic (Sanacora et al, 2002 ; Brennan et al, 2017 ; Silberbauer et al, 2020 ) or the glutamatergic system (Rowland et al, 2005 ; Taylor et al, 2008 ; Spurny et al, 2021 ). Moreover, certain antidepressants directly interfere with the glutamatergic or GABAergic system.…”

Section: Introductionmentioning

confidence: 99%

The Impact of Theta-Burst Stimulation on Cortical GABA and Glutamate in Treatment-Resistant Depression: A Surface-Based MRSI Analysis Approach

Spurny-Dworak

Godbersen

Reed

et al. 2022

Front. Mol. Neurosci.

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Background: Theta burst stimulation (TBS) belongs to one of the biological antidepressant treatment options. When applied bilaterally, excitatory intermittent TBS (iTBS) is commonly targeted to the left and inhibitory continuous TBS (cTBS) to the right dorsolateral prefrontal cortex. TBS was shown to influence neurotransmitter systems, while iTBS is thought to interfere with glutamatergic circuits and cTBS to mediate GABAergic neurotransmission.Objectives: We aimed to expand insights into the therapeutic effects of TBS on the GABAergic and glutamatergic system utilizing 3D-multivoxel magnetic resonance spectroscopy imaging (MRSI) in combination with a novel surface-based MRSI analysis approach to investigate changes of cortical neurotransmitter levels in patients with treatment-resistant depression (TRD).Methods: Twelve TRD patients (five females, mean age ± SD = 35 ± 11 years) completed paired MRSI measurements, using a GABA-edited 3D-multivoxel MEGA-LASER sequence, before and after 3 weeks of bilateral TBS treatment. Changes in cortical distributions of GABA+/tNAA (GABA+macromolecules relative to total N-acetylaspartate) and Glx/tNAA (Glx = mixed signal of glutamate and glutamine), were investigated in a surface-based region-of-interest (ROI) analysis approach.Results: ANCOVAs revealed a significant increase in Glx/tNAA ratios in the left caudal middle frontal area (pcorr. = 0.046, F = 13.292), an area targeted by iTBS treatment. Whereas, contralateral treatment with cTBS evoked no alterations in glutamate or GABA concentrations.Conclusion: This study demonstrates surface-based adaptions in the stimulation area to the glutamate metabolism after excitatory iTBS but not after cTBS, using a novel surface-based analysis of 3D-MRSI data. The reported impact of facilitatory iTBS on glutamatergic neurotransmission provides further insight into the neurobiological effects of TBS in TRD.

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Effects of SSRI treatment on GABA and glutamate levels in an associative relearning paradigm

Cited by 25 publications

References 111 publications

Escitalopram Administration, Neuroplastic Effects and Relearning: A Diffusion Tensor Imaging Study in Healthy Individuals

Escitalopram Administration, Neuroplastic Effects and Relearning: A Diffusion Tensor Imaging Study in Healthy Individuals

Effects of sex hormones on brain GABA and glutamate levels in a cis- and transgender cohort

The Impact of Theta-Burst Stimulation on Cortical GABA and Glutamate in Treatment-Resistant Depression: A Surface-Based MRSI Analysis Approach

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