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

Spurny-Dworak, Benjamin; Godbersen, Godber Mathis; Reed, Murray Bruce; Unterholzner, Jakob; Vanicek, Thomas; Baldinger-Melich, Pia; Hahn, Andreas; Kranz, Georg S.; Bogner, Wolfgang; Lanzenberger, Rupert; Kasper, S.

doi:10.3389/fnmol.2022.913274

Cited by 5 publications

(3 citation statements)

References 57 publications

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“…Recent studies have also shown that subthreshold iTBS over the L-DLPFC leads to DA release in the striatum using PET (Shaikh, Pellicano et al 2024, Shaikh, Pellicano et al 2024). In a clinical context, suprathreshold iTBS over L-DLPFC increased cortical GABA and Glu in treatment-resistant depression (Spurny-Dworak, Godbersen et al 2022).…”

Section: Discussionmentioning

confidence: 99%

Intermittent theta burst stimulation (iTBS)-induced changes of resting-state brain entropy (BEN)

Liu,

Song,

Deng

et al. 2024

Preprint

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Intermittent theta burst stimulation (iTBS) is a novel protocol of repetitive transcranial magnetic stimulation (rTMS). While iTBS has shown better therapeutic effects for depression than conventional high-frequency rTMS (HF-rTMS), its underlying neuronal mechanism remains elusive. Brain entropy (BEN), a measure of irregularity of brain activity, has recently emerged as a novel marker of regional brain activity. Our previous studies have shown the sensitivity of BEN to depression and HF-rTMS, suggesting BEN as a sensitive tool for understanding the brain mechanism of iTBS. To assess this possibility, we calculated BEN using resting state fMRI data provided by an open dataset in OpenNeuro. Sixteen healthy participants underwent 600 pulses of iTBS applied over the left dorsolateral prefrontal cortex (L-DLPFC) at two intensities (90% and 120% of individual resting motor threshold (rMT)) on separate days. We assessed the pre-post stimulation BEN difference and its associations with neurotransmitter receptor and transporter binding maps. Our results showed that subthreshold iTBS (90% rMT) decreased striatal BEN, while suprathreshold iTBS (120% rMT) increased striatal BEN. We also found significant differences in the spatial correlation between BEN changes induced by different stimulation intensities and various neurotransmitters. These results suggest that differences in BEN caused by iTBS stimulation intensity may be related to the release of other neurotransmitters. The study underscores the significance of iTBS stimulation intensity and provides a basis for future clinical investigations to identify stimulation intensities with good therapeutic benefits.

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Section: Discussionmentioning

confidence: 99%

Intermittent theta burst stimulation (iTBS)-induced changes of resting-state brain entropy (BEN)

Liu,

Song,

Deng

et al. 2024

Preprint

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“…Additionally, Luborzewski et al (2007) noted an elevation in the level of glutamate within the targeted area. Moreover, a recent study by Spurny-Dworak et al (2022) showcased an increase in glutamate transmission also induced by facilitatory TMS (iTBS, intermittent theta-burst stimulation). Importantly, both neurotransmitters are deficient in depression.…”

Section: Rtms-induced Neuroplasticitymentioning

confidence: 98%

Transcranial magnetic stimulation and ketamine: implications for combined treatment in depression

Dębowska,

Więdłocha,

Dębowska

et al. 2023

Front. Neurosci.

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Drug-resistant mental disorders, particularly treatment-resistant depression, pose a significant medical and social problem. To address this challenge, modern psychiatry is constantly exploring the use of novel treatment methods, including biological treatments, such as transcranial magnetic stimulation (TMS), and novel rapid-acting antidepressants, such as ketamine. While both TMS and ketamine demonstrate high effectiveness in reducing the severity of depressive symptoms, some patients still do not achieve the desired improvement. Recent literature suggests that combining these two methods may yield even stronger and longer-lasting results. This review aims to consolidate knowledge in this area and elucidate the potential mechanisms of action underlying the increased efficacy of combined treatment, which would provide a foundation for the development and optimization of future treatment protocols.

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“…Neurostimulatory treatments evaluated in TRD include vagus nerve stimulation (VNS), ECT, rTMS, magnetic seizure therapy, deep brain stimulation, and transcranial direct current stimulation [227][228][229][230][231][232][233] .…”

Section: Neurostimulationmentioning

confidence: 99%

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

McIntyre,

Alsuwaidan,

Baune

et al. 2023

World Psychiatry

Self Cite

105

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Treatment‐resistant depression (TRD) is common and associated with multiple serious public health implications. A consensus definition of TRD with demonstrated predictive utility in terms of clinical decision‐making and health outcomes does not currently exist. Instead, a plethora of definitions have been proposed, which vary significantly in their conceptual framework. The absence of a consensus definition hampers precise estimates of the prevalence of TRD, and also belies efforts to identify risk factors, prevention opportunities, and effective interventions. In addition, it results in heterogeneity in clinical practice decision‐making, adversely affecting quality of care. The US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have adopted the most used definition of TRD (i.e., inadequate response to a minimum of two antidepressants despite adequacy of the treatment trial and adherence to treatment). It is currently estimated that at least 30% of persons with depression meet this definition. A significant percentage of persons with TRD are actually pseudo‐resistant (e.g., due to inadequacy of treatment trials or non‐adherence to treatment). Although multiple sociodemographic, clinical, treatment and contextual factors are known to negatively moderate response in persons with depression, very few factors are regarded as predictive of non‐response across multiple modalities of treatment. Intravenous ketamine and intranasal esketamine (co‐administered with an antidepressant) are established as efficacious in the management of TRD. Some second‐generation antipsychotics (e.g., aripiprazole, brexpiprazole, cariprazine, quetiapine XR) are proven effective as adjunctive treatments to antidepressants in partial responders, but only the olanzapine‐fluoxetine combination has been studied in FDA‐defined TRD. Repetitive transcranial magnetic stimulation (TMS) is established as effective and FDA‐approved for individuals with TRD, with accelerated theta‐burst TMS also recently showing efficacy. Electroconvulsive therapy is regarded as an effective acute and maintenance intervention in TRD, with preliminary evidence suggesting non‐inferiority to acute intravenous ketamine. Evidence for extending antidepressant trial, medication switching and combining antidepressants is mixed. Manual‐based psychotherapies are not established as efficacious on their own in TRD, but offer significant symptomatic relief when added to conventional antidepressants. Digital therapeutics are under study and represent a potential future clinical vista in this population.

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

Cited by 5 publications

References 57 publications

Intermittent theta burst stimulation (iTBS)-induced changes of resting-state brain entropy (BEN)

Intermittent theta burst stimulation (iTBS)-induced changes of resting-state brain entropy (BEN)

Transcranial magnetic stimulation and ketamine: implications for combined treatment in depression

Treatment‐resistant depression: definition, prevalence, detection, management, and investigational interventions

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