Increase in ACC GABA+ levels correlate with decrease in migraine frequency, intensity and disability over time

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Abstract

Background

An imbalance between inhibitory and excitatory neurometabolites has been implicated in chronic pain. Prior work identified elevated levels of Gamma-aminobutyric acid + macromolecules (“GABA+”) using magnetic resonance spectroscopy (MRS) in people with migraine. What is not understood is whether this increase in GABA+ is a cause, or consequence of living with, chronic migraine. Therefore, to further elucidate the nature of the elevated GABA+ levels reported in migraine, this study aimed to observe how GABA+ levels change in response to changes in the clinical characteristics of migraine over time.

Methods

We observed people with chronic migraine (ICHD-3) over 3-months as their treatment was escalated in line with the Australian Pharmaceutical Benefits Scheme (PBS). Participants underwent an MRS scan and completed questionnaires regarding migraine frequency, intensity (HIT-6) and disability (WHODAS) at baseline and following the routine 3 months treatment escalation to provide the potential for some participants to recover. We were therefore able to monitor changes in brain neurochemistry as clinical characteristics potentially changed over time.

Results

The results, from 18 participants who completed both baseline and follow-up measures, demonstrated that improvements in migraine frequency, intensity and disability were associated with an increase in GABA+ levels in the anterior cingulate cortex (ACC); migraine frequency ( r = − 0.51, p = 0.03), intensity ( r = − 0.51, p = 0.03) and disability ( r = − 0.53, p = 0.02). However, this was not seen in the posterior cingulate gyrus (PCG). An incidental observation found those who happened to have their treatment escalated with CGRP-monoclonal antibodies (CGRP-mAbs) ( n = 10) had a greater increase in ACC GABA+ levels (mean difference 0.54 IU IQR [0.02 to 1.05], p = 0.05) and reduction in migraine frequency (mean difference 10.3 IQR [2.52 to 18.07], p = 0.01) compared to those who did not ( n = 8).

Conclusion

The correlation between an increase in ACC GABA+ levels with improvement in clinical characteristics of migraine, suggest previously reported elevated GABA+ levels may not be a cause of migraine, but a protective mechanism attempting to suppress further migraine attacks.

Supplementary Information

The online version contains supplementary material available at 10.1186/s10194-021-01352-1.

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Most cited references 54

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The structure of negative emotional states: Comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories

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The psychometric properties of the Depression Anxiety Stress Scales (DASS) were evaluated in a normal sample of N = 717 who were also administered the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). The DASS was shown to possess satisfactory psychometric properties, and the factor structure was substantiated both by exploratory and confirmatory factor analysis. In comparison to the BDI and BAI, the DASS scales showed greater separation in factor loadings. The DASS Anxiety scale correlated 0.81 with the BAI, and the DASS Depression scale correlated 0.74 with the BDI. Factor analyses suggested that the BDI differs from the DASS Depression scale primarily in that the BDI includes items such as weight loss, insomnia, somatic preoccupation and irritability, which fail to discriminate between depression and other affective states. The factor structure of the combined BDI and BAI items was virtually identical to that reported by Beck for a sample of diagnosed depressed and anxious patients, supporting the view that these clinical states are more severe expressions of the same states that may be discerned in normals. Implications of the results for the conceptualisation of depression, anxiety and tension/stress are considered, and the utility of the DASS scales in discriminating between these constructs is discussed.

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Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition

(2018)

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Author and article information

Contributors

Aimie L. Peek:

ORCID: http://orcid.org/0000-0001-8943-7951

apee6909@uni.sydney.edu.au , aimie.peek@yahoo.com

Andrew M. Leaver: andrew.leaver@sydney.edu.au

Sheryl Foster: sheryl.foster@sydney.edu.au

Nicolaas A. Puts: nicolaas.puts@kcl.ac.uk

Georg Oeltzschner: goeltzs1@jhmi.edu

Luke Henderson: luke.henderson@sydney.edu.au

Graham Galloway: g.galloway@uq.edu.au

Karl Ng: karl.ng@health.nsw.gov.au

Kathryn Refshauge: kathryn.refshauge@sydney.edu.au

Trudy Rebbeck: trudy.rebbeck@sydney.edu.au

Journal

Journal ID (nlm-ta): J Headache Pain

Journal ID (iso-abbrev): J Headache Pain

Title: The Journal of Headache and Pain

Publisher: Springer Milan (Milan )

ISSN (Print): 1129-2369

ISSN (Electronic): 1129-2377

Publication date (Electronic): 13 December 2021

Publication date PMC-release: 13 December 2021

Publication date Collection: 2021

Volume: 22

Issue: 1

Electronic Location Identifier: 150

Affiliations

[1 ]GRID grid.1013.3, ISNI 0000 0004 1936 834X, Faculty of Medicine and Health, , University of Sydney, ; Camperdown, New South Wales 2141 Australia

[2 ]NHMRC Centre of Research Excellence in Road Traffic Injury Recovery, Brisbane, Queensland Australia

[3 ]GRID grid.413252.3, ISNI 0000 0001 0180 6477, Department of Radiology, , Westmead Hospital, ; Hawkesbury Road, Westmead, New South Wales 2145 Australia

[4 ]GRID grid.13097.3c, ISNI 0000 0001 2322 6764, Department of Forensic and Neurodevelopmental Sciences, Sackler Institute for Translational Neurodevelopment, , Institute of Psychiatry, Psychology, and Neuroscience, Kings College London, ; London, UK

[5 ]GRID grid.21107.35, ISNI 0000 0001 2171 9311, Department of Radiology and Radiological Science, , Johns Hopkins University School of Medicine, ; Baltimore, MD 21287 USA

[6 ]GRID grid.240023.7, ISNI 0000 0004 0427 667X, F.M. Kirby Research Center for Functional Brain Imaging, , Kennedy Krieger Institute, ; Baltimore, MD 21205 USA

[7 ]GRID grid.1013.3, ISNI 0000 0004 1936 834X, School of Medical Sciences, Brain and Mind Centre, , University of Sydney, ; Camperdown, Australia

[8 ]GRID grid.1003.2, ISNI 0000 0000 9320 7537, The University of Queensland, ; St Lucia, Queensland 4072 Australia

[9 ]GRID grid.489335.0, ISNI 0000000406180938, Translational Research Institute, ; 37 Kent Street, Woolloongabba, Queensland 4102 Australia

[10 ]GRID grid.412703.3, ISNI 0000 0004 0587 9093, Department of Neurology, , Royal North Shore Hospital, ; Reserve Road, St Leonards, New South Wales 2065 Australia

Author information

Aimie L. Peek http://orcid.org/0000-0001-8943-7951

Article

Publisher ID: 1352

DOI: 10.1186/s10194-021-01352-1

PMC ID: 8903525

PubMed ID: 34903165

SO-VID: 6b364502-6a29-4695-a354-8773259176e4

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 25 August 2021

Date accepted : 3 November 2021

Funding

Funded by: FundRef http://dx.doi.org/10.13039/501100000925, National Health and Medical Research Council;

Award ID: APP1079022

Award ID: APP1161467

Award Recipient : Trudy Rebbeck

Funded by: The University of Sydney

Award ID: SOAR Research Accelerator

Award Recipient : Trudy Rebbeck

Custom metadata

ScienceOpen disciplines: Anesthesiology & Pain management

Keywords: gaba,mrs,migraine,anti-cgrp,pain,longitudinal

Data availability:

ScienceOpen disciplines: Anesthesiology & Pain management

Keywords: gaba, mrs, migraine, anti-cgrp, pain, longitudinal

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Increase in ACC GABA+ levels correlate with decrease in migraine frequency, intensity and disability over time

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Abstract

Background

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Results

Conclusion

Supplementary Information

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Irish Journal of Paramedicine

Most cited references 54

Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support.

The structure of negative emotional states: Comparison of the Depression Anxiety Stress Scales (DASS) with the Beck Depression and Anxiety Inventories

Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition

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