Revealing GABA Induced Depression: Dual Validation of Animal Experiments and Clinical Data

Research Article
Open access

Revealing GABA Induced Depression: Dual Validation of Animal Experiments and Clinical Data

Sihang Chen 1*
  • 1 Kyiv College, Qilu University of Technology, Jinan, China    
  • *corresponding author 15318824796@163.com
TNS Vol.117
ISSN (Print): 2753-8826
ISSN (Online): 2753-8818
ISBN (Print): 978-1-80590-199-0
ISBN (Online): 978-1-80590-200-3

Abstract

At present, the scientific research field has conducted in-depth research on its pathogenesis, and a large number of studies have shown that Gamma-Aminobutyric Acid (GABA) ergic neuronal downregulation plays a key role in the pathogenesis of major depression. As a critical inhibitory neurotransmitter in the central nervous system, the abnormal downregulation of GABA neurons will break the balance of the neurotransmitter system. This disruption subsequently interferes with the normal transmission and regulation of neural signals, ultimately leading to multifaceted abnormalities in emotional, cognitive, and physiological functions—processes that collectively drive the onset and progression of major depression. This article reviews the existing experimental evidence of GABA's influence on the development of depression, and provides the basis for further research.

Keywords:

GABA, depression, Sprague-Dawley rats, GAD67, Postmenopausal women

Chen,S. (2025). Revealing GABA Induced Depression: Dual Validation of Animal Experiments and Clinical Data. Theoretical and Natural Science,117,8-13.
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References

[1]. Dai, F., et al., Lack of association between pretreatment glutamate/GABA and major depressive disorder treatment response. Transl Psychiatry, 2025. 15(1): p. 71.

[2]. Tette, F.M., S.K. Kwofie, and M.D. Wilson, Therapeutic Anti-Depressant Potential of Microbial GABA Produced by Lactobacillus rhamnosus Strains for GABAergic Signaling Restoration and Inhibition of Addiction-Induced HPA Axis Hyperactivity. Curr Issues Mol Biol, 2022. 44(4): p. 1434-1451.

[3]. Zhang, Q., et al., Insights and progress on the biosynthesis, metabolism, and physiological functions of gamma-aminobutyric acid (GABA): a review. PeerJ, 2024. 12: p. e18712.

[4]. Jewett, B.E. and S. Sharma, Physiology, GABA, in StatPearls. 2025, StatPearls Publishing Copyright © 2025, StatPearls Publishing LLC.: Treasure Island (FL).

[5]. Zink, M., et al., Reduced expression of GABA transporter GAT3 in helpless rats, an animal model of depression. Neurochem Res, 2009. 34(9): p. 1584-93.

[6]. Smith, K.M., Hyperactivity in mice lacking one allele of the glutamic acid decarboxylase 67 gene. Atten Defic Hyperact Disord, 2018. 10(4): p. 267-271.

[7]. Nullmeier, S., et al., Glutamic acid decarboxylase 67 haplodeficiency in mice: consequences of postweaning social isolation on behavior and changes in brain neurochemical systems. Brain Struct Funct, 2020. 225(6): p. 1719-1742.

[8]. Gu, S.M., et al., Different development patterns of reward behaviors induced by ketamine and JWH-018 in striatal GAD67 knockdown mice. J Vet Sci, 2024. 25(5): p. e63.

[9]. Wang, Z., et al., GABA+ levels in postmenopausal women with mild-to-moderate depression: A preliminary study. Medicine (Baltimore), 2016. 95(39): p. e4918.

[10]. Guimarães, A.P., et al., GABA Supplementation, Increased Heart-Rate Variability, Emotional Response, Sleep Efficiency and Reduced Depression in Sedentary Overweight Women Undergoing Physical Exercise: Placebo-Controlled, Randomized Clinical Trial. J Diet Suppl, 2024. 21(4): p. 512-526.

[11]. Gabbay, V., et al., Anterior cingulate cortex γ-aminobutyric acid deficits in youth with depression. Transl Psychiatry, 2017. 7(8): p. e1216.

[12]. Epperson, C.N., et al., Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program. J Affect Disord, 2023. 320: p. 353-359.

[13]. Deligiannidis, K.M., et al., Zuranolone for the Treatment of Postpartum Depression. Am J Psychiatry, 2023. 180(9): p. 668-675.

[14]. Bosch, O.G., et al., Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone. Psychoneuroendocrinology, 2015. 62: p. 1-10.

[15]. Bruijn, J.A., et al., Trait anxiety and the effect of a single high dose of diazepam in unipolar depression. J Psychiatr Res, 2001. 35(6): p. 331-7.

[16]. Laws, D., J.J. Ashford, and J.A. Anstee, A multicentre double-blind comparative trial of fluvoxamine versus lorazepam in mixed anxiety and depression treated in general practice. Acta Psychiatr Scand, 1990. 81(2): p. 185-9.


Cite this article

Chen,S. (2025). Revealing GABA Induced Depression: Dual Validation of Animal Experiments and Clinical Data. Theoretical and Natural Science,117,8-13.

Data availability

The datasets used and/or analyzed during the current study will be available from the authors upon reasonable request.

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About volume

Volume title: Proceedings of ICBioMed 2025 Symposium: Computational Modelling and Simulation for Biology and Medicine

ISBN:978-1-80590-199-0(Print) / 978-1-80590-200-3(Online)
Editor:Alan Wang, Roman Bauer
Conference date: 19 September 2025
Series: Theoretical and Natural Science
Volume number: Vol.117
ISSN:2753-8818(Print) / 2753-8826(Online)

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References

[1]. Dai, F., et al., Lack of association between pretreatment glutamate/GABA and major depressive disorder treatment response. Transl Psychiatry, 2025. 15(1): p. 71.

[2]. Tette, F.M., S.K. Kwofie, and M.D. Wilson, Therapeutic Anti-Depressant Potential of Microbial GABA Produced by Lactobacillus rhamnosus Strains for GABAergic Signaling Restoration and Inhibition of Addiction-Induced HPA Axis Hyperactivity. Curr Issues Mol Biol, 2022. 44(4): p. 1434-1451.

[3]. Zhang, Q., et al., Insights and progress on the biosynthesis, metabolism, and physiological functions of gamma-aminobutyric acid (GABA): a review. PeerJ, 2024. 12: p. e18712.

[4]. Jewett, B.E. and S. Sharma, Physiology, GABA, in StatPearls. 2025, StatPearls Publishing Copyright © 2025, StatPearls Publishing LLC.: Treasure Island (FL).

[5]. Zink, M., et al., Reduced expression of GABA transporter GAT3 in helpless rats, an animal model of depression. Neurochem Res, 2009. 34(9): p. 1584-93.

[6]. Smith, K.M., Hyperactivity in mice lacking one allele of the glutamic acid decarboxylase 67 gene. Atten Defic Hyperact Disord, 2018. 10(4): p. 267-271.

[7]. Nullmeier, S., et al., Glutamic acid decarboxylase 67 haplodeficiency in mice: consequences of postweaning social isolation on behavior and changes in brain neurochemical systems. Brain Struct Funct, 2020. 225(6): p. 1719-1742.

[8]. Gu, S.M., et al., Different development patterns of reward behaviors induced by ketamine and JWH-018 in striatal GAD67 knockdown mice. J Vet Sci, 2024. 25(5): p. e63.

[9]. Wang, Z., et al., GABA+ levels in postmenopausal women with mild-to-moderate depression: A preliminary study. Medicine (Baltimore), 2016. 95(39): p. e4918.

[10]. Guimarães, A.P., et al., GABA Supplementation, Increased Heart-Rate Variability, Emotional Response, Sleep Efficiency and Reduced Depression in Sedentary Overweight Women Undergoing Physical Exercise: Placebo-Controlled, Randomized Clinical Trial. J Diet Suppl, 2024. 21(4): p. 512-526.

[11]. Gabbay, V., et al., Anterior cingulate cortex γ-aminobutyric acid deficits in youth with depression. Transl Psychiatry, 2017. 7(8): p. e1216.

[12]. Epperson, C.N., et al., Effect of brexanolone on depressive symptoms, anxiety, and insomnia in women with postpartum depression: Pooled analyses from 3 double-blind, randomized, placebo-controlled clinical trials in the HUMMINGBIRD clinical program. J Affect Disord, 2023. 320: p. 353-359.

[13]. Deligiannidis, K.M., et al., Zuranolone for the Treatment of Postpartum Depression. Am J Psychiatry, 2023. 180(9): p. 668-675.

[14]. Bosch, O.G., et al., Gamma-hydroxybutyrate enhances mood and prosocial behavior without affecting plasma oxytocin and testosterone. Psychoneuroendocrinology, 2015. 62: p. 1-10.

[15]. Bruijn, J.A., et al., Trait anxiety and the effect of a single high dose of diazepam in unipolar depression. J Psychiatr Res, 2001. 35(6): p. 331-7.

[16]. Laws, D., J.J. Ashford, and J.A. Anstee, A multicentre double-blind comparative trial of fluvoxamine versus lorazepam in mixed anxiety and depression treated in general practice. Acta Psychiatr Scand, 1990. 81(2): p. 185-9.