Pathological Research and Target Exploration of Anxiety Disorders

Zihao Xia

doi:10.54097/80n0er58

Authors

Zihao Xia

DOI:

https://doi.org/10.54097/80n0er58

Keywords:

Anxiety Disorder, Serotonin, γ-aminobutyric Acid, Mental Health, Psychiatric Diagnosis

Abstract

Anxiety disorders are widespread mental health problems, impacting around 4% of the global population and showing a 7.57% lifetime prevalence among Chinese adults. These conditions are mainly marked by intense worry and tension without actual threats, presenting in various forms and symptoms. Abnormalities in the structure and function of certain brain areas, along with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, have been linked to the development of anxiety disorders. For instance, changes in brain structures like the amygdala and parahippocampal gyrus can disrupt the regulation of emotions and memory processing. The understanding of what causes anxiety disorders has evolved significantly over time. Although the serotonin hypothesis has faced increasing doubts, the 5-hydroxytryptamine (5-HT) system remains a crucial target for treatment. The 5-HT system consists of multiple receptor subtypes that control different physiological processes. Medications such as selective serotonin reuptake inhibitors (SSRI) and serotonin-norepinephrine reuptake inhibitors (SNRI) work by preventing the reuptake of neurotransmitters. Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain, is essential for the synthesis, metabolism, and receptor activities related to anxiety disorders. Benzodiazepines relieve anxiety symptoms by adjusting GABAergic activity. Studies on the pathophysiology and treatment targets of anxiety disorders lay the groundwork for the development of new diagnostic methods and treatment approaches.

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References

[1] Tian, W. (2025) Burden of depressive and anxiety disorders in China and its provinces, 1990-2021. Br J Psychiatry, 22:1-11.

[2] Terlizzi, E.P. (2024) Symptoms of Anxiety and Depression Among Adults: United States, 2019 and 2022. Natl Health Stat Report. PMID: 39591466; PMCID: PMC11616099.

[3] American Psychiatric Association. (2013). Anxiety disorders. In Diagnostic and statistical manual of mental disorders (5th ed.). Cooper, R. (2014). Diagnosing the Diagnostic and Statistical Manual of Mental Disorders: Fifth Edition (1st ed.). Routledge. https://doi.org/10.4324/9780429473678.

[4] Lai, C.H. (2011) Gray matter deficits in panic disorder: a pilot study of meta-analysis. J Clin Psychopharmacol, 31(3):287-93.

[5] Hayano, F., Nakamura, M., Asami, T. (2009) Smaller amygdala is associated with anxiety in patients with panic disorder. Psychiatry Clin Neurosci, 63(3):266-76.

[6] Massana, G., Serra-Grabulosa, J.M., Salgado-Pineda, P. (2003) Parahippocampal gray matter density in panic disorder: a voxel-based morphometric study. Am J Psychiatry, 160 (3): 566-8.

[7] Sobanski, T., Wagner, G., Peikert, G. (2010) Temporal and right frontal lobe alterations in panic disorder: a quantitative volumetric and voxel-based morphometric MRI study. Psychol Med, 40(11):1879-86.

[8] Martin, E.I., Ressler, K.J., Binder, E. (2010) The neurobiology of anxiety disorders: brain imaging, genetics, and psychoneuroendocrinology. Clin Lab Med, 30(4):865-91.

[9] Holzschneider, K., Mulert, C. (2011) Neuroimaging in anxiety disorders. Dialogues Clin Neurosci, 13(4):453-61.

[10] Espinoza, O.D.A., Shaw, M.E., Alateeq, K. (2020) Volumetric brain differences in clinical depression in association with anxiety: a systematic review with meta-analysis. J Psychiatry Neurosci, 45(6):406-429.

[11] Holzschneider, K., Mulert, C. (2011) Neuroimaging in anxiety disorders. Dialogues Clin Neurosci, 13(4):453-61.

[12] Lai, C.H. (2011) Gray matter deficits in panic disorder: a pilot study of meta-analysis. J Clin Psychopharmacol, 31(3):287-93.

[13] Schildkraut, J.J. (1965) The catecholamine hypothesis of affective disorders: a review of supporting evidence. Am J Psychiatry, 122(5):509-22.

[14] Moncrieff, J., Cooper, R.E., Stockmann, T. (2023) The serotonin theory of depression: a systematic umbrella review of the evidence. Mol Psychiatry, 28, 3243–3256.

[15] Pilkington PD, Reavley NJ, Jorm AF. The Australian public's beliefs about the causes of depression: associated factors and changes over 16 years. J Affect Disord. 2013 Sep 5;150(2):356-62. doi: 10.1016/j.jad.2013.04.019. Epub 2013 May 18. PMID: 23688917.

[16] Nutt, D. (2004). Anxiety and depression: individual entities or two sides of the same coin? International Journal of Psychiatry in Clinical Practice, 8(sup1), 19–24.

[17] Cardon, I., Grobecker, S., Jenne, F. (2024) Serotonin effects on human iPSC-derived neural cell functions: from mitochondria to depression. Mol Psychiatry, 29(9):2689-2700.

[18] Yohn, C.N., Gergues, M.M., Samuels, B.A. (2017) The role of 5-HT receptors in depression. Mol Brain, 10(1):28.

[19] Olivier, J.D.A, Olivier, B. (2020) Translational Studies in the Complex Role of Neurotransmitter Systems in Anxiety and Anxiety Disorders. Adv Exp Med Biol, 1191:121-140.

[20] Xu, P., Huang, S., Zhang, H. (2021) Structural insights into the lipid and ligand regulation of serotonin receptors. Nature, 592(7854):469-473.

[21] Polovinkin, L., Hassaine, G., Perot, J. (2018) Conformational transitions of the serotonin 5-HT3 receptor. Nature, 563(7730): 275-279.

[22] Tan, Y., Xu, P., Huang, S. (2022) Structural insights into the ligand binding and Gi coupling of serotonin receptor 5-HT5A. Cell Discov, 8(1):50.

[23] Zhang Y, Zhang P, Shin M, Chang Y, Abbott SBG, Venton BJ, Zhu JJ. Coding principles and mechanisms of serotonergic transmission modes. Mol Psychiatry. 2025 Feb 22. doi: 10.1038/s41380-025-02930-4. Epub ahead of print. PMID: 39987232.

[24] Dandan, R. hilal. (n.d.). Goodman and Gilman’s Manual of Pharmacology and Therapeutics. Brunton, L., Goodman, L. S., Gilman,A., Blumenthal, D., Buxton, I., Parker, K. (2007). Goodman and Gilman's Manual of Pharmacology and Therapeutics. Britain: McGraw-Hill Education.

[25] Stefánsdóttir ÍH, Ivarsson T, Skarphedinsson G. Efficacy and safety of serotonin reuptake inhibitors (SSRI) and serotonin noradrenaline reuptake inhibitors (SNRI) for children and adolescents with anxiety disorders: a systematic review and meta-analysis. Nord J Psychiatry. 2023 Feb;77(2):137-146. doi: 10.1080/08039488.2022.2075460. Epub 2022 May 19. PMID: 35587815.

[26] Koh, W., Kwak, H., Cheong, E., (2023). GABA tone regulation and its cognitive functions in the brain. Nat Rev Neurosci, 24(9):523-539.

[27] Zhu, S., Noviello, C.M., Teng, J. (2018) Structure of a human synaptic GABAA receptor. Nature, 559(7712):67-72.

[28] Wang, X., Bi, S., Yue, Z. (2025) GABAergic neurons in central amygdala contribute to orchestrating anxiety-like behaviors and breathing patterns. Nat Commun, 16(1):3544.

[29] Koh, W., Lee, C.J. (2024) Diagnostic and therapeutic potential of tonic gamma-aminobutyric acid from reactive astrocytes in brain diseases. Clin Transl Med, 14(4): e1642.

[30] Xia, G., Han, Y., Meng, F. (2021) Reciprocal control of obesity and anxiety-depressive disorder via a GABA and serotonin neural circuit. Mol Psychiatry, 26(7):2837-2853.