medsovetМедицинский СоветMeditsinskiy sovet = Medical Council2079-701X2658-5790REMEDIUM GROUP Ltd.10.21518/ms2023-235medsovet-7645Research ArticleНЕРВНО-ПСИХИЧЕСКИЕ РАССТРОЙСТВАNEUROPSYCHIATRIC DISORDERSТревожные расстройства в клинической практике: от механизмов развития к дифференцированной терапииAnxiety disorders in clinical practice: from development mechanisms to differentiated therapyhttps://orcid.org/0000-0002-2600-0573ВасенинаЕ. Е.VaseninaE. E.

Васенина Елена Евгеньевна, д.м.н., доцент

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1 

Elena E. Vasenina, Dr. Sci. (Med.), Associate Professor

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

hel_vas@mail.ruhttps://orcid.org/0000-0002-8714-2698ГанькинаО. А.GankinaO. A.

Ганькина Ольга Александровна, к.м.н., ассистент

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1 

Olga A. Gankina, Cand. Sci. (Med.), Assistant

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

ganya1987@mail.ruЛевинО. С.LevinO. S.

Левин Олег Семенович, д.м.н., профессор

125993, Москва, ул. Баррикадная, д. 2/1, стр. 1 

Oleg S. Levin, Dr. Sci. (Med.), Professor

2/1, Bldg. 1, Barrikadnaya St., Moscow, 125993

neurolev@mail.ruРоссийская медицинская академия непрерывного профессионального образованияРоссияRussian Medical Academy of Continuous Professional EducationRussian Federation20232407202301089–96Copyright © Васенина Е.Е., Ганькина О.А., Левин О.С., 20232023Васенина Е.Е., Ганькина О.А., Левин О.С.Vasenina E.E., Gankina O.A., Levin O.S.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-sovet.pro/jour/article/view/7645

Аффективные нарушения – крайне актуальная проблема современного здравоохранения. Распространенность тревожных расстройств в клинической практике значительно выросла с 2019 г., что связано с различными ситуационными причинами, и, вероятно, негативные тенденции сохранятся в ближайшие годы. Кроме того, в связи с постарением населения и значительным приростом количества пациентов с нейродегенеративными заболеваниями отмечается увеличение и т. н. вторичных аффективных нарушений. Они связаны с органическим поражением стратегически важных для реализации эмоциональных процессов зон и повреждением нейронов ключевых нейротрансмиттерных систем, что часто встречается в рамках нейродегенеративного патологического процесса. В основе развития тревоги в первую очередь лежит дефект связи «угроза – страх», когда реакция, возникающ ая в организме, неадекватна и неэквивалента степени опасности. На патофизиологическом уровне это можно объяснить нарушением взаимодействия между структурами лимбической системы, обеспечивающ ей рефлекторный ответ на угрожаю щий стимул по принципу «драться или убегать», и неокортексом, который отвечает за когнитивную обработку и адаптацию наших эмоциональных реакций. Можно выделить 3 ключевые теории развития тревоги: недостаточность контроля, генерализация страха и гиперсенсибилиация к опасности. Первый механизм чаще всего связан с формированием генерализованного тревожного расстройства; вторая теория наиболее полно раскрывает механизмы развития посттравматического стрессового расстройства, а гиперсенсибилизация префронтальной коры лучше всего позволяет объяснить развитие социофобии. Важным механизмом развития и хронизации различных аффективных нарушений является нейровоспаление, роль которого также будет подробно освящаться в данном обзоре. Понимание механизмов формирования расстройств тревожного спектра важно для дифференцированной медикаментозной и немедикаментозной терапии и выбора оптимальной стратегии лечения таких пациентов.

Affective disorders represent an extremely topical issue in modern healthcare. Prevalence of anxiety disorders in clinical practice increased significantly since 2019 due to various situational causes, and the trend will probably continue in the coming years. Besides, due to aging of the population and significant growth of the number of patients with neurodegenerative diseases, so called secondary affective disorders also increase. These are linked to organic lesion of the zones strategically important for emotional process implementation, and damaging of the key neurotransmitter systems neurons often seen in neurodegenerative pathological process. Development of anxiety is chiefly based on the defect of the “threat-fear” bound, with the reaction developing in the organism not equivalent to the degree of danger. On pathophysiological level this can be explained by disruption of interaction between limbic system structures that provide “fight or flight” reflex response to the threat, and the neocortex responsible for cognitive processing and adaptation of out emotional reactions. Three key theories of anxiety development can be identified: insufficiency of control, generalization of fear, and hypersensibilization to threat. The first mechanism is most often linked to development of generalized anxiety disorder, the second theory reveals most fully the mechanisms of post-traumatic stress disorder development, while the hypersensibilization of prefrontal cortex best allows to explain sociophobia development. An important mechanism of development and chronification of various affective disorders is neuroinflammation, the role of which will also be highlighted in detail in this review. Understanding of the mechanisms of anxiety spectrum disorders development is important for differentiated drug and non-drug therapy and establishing the optimal strategy of treatment for such patients.

аффективные нарушениятревогадепрессияминдалинапрефронтальная коранейровоспалениебуспиронaffective disordersanxietydepressionamygdalaprefrontal cortexneuroinflammationbuspironeReferencesAbdoli N., Salari N., Darvishi N., Jafarpour S., Solaymani M., Mohammadi M., Shohaimi S. The global prevalence of major depressive disorder (MDD) among the elderly: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2022;132:1067–1073. https://doi.org/10.1016/j.neubiorev.2021.10.041.Abdoli N., Salari N., Darvishi N., Jafarpour S., Solaymani M., Mohammadi M., Shohaimi S. The global prevalence of major depressive disorder (MDD) among the elderly: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2022;132:1067–1073. https://doi.org/10.1016/j.neubiorev.2021.10.041.Глущенко Я.Ю., Славгородская М.С., Дмитриев М.Н. Аффективные расстройства, впервые возникшие в постковидный период: анализ клинических случаев. Главный врач Юга России. 2023;(1):33–37. Режим доступа: http://akvarel2002.ru/assets/files/GV_1%20(87)%202023-prev.pdf.Glushchenko Ya.Yu., Slavgorodskaya M.S., Dmitriev M.N. New-onset mood disorders in the post-covid period: a case reports study. Glavnyy Vrach Yuga Rossii. 2023;(1):33–37. (In Russ.) Available at: http://akvarel2002.ru/assets/files/GV_1%20(87)%202023-prev.pdf.Cheng X., Wang Q., Wang R., Wang Y., Chen X., Mi G. et al. Prevalence of depressive disorders and associated demographic characteristics in Shandong: An epidemiological investigation. J Affect Disord. 2022;311:198–204. https://doi.org/10.1016/j.jad.2022.05.084.Cheng X., Wang Q., Wang R., Wang Y., Chen X., Mi G. et al. Prevalence of depressive disorders and associated demographic characteristics in Shandong: An epidemiological investigation. J Affect Disord. 2022;311:198–204. https://doi.org/10.1016/j.jad.2022.05.084.Andreescu C., Lee S. Anxiety Disorders in the Elderly. Adv Exp Med Biol. 2020;1191:561–576. https://doi.org/10.1007/978-981-32-9705-0_28.Andreescu C., Lee S. Anxiety Disorders in the Elderly. Adv Exp Med Biol. 2020;1191:561–576. https://doi.org/10.1007/978-981-32-9705-0_28.Premraj L., Kannapadi N.V., Briggs J., Seal S.M., Battaglini D., Fanning J. et al. Mid and long-term neurological and neuropsychiatric manifestations of post- COVID- 19 syndrome: A meta-analysis. J Neurol Sci. 2022;434:120162. https://doi.org/10.1016/j.jns.2022.120162.Premraj L., Kannapadi N.V., Briggs J., Seal S.M., Battaglini D., Fanning J. et al. Mid and long-term neurological and neuropsychiatric manifestations of post- COVID- 19 syndrome: A meta-analysis. J Neurol Sci. 2022;434:120162. https://doi.org/10.1016/j.jns.2022.120162.Lyra E., Silva N.M., Barros-A ragão F.G.Q., De Felice F.G., Ferreira S.T. Inflammation at the crossroads of COVID- 19, cognitive deficits and depression. Neuropharmacology. 2022;209:109023. https://doi.org/10.1016/j.neuropharm.2022.109023.Lyra E., Silva N.M., Barros-A ragão F.G.Q., De Felice F.G., Ferreira S.T. Inflammation at the crossroads of COVID- 19, cognitive deficits and depression. Neuropharmacology. 2022;209:109023. https://doi.org/10.1016/j.neuropharm.2022.109023.Onaemo V.N., Fawehinmi T.O., D’Arcy C. Comorbid Cannabis Use Disorder with Major Depression and Generalized Anxiety Disorder: A Systematic Review with Meta-analysis of Nationally Representative Epidemiological Surveys. J Affect Disord. 2021;281:467–475. https://doi.org/10.1016/j.jad.2020.12.043.Onaemo V.N., Fawehinmi T.O., D’Arcy C. Comorbid Cannabis Use Disorder with Major Depression and Generalized Anxiety Disorder: A Systematic Review with Meta-analysis of Nationally Representative Epidemiological Surveys. J Affect Disord. 2021;281:467–475. https://doi.org/10.1016/j.jad.2020.12.043.Zehravi M., Maqbool M., Ara I. Depression and anxiety in women with polycystic ovarian syndrome: a literature survey. Int J Adolesc Med Health. MEDITSINSKIY SOVET 2021;33(6):367–373. https://doi.org/10.1515/ijamh-2021-0092.Zehravi M., Maqbool M., Ara I. Depression and anxiety in women with polycystic ovarian syndrome: a literature survey. Int J Adolesc Med Health. MEDITSINSKIY SOVET 2021;33(6):367–373. https://doi.org/10.1515/ijamh-2021-0092.Pizzagalli D.A., Roberts A.C. Prefrontal cortex and depression. Neuropsychopharmacology. 2022;47(1):225–246. https://doi.org/10.1038/s41386-021-01101-7.Pizzagalli D.A., Roberts A.C. Prefrontal cortex and depression. Neuropsychopharmacology. 2022;47(1):225–246. https://doi.org/10.1038/s41386-021-01101-7.Meisner O.C., Nair A., Chang S.W.C. Amygdala connectivity and implications for social cognition and disorders. Handb Clin Neurol. 2022;187:381–403. https://doi.org/10.1016/B978-0-12-823493-8.00017-1.Meisner O.C., Nair A., Chang S.W.C. Amygdala connectivity and implications for social cognition and disorders. Handb Clin Neurol. 2022;187:381–403. https://doi.org/10.1016/B978-0-12-823493-8.00017-1.Васенина Е.Е., Ганькина О.А., Левин О.С. Стресс, астения и когнитивные расстройства. Журнал неврологии и психиатрии им. С.С. Корсакова. 2022;122(5):23–29.Vasenina E.E., Gankina O.A., Levin O.S. Stress, asthenia and cognitive disorders. Zhurnal Nevrologii i Psikhiatrii imeni S.S. Korsakova. 2022;122(5):23–29. (In Russ.) https://doi.org/10.17116/jnevro202212205123.https://doi.org/10.17116/jnevro202212205123.Vasenina E.E., Veryugina N.I., Levin O.S. Postinfectious asthenia and COVID- 19. Therapy.2021;(9):125–136. (In Russ.) https://doi.org/10.18565/ therapy.2021.9.125-136.Васенина Е.Е., Верюгина Н.И., Левин О.С. Постинфекционная астения и COVID- 19. Терапия.2021;(9):125–136. https://doi.org/10.18565/therapy. 2021.9.125-136.Belleau E.L., Treadway M.T., Pizzagalli D.A. The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology. Biol Psychiatry. 2019;85(6):443–453. https://doi.org/10.1016/j.biopsych.2018.09.031.Belleau E.L., Treadway M.T., Pizzagalli D.A. The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology. Biol Psychiatry. 2019;85(6):443–453. https://doi.org/10.1016/j.biopsych.2018.09.031.Morel C., Montgomery S.E., Li L., Durand-de Cuttoli R., Teichman E.M., Juarez B. et al. Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors. Nat Commun. 2022;13(1):1532. https://doi.org/10.1038/s41467-022-29155-1.Morel C., Montgomery S.E., Li L., Durand-de Cuttoli R., Teichman E.M., Juarez B. et al. Midbrain projection to the basolateral amygdala encodes anxiety-like but not depression-like behaviors. Nat Commun. 2022;13(1):1532. https://doi.org/10.1038/s41467-022-29155-1.Rogers J., Renoir T., Hannan A.J. Gene-environment interactions informing therapeutic approaches to cognitive and affective disorders. Neuropharmacology. 2019;145:37–48. https://doi.org/10.1016/j.neuropharm.2017.12.038.Rogers J., Renoir T., Hannan A.J. Gene-environment interactions informing therapeutic approaches to cognitive and affective disorders. Neuropharmacology. 2019;145:37–48. https://doi.org/10.1016/j.neuropharm.2017.12.038.Howard D.M., Adams M.J., Clarke T.K., Hafferty J.D., Gibson J., Shirali M. et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci. 2019;22(3):343–352. https://doi.org/10.1038/s41593-018-0326-7.Howard D.M., Adams M.J., Clarke T.K., Hafferty J.D., Gibson J., Shirali M. et al. Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions. Nat Neurosci. 2019;22(3):343–352. https://doi.org/10.1038/s41593-018-0326-7.Meyer J.H., Cervenka S., Kim M.J., Kreisl W.C., Henter I.D., Innis R.B. Neuroinflammation in psychiatric disorders: PET imaging and promising new targets. Lancet Psychiatry. 2020;7(12):1064–1074. https://doi.org/10.1016/S2215-0366(20)30255-8.Meyer J.H., Cervenka S., Kim M.J., Kreisl W.C., Henter I.D., Innis R.B. Neuroinflammation in psychiatric disorders: PET imaging and promising new targets. Lancet Psychiatry. 2020;7(12):1064–1074. https://doi.org/10.1016/S2215-0366(20)30255-8.Troubat R., Barone P., Leman S., Desmidt T., Cressant A., Atanasova B. et al. Neuroinflammation and depression: A review. Eur J Neurosci. 2021;53(1):151–171. https://doi.org/10.1111/ejn.14720.Troubat R., Barone P., Leman S., Desmidt T., Cressant A., Atanasova B. et al. Neuroinflammation and depression: A review. Eur J Neurosci. 2021;53(1):151–171. https://doi.org/10.1111/ejn.14720.Li W., Ali T., He K., Liu Z., Shah F.A., Ren Q. et al. Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression. Brain Behav Immun. 2021;92:10–24. https://doi.org/10.1016/j.bbi.2020.11.008.Li W., Ali T., He K., Liu Z., Shah F.A., Ren Q. et al. Ibrutinib alleviates LPS-induced neuroinflammation and synaptic defects in a mouse model of depression. Brain Behav Immun. 2021;92:10–24. https://doi.org/10.1016/j.bbi.2020.11.008.Shi Y., Wei B., Li L., Wang B., Sun M. Th17 cells and inflammation in neurological disorders: Possible mechanisms of action. Front Immunol. 2022;13:932152. https://doi.org/10.3389/fimmu.2022.932152.Shi Y., Wei B., Li L., Wang B., Sun M. Th17 cells and inflammation in neurological disorders: Possible mechanisms of action. Front Immunol. 2022;13:932152. https://doi.org/10.3389/fimmu.2022.932152.Lama A., Pirozzi C., Severi I., Morgese M.G., Senzacqua M., Annunziata C. et al. Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice. Brain Behav Immun. 2022;102:110–123. https://doi.org/10.1016/j.bbi.2022.02.008.Lama A., Pirozzi C., Severi I., Morgese M.G., Senzacqua M., Annunziata C. et al. Palmitoylethanolamide dampens neuroinflammation and anxiety-like behavior in obese mice. Brain Behav Immun. 2022;102:110–123. https://doi.org/10.1016/j.bbi.2022.02.008.Zheng Z.H., Tu J.L., Li X.H., Hua Q., Liu W.Z., Liu Y. et al. Neuroinflammation induces anxiety- and depressive-like behavior by modulating neuronal plasticity in the basolateral amygdala. Brain Behav Immun. 2021;91:505–518. https://doi.org/10.1016/j.bbi.2020.11.007.Zheng Z.H., Tu J.L., Li X.H., Hua Q., Liu W.Z., Liu Y. et al. Neuroinflammation induces anxiety- and depressive-like behavior by modulating neuronal plasticity in the basolateral amygdala. Brain Behav Immun. 2021;91:505–518. https://doi.org/10.1016/j.bbi.2020.11.007.Zhuang X., Zhan B., Jia Y., Li C., Wu N., Zhao M. et al. IL-33 in the basolateral amygdala integrates neuroinflammation into anxiogenic circuits via modulating BDNF expression. Brain Behav Immun. 2022;102:98–109. https://doi.org/10.1016/j.bbi.2022.02.019.Zhuang X., Zhan B., Jia Y., Li C., Wu N., Zhao M. et al. IL-33 in the basolateral amygdala integrates neuroinflammation into anxiogenic circuits via modulating BDNF expression. Brain Behav Immun. 2022;102:98–109. https://doi.org/10.1016/j.bbi.2022.02.019.Li Q.Y., Chen S.X., Liu J.Y., Yao P.W., Duan Y.W., Li Y.Y., Zang Y. Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror- image pain following motor fiber injury. J Neuroinflammation. 2022;19(1):162. https://doi.org/10.1186/s12974-022-02525-8.Li Q.Y., Chen S.X., Liu J.Y., Yao P.W., Duan Y.W., Li Y.Y., Zang Y. Neuroinflammation in the anterior cingulate cortex: the potential supraspinal mechanism underlying the mirror- image pain following motor fiber injury. J Neuroinflammation. 2022;19(1):162. https://doi.org/10.1186/s12974-022-02525-8.He Y., Wang Y., Yu H., Tian Y., Chen X., Chen C. et al. Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex. Pharmacol Res. 2023;191:106717. https://doi.org/10.1016/j.phrs.2023.106717.He Y., Wang Y., Yu H., Tian Y., Chen X., Chen C. et al. Protective effect of Nr4a2 (Nurr1) against LPS-induced depressive-like behaviors via regulating activity of microglia and CamkII neurons in anterior cingulate cortex. Pharmacol Res. 2023;191:106717. https://doi.org/10.1016/j.phrs.2023.106717.McEwen B.S., Akil H. Revisiting the Stress Concept: Implications for Affective Disorders. J Neurosci. 2020;40(1):12–21. https://doi.org/10.1523/JNEUROSCI.0733-19.2019.McEwen B.S., Akil H. Revisiting the Stress Concept: Implications for Affective Disorders. J Neurosci. 2020;40(1):12–21. https://doi.org/10.1523/JNEUROSCI.0733-19.2019.Amanollahi M., Jameie M., Heidari A., Rezaei N. The Dialogue Between Neuroinflammation and Adult Neurogenesis: Mechanisms Involved and Alterations in Neurological Diseases. Mol Neurobiol. 2023;60(2):923–959. https://doi.org/10.1007/s12035-022-03102-z.Amanollahi M., Jameie M., Heidari A., Rezaei N. The Dialogue Between Neuroinflammation and Adult Neurogenesis: Mechanisms Involved and Alterations in Neurological Diseases. Mol Neurobiol. 2023;60(2):923–959. https://doi.org/10.1007/s12035-022-03102-z.Xu R., Zhang Y.W., Gu Q., Yuan T.J., Fan B.Q., Xia J.M. et al. Alteration of neural activity and neuroinflammatory factors in the insular cortex of mice with corneal neuropathic pain. Genes Brain Behav. 2023;22(2):e12842. https://doi.org/10.1111/gbb.12842.Xu R., Zhang Y.W., Gu Q., Yuan T.J., Fan B.Q., Xia J.M. et al. Alteration of neural activity and neuroinflammatory factors in the insular cortex of mice with corneal neuropathic pain. Genes Brain Behav. 2023;22(2):e12842. https://doi.org/10.1111/gbb.12842.Duman R.S., Sanacora G., Krystal J.H. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron. 2019;102(1):75–90. https://doi.org/10.1016/j.neuron.2019.03.013.Duman R.S., Sanacora G., Krystal J.H. Altered Connectivity in Depression: GABA and Glutamate Neurotransmitter Deficits and Reversal by Novel Treatments. Neuron. 2019;102(1):75–90. https://doi.org/10.1016/j.neuron.2019.03.013.Wang H., He Y., Sun Z., Ren S., Liu M., Wang G., Yang J. Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression. J Neuroinflammation. 2022;19(1):132. https://doi.org/10.1186/s12974-022-02492-0.Wang H., He Y., Sun Z., Ren S., Liu M., Wang G., Yang J. Microglia in depression: an overview of microglia in the pathogenesis and treatment of depression. J Neuroinflammation. 2022;19(1):132. https://doi.org/10.1186/s12974-022-02492-0.Zhang F.F., Peng W., Sweeney J.A., Jia Z.Y., Gong Q.Y. Brain structure alterations in depression: Psychoradiological evidence. CNS Neurosci Ther. 2018;24(11):994–1003. https://doi.org/10.1111/cns.12835.Zhang F.F., Peng W., Sweeney J.A., Jia Z.Y., Gong Q.Y. Brain structure alterations in depression: Psychoradiological evidence. CNS Neurosci Ther. 2018;24(11):994–1003. https://doi.org/10.1111/cns.12835.Heshmati M., Christoffel D.J., LeClair K., Cathomas F., Golden S.A., Aleyasin H. et al. Depression and Social Defeat Stress Are Associated with Inhibitory Synaptic Changes in the Nucleus Accumbens. J Neurosci. 2020;40(32):6228–6233. https://doi.org/10.1523/JNEUROSCI.2568-19.2020.Heshmati M., Christoffel D.J., LeClair K., Cathomas F., Golden S.A., Aleyasin H. et al. Depression and Social Defeat Stress Are Associated with Inhibitory Synaptic Changes in the Nucleus Accumbens. J Neurosci. 2020;40(32):6228–6233. https://doi.org/10.1523/JNEUROSCI.2568-19.2020.Coccurello R. Anhedonia in depression symptomatology: Appetite dysregulation and defective brain reward processing. Behav Brain Res. 2019;372:112041. https://doi.org/10.1016/j.bbr.2019.112041.Coccurello R. Anhedonia in depression symptomatology: Appetite dysregulation and defective brain reward processing. Behav Brain Res. 2019;372:112041. https://doi.org/10.1016/j.bbr.2019.112041.Brakel K., Hook M.A. SCI and depression: Does inflammation commandeer the brain? Exp Neurol. 2019;320:112977. https://doi.org/10.1016/j.expneurol.2019.112977.Brakel K., Hook M.A. SCI and depression: Does inflammation commandeer the brain? Exp Neurol. 2019;320:112977. https://doi.org/10.1016/j.expneurol.2019.112977.Balon R., Starcevic V. Role of Benzodiazepines in Anxiety Disorders. Adv Exp Med Biol. 2020;1191:367–388. https://doi.org/10.1007/978-981-32-9705-0_20.Balon R., Starcevic V. Role of Benzodiazepines in Anxiety Disorders. Adv Exp Med Biol. 2020;1191:367–388. https://doi.org/10.1007/978-981-32-9705-0_20.Chapoutot M., Peter- Derex L., Bastuji H., Leslie W., Schoendorff B., Heinzer R. et al. Cognitive Behavioral Therapy and Acceptance and Commitment Therapy for the Discontinuation of Long-Term Benzodiazepine Use in Insomnia and Anxiety Disorders. Int J Environ Res Public Health. 2021;18(19):10222. https://doi.org/10.3390/ijerph181910222.Chapoutot M., Peter- Derex L., Bastuji H., Leslie W., Schoendorff B., Heinzer R. et al. Cognitive Behavioral Therapy and Acceptance and Commitment Therapy for the Discontinuation of Long-Term Benzodiazepine Use in Insomnia and Anxiety Disorders. Int J Environ Res Public Health. 2021;18(19):10222. https://doi.org/10.3390/ijerph181910222.Garakani A., Murrough J.W., Freire R.C., Thom R.P., Larkin K., Buono F.D. Iosifescu D.V. Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Front Psychiatry. 2020;11:595584. https://doi.org/10.3389/fpsyt.2020.595584.Garakani A., Murrough J.W., Freire R.C., Thom R.P., Larkin K., Buono F.D. Iosifescu D.V. Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Front Psychiatry. 2020;11:595584. https://doi.org/10.3389/fpsyt.2020.595584.Kim J.K., Han S.K., Joo M.K., Kim D.H. Buspirone alleviates anxiety, depression, and colitis; and modulates gut microbiota in mice. Sci Rep. 2021;11(1):6094. https://doi.org/10.1038/s41598-021-85681-w.Kim J.K., Han S.K., Joo M.K., Kim D.H. Buspirone alleviates anxiety, depression, and colitis; and modulates gut microbiota in mice. Sci Rep. 2021;11(1):6094. https://doi.org/10.1038/s41598-021-85681-w.Thomas Broome S., Fisher T., Faiz A., Keay K.A., Musumeci G., Al-B adri G., Castorina A. Assessing the Anti- Inflammatory Activity of the Anxiolytic Drug Buspirone Using CRISPR-Cas9 Gene Editing in LPS-Stimulated BV-2 Microglial Cells. Cells. 2021;10(6):1312. https://doi.org/10.3390/cells10061312.Thomas Broome S., Fisher T., Faiz A., Keay K.A., Musumeci G., Al-B adri G., Castorina A. Assessing the Anti- Inflammatory Activity of the Anxiolytic Drug Buspirone Using CRISPR-Cas9 Gene Editing in LPS-Stimulated BV-2 Microglial Cells. Cells. 2021;10(6):1312. https://doi.org/10.3390/cells10061312.Thomas Broome S., Castorina A. The Anxiolytic Drug Buspirone Prevents Rotenone- Induced Toxicity in a Mouse Model of Parkinson’s Disease. Int J Mol Sci. 2022;23(3):1845. https://doi.org/10.3390/ijms23031845.Thomas Broome S., Castorina A. The Anxiolytic Drug Buspirone Prevents Rotenone- Induced Toxicity in a Mouse Model of Parkinson’s Disease. Int J Mol Sci. 2022;23(3):1845. https://doi.org/10.3390/ijms23031845.Thomas Broome S., Castorina A. The Anxiolytic Drug Buspirone Prevents Rotenone- Induced Toxicity in a Mouse Model of Parkinson’s Disease. Int J Mol Sci. 2022;23(3):1845. https://doi.org/10.3390/ijms23031845.

The authors declare that there are no conflicts of interest present.