Advances in Experimental Medicine and Biology 1191 Yong-Ku Kim Editor Anxiety Disorders Rethinking and Understanding Recent Discoveries Advances in Experimental Medicine and Biology Volume 1191 Series Editors Wim E. Crusio, CNRS University of Bordeaux UMR 5287, Institut de Neurosciences Cognitives et Intégratives d’Aquitaine, Pessac Cedex, France John D. Lambris, University of Pennsylvania, Philadelphia, PA, USA Nima Rezaei, Children’s Medical Center Hospital, Tehran University of Medical Sciences, Tehran, Iran More information about this series at http://www.springer.com/series/5584 Yong-Ku Kim Editor Anxiety Disorders Rethinking and Understanding Recent Discoveries Editor Yong-Ku Kim College of Medicine Korea University Gyeonggido, South Korea ISSN 0065-2598 ISSN 2214-8019 (electronic) Advances in Experimental Medicine and Biology ISBN 978-981-32-9704-3 ISBN 978-981-32-9705-0 (eBook) https://doi.org/10.1007/978-981-32-9705-0 © Springer Nature Singapore Pte Ltd. 2020 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore Contents Part I Brain Network Concepts 1 Task MRI-Based Functional Brain Network of Anxiety ���������������������� 3 Chien-Han Lai 2 Phenotype Network and Brain Structural Covariance Network of Anxiety ���������������������������������������������������������������������������������� 21 Je-Yeon Yun and Yong-Ku Kim 3 Linear and Nonlinear EEG-Based Functional Networks in Anxiety Disorders �������������������������������������������������������������������������������� 35 Poppy L. A. Schoenberg 4 White Matter-Based Structural Brain Network of Anxiety . 61 Kang Soo Lee and Sang Hyuk Lee 5 Anxiety Disorders and the Brain’s Resting State Networks: From Altered Spatiotemporal Synchronization to Psychopathological Symptoms . 71 Georg Northoff Part II Neurobiological Aspects 6 Gene-Environment Interactions and Role of Epigenetics in Anxiety Disorders �������������������������������������������������������������������������������� 93 Eugene Lin and Shih-Jen Tsai 7 The Role of the Oxytocin System in Anxiety Disorders ������������������������ 103 Seoyoung Yoon and Yong-Ku Kim 8 Translational Studies in the Complex Role of Neurotransmitter Systems in Anxiety and Anxiety Disorders . 121 Jocelien D. A. Olivier and Berend Olivier 9 The Role of Early Life Stress in HPA Axis and Anxiety . 141 Mario F. Juruena, Filip Eror, Anthony J. Cleare, and Allan H. Young v vi Contents 10 Immune-Kynurenine Pathways and the Gut Microbiota-Brain Axis in Anxiety Disorders . 155 Alper Evrensel, Barış Önen Ünsalver, and Mehmet Emin Ceylan 11 Experimental Anxiety Model for Anxiety Disorders: Relevance to Drug Discovery ������������������������������������������������������������������ 169 Michel Bourin Part III Diagnostic and Clinical Issues of Anxiety Disorders 12 Anxiety Disorders in the DSM-5: Changes, Controversies, and Future Directions ������������������������������������������������������������������������������ 187 Seon-Cheol Park and Yong-Ku Kim 13 Biological and Clinical Markers to Differentiate the Type of Anxiety Disorders . 197 Fiammetta Cosci and Giovanni Mansueto 14 Comorbid Anxiety and Depression: Clinical and Conceptual Consideration and Transdiagnostic Treatment . 219 Kwan Woo Choi, Yong-Ku Kim, and Hong Jin Jeon 15 Anxiety Disorders and Medical Comorbidity: Treatment Implications . 237 Alicia E. Meuret, Natalie Tunnell, and Andres Roque Part IV Therapeutic Issues 16 Biofeedback and Neurofeedback for Anxiety Disorders: A Quantitative and Qualitative Systematic Review ������������������������������ 265 David F. Tolin, Carolyn D. Davies, Danielle M. Moskow, and Stefan G. Hofmann 17 Cognitive Behavioral Therapy, Mindfulness-Based Cognitive Therapy and Acceptance Commitment Therapy for Anxiety Disorders: Integrating Traditional with Digital Treatment Approaches �������������������������������������������������������� 291 Jennifer Apolinário-Hagen, Marie Drüge, and Lara Fritsche 18 Neurostimulation in Anxiety Disorders, Post-traumatic Stress Disorder, and Obsessive-Compulsive Disorder �������������������������� 331 Rafael Christophe Freire, Casimiro Cabrera-Abreu, and Roumen Milev 19 Current and Novel Psychopharmacological Drugs for Anxiety Disorders . 347 Borwin Bandelow Contents vii 20 Role of Benzodiazepines in Anxiety Disorders �������������������������������������� 367 Richard Balon and Vladan Starcevic 21 Virtual Reality for Anxiety Disorders: Rethinking a Field in Expansion . 389 Javier Fernández-Álvarez, Daniele Di Lernia, and Giuseppe Riva 22 Current Research on Complementary and Alternative Medicine (CAM) in the Treatment of Anxiety Disorders: An Evidence-Based Review . 415 Vladimir Trkulja and Hrvoje Barić 23 Contemporary Psychodynamic Approaches to Treating Anxiety: Theory, Research, and Practice . 451 Seth R. Pitman and Daniel P. C. Knauss 24 Well-Being Therapy in Anxiety Disorders . 465 Fiammetta Cosci Part V Anxiety and Precision Psychiatry 25 Personalized Clinical Approaches to Anxiety Disorders ���������������������� 489 Giampaolo Perna, Alessandra Alciati, Erika Sangiorgio, Daniela Caldirola, and Charles B. Nemeroff 26 The Role of Hormonal and Reproductive Status in the Treatment of Anxiety Disorders in Women . 523 Samantha Tang and Bronwyn Margaret Graham 27 Risk Factors and Prevention Strategies for Anxiety Disorders in Childhood and Adolescence ���������������������������������������������� 543 Maria Demma Cabral and Dilip R. Patel 28 Anxiety Disorders in the Elderly ������������������������������������������������������������ 561 Carmen Andreescu and Soyoung Lee Part I Brain Network Concepts Task MRI-Based Functional Brain Network of Anxiety 1 Chien-Han Lai Anxiety, Fear, and Task MRI The anxiety is tended to be associated with fear. The origin of anxiety and fear might be the functional and structural alterations in the amygdala of anxious sub- jects, which would be more specific to the rating and response of anxiety [1]. A heightened degree of amygdala-anterior cingulate cortex (ACC) connectivity would predispose the anxious subjects to focus on the attention related to the environmen- tal threat [2]. The specific risk genotype of anxiety would be also associated with increased reactivity of the amygdala and hippocampus to threat stimuli [3]. A study of clinically anxious individuals showed that the frontal region would evaluate the meaning of stimuli and exhibit the inhibitory action toward the heightened responses of the amygdala, which suggested a significant role of prefrontal-limbic control circuit in the pathophysiology of anxiety [4]. The explicit threat memory and threat appraisal condition would also provoke alterations in the amygdala-frontal circuit [5]. The cannabinoid administration-related anxiety in healthy subjects during the fear-processing task would also be associated with the cannabinoid receptors of the amygdala [6]. The threat-related anxiety due to fear was related to the inflammatory biomarker of human body [7]. The neuroticism personality, which would be predis- posed to anxiety, has been mentioned to be altered in the anterior cingulate cortex while processing the fearful facial expressions in the lower serotonin status [8]. The pathological fear network activations might be related to the attention arousal while feeling fearful subjectively [9]. The fear model has been mentioned in certain kinds of anxiety disorders, such as social anxiety disorder (SAD) [10–12], panic disorder (PD) [13–15], specific phobia [16–18], and generalized anxiety disorder (GAD) [9, C.-H. Lai (*) Psychiatry & Neuroscience Clinic, Taoyuan, Taiwan Institute of Biophotonics, National Yang-Ming University, Taipei, Taiwan Department of Psychiatry, Yeezen General Hospital, Taoyuan, Taiwan © Springer Nature Singapore Pte Ltd. 2020 3 Y.-K. Kim (ed.), Anxiety Disorders, Advances in Experimental Medicine and Biology 1191, https://doi.org/10.1007/978-981-32-9705-0_1 4 C.-H. Lai 19, 20]. For the concept of fear-related network in the brain, the typical example would be the hypothesis of “fear network” [14], which included many regions of frontal and limbic areas. The frontal part of this network included the medial frontal gyrus and anterior cingulate. The limbic