Alterations in Amygdala-Prefrontal Functional Connectivity Account for Excessive Worry and Autonomic Dysregulation in Generalized Anxiety Disorder

Biological Psychiatry

Volumn 80, Issue 10, 2016, Pages 786-795

  Makovac, Elena ^a,b   Meeten, Frances ^b,c,d   Watson, David R ^b   Herman, Aleksandra ^b   Garfinkel, Sarah N ^b,d   D Critchley, Hugo ^b,d   Ottaviani, Cristina ^a  

^a IRCCS FONDAZIONE SANTA LUCIA   (Italy)

^b BRIGHTON AND SUSSEX MEDICAL SCHOOL   (United Kingdom)

^c KING'S COLLEGE LONDON   (United Kingdom)

^d UNIVERSITY OF SUSSEX   (United Kingdom)

Author keywords

Amygdala; Functional connectivity; Functional magnetic resonance imaging; Generalized anxiety disorder; Heart rate variability; Perseverative cognition

Indexed keywords

CAFFEINE; NICOTINE;

ADULT; AMYGDALA; ANTERIOR CINGULATE; ARTICLE; AUTONOMIC DYSFUNCTION; AUTONOMIC NERVOUS SYSTEM FUNCTION; BRAIN FUNCTION; BRAIN REGION; CAUDATE NUCLEUS; CINGULATE GYRUS; CLINICAL ARTICLE; COGNITION; CONTROLLED STUDY; FEMALE; FUNCTIONAL CONNECTIVITY; FUNCTIONAL MAGNETIC RESONANCE IMAGING; FUNCTIONAL NEUROIMAGING; GENERALIZED ANXIETY DISORDER; HEART RATE VARIABILITY; HUMAN; MALE; MENTAL PATIENT; NEUROPHYSIOLOGICAL MONITORING; NUCLEAR MAGNETIC RESONANCE SCANNER; PARASYMPATHETIC FUNCTION; PATIENT WORRY; PREFRONTAL CORTEX; PRIORITY JOURNAL; RESTING STATE NETWORK; SUPERIOR FRONTAL GYRUS; SUPRAMARGINAL GYRUS; SYMPTOM; YOUNG ADULT; ANXIETY DISORDER; AUTONOMIC NEUROPATHY; CONNECTOME; HEART RATE; NUCLEAR MAGNETIC RESONANCE IMAGING; PATHOPHYSIOLOGY; PHYSIOLOGY;

ADULT; AMYGDALA; ANXIETY DISORDERS; AUTONOMIC NERVOUS SYSTEM DISEASES; CONNECTOME; FEMALE; HEART RATE; HUMANS; MAGNETIC RESONANCE IMAGING; MALE; PREFRONTAL CORTEX; YOUNG ADULT;

EID: 84949635259     PISSN: 00063223     EISSN: 18732402     Source Type: Journal    
DOI: 10.1016/j.biopsych.2015.10.013     Document Type: Article

References (60)

1. 1 Hoffman, D.L., Dukes, E.M., Wittchen, H.U., Human and economic burden of generalized anxiety disorder. Depress Anxiety 25 (2008), 72–90.
2. 2 Olesen, J., Gustavsson, A., Svensson, M., Wittchen, H.U., Jönsson, B., CDBE2010 study group; European Brain Council. The economic cost of brain disorders in Europe. Eur J Neurol 19 (2012), 155–162.
3. 3 LeDoux, J., The emotional brain, fear, and the amygdala. Cell Mol Neurobiol 23 (2003), 727–738.
4. 4 Hilbert, K., Lueken, U., Beesdo-Baum, K., Neural structures, functioning and connectivity in generalized anxiety disorder and interaction with neuroendocrine systems: A systematic review. J Affect Disord 158 (2014), 114–126.
5. 5 Etkin, A., Prater, K.E., Schatzberg, A.F., Menon, V., Greicius, M.D., Disrupted amygdalar subregion functional connectivity and evidence of a compensatory network in generalized anxiety disorder. Arch Gen Psychiatry 66 (2009), 1361–1372.
6. 6 Monk, C.S., Telzer, E.H., Mogg, K., Bradley, B.P., Mai, X., Louro, H.M., et al. Amygdala and ventrolateral prefrontal cortex activation to masked angry faces in children and adolescents with generalized anxiety disorder. Arch Gen Psychiatry 65 (2008), 568–576.
7. 7 Roy, A.K., Fudge, J.L., Kelly, C., Perry, J.S., Daniele, T., Carlisi, C., et al. Intrinsic functional connectivity of amygdala-based networks in adolescent generalized anxiety disorder. J Am Acad Child Adolesc Psychiatry 52 (2013), 290–299.
8. 8 Hamm, L., Jacobs, R.H., Johnson, M.W., Fitzgerald, D.A., Fitzgerald, K.D., Langenecker, S.A., et al. Aberrant amygdala functional connectivity at rest in pediatric anxiety disorders. Biol Mood Anxiety Disord, 4, 2014, 15.
9. 9 Ball, T.M., Ramsawh, H.J., Campbell-Sills, L., Paulus, M.P., Stein, M.B., Prefrontal dysfunction during emotion regulation in generalized anxiety and panic disorders. Psychol Med 43 (2013), 1475–1486.
10. 10 McClure, E.B., Adler, A., Monk, C.S., Cameron, J., Smith, S., Nelson, E.E., et al. fMRI predictors of treatment outcome in pediatric anxiety disorders. Psychopharmacology 191 (2007), 97–105.
11. 11 Banks, S.J., Eddy, K.T., Angstadt, M., Nathan, P.J., Phan, K.L., Amygdala-frontal connectivity during emotion regulation. Soc Cogn Affect Neurosci 2 (2007), 303–312.
12. 12 Erk, S., Mikschl, A., Stier, S., Ciaramidaro, A., Gapp, V., Weber, B., et al. Acute and sustained effects of cognitive emotion regulation in major depression. J Neurosci 30 (2010), 15726–15734.
13. 13 Borkovec, T.D., Alcaine, O., Behar, E.S., Avoidance theory of worry and generalized anxiety disorder. Heimberg, R., Mennin, D., Turk, C., (eds.) Generalized Anxiety Disorder: Advances in Research and Practice, 2004, Guilford, New York, 77–108.
14. 14 Critchley, H.D., Neural mechanisms of autonomic, affective, and cognitive integration. J Comp Neurol 493 (2005), 154–166.
15. 15 Gianaros, P.J., Onyewuenyi, I.C., Sheu, L.K., Christie, I.C., Critchley, H.D., Brain systems for baroreflex suppression during stress in humans. Hum Brain Mapp 33 (2012), 1700–1716.
16. 16 Ottaviani, C., Thayer, J.F., Verkuil, B., Lonigro, A., Medea, B., Couyoumdjian, A., et al. Physiological concomitants of perseverative cognition: A systematic review and meta-analysis. Psychol Bull 142 (2016), 231–259.
17. 17 Thayer, J.F., Friedman, B.H., Borkovec, T.D., Autonomic characteristics of generalized anxiety disorder and worry. Biol Psychiatry 39 (1996), 255–266.
18. 18 Bijsterbosch, J., Smith, S., Forster, S., John, O.P., Bishop, S.J., Resting state correlates of subdimensions of anxious affect. J Cogn Neurosci 26 (2014), 914–926.
19. 19 Andreescu, C., Sheu, L.K., Tudorascu, D., Gross, J.J., Walker, S., Banihashemi, L., et al. Emotion reactivity and regulation in late-life generalized anxiety disorder: Functional connectivity at baseline and post-treatment. Am J Geriatr Psychiatry 23 (2015), 200–214.
20. 20 Critchley, H.D., Mathias, C.J., Josephs, O., O'Doherty, J., Zanini, S., Dewar, B.K., et al. Human cingulate cortex and autonomic control: Converging neuroimaging and clinical evidence. Brain 126 (2003), 2139–2152.
21. 21 Chang, C., Metzger, C.D., Glover, G.H., Duyn, J.H., Heinze, H., Walter, M., Association between heart rate variability and fluctuations in resting-state functional connectivity. Neuroimage 68 (2013), 93–104.
22. 22 Beissner, F., Meissner, K., Bär, K.J., Napadow, V., The autonomic brain: An activation likelihood estimation meta-analysis for central processing of autonomic function. J Neurosci 33 (2013), 10503–10511.
23. 23 Makovac, E., Garfinkel, S.N., Bassi, A., Basile, B., Macaluso, E., Cercignani, M., Effect of parasympathetic stimulation on brain activity during appraisal of fearful expressions. Neuropsychopharmacology 40 (2015), 1649–1658.
24. 24 Thayer, J.F., Lane, R.D., Claude Bernard and the heart-brain connection: Further elaboration of a model of neurovisceral integration. Neurosci Biobehav Rev 33 (2009), 81–88.
25. 25 Thayer, J.F., Ahs, F., Fredrikson, M., Sollers, J.J. 3rd, Wager, T.D., A meta-analysis of heart rate variability and neuroimaging studies: Implications for heart rate variability as a marker of stress and health. Neurosci Biobehav Rev 33 (2009), 81–88.
26. 26 Williams, D.P., Cash, C., Rankin, C., Bernardi, A., Koenig, J., Thayer, J.F., Resting heart rate variability predicts self-reported difficulties in emotion regulation: A focus on different facets of emotion regulation. Front Psychol, 10, 2015, 261.
27. 27 Ottaviani, C., Shapiro, D., Couyoumdjian, A., Flexibility as the key for somatic health: From mind wandering to perseverative cognition. Biol Psychol 94 (2013), 38–43.
28. 28 Ottaviani, C., Medea, B., Lonigro, A., Tarvainen, M., Couyoumdjian, A., Cognitive rigidity is mirrored by autonomic inflexibility in daily life perseverative cognition. Biol Psychol 107 (2015), 24–30.
29. 29 Olatunji, B.O., Broman-Fulks, J.J., Bergman, S.M., Green, B.A., Zlomke, K.R., A taxometric investigation of the latent structure of worry: Dimensionality and associations with depression, anxiety, and stress. Behav Ther 41 (2010), 212–228.
30. 30 Robinson, M.S., Alloy, L.B., Negative cognitive styles and stress-reactive rumination interact to predict depression: A prospective study. Cognit Ther 27 (2003), 275–292.
31. 31 Nolen-Hoeksema, S., Morrow, J., A prospective study of depression and posttraumatic stress symptoms after a natural disaster: The 1989 Loma Prieta earthquake. J Pers Soc Psychol 61 (1991), 115–121.
32. 32 Meyer, T.J., Miller, M.L., Metzger, R.L., Borkovec, T.D., Development and validation of the Penn State Worry Questionnaire. Behav Res Ther 28 (1990), 487–495.
33. 33 Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: Standards of measurement, physiological interpretation, and clinical use. Circulation 93 (1996), 1043–1065.
34. 34 Alvares, G.A., Quintana, D.S., Kemp, A.H., Van Zwieten, A., Balleine, B.W., Hickie, I.B., et al. Reduced heart rate variability in social anxiety disorder: Associations with gender and symptom severity. PLoS One, 8, 2013, e70468.
35. 35 Nussinovitch, U., Cohen, O., Kaminer, K., Ilani, J., Nussinovitch, N., Evaluating reliability of ultra-short ECG indices of heart rate variability in diabetes mellitus patients. J Diabetes Complications 26 (2012), 450–453.
36. 36 Goedhart, A.D., van der Sluis, S., Houtveen, J.H., Willemsen, G., de Geus, E.J., Comparison of time and frequency domain measures of RSA in ambulatory recordings. Psychophysiology 44 (2007), 203–215.
37. 37 Penttilä, J., Helminen, A., Jartti, T., Kuusela, T., Huikuri, H.V., Tulppo, M.P., et al. Time domain, geometrical and frequency domain analysis of cardiac vagal outflow: Effects of various respiratory patterns. Clin Physiol 21 (2001), 365–376.
38. 38 Saad, Z.S., Gotts, S.J., Murphy, K., Chen, G., Jo, H.J., Martin, A., et al. Trouble at rest: how correlation patterns and group differences become distorted after global signal regression. Brain Connect 2 (2012), 25–32.
39. 39 Tzourio-Mazoyer, N., Landeau, B., Papathanassiou, D., Crivello, F., Etard, O., Delcroix, N., et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain. Neuroimage 15 (2002), 273–289.
40. 40 Dukart, J., Bertolino, A., When structure affects function—the need for partial volume effect correction in functional and resting state magnetic resonance imaging studies. PLoS One, 9, 2014, e114227.
41. 41 Kim, M.J., Gee, D.G., Loucks, R.A., Davis, F.C., Whalen, P.J., Anxiety dissociates dorsal and ventral medial prefrontal cortex functional connectivity with the amygdala at rest. Cereb Cortex 21 (2011), 1667–1673.
42. 42 Prater, K.E., Hosanagar, A., Klumpp, H., Angstadt, M., Phan, K.L., Aberrant amygdala-frontal cortex connectivity during perception of fearful faces and at rest in generalized social anxiety disorder. Depress Anxiety 30 (2013), 234–241.
43. 43 Liao, W., Qiu, C., Gentili, C., Walter, M., Pan, Z., Ding, J., et al. Altered effective connectivity network of the amygdala in social anxiety disorder: A resting-state FMRI study. PLoS One, 5, 2010, e15238.
44. 44 Hahn, A., Stein, P., Windischberger, C., Weissenbacher, A., Spindelegger, C., Moser, E., et al. Reduced resting-state functional connectivity between amygdala and orbitofrontal cortex in social anxiety disorder. Neuroimage 56 (2011), 881–889.
45. 45 Roy, A.K., Shehzad, Z., Margulies, D.S., Kelly, A.M., Uddin, L.Q., Gotimer, K., et al. Functional connectivity of the human amygdala using resting state fMRI. Neuroimage 45 (2009), 614–626.
46. 46 Paulesu, E., Sambugaro, E., Torti, T., Danelli, L., Ferri, F., Scialfa, G., et al. Neural correlates of worry in generalized anxiety disorder and in normal controls: A functional MRI study. Psychol Med 40 (2010), 117–124.
47. 47 McClure, E.B., Monk, C.S., Nelson, E.E., Parrish, J.M., Adler, A., Blair, R.J., et al. Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder. Arch Gen Psychiatry 64 (2007), 97–106.
48. 48 Forster, S., Nunez Elizalde, A.O., Castle, E., Bishop, S.J., Unraveling the anxious mind: Anxiety, worry, and frontal engagement in sustained attention versus off-task processing. Cereb Cortex 25 (2015), 609–618.
49. 49 Baas, D., Aleman, A., Kahn, R.S., Lateralization of amygdala activation: A systematic review of functional neuroimaging studies. Brain Res Brain Res Rev 45 (2004), 96–103.
50. 50 Blair, K., Geraci, M., Devido, J., McCaffrey, D., Chen, G., Vythilingam, M., et al. Neural response to self- and other referential praise and criticism in generalized social phobia. Arch Gen Psychiatry 65 (2008), 1176–1184.
51. 51 Cremers, H.R., Demenescu, L.R., Aleman, A., Renken, R., van Tol, M.J., van der Wee, N.J., et al. Neuroticism modulates amygdala-prefrontal connectivity in response to negative emotional facial expressions. Neuroimage 49 (2010), 963–970.
52. 52 Ahs, F., Sollers, J.J. 3rd, Furmark, T., Fredrikson, M., Thayer, J.F., High-frequency heart rate variability and cortico-striatal activity in men and women with social phobia. Neuroimage 47 (2009), 815–820.
53. 53 Critchley, H.D., Rotshtein, P., Nagai, Y., O'Doherty, J., Mathias, C.J., Dolan, R.J., Activity in the human brain predicting differential heart rate responses to emotional facial expressions. Neuroimage 24 (2005), 751–762.
54. 54 Lane, R.D., McRae, K., Reiman, E.M., Chen, K., Ahern, G.L., Thayer, J.F., Neural correlates of heart rate variability during emotion. Neuroimage 44 (2009), 213–222.
55. 55 Balleine, B.W., Delgado, M.R., Hikosaka, O., The role of the dorsal striatum in reward and decision-making. J Neurosci 27 (2007), 8161–8165.
56. 56 Almeida, I., van Asselen, M., Castelo-Branco, M., The role of the amygdala and the basal ganglia in visual processing of central vs. peripheral emotional content. Neuropsychologia 51 (2013), 2120–2129.
57. 57 Gaebler, M., Daniels, J.K., Lamke, J.P., Fydrich, T., Walter, H., Heart rate variability and its neural correlates during emotional face processing in social anxiety disorder. Biol Psychol 94 (2013), 319–330.
58. 58 Baxter, L.R., Neuroimaging studies of human anxiety disorders: Cutting paths of knowledge through the field of neurotic phenomena. Bloom, F., Kupfer, D., (eds.) Neuropsychopharmacology: The Fourth Generation of Progress, 1995, Raven Press, New York, 1287–1299.
59. 59 Gillan, C.M., Apergis-Schoute, A.M., Morein-Zamir, S., Urcelay, G.P., Sule, A., Fineberg, N.A., et al. Functional neuroimaging of avoidance habits in obsessive-compulsive disorder. Am J Psychiatry 172 (2015), 284–293.
60. 60 Player, M.S., Peterson, L.E., Anxiety disorders, hypertension, and cardiovascular risk: A review. Int J Psychiatry Med, 41, 2011 365–337.