Biomarkers in Panic Disorder

Chien-Han       Lai
doi:10.2174/2666082216999200918163245
Abstract

Background: Panic disorder (PD) is a kind of anxiety disorder that impacts the life quality and functional perspectives in patients. However, the pathophysiological study of PD seems still inadequate and many unresolved issues need to be clarified.
Objectives: In this review article of biomarkers in PD, the investigator will focus on the findings of magnetic resonance imaging (MRI) of the brain in the pathophysiology study. The MRI biomarkers would be divided into several categories, on the basis of structural and functional perspectives.
Methods: The structural category would include the gray matter and white matter tract studies. The functional category would consist of functional MRI (fMRI), resting-state fMRI (Rs-fMRI), and magnetic resonance spectroscopy (MRS). The PD biomarkers revealed by the above methodologies would be discussed in this article.
Results: For the gray matter perspectives, the PD patients would have alterations in the volumes of fear network structures, such as the amygdala, parahippocampal gyrus, thalamus, anterior cingulate cortex, insula, and frontal regions. For the white matter tract studies, the PD patients seemed to have alterations in the fasciculus linking the fear network regions, such as the anterior thalamic radiation, uncinate fasciculus, fronto-occipital fasciculus, and superior longitudinal fasciculus. For the fMRI studies in PD, the significant results also focused on the fear network regions, such as the amygdala, hippocampus, thalamus, insula, and frontal regions. For the Rs-fMRI studies, PD patients seemed to have alterations in the regions of the default mode network and fear network model. At last, the MRS results showed alterations in neuron metabolites of the hippocampus, amygdala, occipital cortex, and frontal regions.
Conclusion: The MRI biomarkers in PD might be compatible with the extended fear network model hypothesis in PD, which included the amygdala, hippocampus, thalamus, insula, frontal regions, and sensory-related cortex.
Keywords: Panic disorder, extended fear network, MRI, biomarkers, amygdala, hippocampus, insula, frontal regions.
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Graphical Abstract

[1] 
Wood WG. The diagnosis and management of panic disorder. Psychiatr Med  1990; 8(3): 197-209.
[PMID: 2202023] 
[2] 
Culpepper L. Identifying and treating panic disorder in primary care. J Clin Psychiatry  2004; 65(Suppl. 5): 19-23.
[PMID: 15078114] 
[3] 
Rubin HC, Rapaport MH, Levine B, et al. Quality of well being in panic disorder: the assessment of psychiatric and general disability. J Affect Disord  2000; 57(1-3): 217-21.
[http://dx.doi.org/10.1016/S0165-0327(99)00030-0] [PMID: 10708834] 
[4] 
Barrera TL, Hiatt EL, Dunn NJ, Teng EJ. Impact of panic disorder on quality of life among veterans in a primary care pilot study. Compr Psychiatry  2013; 54(3): 256-61.
[http://dx.doi.org/10.1016/j.comppsych.2012.09.001] [PMID: 23102729] 
[5] 
Gorman JM, Kent JM, Sullivan GM, Coplan JD. Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry  2000; 157(4): 493-505.
[http://dx.doi.org/10.1176/appi.ajp.157.4.493] [PMID: 10739407] 
[6] 
Dresler T, Guhn A, Tupak SV, et al. Revise the revised? New dimensions of the neuroanatomical hypothesis of panic disorder. J Neural Transm  2013; 120(1): 3-29.
[http://dx.doi.org/10.1007/s00702-012-0811-1] [PMID: 22692647] 
[7] 
Sobanski T, Wagner G. Functional neuroanatomy in panic disorder: status quo of the research. World J Psychiatry  2017; 7(1): 12-33.
[http://dx.doi.org/10.5498/wjp.v7.i1.12] [PMID: 28401046] 
[8] 
Lai CH. Fear network model in panic disorder: the past and the future. Psychiatry Investig  2019; 16(1): 16.
[PMID: 30176707] 
[9] 
Le Bihan D. Functional MRI of the brain principles, applications and limitations. J Neuroradiol  1996; 23(1): 1-5.
[PMID: 8767912] 
[10] 
Zheng D, Sun H, Dong X, et al. Executive dysfunction and gray matter atrophy in amnestic mild cognitive impairment. Neurobiol Aging  2014; 35(3): 548-55.
[http://dx.doi.org/10.1016/j.neurobiolaging.2013.09.007] [PMID: 24119547] 
[11] 
Schmidt-Wilcke T, Poljansky S, Hierlmeier S, Hausner J, Ibach B. Memory performance correlates with gray matter density in the ento-perirhinal cortex and posterior hippocampus in patients with mild cognitive impairment and healthy controls-a voxel based morphometry study. Neuroimage  2009; 47(4): 1914-20.
[http://dx.doi.org/10.1016/j.neuroimage.2009.04.092] [PMID: 19442751] 
[12] 
Helms G. Segmentation of human brain using structural MRI. MAGMA  2016; 29(2): 111-24.
[http://dx.doi.org/10.1007/s10334-015-0518-z] [PMID: 26739264] 
[13] 
Bigler ED. Structural image analysis of the brain in neuropsychology using magnetic resonance imaging (MRI) techniques. Neuropsychol Rev  2015; 25(3): 224-49.
[http://dx.doi.org/10.1007/s11065-015-9290-0] [PMID: 26280751] 
[14] 
Richardson FM, Price CJ. Structural MRI studies of language function in the undamaged brain. Brain Struct Funct  2009; 213(6): 511-23.
[http://dx.doi.org/10.1007/s00429-009-0211-y] [PMID: 19618210] 
[15] 
Bastiani M, Roebroeck A. Unraveling the multiscale structural organization and connectivity of the human brain: the role of diffusion MRI. Front Neuroanat  2015; 9: 77.
[http://dx.doi.org/10.3389/fnana.2015.00077] [PMID: 26106304] 
[16] 
Chen W, Liu X, Zhu XH, Zhang N. Functional MRI study of brain function under resting and activated states. Med Biol Soc  2009; 2009: 4061-3.
[PMID: 19964099] 
[17] 
Andellini M, Cannatà V, Gazzellini S, Bernardi B, Napolitano A. Test-retest reliability of graph metrics of resting state MRI functional brain networks: a review. J Neurosci Methods  2015; 253: 183-92.
[http://dx.doi.org/10.1016/j.jneumeth.2015.05.020] [PMID: 26072249] 
[18] 
Guye M, Bettus G, Bartolomei F, Cozzone PJ. Graph theoretical analysis of structural and functional connectivity MRI in normal and pathological brain networks. MAGMA  2010; 23(5-6): 409-21.
[http://dx.doi.org/10.1007/s10334-010-0205-z] [PMID: 20349109] 
[19] 
Joo SH, Lim HK, Lee CU. Three large-scale functional brain networks from resting-state functional MRI in subjects with different levels of cognitive impairment. Psychiatry Investig  2016; 13(1): 1-7.
[http://dx.doi.org/10.4306/pi.2016.13.1.1] [PMID: 26766941] 
[20] 
Smyser CD, Snyder AZ, Neil JJ. Functional connectivity MRI in infants: exploration of the functional organization of the developing brain. Neuroimage  2011; 56(3): 1437-52.
[http://dx.doi.org/10.1016/j.neuroimage.2011.02.073] [PMID: 21376813] 
[21] 
Port JD. Magnetic resonance spectroscopy for psychiatry: progress in the last decade. Neuroimaging Clin N Am  2020; 30(1): 25-33.
[http://dx.doi.org/10.1016/j.nic.2019.09.002] [PMID: 31759569] 
[22] 
Massana G, Serra-Grabulosa JM, Salgado-Pineda P, et al. Parahippocampal gray matter density in panic disorder: a voxel-based morphometric study. Am J Psychiatry  2003; 160(3): 566-8.
[http://dx.doi.org/10.1176/appi.ajp.160.3.566] [PMID: 12611840] 
[23] 
Massana G, Serra-Grabulosa JM, Salgado-Pineda P, et al. Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging. Neuroimage  2003; 19(1): 80-90.
[http://dx.doi.org/10.1016/S1053-8119(03)00036-3] [PMID: 12781728] 
[24] 
Hayano F, Nakamura M, Asami T, et al. Smaller amygdala is associated with anxiety in patients with panic disorder. Psychiatry Clin Neurosci  2009; 63(3): 266-76.
[http://dx.doi.org/10.1111/j.1440-1819.2009.01960.x] [PMID: 19566756] 
[25] 
Lai CH. Hippocampal and subcortical alterations of first-episode, medication-naïve major depressive disorder with panic disorder patients. J Neuropsychiatry Clin Neurosci  2014; 26(2): 142-9.
[http://dx.doi.org/10.1176/appi.neuropsych.12090230] [PMID: 24509652] 
[26] 
Yoon S, Kim JE, Kim GH, et al. Subregional shape alterations in the amygdala in patients with panic disorder. PLoS One  2016; 11(6)e0157856
[http://dx.doi.org/10.1371/journal.pone.0157856] [PMID: 27336300] 
[27] 
Asami T, Nakamura R, Takaishi M, et al. Smaller volumes in the lateral and basal nuclei of the amygdala in patients with panic disorder. PLoS One  2018; 13(11)e0207163
[http://dx.doi.org/10.1371/journal.pone.0207163] [PMID: 30403747] 
[28] 
Asami T, Yoshida H, Takaishi M, et al. Thalamic shape and volume abnormalities in female patients with panic disorder. PLoS One  2018; 13(12)e0208152
[http://dx.doi.org/10.1371/journal.pone.0208152] [PMID: 30566534] 
[29] 
Reinecke A, Thilo K, Filippini N, Croft A, Harmer CJ. Predicting rapid response to cognitive-behavioural treatment for panic disorder: the role of hippocampus, insula, and dorsolateral prefrontal cortex. Behav Res Ther  2014; 62: 120-8.
[http://dx.doi.org/10.1016/j.brat.2014.07.017] [PMID: 25156399] 
[30] 
Schwartz CE, Kunwar PS, Hirshfeld-Becker DR, et al. Behavioral inhibition in childhood predicts smaller hippocampal volume in adolescent offspring of parents with panic disorder. Transl Psychiatry  2015; 5e605
[http://dx.doi.org/10.1038/tp.2015.95] [PMID: 26196438] 
[31] 
Asami T, Hayano F, Nakamura M, et al. Anterior cingulate cortex volume reduction in patients with panic disorder. Psychiatry Clin Neurosci  2008; 62(3): 322-30.
[http://dx.doi.org/10.1111/j.1440-1819.2008.01800.x] [PMID: 18588593] 
[32] 
Graeff FG, Del-Ben CM. Neurobiology of panic disorder: from animal models to brain neuroimaging. Neurosci Biobehav Rev  2008; 32(7): 1326-35.
[http://dx.doi.org/10.1016/j.neubiorev.2008.05.017] [PMID: 18573531] 
[33] 
Uchida RR, Del-Ben CM, Busatto GF, et al. Regional gray matter abnormalities in panic disorder: a voxel-based morphometry study. Psychiatry Res  2008; 163(1): 21-9.
[http://dx.doi.org/10.1016/j.pscychresns.2007.04.015] [PMID: 18417322] 
[34] 
Shinoura N, Yamada R, Tabei Y, et al. Damage to the right dorsal anterior cingulate cortex induces panic disorder. J Affect Disord  2011; 133(3): 569-72.
[http://dx.doi.org/10.1016/j.jad.2011.04.029] [PMID: 21601289] 
[35] 
Fujiwara A, Yoshida T, Otsuka T, et al. Midbrain volume increase in patients with panic disorder. Psychiatry Clin Neurosci  2011; 65(4): 365-73.
[http://dx.doi.org/10.1111/j.1440-1819.2011.02219.x] [PMID: 21682812] 
[36] 
Asami T, Yamasue H, Hayano F, et al. Sexually dimorphic gray matter volume reduction in patients with panic disorder. Psychiatry Res  2009; 173(2): 128-34.
[http://dx.doi.org/10.1016/j.pscychresns.2008.10.004] [PMID: 19560907] 
[37] 
Roppongi T, Nakamura M, Asami T, et al. Posterior orbitofrontal sulcogyral pattern associated with orbitofrontal cortex volume reduction and anxiety trait in panic disorder. Psychiatry Clin Neurosci  2010; 64(3): 318-26.
[http://dx.doi.org/10.1111/j.1440-1819.2010.02085.x] [PMID: 20602731] 
[38] 
Na KS, Ham BJ, Lee MS, et al. Decreased gray matter volume of the medial orbitofrontal cortex in panic disorder with agoraphobia: a preliminary study. Prog Neuropsychopharmacol Biol Psychiatry  2013; 45: 195-200.
[http://dx.doi.org/10.1016/j.pnpbp.2013.04.014] [PMID: 23628432] 
[39] 
Sobanski T, Wagner G, Peikert G, et al. Temporal and right frontal lobe alterations in panic disorder: a quantitative volumetric and voxel-based morphometric MRI study. Psychol Med  2010; 40(11): 1879-86.
[http://dx.doi.org/10.1017/S0033291709991930] [PMID: 20056020] 
[40] 
Lai CH, Wu YT. Fronto-temporo-insula gray matter alterations of first-episode, drug-naïve and very late-onset panic disorder patients. J Affect Disord  2012; 140(3): 285-91.
[http://dx.doi.org/10.1016/j.jad.2012.01.049] [PMID: 22386047] 
[41] 
Wu Y, Zhong Y, Ma Z, et al. Gray matter changes in panic disorder: a voxel-based meta-analysis and meta-analytic connectivity modeling. Psychiatry Res Neuroimaging  2018; 282: 82-9.
[http://dx.doi.org/10.1016/j.pscychresns.2018.09.009] [PMID: 30340800] 
[42] 
Lai CH, Wu YT. Changes in gray matter volume of remitted first-episode, drug-naïve, panic disorder patients after 6-week antidepressant therapy. J Psychiatr Res  2013; 47(1): 122-7.
[http://dx.doi.org/10.1016/j.jpsychires.2012.09.013] [PMID: 23079534] 
[43] 
Lai CH, Wu YT. The gray matter alterations in major depressive disorder and panic disorder: putative differences in the pathogenesis. J Affect Disord  2015; 186: 1-6.
[http://dx.doi.org/10.1016/j.jad.2015.07.022] [PMID: 26208214] 
[44] 
Lai CH. The neural markers of MRI to differentiate depression and panic disorder. Prog Neuropsychopharmacol Biol Psychiatry  2019; 91: 72-8.
[http://dx.doi.org/10.1016/j.pnpbp.2018.04.013] [PMID: 29705713] 
[45] 
Yoo HK, Kim MJ, Kim SJ, et al. Putaminal gray matter volume decrease in panic disorder: an optimized voxel-based morphometry study. Eur J Neurosci  2005; 22(8): 2089-94.
[http://dx.doi.org/10.1111/j.1460-9568.2005.04394.x] [PMID: 16262646] 
[46] 
Protopopescu X, Pan H, Tuescher O, et al. Increased brainstem volume in panic disorder: a voxel-based morphometric study. Neuroreport  2006; 17(4): 361-3.
[http://dx.doi.org/10.1097/01.wnr.0000203354.80438.1] [PMID: 16514359] 
[47] 
Han DH, Renshaw PF, Dager SR, et al. Altered cingulate white matter connectivity in panic disorder patients. J Psychiatr Res  2008; 42(5): 399-407.
[http://dx.doi.org/10.1016/j.jpsychires.2007.03.002] [PMID: 17482647] 
[48] 
Bae S, Kim JE, Hwang J, et al. Increased prevalence of white matter hyperintensities in patients with panic disorder. J Psychopharmacol (Oxford)  2010; 24(5): 717-23.
[http://dx.doi.org/10.1177/0269881108098476] [PMID: 18957476] 
[49] 
Kim B, Yoo E, Lee JY, et al. The effects of the catechol-O-methyltransferase val158met polymorphism on white matter connectivity in patients with panic disorder. J Affect Disord  2013; 147(1-3): 64-71.
[http://dx.doi.org/10.1016/j.jad.2012.10.009] [PMID: 23141115] 
[50] 
Kim B, Oh J, Kim MK, et al. White matter alterations are associated with suicide attempt in patients with panic disorder. J Affect Disord  2015; 175: 139-46.
[http://dx.doi.org/10.1016/j.jad.2015.01.001] [PMID: 25617685] 
[51] 
Kim MK, Kim B, Kiu Choi T, Lee SH. White matter correlates of anxiety sensitivity in panic disorder. J Affect Disord  2017; 207: 148-56.
[http://dx.doi.org/10.1016/j.jad.2016.08.043] [PMID: 27721189] 
[52] 
Yu ST, Lee KS, Lee SH. Fornix microalterations associated with early trauma in panic disorder. J Affect Disord  2017; 220: 139-46.
[http://dx.doi.org/10.1016/j.jad.2017.05.043] [PMID: 28622552] 
[53] 
Kim B, Kim JH, Kim MK, et al. Frontal white matter alterations in short-term medicated panic disorder patients without comorbid conditions: a diffusion tensor imaging study. PLoS One  2014; 9(4)e95279
[http://dx.doi.org/10.1371/journal.pone.0095279] [PMID: 24788587] 
[54] 
Lai CH, Wu YT, Yu PL, Yuan W. Improvements in white matter micro-structural integrity of right uncinate fasciculus and left fronto-occipital fasciculus of remitted first-episode medication-naïve panic disorder patients. J Affect Disord  2013; 150(2): 330-6.
[http://dx.doi.org/10.1016/j.jad.2013.04.014] [PMID: 23680435] 
[55] 
Kim SW, Kim MK, Kim B, Choi TK, Lee SH. White matter connectivity differences between treatment responders and non-responders in patients with panic disorder. J Affect Disord  2020; 260: 527-35.
[http://dx.doi.org/10.1016/j.jad.2019.09.032] [PMID: 31539689] 
[56] 
Domschke K, Braun M, Ohrmann P, et al. Association of the functional -1019C/G 5-HT1A polymorphism with prefrontal cortex and amygdala activation measured with 3 T fMRI in panic disorder. Int J Neuropsychopharmacol  2006; 9(3): 349-55.
[http://dx.doi.org/10.1017/S1461145705005869] [PMID: 16316476] 
[57] 
Pillay SS, Rogowska J, Gruber SA, Simpson N, Yurgelun-Todd DA. Recognition of happy facial affect in panic disorder: an fMRI study. J Anxiety Disord  2007; 21(3): 381-93.
[http://dx.doi.org/10.1016/j.janxdis.2006.04.001] [PMID: 16860973] 
[58] 
Ottaviani C, Cevolani D, Nucifora V, et al. Amygdala responses to masked and low spatial frequency fearful faces: a preliminary fMRI study in panic disorder. Psychiatry Res  2012; 203(2-3): 159-65.
[http://dx.doi.org/10.1016/j.pscychresns.2011.12.010] [PMID: 22944369] 
[59] 
Demenescu LR, Kortekaas R, Cremers HR, et al. Amygdala activation and its functional connectivity during perception of emotional faces in social phobia and panic disorder. J Psychiatr Res  2013; 47(8): 1024-31.
[http://dx.doi.org/10.1016/j.jpsychires.2013.03.020] [PMID: 23643103] 
[60] 
Smoller JW, Gallagher PJ, Duncan LE, et al. The human ortholog of acid-sensing ion channel gene ASIC1a is associated with panic disorder and amygdala structure and function. Biol Psychiatry  2014; 76(11): 902-10.
[http://dx.doi.org/10.1016/j.biopsych.2013.12.018] [PMID: 24529281] 
[61] 
Poletti S, Radaelli D, Cucchi M, et al. Neural correlates of anxiety sensitivity in panic disorder: a functional magnetic resonance imaging study. Psychiatry Res  2015; 233(2): 95-101.
[http://dx.doi.org/10.1016/j.pscychresns.2015.05.013] [PMID: 26071623] 
[62] 
Reinecke A, Filippini N, Berna C, et al. Effective emotion regulation strategies improve fMRI and ECG markers of psychopathology in panic disorder: implications for psychological treatment action. Transl Psychiatry  2015; 5e673
[http://dx.doi.org/10.1038/tp.2015.160] [PMID: 26529426] 
[63] 
Engel KR, Obst K, Bandelow B, et al. Functional MRI activation in response to panic-specific, non-panic aversive, and neutral pictures in patients with panic disorder and healthy controls. Eur Arch Psychiatry Clin Neurosci  2016; 266(6): 557-66.
[http://dx.doi.org/10.1007/s00406-015-0653-6] [PMID: 26585457] 
[64] 
Feldker K, Heitmann CY, Neumeister P, et al. Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder. J Psychiatry Neurosci  2018; 43(1): 26-36.
[http://dx.doi.org/10.1503/jpn.160226] [PMID: 29252163] 
[65] 
Burkhardt A, Buff C, Brinkmann L, et al. Brain activation during disorder-related script-driven imagery in panic disorder: a pilot study. Sci Rep  2019; 9(1): 2415.
[http://dx.doi.org/10.1038/s41598-019-38990-0] [PMID: 30787382] 
[66] 
Gechter J, Liebscher C, Geiger MJ, et al. Association of NPSR1 gene variation and neural activity in patients with panic disorder and agoraphobia and healthy controls. Neuroimage Clin 2019.24102029
[http://dx.doi.org/10.1016/j.nicl.2019.102029] [PMID: 31734525] 
[67] 
van den Heuvel OA, Mataix-Cols D, Zwitser G, et al. Common limbic and frontal-striatal disturbances in patients with obsessive compulsive disorder, panic disorder and hypochondriasis. Psychol Med  2011; 41(11): 2399-410.
[http://dx.doi.org/10.1017/S0033291711000535] [PMID: 21557892] 
[68] 
Wittmann A, Schlagenhauf F, John T, et al. A new paradigm (Westphal-Paradigm) to study the neural correlates of panic disorder with agoraphobia. Eur Arch Psychiatry Clin Neurosci  2011; 261(3): 185-94.
[http://dx.doi.org/10.1007/s00406-010-0167-1] [PMID: 21113608] 
[69] 
Wittmann A, Schlagenhauf F, Guhn A, et al. Anticipating agoraphobic situations: the neural correlates of panic disorder with agoraphobia. Psychol Med  2014; 44(11): 2385-96.
[http://dx.doi.org/10.1017/S0033291713003085] [PMID: 24398049] 
[70] 
Feldker K, Heitmann CY, Neumeister P, et al. Brain responses to disorder-related visual threat in panic disorder. Hum Brain Mapp  2016; 37(12): 4439-53.
[http://dx.doi.org/10.1002/hbm.23320] [PMID: 27436308] 
[71] 
Pfleiderer B, Zinkirciran S, Michael N, et al. Altered auditory processing in patients with panic disorder: a pilot study. World J Biol Psychiatry  2010; 11(8): 945-55.
[http://dx.doi.org/10.3109/15622975.2010.490273] [PMID: 20586534] 
[72] 
Brinkmann L, Buff C, Feldker K, et al. Distinct phasic and sustained brain responses and connectivity of amygdala and bed nucleus of the stria terminalis during threat anticipation in panic disorder. Psychol Med  2017; 47(15): 2675-88.
[http://dx.doi.org/10.1017/S0033291717001192] [PMID: 28485259] 
[73] 
Domschke K, Ohrmann P, Braun M, et al. Influence of the catechol-O-methyltransferase val158met genotype on amygdala and prefrontal cortex emotional processing in panic disorder. Psychiatry Res  2008; 163(1): 13-20.
[http://dx.doi.org/10.1016/j.pscychresns.2007.04.016] [PMID: 18440204] 
[74] 
Weber H, Richter J, Straube B, et al. Allelic variation in CRHR1 predisposes to panic disorder: evidence for biased fear processing. Mol Psychiatry  2016; 21(6): 813-22.
[http://dx.doi.org/10.1038/mp.2015.125] [PMID: 26324098] 
[75] 
Domschke K, Reif A, Weber H, et al. Neuropeptide S receptor gene - converging evidence for a role in panic disorder. Mol Psychiatry  2011; 16(9): 938-48.
[http://dx.doi.org/10.1038/mp.2010.81] [PMID: 20603625] 
[76] 
Dresler T, Hindi Attar C, Spitzer C, et al. Neural correlates of the emotional Stroop task in panic disorder patients: an event-related fMRI study. J Psychiatr Res  2012; 46(12): 1627-34.
[http://dx.doi.org/10.1016/j.jpsychires.2012.09.004] [PMID: 23058446] 
[77] 
Killgore WD, Britton JC, Schwab ZJ, et al. Cortico-limbic responses to masked affective faces across ptsd, panic disorder, and specific phobia. Depress Anxiety  2014; 31(2): 150-9.
[http://dx.doi.org/10.1002/da.22156] [PMID: 23861215] 
[78] 
Fonzo GA, Ramsawh HJ, Flagan TM, et al. Common and disorder-specific neural responses to emotional faces in generalised anxiety, social anxiety and panic disorders. Br J Psychiatry  2015; 206(3): 206-15.
[http://dx.doi.org/10.1192/bjp.bp.114.149880] [PMID: 25573399] 
[79] 
Inoue A, Akiyoshi J, Muronaga M, et al. Association of TMEM132D, COMT, and GABRA6 genotypes with cingulate, frontal cortex and hippocampal emotional processing in panic and major depressive disorder. Int J Psychiatry Clin Pract  2015; 19(3): 192-200.
[http://dx.doi.org/10.3109/13651501.2015.1043133] [PMID: 25974322] 
[80] 
Petrowski K, Wintermann G, Smolka MN, Huebner T, Donix M. The neural representation of emotionally neutral faces and places in patients with panic disorder with agoraphobia. J Affect Disord  2014; 152-154: 454-61.
[http://dx.doi.org/10.1016/j.jad.2013.10.016] [PMID: 24176537] 
[81] 
Lueken U, Straube B, Reinhardt I, et al. Altered top-down and bottom-up processing of fear conditioning in panic disorder with agoraphobia. Psychol Med  2014; 44(2): 381-94.
[http://dx.doi.org/10.1017/S0033291713000792] [PMID: 23611156] 
[82] 
Schwarzmeier H, Kleint NI, Wittchen HU, Ströhle A, Hamm AO, Lueken U. Characterizing the nature of emotional-associative learning deficits in panic disorder: an fMRI study on fear conditioning, extinction training and recall. Eur Neuropsychopharmacol  2019; 29(2): 306-18.
[http://dx.doi.org/10.1016/j.euroneuro.2018.11.1108] [PMID: 30497840] 
[83] 
Lueken U, Straube B, Yang Y, et al. Separating depressive comorbidity from panic disorder: a combined functional magnetic resonance imaging and machine learning approach. J Affect Disord  2015; 184: 182-92.
[http://dx.doi.org/10.1016/j.jad.2015.05.052] [PMID: 26093832] 
[84] 
Beutel ME, Stark R, Pan H, Silbersweig D, Dietrich S. Changes of brain activation pre- post short-term psychodynamic inpatient psychotherapy: an fMRI study of panic disorder patients. Psychiatry Res  2010; 184(2): 96-104.
[http://dx.doi.org/10.1016/j.pscychresns.2010.06.005] [PMID: 20933374] 
[85] 
Wittmann A, Schlagenhauf F, Guhn A, et al. Effects of cognitive behavioral therapy on neural processing of agoraphobia-specific stimuli in panic disorder and agoraphobia. Psychother Psychosom  2018; 87(6): 350-65.
[http://dx.doi.org/10.1159/000493146] [PMID: 30269148] 
[86] 
Kircher T, Arolt V, Jansen A, et al. Effect of cognitive-behavioral therapy on neural correlates of fear conditioning in panic disorder. Biol Psychiatry  2013; 73(1): 93-101.
[http://dx.doi.org/10.1016/j.biopsych.2012.07.026] [PMID: 22921454] 
[87] 
Lueken U, Straube B, Konrad C, et al. Neural substrates of treatment response to cognitive-behavioral therapy in panic disorder with agoraphobia. Am J Psychiatry  2013; 170(11): 1345-55.
[http://dx.doi.org/10.1176/appi.ajp.2013.12111484] [PMID: 23982225] 
[88] 
Reif A, Richter J, Straube B, et al. MAOA and mechanisms of panic disorder revisited: from bench to molecular psychotherapy. Mol Psychiatry  2014; 19(1): 122-8.
[http://dx.doi.org/10.1038/mp.2012.172] [PMID: 23319006] 
[89] 
Lueken U, Straube B, Wittchen HU, et al. Therapygenetics: anterior cingulate cortex-amygdala coupling is associated with 5-HTTLPR and treatment response in panic disorder with agoraphobia. J Neural Transm (Vienna)  2015; 122(1): 135-44.
[http://dx.doi.org/10.1007/s00702-014-1311-2] [PMID: 25223844] 
[90] 
Gottschalk MG, Richter J, Ziegler C, et al. Orexin in the anxiety spectrum: association of a HCRTR1 polymorphism with panic disorder/agoraphobia, CBT treatment response and fear-related intermediate phenotypes. Transl Psychiatry  2019; 9(1): 75.
[http://dx.doi.org/10.1038/s41398-019-0415-8] [PMID: 30718541] 
[91] 
Grambal A, Tüdös Z, Hok P, et al. Predictors of poor treatment response to additional CBT in real panic disorder patients: the role of DLPF, orbitofrontal cortex, parietal lobule, frontal eye field and amygdala in PD. Neuroendocrinol Lett  2015; 36(3): 269-81.
[PMID: 26313395] 
[92] 
Liebscher C, Wittmann A, Gechter J, et al. Facing the fear-clinical and neural effects of cognitive behavioural and pharmacotherapy in panic disorder with agoraphobia. Eur Neuropsychopharmacol  2016; 26(3): 431-44.
[http://dx.doi.org/10.1016/j.euroneuro.2016.01.004] [PMID: 26837851] 
[93] 
Hahn T, Kircher T, Straube B, et al. Predicting treatment response to cognitive behavioral therapy in panic disorder with agoraphobia by integrating local neural information. JAMA Psychiatry  2015; 72(1): 68-74.
[http://dx.doi.org/10.1001/jamapsychiatry.2014.1741] [PMID: 25409415] 
[94] 
Yang Y, Kircher T, Straube B. The neural correlates of cognitive behavioral therapy: recent progress in the investigation of patients with panic disorder. Behav Res Ther  2014; 62: 88-96.
[http://dx.doi.org/10.1016/j.brat.2014.07.011] [PMID: 25124776] 
[95] 
Sundermann B, Bode J, Lueken U, et al. Support vector machine analysis of functional magnetic resonance imaging of interoception does not reliably predict individual outcomes of cognitive behavioral therapy in panic disorder with agoraphobia. Front Psychiatry  2017; 8: 99.
[http://dx.doi.org/10.3389/fpsyt.2017.00099] [PMID: 28649205] 
[96] 
Chechko N, Wehrle R, Erhardt A, Holsboer F, Czisch M, Sämann PG. Unstable prefrontal response to emotional conflict and activation of lower limbic structures and brainstem in remitted panic disorder. PLoS One  2009; 4(5)e5537
[http://dx.doi.org/10.1371/journal.pone.0005537] [PMID: 19462002] 
[97] 
de Carvalho MR, Dias GP, Cosci F, et al. Current findings of fMRI in panic disorder: contributions for the fear neurocircuitry and CBT effects. Expert Rev Neurother  2010; 10(2): 291-303.
[http://dx.doi.org/10.1586/ern.09.161] [PMID: 20136384] 
[98] 
Marchand WR, Lee JN, Healy L, et al. An fMRI motor activation paradigm demonstrates abnormalities of putamen activation in females with panic disorder. J Affect Disord  2009; 116(1-2): 121-5.
[http://dx.doi.org/10.1016/j.jad.2008.10.026] [PMID: 19046771] 
[99] 
Goossens L, Leibold N, Peeters R, et al. Brainstem response to hypercapnia: a symptom provocation study into the pathophysiology of panic disorder. J Psychopharmacol (Oxford)  2014; 28(5): 449-56.
[http://dx.doi.org/10.1177/0269881114527363] [PMID: 24646808] 
[100] 
Held-Poschardt D, Sterzer P, Schlagenhauf F, et al. Reward and loss anticipation in panic disorder: an fMRI study. Psychiatry Res Neuroimaging  2018; 271: 111-7.
[http://dx.doi.org/10.1016/j.pscychresns.2017.11.005] [PMID: 29169660] 
[101] 
Zou QH, Zhu CZ, Yang Y, et al. An improved approach to detection of amplitude of low-frequency fluctuation (ALFF) for resting-state fMRI: fractional ALFF. J Neurosci Methods  2008; 172(1): 137-41.
[http://dx.doi.org/10.1016/j.jneumeth.2008.04.012] [PMID: 18501969] 
[102] 
Zang Y, Jiang T, Lu Y, He Y, Tian L. Regional homogeneity approach to fMRI data analysis. Neuroimage  2004; 22(1): 394-400.
[http://dx.doi.org/10.1016/j.neuroimage.2003.12.030] [PMID: 15110032] 
[103] 
Zuo XN, Kelly C, Di Martino A, et al. Growing together and growing apart: regional and sex differences in the lifespan developmental trajectories of functional homotopy. J Neurosci  2010; 30(45): 15034-43.
[http://dx.doi.org/10.1523/JNEUROSCI.2612-10.2010] [PMID: 21068309] 
[104] 
Biswal B, Yetkin FZ, Haughton VM, Hyde JS. Functional connectivity in the motor cortex of resting human brain using echo-planar MRI. Magn Reson Med  1995; 34(4): 537-41.
[http://dx.doi.org/10.1002/mrm.1910340409] [PMID: 8524021] 
[105] 
Fox MD, Raichle ME. Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging. Nat Rev Neurosci  2007; 8(9): 700-11.
[http://dx.doi.org/10.1038/nrn2201] [PMID: 17704812] 
[106] 
Salvador R, Suckling J, Coleman MR, Pickard JD, Menon D, Bullmore E. Neurophysiological architecture of functional magnetic resonance images of human brain. Cereb Cortex  2005; 15(9): 1332-42.
[http://dx.doi.org/10.1093/cercor/bhi016] [PMID: 15635061] 
[107] 
Lai CH, Wu YT. Patterns of fractional amplitude of low-frequency oscillations in occipito-striato-thalamic regions of first-episode drug-naïve panic disorder. J Affect Disord  2012; 142(1-3): 180-5.
[http://dx.doi.org/10.1016/j.jad.2012.04.021] [PMID: 22770722] 
[108] 
Lai CH, Wu YT. The changes in the low-frequency fluctuations of cingulate cortex and postcentral gyrus in the treatment of panic disorder: The MRI study. World J Biol Psychiatry  2016; 17(1): 58-65.
[http://dx.doi.org/10.3109/15622975.2015.1017604] [PMID: 25789962] 
[109] 
Lai CH, Wu YT. Decreased regional homogeneity in lingual gyrus, increased regional homogeneity in cuneus and correlations with panic symptom severity of first-episode, medication-naïve and late-onset panic disorder patients. Psychiatry Res  2013; 211(2): 127-31.
[http://dx.doi.org/10.1016/j.pscychresns.2012.11.006] [PMID: 23352831] 
[110] 
Lai CH, Wu YT. Changes in regional homogeneity of parieto-temporal regions in panic disorder patients who achieved remission with antidepressant treatment. J Affect Disord  2013; 151(2): 709-14.
[http://dx.doi.org/10.1016/j.jad.2013.08.006] [PMID: 23993443] 
[111] 
Pannekoek JN, Veer IM, van Tol MJ, et al. Aberrant limbic and salience network resting-state functional connectivity in panic disorder without comorbidity. J Affect Disord  2013; 145(1): 29-35.
[http://dx.doi.org/10.1016/j.jad.2012.07.006] [PMID: 22858265] 
[112] 
Cui H, Zhang J, Liu Y, et al. Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder. Hum Brain Mapp  2016; 37(4): 1459-73.
[http://dx.doi.org/10.1002/hbm.23113] [PMID: 26800659] 
[113] 
Shin YW, Dzemidzic M, Jo HJ, et al. Increased resting-state functional connectivity between the anterior cingulate cortex and the precuneus in panic disorder: resting-state connectivity in panic disorder. J Affect Disord  2013; 150(3): 1091-5.
[http://dx.doi.org/10.1016/j.jad.2013.04.026] [PMID: 23688914] 
[114] 
Lai CH, Wu YT. The explorative analysis to revise fear network model for panic disorder: functional connectome statistics. Medicine  2016; 95(18)e3597
[http://dx.doi.org/10.1097/MD.0000000000003597] [PMID: 27149492] 
[115] 
Pang M, Zhong Y, Hao Z, et al. Resting-state causal connectivity of the bed nucleus of the stria terminalis in panic disorder. Brain Imaging Behav 2019.
[http://dx.doi.org/10.1007/s11682-019-00229-x] [PMID: 31833015] 
[116] 
Lai CH, Wu YT. The alterations in inter-hemispheric functional coordination of patients with panic disorder: the findings in the posterior sub-network of default mode network. J Affect Disord  2014; 166: 279-84.
[http://dx.doi.org/10.1016/j.jad.2014.05.022] [PMID: 25012442] 
[117] 
Massana G, Gastó C, Junqué C, et al. Reduced levels of creatine in the right medial temporal lobe region of panic disorder patients detected with 1H magnetic resonance spectroscopy. Neuroimage  2002; 16(3): 836-42.
[http://dx.doi.org/10.1006/nimg.2002.1083] [PMID: 12169267] 
[118] 
Trzesniak C, Uchida RR, Araújo D, et al. 1H magnetic resonance spectroscopy imaging of the hippocampus in patients with panic disorder. Psychiatry Res  2010; 182(3): 261-5.
[http://dx.doi.org/10.1016/j.pscychresns.2010.03.008] [PMID: 20488674] 
[119] 
Goddard AW, Mason GF, Appel M, et al. Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder. Am J Psychiatry  2004; 161(12): 2186-93.
[http://dx.doi.org/10.1176/appi.ajp.161.12.2186] [PMID: 15569888] 
[120] 
Maddock RJ, Buonocore MH, Copeland LE, Richards AL. Elevated brain lactate responses to neural activation in panic disorder: a dynamic 1H-MRS study. Mol Psychiatry  2009; 14(5): 537-45.
[http://dx.doi.org/10.1038/sj.mp.4002137] [PMID: 18180759] 
[121] 
Maddock RJ, Buonocore MH, Miller AR, Yoon JH, Soosman SK, Unruh AM. Abnormal activity-dependent brain lactate and glutamate+glutamine responses in panic disorder. Biol Psychiatry  2013; 73(11): 1111-9.
[http://dx.doi.org/10.1016/j.biopsych.2012.12.015] [PMID: 23332354] 
[122] 
Ham BJ, Sung Y, Kim N, et al. Decreased GABA levels in anterior cingulate and basal ganglia in medicated subjects with panic disorder: a proton magnetic resonance spectroscopy (1H-MRS) study. Prog Neuropsychopharmacol Biol Psychiatry  2007; 31(2): 403-11.
[http://dx.doi.org/10.1016/j.pnpbp.2006.10.011] [PMID: 17141385] 
[123] 
Long Z, Medlock C, Dzemidzic M, Shin YW, Goddard AW, Dydak U. Decreased GABA levels in anterior cingulate cortex/medial prefrontal cortex in panic disorder. Prog Neuropsychopharmacol Biol Psychiatry  2013; 44: 131-5.
[http://dx.doi.org/10.1016/j.pnpbp.2013.01.020] [PMID: 23391588] 
[124] 
Hasler G, van der Veen JW, Geraci M, Shen J, Pine D, Drevets WC. Prefrontal cortical gamma-aminobutyric acid levels in panic disorder determined by proton magnetic resonance spectroscopy. Biol Psychiatry  2009; 65(3): 273-5.
[http://dx.doi.org/10.1016/j.biopsych.2008.06.023] [PMID: 18692172] 
[125] 
Preuss N, Salehi B, van der Veen JW, et al. Associations between prefrontal γ-aminobutyric acid concentration and the tryptophan hydroxylase isoform 2 gene, a panic disorder risk allele in women. Int J Neuropsychopharmacol  2013; 16(8): 1707-17.
[http://dx.doi.org/10.1017/S1461145713000254] [PMID: 23552096] 
[126] 
Pannekoek JN, van der Werff SJ, Stein DJ, van der Wee NJ. Advances in the neuroimaging of panic disorder. Hum Psychopharmacol  2013; 28(6): 608-11.
[http://dx.doi.org/10.1002/hup.2349] [PMID: 24038132] 
[127] 
Grambal A, Hluštík P, Praško J. What fMRI can tell as about panic disorder: bridging the gap between neurobiology and psychotherapy. Neuroendocrinol Lett 2015; 36(3): 214-5.
[PMID: 26313386] 
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DOI https://dx.doi.org/10.2174/2666082216999200918163245	Print ISSN 2666-0822
Publisher Name Bentham Science Publisher	Online ISSN 2666-0830
Current Psychiatry Research and Reviews

Biomarkers in Panic Disorder

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