Browse > Article

Reduced Gray Matter Density in the Posterior Cerebellum of Patients with Panic Disorder : A Voxel-Based Morphometry Study  

Lee, Junghyun H. (Psychological Trauma Center, Seoul National Hospital)
Jeon, Yujin (Ewha Brain Institute, Ewha Womans University)
Bae, Sujin (Department of Psychiatry, Chung-Ang University Hospital)
Jeong, Jee Hyang (Department of Neurology and Medical Research Institute, Ewha Womans University School of Medicine)
Namgung, Eun (Ewha Brain Institute, Ewha Womans University)
Kim, Bori R. (Ewha Brain Institute, Ewha Womans University)
Ban, Soonhyun (Ewha Brain Institute, Ewha Womans University)
Jeon, Saerom (Ewha Brain Institute, Ewha Womans University)
Kang, Ilhyang (Ewha Brain Institute, Ewha Womans University)
Lim, Soo Mee (Department of Radiology, Ewha Womans University Mokdong Hospital)
Publication Information
Korean Journal of Biological Psychiatry / v.22, no.1, 2015 , pp. 20-27 More about this Journal
Abstract
Objectives It is increasingly thought that the human cerebellum plays an important role in emotion and cognition. Although recent evidence suggests that the cerebellum may also be implicated in fear learning, only a limited number of studies have investigated the cerebellar abnormalities in panic disorder. The aim of this study was to evaluate the cerebellar gray matter deficits and their clinical correlations among patients with panic disorder. Methods Using a voxel-based morphometry approach with a high-resolution spatially unbiased infratentorial template, regional cerebellar gray matter density was compared between 23 patients with panic disorder and 33 healthy individuals. Results The gray matter density in the right posterior-superior (lobule Crus I) and left posterior-inferior (lobules Crus II, VIIb, VIIIa) cerebellum was significantly reduced in the panic disorder group compared to healthy individuals (p < 0.05, false discovery rate corrected, extent threshold = 100 voxels). Additionally, the gray matter reduction in the left posterior-inferior cerebellum (lobule VIIIa) was significantly associated with greater panic symptom severity (r = -0.55, p = 0.007). Conclusions Our findings suggest that the gray matter deficits in the posterior cerebellum may be involved in the pathogenesis of panic disorder. Further studies are needed to provide a comprehensive understanding of the cerebro-cerebellar network in panic disorder.
Keywords
Panic disorder; Cerebellum; Voxel-based morphometry; Gray matter;
Citations & Related Records
연도 인용수 순위
  • Reference
1 American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-IV-TR. 4th ed., text revision. Washington, DC: American Psychiatric Association;2000.
2 Massana G, Serra-Grabulosa JM, Salgado-Pineda P, Gasto C, Junque C, Massana J, et al. Amygdalar atrophy in panic disorder patients detected by volumetric magnetic resonance imaging. Neuroimage 2003;19:80-90.   DOI
3 Pillay SS, Gruber SA, Rogowska J, Simpson N, Yurgelun-Todd DA. fMRI of fearful facial affect recognition in panic disorder: the cingulate gyrus-amygdala connection. J Affect Disord 2006;94:173-181.   DOI
4 Han DH, Renshaw PF, Dager SR, Chung A, Hwang J, Daniels MA, et al. Altered cingulate white matter connectivity in panic disorder patients. J Psychiatr Res 2008;42:399-407.   DOI
5 Chechko N, Wehrle R, Erhardt A, Holsboer F, Czisch M, Samann PG. Unstable prefrontal response to emotional conflict and activation of lower limbic structures and brainstem in remitted panic disorder. PLoS One 2009;4:e5537.   DOI
6 Yoon S, Jun CS, Jeong HS, Lee S, Lim SM, Ma J, et al. Altered cortical gyrification patterns in panic disorder: deficits and potential compensation. J Psychiatr Res 2013;47:1446-1454.   DOI
7 Gorman JM, Kent JM, Sullivan GM, Coplan JD. Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 2000;157:493-505.   DOI
8 Exner C, Weniger G, Irle E. Cerebellar lesions in the PICA but not SCA territory impair cognition. Neurology 2004;63:2132-2135.   DOI
9 Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum - insights from the clinic. Cerebellum 2007;6:254-267.   DOI
10 Tavano A, Grasso R, Gagliardi C, Triulzi F, Bresolin N, Fabbro F, et al. Disorders of cognitive and affective development in cerebellar malformations. Brain 2007;130(Pt 10):2646-2660.   DOI
11 Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage 2009;44:489-501.   DOI
12 Stoodley CJ, Valera EM, Schmahmann JD. An fMRI study of intraindividual functional topography in the human cerebellum. Behav Neurol 2010;23:65-79.   DOI
13 Ito M. Control of mental activities by internal models in the cerebellum. Nat Rev Neurosci 2008;9:304-313.   DOI
14 Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 2010;46:831-844.   DOI
15 Ramnani N. The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci 2006;7:511-522.   DOI
16 Ramnani N. Frontal lobe and posterior parietal contributions to the cortico-cerebellar system. Cerebellum 2012;11:366-383.   DOI
17 Moulton EA, Elman I, Pendse G, Schmahmann J, Becerra L, Borsook D. Aversion-related circuitry in the cerebellum: responses to noxious heat and unpleasant images. J Neurosci 2011;31:3795-3804.   DOI
18 Nopoulos PC, Ceilley JW, Gailis EA, Andreasen NC. An MRI study of cerebellar vermis morphology in patients with schizophrenia: evidence in support of the cognitive dysmetria concept. Biol Psychiatry 1999;46:703-711.   DOI
19 Okugawa G, Sedvall G, Nordstrom M, Andreasen N, Pierson R, Magnotta V, et al. Selective reduction of the posterior superior vermis in men with chronic schizophrenia. Schizophr Res 2002;55:61-67.   DOI
20 De Bellis MD, Kuchibhatla M. Cerebellar volumes in pediatric maltreatment-related posttraumatic stress disorder. Biol Psychiatry 2006;60:697-703.   DOI
21 Monkul ES, Hatch JP, Sassi RB, Axelson D, Brambilla P, Nicoletti MA, et al. MRI study of the cerebellum in young bipolar patients. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:613-619.   DOI
22 Eser D, Leicht G, Lutz J, Wenninger S, Kirsch V, Schule C, et al. Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers. Hum Brain Mapp 2009;30:511-522.   DOI
23 Sakai Y, Kumano H, Nishikawa M, Sakano Y, Kaiya H, Imabayashi E, et al. Cerebral glucose metabolism associated with a fear network in panic disorder. Neuroreport 2005;16:927-931.   DOI
24 Sakai Y, Kumano H, Nishikawa M, Sakano Y, Kaiya H, Imabayashi E, et al. Changes in cerebral glucose utilization in patients with panic disorder treated with cognitive-behavioral therapy. Neuroimage 2006;33:218-226.   DOI
25 Asami T, Yamasue H, Hayano F, Nakamura M, Uehara K, Otsuka T, et al. Sexually dimorphic gray matter volume reduction in patients with panic disorder. Psychiatry Res 2009;173:128-134.   DOI
26 Lai CH, Hsu YY. A subtle grey-matter increase in first-episode, drug-naive major depressive disorder with panic disorder after 6 weeks’ duloxetine therapy. Int J Neuropsychopharmacol 2011;14:225-235.   DOI
27 Kim JJ, Jung MW. Neural circuits and mechanisms involved in Pavlovian fear conditioning: a critical review. Neurosci Biobehav Rev 2006;30:188-202.   DOI
28 Timmann D, Drepper J, Frings M, Maschke M, Richter S, Gerwig M, et al. The human cerebellum contributes to motor, emotional and cognitive associative learning. A review. Cortex 2010;46:845-857.   DOI
29 Maschke M, Drepper J, Kindsvater K, Kolb FP, Diener HC, Timmann D. Involvement of the human medial cerebellum in long-term habituation of the acoustic startle response. Exp Brain Res 2000;133:359-367.   DOI
30 Maschke M, Schugens M, Kindsvater K, Drepper J, Kolb FP, Diener HC, et al. Fear conditioned changes of heart rate in patients with medial cerebellar lesions. J Neurol Neurosurg Psychiatry 2002;72:116-118.   DOI
31 Ploghaus A, Tracey I, Clare S, Gati JS, Rawlins JN, Matthews PM. Learning about pain: the neural substrate of the prediction error for aversive events. Proc Natl Acad Sci U S A 2000;97:9281-9286.   DOI
32 Ploghaus A, Tracey I, Gati JS, Clare S, Menon RS, Matthews PM, et al. Dissociating pain from its anticipation in the human brain. Science 1999;284:1979-1981.   DOI
33 Damasio AR, Grabowski TJ, Bechara A, Damasio H, Ponto LL, Parvizi J, et al. Subcortical and cortical brain activity during the feeling of self-generated emotions. Nat Neurosci 2000;3:1049-1056.   DOI
34 Ashburner J, Friston KJ. Voxel-based morphometry--the methods. Neuroimage 2000;11(6 Pt 1):805-821.   DOI
35 Diedrichsen J. A spatially unbiased atlas template of the human cerebellum. Neuroimage 2006;33:127-138.   DOI
36 Diedrichsen J, Balsters JH, Flavell J, Cussans E, Ramnani N. A probabilistic MR atlas of the human cerebellum. Neuroimage 2009;46:39-46.   DOI
37 First MB, Spitzer RL, Gibbon M, Williams JBW. Structured clinical interview for DSM-IV axis I disorders (SCID-I). Washington, DC: American Psychiatric Press;1997.
38 Hyler SE. PDQ-4+ Personality Questionnaire. New York: New York State Psychiatric Institute;1994.
39 Lim YJ, Yu BH, Kim JH. Korean panic disorder severity scale: construct validity by confirmatory factor analysis. Depress Anxiety 2007;24:95-102.   DOI
40 Shear MK, Rucci P, Williams J, Frank E, Grochocinski V, Vander Bilt J, et al. Reliability and validity of the Panic Disorder Severity Scale: replication and extension. J Psychiatr Res 2001;35:293-296.   DOI
41 Zung WW. A rating instrument for anxiety disorders. Psychosomatics 1971;12:371-379.   DOI
42 Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.   DOI
43 Friston KJ, Worsley KJ, Frackowiak RS, Mazziotta JC, Evans AC. Assessing the significance of focal activations using their spatial extent. Hum Brain Mapp 1994;1:210-220.   DOI
44 Larsell O, Jansen J. The Comparative Anatomy and Histology of the Cerebellum: from monotremes through apes. Minneapolis: University of Minnesota Press;1967.
45 Sacchetti B, Scelfo B, Strata P. The cerebellum: synaptic changes and fear conditioning. Neuroscientist 2005;11:217-227.   DOI
46 Sacchetti B, Baldi E, Lorenzini CA, Bucherelli C. Cerebellar role in fear-conditioning consolidation. Proc Natl Acad Sci U S A 2002;99:8406-8411.   DOI
47 Javanmard M, Shlik J, Kennedy SH, Vaccarino FJ, Houle S, Bradwejn J. Neuroanatomic correlates of CCK-4-induced panic attacks in healthy humans: a comparison of two time points. Biol Psychiatry 1999;45:872-882.   DOI
48 Moers-Hornikx VM, Vles JS, Lim LW, Ayyildiz M, Kaplan S, Gavilanes AW, et al. Periaqueductal grey stimulation induced panic-like behaviour is accompanied by deactivation of the deep cerebellar nuclei. Cerebellum 2011;10:61-69.   DOI
49 Schunck T, Erb G, Mathis A, Gilles C, Namer IJ, Hode Y, et al. Functional magnetic resonance imaging characterization of CCK-4-induced panic attack and subsequent anticipatory anxiety. Neuroimage 2006;31:1197-1208.   DOI
50 Reiman EM. The application of positron emission tomography to the study of normal and pathologic emotions. J Clin Psychiatry 1997;58 Suppl 16:4-12.
51 Grillon C. Associative learning deficits increase symptoms of anxiety in humans. Biol Psychiatry 2002;51:851-858.   DOI
52 Grillon C, Lissek S, McDowell D, Levenson J, Pine DS. Reduction of trace but not delay eyeblink conditioning in panic disorder. Am J Psychiatry 2007;164:283-289.   DOI
53 Chen SH, Desmond JE. Cerebrocerebellar networks during articulatory rehearsal and verbal working memory tasks. Neuroimage 2005;24:332-338.   DOI
54 Kirschen MP, Chen SH, Schraedley-Desmond P, Desmond JE. Load- and practice-dependent increases in cerebro-cerebellar activation in verbal working memory: an fMRI study. Neuroimage 2005;24:462-472.   DOI
55 Carter RM, Hofstotter C, Tsuchiya N, Koch C. Working memory and fear conditioning. Proc Natl Acad Sci U S A 2003;100:1399-1404.   DOI
56 Ravizza SM, McCormick CA, Schlerf JE, Justus T, Ivry RB, Fiez JA. Cerebellar damage produces selective deficits in verbal working memory. Brain 2006;129(Pt 2):306-320.   DOI
57 Bostan AC, Dum RP, Strick PL. Cerebellar networks with the cerebral cortex and basal ganglia. Trends Cogn Sci 2013;17:241-254.   DOI
58 Morrell MJ, Jackson ML, Twigg GL, Ghiassi R, McRobbie DW, Quest RA, et al. Changes in brain morphology in patients with obstructive sleep apnoea. Thorax 2010;65:908-914.   DOI
59 Lai CH. Duloxetine related effects of brain structure on a patient of major depressive disorder with panic disorder. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:240-241.   DOI
60 Yoo HK, Kim MJ, Kim SJ, Sung YH, Sim ME, Lee YS, et al. Putaminal gray matter volume decrease in panic disorder: an optimized voxel-based morphometry study. Eur J Neurosci 2005;22:2089-2094.   DOI