Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
권호 표지

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)
  • Received : 2015.01.27
  • Accepted : 2015.02.05
  • Published : 2015.02.28
Download PDF
⟨ Previous Next ⟩

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

References

  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. https://doi.org/10.1016/S1053-8119(03)00036-3
  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. https://doi.org/10.1016/j.jad.2006.04.007
  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. https://doi.org/10.1016/j.jpsychires.2007.03.002
  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. https://doi.org/10.1371/journal.pone.0005537
  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. https://doi.org/10.1016/j.jpsychires.2013.06.015
  7. Gorman JM, Kent JM, Sullivan GM, Coplan JD. Neuroanatomical hypothesis of panic disorder, revised. Am J Psychiatry 2000;157:493-505. https://doi.org/10.1176/appi.ajp.157.4.493
  8. Exner C, Weniger G, Irle E. Cerebellar lesions in the PICA but not SCA territory impair cognition. Neurology 2004;63:2132-2135. https://doi.org/10.1212/01.WNL.0000146197.44568.CD
  9. Schmahmann JD, Weilburg JB, Sherman JC. The neuropsychiatry of the cerebellum - insights from the clinic. Cerebellum 2007;6:254-267. https://doi.org/10.1080/14734220701490995
  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. https://doi.org/10.1093/brain/awm201
  11. Stoodley CJ, Schmahmann JD. Functional topography in the human cerebellum: a meta-analysis of neuroimaging studies. Neuroimage 2009;44:489-501. https://doi.org/10.1016/j.neuroimage.2008.08.039
  12. Stoodley CJ, Valera EM, Schmahmann JD. An fMRI study of intraindividual functional topography in the human cerebellum. Behav Neurol 2010;23:65-79. https://doi.org/10.1155/2010/840942
  13. Stoodley CJ, Schmahmann JD. Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing. Cortex 2010;46:831-844. https://doi.org/10.1016/j.cortex.2009.11.008
  14. Ramnani N. The primate cortico-cerebellar system: anatomy and function. Nat Rev Neurosci 2006;7:511-522. https://doi.org/10.1038/nrn1953
  15. Ramnani N. Frontal lobe and posterior parietal contributions to the cortico-cerebellar system. Cerebellum 2012;11:366-383. https://doi.org/10.1007/s12311-011-0272-3
  16. Ito M. Control of mental activities by internal models in the cerebellum. Nat Rev Neurosci 2008;9:304-313. https://doi.org/10.1038/nrn2332
  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. https://doi.org/10.1523/JNEUROSCI.6709-10.2011
  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. https://doi.org/10.1016/S0006-3223(99)00093-1
  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. https://doi.org/10.1016/S0920-9964(01)00248-1
  20. De Bellis MD, Kuchibhatla M. Cerebellar volumes in pediatric maltreatment-related posttraumatic stress disorder. Biol Psychiatry 2006;60:697-703. https://doi.org/10.1016/j.biopsych.2006.04.035
  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. https://doi.org/10.1016/j.pnpbp.2007.09.016
  22. 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. https://doi.org/10.1097/00001756-200506210-00010
  23. 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. https://doi.org/10.1016/j.neuroimage.2006.06.017
  24. 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. https://doi.org/10.1016/j.pscychresns.2008.10.004
  25. 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. https://doi.org/10.1002/hbm.20522
  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. https://doi.org/10.1017/S1461145710000829
  27. Kim JJ, Jung MW. Neural circuits and mechanisms involved in Pavlovian fear conditioning: a critical review. Neurosci Biobehav Rev 2006;30:188-202. https://doi.org/10.1016/j.neubiorev.2005.06.005
  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. https://doi.org/10.1016/j.cortex.2009.06.009
  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. https://doi.org/10.1007/s002210000417
  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. https://doi.org/10.1136/jnnp.72.1.116
  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. https://doi.org/10.1073/pnas.160266497
  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. https://doi.org/10.1126/science.284.5422.1979
  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. https://doi.org/10.1038/79871
  34. Ashburner J, Friston KJ. Voxel-based morphometry--the methods. Neuroimage 2000;11(6 Pt 1):805-821. https://doi.org/10.1006/nimg.2000.0582
  35. Diedrichsen J. A spatially unbiased atlas template of the human cerebellum. Neuroimage 2006;33:127-138. https://doi.org/10.1016/j.neuroimage.2006.05.056
  36. Diedrichsen J, Balsters JH, Flavell J, Cussans E, Ramnani N. A probabilistic MR atlas of the human cerebellum. Neuroimage 2009;46:39-46. https://doi.org/10.1016/j.neuroimage.2009.01.045
  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. 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. https://doi.org/10.1016/S0022-3956(01)00028-0
  40. Lim YJ, Yu BH, Kim JH. Korean panic disorder severity scale: construct validity by confirmatory factor analysis. Depress Anxiety 2007;24:95-102. https://doi.org/10.1002/da.20206
  41. Zung WW. A rating instrument for anxiety disorders. Psychosomatics 1971;12:371-379. https://doi.org/10.1016/S0033-3182(71)71479-0
  42. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62. https://doi.org/10.1136/jnnp.23.1.56
  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. https://doi.org/10.1002/hbm.460010306
  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. https://doi.org/10.1177/1073858405276428
  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. https://doi.org/10.1073/pnas.112660399
  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. https://doi.org/10.1016/S0006-3223(98)00348-5
  48. 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. https://doi.org/10.1016/j.neuroimage.2006.01.035
  49. 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.
  50. 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. https://doi.org/10.1007/s12311-010-0228-z
  51. Grillon C. Associative learning deficits increase symptoms of anxiety in humans. Biol Psychiatry 2002;51:851-858. https://doi.org/10.1016/S0006-3223(01)01370-1
  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. https://doi.org/10.1176/ajp.2007.164.2.283
  53. Chen SH, Desmond JE. Cerebrocerebellar networks during articulatory rehearsal and verbal working memory tasks. Neuroimage 2005;24:332-338. https://doi.org/10.1016/j.neuroimage.2004.08.032
  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. https://doi.org/10.1016/j.neuroimage.2004.08.036
  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. https://doi.org/10.1073/pnas.0334049100
  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. https://doi.org/10.1093/brain/awh685
  57. 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. https://doi.org/10.1136/thx.2009.126730
  58. 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. https://doi.org/10.1016/j.pnpbp.2009.10.004
  59. 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. https://doi.org/10.1111/j.1460-9568.2005.04394.x
  60. Bostan AC, Dum RP, Strick PL. Cerebellar networks with the cerebral cortex and basal ganglia. Trends Cogn Sci 2013;17:241-254. https://doi.org/10.1016/j.tics.2013.03.003