Korean Journal of Biological Psychiatry (생물정신의학)

The Korean Society of Biological Psychiatry (대한생물정신의학회)
권호 표지

Morphologic Alterations in Amygdala Subregions of Adult Patients with Bipolar Disorder

  • Lee, Hyun-Jae (Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine) ;
  • Han, Kyu-Man (Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine) ;
  • Kim, Aram (Department of Biomedical Sciences, Korea University College of Medicine) ;
  • Kang, Wooyoung (Department of Biomedical Sciences, Korea University College of Medicine) ;
  • Kang, Youbin (Department of Biomedical Sciences, Korea University College of Medicine) ;
  • Kang, June (Department of Brain and Cognitive Engineering, Korea University) ;
  • Won, Eunsoo (Department of Psychiatry, CHA Bundang Medical Center, CHA University) ;
  • Tae, Woo-Suk (Brain Convergence Research Center, Korea University Anam Hospital) ;
  • Ham, Byung-Joo (Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine)
  • Received : 2019.04.01
  • Accepted : 2019.04.10
  • Published : 2019.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives Previous studies have revealed inconsistent results on amygdala volume in adult bipolar disorder (BD) patients compared to healthy controls (HC). Since the amygdala encompasses multiple subregions, the subtle volume changes in each amygdala nucleus might have not been fully reflected in the measure of the total amygdala volume, causing discrepant results. Thus, we aimed to investigate volume changes in each amygdala subregion and their association with subtypes of BD, lithium use and clinical status of BD. Methods Fifty-five BD patients and 55 HC underwent T1-weighted structural magnetic resonance imaging. We analyzed volumes of the whole amygdala and each amygdala subregion, including the anterior amygdaloid area, cortico-amygdaloid transition area, basal, lateral, accessory basal, central, cortical, medial and paralaminar nuclei using the atlas in the FreeSurfer. The volume difference was analyzed using a one-way analysis of covariance with individual volumes as dependent variables, and age, sex, and total intracranial volume as covariates. Results The volumes of whole right amygdala and subregions including basal nucleus, accessory basal nucleus, anterior amygdaloid area, and cortico-amygdaloid transition area in the right amygdala of BD patients were significantly smaller for the HC group. No significant volume difference between bipolar I disorder and bipolar II disorder was found after the Bonferroni correction. The trend of larger volume in medial nucleus with lithium treatment was not significant after the Bonferroni correction. No significant correlation between illness duration and amygdala volume, and insignificant negative correlation were found between right central nucleus volume and depression severity. Conclusions Significant volume decrements of the whole amygdala, basal nucleus, accessory basal nucleus, anterior amygdaloid area, and cortico-amygdaloid transition area were found in the right hemisphere in adult BD patients, compared to HC group. We postulate that such volume changes are associated with altered functional activity and connectivity of amygdala nuclei in BD.

Keywords

References

  1. Merikangas KR, Akiskal HS, Angst J, Greenberg PE, Hirschfeld RM, Petukhova M, et al. Lifetime and 12-month prevalence of bipolar spectrum disorder in the National Comorbidity Survey replication. Arch Gen Psychiatry 2007;64:543-552. https://doi.org/10.1001/archpsyc.64.5.543
  2. Kupfer DJ. The increasing medical burden in bipolar disorder. JAMA 2005;293:2528-2530. https://doi.org/10.1001/jama.293.20.2528
  3. Osby U, Brandt L, Correia N, Ekbom A, SparEn P. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry 2001;58:844-850. https://doi.org/10.1001/archpsyc.58.9.844
  4. Phillips ML, Swartz HA. A critical appraisal of neuroimaging studies of bipolar disorder: toward a new conceptualization of underlying neural circuitry and a road map for future research. Am J Psychiatry 2014;171:829-843. https://doi.org/10.1176/appi.ajp.2014.13081008
  5. Phillips ML, Ladouceur CD, Drevets WC. A neural model of voluntary and automatic emotion regulation: implications for understanding the pathophysiology and neurodevelopment of bipolar disorder. Mol Psychiatry 2008;13:829, 833-857.
  6. Strakowski SM, Adler CM, Almeida J, Altshuler LL, Blumberg HP, Chang KD, et al. The functional neuroanatomy of bipolar disorder: a consensus model. Bipolar Disord 2012;14:313-325. https://doi.org/10.1111/j.1399-5618.2012.01022.x
  7. Stanfield AC, Moorhead TW, Job DE, McKirdy J, Sussmann JE, Hall J, et al. Structural abnormalities of ventrolateral and orbitofrontal cortex in patients with familial bipolar disorder. Bipolar Disord 2009;11:135-144. https://doi.org/10.1111/j.1399-5618.2009.00666.x
  8. Matsuo K, Kopecek M, Nicoletti MA, Hatch JP, Watanabe Y, Nery FG, et al. New structural brain imaging endophenotype in bipolar disorder. Mol Psychiatry 2012;17:412-420. https://doi.org/10.1038/mp.2011.3
  9. van der Schot AC, Vonk R, Brouwer RM, van Baal GC, Brans RG, van Haren NE, et al. Genetic and environmental influences on focal brain density in bipolar disorder. Brain 2010;133:3080-3092. https://doi.org/10.1093/brain/awq236
  10. van der Schot AC, Vonk R, Brans RG, van Haren NE, Koolschijn PC, Nuboer V, et al. Influence of genes and environment on brain volumes in twin pairs concordant and discordant for bipolar disorder. Arch Gen Psychiatry 2009;66:142-151. https://doi.org/10.1001/archgenpsychiatry.2008.541
  11. Selvaraj S, Arnone D, Job D, Stanfield A, Farrow TF, Nugent AC, et al. Grey matter differences in bipolar disorder: a meta-analysis of voxel-based morphometry studies. Bipolar Disord 2012;14:135-145. https://doi.org/10.1111/j.1399-5618.2012.01000.x
  12. Tost H, Ruf M, Schmal C, Schulze TG, Knorr C, Vollmert C, et al. Prefrontal-temporal gray matter deficits in bipolar disorder patients with persecutory delusions. J Affect Disord 2010;120:54-61. https://doi.org/10.1016/j.jad.2009.04.009
  13. Almeida JR, Akkal D, Hassel S, Travis MJ, Banihashemi L, Kerr N, et al. Reduced gray matter volume in ventral prefrontal cortex but not amygdala in bipolar disorder: significant effects of gender and trait anxiety. Psychiatry Res 2009;171:54-68. https://doi.org/10.1016/j.pscychresns.2008.02.001
  14. Haller S, Xekardaki A, Delaloye C, Canuto A, Lovblad KO, Gold G, et al. Combined analysis of grey matter voxel-based morphometry and white matter tract-based spatial statistics in late-life bipolar disorder. J Psychiatry Neurosci 2011;36:391-401. https://doi.org/10.1503/jpn.100140
  15. Ivleva EI, Bidesi AS, Keshavan MS, Pearlson GD, Meda SA, Dodig D, et al. Gray matter volume as an intermediate phenotype for psychosis: Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). Am J Psychiatry 2013;170:1285-1296. https://doi.org/10.1176/appi.ajp.2013.13010126
  16. Wijeratne C, Sachdev S, Wen W, Piguet O, Lipnicki DM, Malhi GS, et al. Hippocampal and amygdala volumes in an older bipolar disorder sample. Int Psychogeriatr 2013;25:54-60. https://doi.org/10.1017/S1041610212001469
  17. Muller VI, Habel U, Derntl B, Schneider F, Zilles K, Turetsky BI, et al. Incongruence effects in crossmodal emotional integration. Neuroimage 2011;54:2257-2266. https://doi.org/10.1016/j.neuroimage.2010.10.047
  18. Phelps EA, LeDoux JE. Contributions of the amygdala to emotion processing: from animal models to human behavior. Neuron 2005;48:175-187. https://doi.org/10.1016/j.neuron.2005.09.025
  19. Goodwin FK, Jamison KR. Manic-Depressive Illness: Bipolar Disorders and Recurrent Depression. 2nd ed. New York, NY: Oxford University Press;2007.
  20. Swanson LW. The amygdala and its place in the cerebral hemisphere. Ann N Y Acad Sci 2003;985:174-184. https://doi.org/10.1111/j.1749-6632.2003.tb07081.x
  21. Altshuler L, Bookheimer S, Proenza MA, Townsend J, Sabb F, Firestine A, et al. Increased amygdala activation during mania: a functional magnetic resonance imaging study. Am J Psychiatry 2005;162:1211-1213. https://doi.org/10.1176/appi.ajp.162.6.1211
  22. Lawrence NS, Williams AM, Surguladze S, Giampietro V, Brammer MJ, Andrew C, et al. Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression. Biol Psychiatry 2004;55:578-587. https://doi.org/10.1016/j.biopsych.2003.11.017
  23. Blumberg HP, Kaufman J, Martin A, Whiteman R, Zhang JH, Gore JC, et al. Amygdala and hippocampal volumes in adolescents and adults with bipolar disorder. Arch Gen Psychiatry 2003;60:1201-1208. https://doi.org/10.1001/archpsyc.60.12.1201
  24. Chang K, Karchemskiy A, Barnea-Goraly N, Garrett A, Simeonova DI, Reiss A. Reduced amygdalar gray matter volume in familial pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry 2005;44:565-573. https://doi.org/10.1097/01.chi.0000159948.75136.0d
  25. DelBello MP, Zimmerman ME, Mills NP, Getz GE, Strakowski SM. Magnetic resonance imaging analysis of amygdala and other subcortical brain regions in adolescents with bipolar disorder. Bipolar Disord 2004;6:43-52. https://doi.org/10.1046/j.1399-5618.2003.00087.x
  26. Kalmar JH, Wang F, Chepenik LG, Womer FY, Jones MM, Pittman B, et al. Relation between amygdala structure and function in adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2009;48:636-642. https://doi.org/10.1097/CHI.0b013e31819f6fbc
  27. Pearlson GD, Barta PE, Powers RE, Menon RR, Richards SS, Aylward EH, et al. Ziskind-Somerfeld Research Award 1996. Medial and superior temporal gyral volumes and cerebral asymmetry in schizophrenia versus bipolar disorder. Biol Psychiatry 1997;41:1-14. https://doi.org/10.1016/S0006-3223(96)00373-3
  28. Chen BK, Sassi R, Axelson D, Hatch JP, Sanches M, Nicoletti M, et al. Cross-sectional study of abnormal amygdala development in adolescents and young adults with bipolar disorder. Biol Psychiatry 2004;56:399-405. https://doi.org/10.1016/j.biopsych.2004.06.024
  29. Altshuler LL, Bartzokis G, Grieder T, Curran J, Jimenez T, Leight K, et al. An MRI study of temporal lobe structures in men with bipolar disorder or schizophrenia. Biol Psychiatry 2000;48:147-162. https://doi.org/10.1016/S0006-3223(00)00836-2
  30. Strakowski SM, DelBello MP, Sax KW, Zimmerman ME, Shear PK, Hawkins JM, et al. Brain magnetic resonance imaging of structural abnormalities in bipolar disorder. Arch Gen Psychiatry 1999;56:254-260. https://doi.org/10.1001/archpsyc.56.3.254
  31. Brambilla P, Harenski K, Nicoletti M, Sassi RB, Mallinger AG, Frank E, et al. MRI investigation of temporal lobe structures in bipolar patients. J Psychiatr Res 2003;37:287-295. https://doi.org/10.1016/S0022-3956(03)00024-4
  32. Holland PC, Gallagher M. Amygdala circuitry in attentional and representational processes. Trends Cogn Sci 1999;3:65-73. https://doi.org/10.1016/S1364-6613(98)01271-6
  33. Cardinal RN, Parkinson JA, Hall J, Everitt BJ. Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex. Neurosci Biobehav Rev 2002;26:321-352. https://doi.org/10.1016/S0149-7634(02)00007-6
  34. LeDoux JE. Emotion circuits in the brain. Annu Rev Neurosci 2000;23:155-184. https://doi.org/10.1146/annurev.neuro.23.1.155
  35. Halgren E. Emotional neurophysiology of the amygdala within the context of human cognition. In: Aggleton JP, editor. The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. 1st ed. New York, NY: Wiley-Liss;1992. p.191-228.
  36. Gloor P. Role of the human limbic system in perception, memory and affect: lessons from temporal lobe epilepsy. In: Doane BK, Livingston KE, editors. The Limbic System: Functional Organization and Clinical Disorders. New York, NY: Raven Press;1986. p.159-169.
  37. Amaral DG, Price JL, Pitkanen A, Carmichael ST. Anatomical organization of the primate amygdaloid complex. In: Aggleton JP, editor. The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. 1st ed. New York, NY: Wiley-Liss;1992. p.1-66.
  38. LeDoux J. The amygdala. Curr Biol 2007;17:R868-R874. https://doi.org/10.1016/j.cub.2007.08.005
  39. Saygin ZM, Kliemann D, Iglesias JE, van der Kouwe AJW, Boyd E, Reuter M, et al.; Alzheimer's Disease Neuroimaging Initiative. Highresolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas. Neuroimage 2017;155:370-382. https://doi.org/10.1016/j.neuroimage.2017.04.046
  40. Avino TA, Barger N, Vargas MV, Carlson EL, Amaral DG, Bauman MD, et al. Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism. Proc Natl Acad Sci U S A 2018;115:3710-3715. https://doi.org/10.1073/pnas.1801912115
  41. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62. https://doi.org/10.1136/jnnp.23.1.56
  42. Sled JG, Zijdenbos AP, Evans AC. A nonparametric method for automatic correction of intensity nonuniformity in MRI data. IEEE Trans Med Imaging 1998;17:87-97. https://doi.org/10.1109/42.668698
  43. Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, et al. Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 2002;33:341-355. https://doi.org/10.1016/S0896-6273(02)00569-X
  44. Fischl B, van der Kouwe A, Destrieux C, Halgren E, SEgonne F, Salat DH, et al. Automatically parcellating the human cerebral cortex. Cereb Cortex 2004;14:11-22. https://doi.org/10.1093/cercor/bhg087
  45. Tae WS, Kim SS, Lee KU, Nam EC, Kim KW. Validation of hippocampal volumes measured using a manual method and two automated methods (FreeSurfer and IBASPM) in chronic major depressive disorder. Neuroradiology 2008;50:569-581. https://doi.org/10.1007/s00234-008-0383-9
  46. Kelley R, Chang KD, Garrett A, Alegria D, Thompson P, Howe M, et al. Deformations of amygdala morphology in familial pediatric bipolar disorder. Bipolar Disord 2013;15:795-802. https://doi.org/10.1111/bdi.12114
  47. Mahon PB, Lee DS, Trinh H, Tward D, Miller MI, Younes L, et al. Morphometry of the amygdala in schizophrenia and psychotic bipolar disorder. Schizophr Res 2015;164:199-202. https://doi.org/10.1016/j.schres.2015.02.011
  48. Berretta S, Pantazopoulos H, Lange N. Neuron numbers and volume of the amygdala in subjects diagnosed with bipolar disorder or schizophrenia. Biol Psychiatry 2007;62:884-893. https://doi.org/10.1016/j.biopsych.2007.04.023
  49. Sah P, Faber ES, Lopez De Armentia M, Power J. The amygdaloid complex: anatomy and physiology. Physiol Rev 2003;83:803-834. https://doi.org/10.1152/physrev.00002.2003
  50. Bzdok D, Laird AR, Zilles K, Fox PT, Eickhoff SB. An investigation of the structural, connectional, and functional subspecialization in the human amygdala. Hum Brain Mapp 2013;34:3247-3266. https://doi.org/10.1002/hbm.22138
  51. Singh MK, Kelley RG, Chang KD, Gotlib IH. Intrinsic amygdala functional connectivity in youth with bipolar I disorder. J Am Acad Child Adolesc Psychiatry 2015;54:763-770. https://doi.org/10.1016/j.jaac.2015.06.016
  52. Davis M, Whalen PJ. The amygdala: vigilance and emotion. Mol Psychiatry 2001;6:13-34. https://doi.org/10.1038/sj.mp.4000812
  53. Boucsein K, Weniger G, Mursch K, Steinhoff BJ, Irle E. Amygdala lesion in temporal lobe epilepsy subjects impairs associative learning of emotional facial expressions. Neuropsychologia 2001;39:231-236. https://doi.org/10.1016/S0028-3932(00)00117-2
  54. Gallagher M, Chiba AA. The amygdala and emotion. Curr Opin Neurobiol 1996;6:221-227. https://doi.org/10.1016/S0959-4388(96)80076-6
  55. LeDoux J. The emotional brain, fear, and the amygdala. Cell Mol Neurobiol 2003;23:727-738. https://doi.org/10.1023/A:1025048802629
  56. Gur RC, Schroeder L, Turner T, McGrath C, Chan RM, Turetsky BI, et al. Brain activation during facial emotion processing. Neuroimage 2002;16:651-662. https://doi.org/10.1006/nimg.2002.1097
  57. Pitkanen A, Stefanacci L, Farb CR, Go GG, LeDoux JE, Amaral DG. Intrinsic connections of the rat amygdaloid complex: projections originating in the lateral nucleus. J Comp Neurol 1995;356:288-310. https://doi.org/10.1002/cne.903560211
  58. Smith Y, ParE D. Intra-amygdaloid projections of the lateral nucleus in the cat: PHA-L anterograde labeling combined with postembedding GABA and glutamate immunocytochemistry. J Comp Neurol 1994;342:232-248. https://doi.org/10.1002/cne.903420207
  59. Amaral DG, Behniea H, Kelly JL. Topographic organization of projections from the amygdala to the visual cortex in the macaque monkey. Neuroscience 2003;118:1099-1120. https://doi.org/10.1016/S0306-4522(02)01001-1
  60. Pitkanen A, Kelly JL, Amaral DG. Projections from the lateral, basal, and accessory basal nuclei of the amygdala to the entorhinal cortex in the macaque monkey. Hippocampus 2002;12:186-205. https://doi.org/10.1002/hipo.1099
  61. Fudge JL, Kunishio K, Walsh P, Richard C, Haber SN. Amygdaloid projections to ventromedial striatal subterritories in the primate. Neuroscience 2002;110:257-275. https://doi.org/10.1016/S0306-4522(01)00546-2
  62. Pitkanen A, Amaral DG. Organization of the intrinsic connections of the monkey amygdaloid complex: projections originating in the lateral nucleus. J Comp Neurol 1998;398:431-458. https://doi.org/10.1002/(SICI)1096-9861(19980831)398:3<431::AID-CNE9>3.0.CO;2-0
  63. Pikkarainen M, Pitkanen A. Projections from the lateral, basal and accessory basal nuclei of the amygdala to the perirhinal and postrhinal cortices in rat. Cereb Cortex 2001;11:1064-1082. https://doi.org/10.1093/cercor/11.11.1064
  64. Moreno N, Gonzalez A. Evolution of the amygdaloid complex in vertebrates, with special reference to the anamnio-amniotic transition. J Anat 2007;211:151-163. https://doi.org/10.1111/j.1469-7580.2007.00780.x
  65. Carr L, Iacoboni M, Dubeau MC, Mazziotta JC, Lenzi GL. Neural mechanisms of empathy in humans: a relay from neural systems for imitation to limbic areas. Proc Natl Acad Sci U S A 2003;100:5497-5502. https://doi.org/10.1073/pnas.0935845100
  66. Wicker B, Keysers C, Plailly J, Royet JP, Gallese V, Rizzolatti G. Both of us disgusted in My insula: the common neural basis of seeing and feeling disgust. Neuron 2003;40:655-664. https://doi.org/10.1016/S0896-6273(03)00679-2
  67. Roy AK, Shehzad Z, Margulies DS, Kelly AM, Uddin LQ, Gotimer K, et al. Functional connectivity of the human amygdala using resting state fMRI. Neuroimage 2009;45:614-626. https://doi.org/10.1016/j.neuroimage.2008.11.030
  68. Kilts CD, Egan G, Gideon DA, Ely TD, Hoffman JM. Dissociable neural pathways are involved in the recognition of emotion in static and dynamic facial expressions. Neuroimage 2003;18:156-168. https://doi.org/10.1006/nimg.2002.1323
  69. Lanteaume L, Khalfa S, REgis J, Marquis P, Chauvel P, Bartolomei F. Emotion induction after direct intracerebral stimulations of human amygdala. Cereb Cortex 2007;17:1307-1313. https://doi.org/10.1093/cercor/bhl041
  70. Caseras X, Lawrence NS, Murphy K, Wise RG, Phillips ML. Ventral striatum activity in response to reward: differences between bipolar I and II disorders. Am J Psychiatry 2013;170:533-541. https://doi.org/10.1176/appi.ajp.2012.12020169
  71. Caseras X, Murphy K, Lawrence NS, Fuentes-Claramonte P, Watts J, Jones DK, et al. Emotion regulation deficits in euthymic bipolar I versus bipolar II disorder: a functional and diffusion-tensor imaging study. Bipolar Disord 2015;17:461-470. https://doi.org/10.1111/bdi.12292
  72. Hozer F, Houenou J. Can neuroimaging disentangle bipolar disorder? J Affect Disord 2016;195:199-214. https://doi.org/10.1016/j.jad.2016.01.039
  73. Foland-Ross LC, Brooks JO 3rd, Mintz J, Bartzokis G, Townsend J, Thompson PM, et al. Mood-state effects on amygdala volume in bipolar disorder. J Affect Disord 2012;139:298-301. https://doi.org/10.1016/j.jad.2012.03.003
  74. Foland LC, Altshuler LL, Sugar CA, Lee AD, Leow AD, Townsend J, et al. Increased volume of the amygdala and hippocampus in bipolar patients treated with lithium. Neuroreport 2008;19:221-224. https://doi.org/10.1097/WNR.0b013e3282f48108
  75. Johnson SA, Wang JF, Sun X, McEwen BS, Chattarji S, Young LT. Lithium treatment prevents stress-induced dendritic remodeling in the rodent amygdala. Neuroscience 2009;163:34-39. https://doi.org/10.1016/j.neuroscience.2009.06.005