Advertisement

Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive–compulsive disorder

  • Katia Cristina de Oliveira
  • Lea Tenenholz Grinberg
  • Marcelo Queiroz Hoexter
  • Helena Brentani
  • Claudia Kimie Suemoto
  • Fabiano Gonçalves Nery
  • Luzia Carreira Lima
  • Ana Tereza Di Lorenzo Alho
  • José Marcelo Farfel
  • Renata Eloah de Lucena Ferretti-Rebustini
  • Renata Elaine Paraizo Leite
  • Ariane Cristine Moretto
  • Alexandre Valotta da Silva
  • Beny Lafer
  • Eurípedes Constantino Miguel
  • Ricardo Nitrini
  • Wilson Jacob-Filho
  • Helmut Heinsen
  • Carlos Augusto Pasqualucci
Original Article
  • 92 Downloads

Abstract

Neurobiological models have provided consistent evidence of the involvement of cortical–subcortical circuitry in obsessive–compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.

Keywords

Human brain Cerebral cortex Cell count Biomedical research Obsessive–compulsive disorder Obsessive–compulsive symptoms 

Notes

Acknowledgements

This work was supported by Grants no. 2009/51482-0 and 2011/21357-9 provided by the São Paulo Research Foundation (FAPESP) and the National Council of Technological and Scientific Development (CNPq), no. 476647/2010. Kátia Cristina de Oliveira was supported by the Coordination for the Improvement of Higher Education Personnel (CAPES). We are grateful to the families that donated the brains for this study. We would like thank all the members of the Brain Bank of Brazilian Aging Study Group. We would also thank Eduardo Alho MD, PhD for his assistance when using the 3D reconstruction software, the support of the staff from the Department of Psychiatry, Psychosomatics and Psychotherapy of the Mental Health Center of the University Hospital Würzburg, and the following psychiatrists, who contributed to the OCS diagnosis: E. Serap Monkul, MD, Ricardo Toniolo, MD, Alexandre Gigante, MD, PhD, Ana Gabriela Hounie, MD, Ph.D., Roseli Gedanke Shavitt, MD, Ph.D., Antonio Carlos Lopes, MD, Ph.D., Juliana B Diniz, MD, Ph.D.

Compliance with ethical standards

Conflict of interest

The authors report no biomedical financial interests or potential conflicts of interest.

Supplementary material

429_2018_1752_MOESM1_ESM.docx (13 kb)
Supplementary material 1 (DOCX 13 KB)
429_2018_1752_MOESM2_ESM.doc (34 kb)
Supplementary material 2 (DOC 34 KB)

References

  1. Alegro MAE, Loring B, Heinsen H, Alho E, Zöllei L, Ushizima D, Grinberg LT(2016). Multimodal whole brain registration: MRI and high resolution histology. In: 2016 IEEE conference on computer vision and pattern recognition workshops (CVPRW), pp 634–642Google Scholar
  2. Alho EJL, Alho ATDL, Grinberg L, Amaro E, Dos Santos GAB, da Silva RE, Neves RC, Alegro M, Coelho DB, Teixeira MJ, Fonoff ET, Heinsen H (2018) High thickness histological sections as alternative to study the three-dimensional microscopic human sub-cortical neuroanatomy. Brain Struct Funct 223(3):1121–1132PubMedGoogle Scholar
  3. Beasley CL, Chana G, Honavar M, Landau S, Everall IP, Cotter D (2005) Evidence for altered neuronal organisation within the planum temporale in major psychiatric disorders. Schizophr Res 73(1):69–78CrossRefGoogle Scholar
  4. Beck EA (1949) A cytoarchitectural investigation into the boundaries of cortical areas 13 and 14 in the human brain. J Anat 83(2):147–157PubMedPubMedCentralGoogle Scholar
  5. Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82(4):239–259CrossRefGoogle Scholar
  6. Brodmann K (1909) Vergleichende Lokalisationslehre der Großhirnrinde. Barth, LeipzigGoogle Scholar
  7. Chamberlain SR, Menzies L, Hampshire A, Suckling J, Fineberg NA, del Campo N, Aitken M, Craig K, Owen AM, Bullmore ET, Robbins TW, Sahakian BJ (2008) Orbitofrontal dysfunction in patients with obsessive–compulsive disorder and their unaffected relatives. Science 321(5887):421–422CrossRefGoogle Scholar
  8. Chiavaras MM, Petrides M (2000) Orbitofrontal sulci of the human and macaque monkey brain. J Comp Neurol 422(1):35–54CrossRefGoogle Scholar
  9. Christian CJ, Lencz T, Robinson DG, Burdick KE, Ashtari M, Malhotra AK, Betensky JD, Szeszko PR (2008) Gray matter structural alterations in obsessive–compulsive disorder: relationship to neuropsychological functions. Psychiatry Res 164(2):123–131CrossRefGoogle Scholar
  10. Cotter D, Hudson L, Landau S (2005) Evidence for orbitofrontal pathology in bipolar disorder and major depression, but not in schizophrenia. Bipolar Disord 7(4):358–369CrossRefGoogle Scholar
  11. de Oliveira KC, Nery FG, Ferreti REL, Lima MC, Cappi C, Machado-Lima A, Polichiso L, Carreira LL, Avila C, Alho ATDL, Brentani HP, Miguel EC, Heinsen H, Jacob-Filho W, Pasqualucci CA, Lafer B, Grinberg LT (2012) Brazilian psychiatric brain bank: a new contribution tool to network studies. Cell Tissue Bank 13(2):315–326CrossRefGoogle Scholar
  12. de Wit SJ, Alonso P, Schweren L, Mataix-Cols D, Lochner C, Menchón JM, Stein DJ, Fouche JP, Soriano-Mas C, Sato JR, Hoexter MQ, Denys D, Nakamae T, Nishida S, Kwon JS, Jang JH, Busatto GF, Cardoner N, Cath DC, Fukui K, Jung WH, Kim SN, Miguel EC, Narumoto J, Phillips ML, Pujol J, Remijnse PL, Sakai Y, Shin NY, Yamada K, Veltman DJ, van den Heuvel AO (2014) Multicenter voxel-based morphometry mega-analysis of structural brain scans in obsessive–compulsive disorder. Am J Psychiatry 171(3):340–349CrossRefGoogle Scholar
  13. Del-Ben CM, Rodrigues CR, Zuardi AW (1996) Reliability of the Portuguese version of the structured clinical interview for DSM-III-R (SCID) in a Brazilian sample of psychiatric outpatients. Braz J Med Biol Res 29(12):1675–1682PubMedGoogle Scholar
  14. DuPont RL, Rice DP, Shiraki S, Rowland CR (1995) Economic costs of obsessive–compulsive disorder. Med Interface 8(4):102–109PubMedGoogle Scholar
  15. Eberstaller O (1890) Das Stirnhirn. Ein Beitrag zur Anatomie der Oberfläche des Grosshirns. Urban und Schwarzenberg, LeipzigGoogle Scholar
  16. Economo CV, Koskinas GN (1925) Die Cytoarchitekonik der Hirnrinde des erwachsenen Menschen. Julius Springer, BerlinGoogle Scholar
  17. Einarson L (1932) A Method for Progressive Selective Staining of Nissl and Nuclear Substance in Nerve Cells. Am J Pathol 8(3):295–308 295PubMedPubMedCentralGoogle Scholar
  18. Ferretti REL, Damin AE, Brucki SMD, Morillo LS, Perroco TR, Campora F, Moreira EG, Balbino ES, Lima MCAL, Battela C, Ruiz M, Grinberg LT, Farfel JM, Leite REPSCK, Pasqualucci CARSPHJ-FWNR (2010) Post-mortem diagnosis of dementia by informant interwiew. Dement Neuropsychol 4(2):138–144CrossRefGoogle Scholar
  19. First M, Spitzer R, Gibbon M, Williams J (2002) Structured Clinical Interview for DSM-IV-TR Axis I Disorders, Research Version, Patient Edition (SCID-I/P). Psychiatric Institute, New YorkGoogle Scholar
  20. Gillan CM, Apergis-Schoute AM, Morein-Zamir S, Urcelay GP, Sule A, Fineberg NA, Sahakian BJ, Robbins TW (2015) Functional neuroimaging of avoidance habits in obsessive–compulsive disorder. Am J Psychiatry 172(3):284–293CrossRefGoogle Scholar
  21. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, Heninger GR, Charney DS (1989) The Yale–Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry 46(11):1006–1011CrossRefGoogle Scholar
  22. Grinberg LT, Amaro E, Teipel S, dos Santos DD, Pasqualucci CA, Leite REP, Camargo CR, Goncalves JA, Sanches AG, Santana M, Ferretti REL, Jacob-Filho W, Nitrini R, Heinsen H, Brazilian Aging Brain Study G (2008) Assessment of factors that confound MRI and neuropathological correlation of human postmortem brain tissue. Cell Tissue Bank 9(3):195–203CrossRefGoogle Scholar
  23. Haber SN, Kunishio K, Mizobuchi M, Lynd-Balta E (1995) The orbital and medial prefrontal circuit through the primate basal ganglia. J Neurosci 15(7 Pt 1):4851–4867CrossRefGoogle Scholar
  24. Harrison BJ, Pujol J, Soriano-Mas C, Hernandez-Ribas R, Lopez-Sola M, Ortiz H, Alonso P, Deus J, Menchon JM, Real E, Segalas C, Contreras-Rodriguez O, Blanco-Hinojo L, Cardoner N (2012) Neural correlates of moral sensitivity in obsessive–compulsive disorder. Arch Gen Psychiatry 69(7):741–749CrossRefGoogle Scholar
  25. Heinsen H, Strik M, Bauer M, Luther K, Ulmar G, Gangnus D, Jungkunz G, Eisenmenger W, Gotz M (1994) Cortical and striatal neurone number in Huntington’s disease. Acta Neuropathol 88(4):320–333CrossRefGoogle Scholar
  26. Heinsen H, Rub U, Bauer M, Ulmar G, Bethke B, Schuler M, Bocker F, Eisenmenger W, Gotz M, Korr H, Schmitz C (1999) Nerve cell loss in the thalamic mediodorsal nucleus in Huntington’s disease. Acta Neuropathol 97(6):613–622CrossRefGoogle Scholar
  27. Henssen A, Zilles K, Palomero-Gallagher N, Schleicher A, Mohlberg H, Gerboga F, Eickhoff SB, Bludau S, Amunts K (2016) Cytoarchitecture and probability maps of the human medial orbitofrontal cortex. Cortex 75:87–112CrossRefGoogle Scholar
  28. Hoexter MQ, de Souza Duran FL, D’Alcante CC, Dougherty DD, Shavitt RG, Lopes AC, Diniz JB, Deckersbach T, Batistuzzo MC, Bressan RA, Miguel EC, Busatto GF (2012) Gray matter volumes in obsessive–compulsive disorder before and after fluoxetine or cognitive-behavior therapy: a randomized clinical trial. Neuropsychopharmacology 37(3):734–745CrossRefGoogle Scholar
  29. Hoexter MQ, Diniz JB, Lopes AC, Batistuzzo MC, Shavitt RG, Dougherty DD, Duran FL, Bressan RA, Busatto GF, Miguel EC, Sato JR (2015) Orbitofrontal thickness as a measure for treatment response prediction in obsessive–compulsive disorder. Depression Anxiety 32(12):900–908CrossRefGoogle Scholar
  30. Hof PR, Mufson EJ, Morrison JH (1995) Human orbitofrontal cortex: cytoarchitecture and quantitative immunohistochemical parcellation. J Comp Neurol 359(1):48–68CrossRefGoogle Scholar
  31. Kim JJ, Lee MC, Kim J, Kim IY, Kim SI, Han MH, Chang KH, Kwon JS (2001) Grey matter abnormalities in obsessive–compulsive disorder: statistical parametric mapping of segmented magnetic resonance images. Br J Psychiatry 179:330–334CrossRefGoogle Scholar
  32. Kretschmann HJ, Tafesse U, Herrmann A (1982) Different volume changes of cerebral cortex and white matter during histological preparation. Microsc Acta 86(1):13–24PubMedGoogle Scholar
  33. Law AJ, Harrison PJ (2003) The distribution and morphology of prefrontal cortex pyramidal neurons identified using anti-neurofilament antibodies SMI32, N200 and FNP7. Normative data and a comparison in subjects with schizophrenia, bipolar disorder or major depression. J Psychiatr Res 37(6):487–499CrossRefGoogle Scholar
  34. Liu J, Heinsen H, Grinberg LT, Alho E, Amaro E, Pasqualucci CA, Rüb U, Seidel K, den Dunnen W, Arzberger T, Schmitz C, Kiessling MC, Bader B, Danek A (2018) Pathoarchitectonics of the cerebral cortex in chorea-acanthocytosis and HD. Neuropathol Appl Neurobiol.  https://doi.org/10.1111/nan.12495 CrossRefPubMedGoogle Scholar
  35. Mackey S, Petrides M (2010) Quantitative demonstration of comparable architectonic areas within the ventromedial and lateral orbital frontal cortex in the human and the macaque monkey brains. Eur J Neurosci 32(11):1940–1950CrossRefGoogle Scholar
  36. Maltby N, Tolin DF, Worhunsky P, O’Keefe TM, Kiehl KA (2005) Dysfunctional action monitoring hyperactivates frontal–striatal circuits in obsessive–compulsive disorder: an event-related fMRI study. Neuroimage 24(2):495–503CrossRefGoogle Scholar
  37. Mattheisen M, Samuels JF, Wang Y, Greenberg BD, Fyer AJ, McCracken JT, Geller DA, Murphy DL, Knowles JA, Grados MA, Riddle MA, Rasmussen SA, McLaughlin NC, Nurmi EL, Askland KD, Qin HD, Cullen BA, Piacentini J, Pauls DL, Bienvenu OJ, Stewart SE, Liang KY, Goes FS, Maher B, Pulver AE, Shugart YY, Valle D, Lange C, Nestadt G (2015) Genome-wide association study in obsessive–compulsive disorder: results from the OCGAS. Mol Psychiatry 20(3):337–344CrossRefGoogle Scholar
  38. Meldrum BS (2000) Glutamate as a neurotransmitter in the brain: review of physiology and pathology. J Nutr 130(4S Suppl):1007s–1015sCrossRefGoogle Scholar
  39. Milad MR, Rauch SL (2007) The role of the orbitofrontal cortex in anxiety disorders. Ann N Y Acad Sci 1121:546–561CrossRefGoogle Scholar
  40. Milad MR, Rauch SL (2012) Obsessive–compulsive disorder: beyond segregated cortico-striatal pathways. Trends Cogn Sci 16(1):43–51CrossRefGoogle Scholar
  41. Mirra SS, Heyman A, McKeel D, Sumi SM, Crain BJ, Brownlee LM, Vogel FS, Hughes JP, van Belle G, Berg L (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41(4):479–486CrossRefGoogle Scholar
  42. Murray CJL, Lopez AD (1996) Global burden of disease: a comprehensive assessment of mortality and morbidity from diseases, injuries and risk factors in 1990 and projected to 2020. World Health Organization. GenevaGoogle Scholar
  43. Nieuwenhuys R, Voogd J, van Huijzen C (2008) The human central nervous system. Springer, BerlinCrossRefGoogle Scholar
  44. Ongur D, Ferry AT, Price JL (2003) Architectonic subdivision of the human orbital and medial prefrontal cortex. J Comp Neurol 460(3):425–449CrossRefGoogle Scholar
  45. Oorschot DE (1994) Are you using neuronal densities, synaptic densities or neurochemical densities as your definitive data? There is a better way to go. Prog Neurobiol 44(3):233–247CrossRefGoogle Scholar
  46. Pakkenberg B (1990) Pronounced reduction of total neuron number in mediodorsal thalamic nucleus and nucleus accumbens in schizophrenics. Arch Gen Psychiatry 47(11):1023–1028CrossRefGoogle Scholar
  47. Pandya DN, Yeterian EH (1985) Architecture and connections of cortical association areas. In: Peters A, Jones EG (eds) Cerebral cortex. Plenum Press, New York, pp 3–61Google Scholar
  48. Pujol J, Soriano-Mas C, Alonso P, Cardoner N, Menchon JM, Deus J, Vallejo J (2004) Mapping structural brain alterations in obsessive–compulsive disorder. Arch Gen Psychiatry 61(7):720–730CrossRefGoogle Scholar
  49. Radua J, Mataix-Cols D (2009) Voxel-wise meta-analysis of grey matter changes in obsessive–compulsive disorder. Br J Psychiatry 195(5):393–402CrossRefGoogle Scholar
  50. Rajkowska G, Halaris A, Selemon LD (2001) Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry 49(9):741–752CrossRefGoogle Scholar
  51. Rauch SL, Jenike MA, Alpert NM, Baer L, Breiter HC, Savage CR, Fischman AJ (1994a) Regional cerebral blood flow measured during symptom provocation in obsessive–compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch Gen Psychiatry 51(1):62–70CrossRefGoogle Scholar
  52. Rauch SL, Jenike MA, Alpert NM, Baer L, Breiter HC, Savage CR, Fischman AJ (1994b) Regional cerebral blood flow measured during symptom provocation in obsessive–compulsive disorder using oxygen 15-labeled carbon dioxide and positron emission tomography. Arch GenPsychiatry 51(1):62–70CrossRefGoogle Scholar
  53. Rosario-Campos MC, Miguel EC, Quatrano S, Chacon P, Ferrao Y, Findley D, Katsovich L, Scahill L, King RA, Woody SR, Tolin D, Hollander E, Kano Y, Leckman JF (2006) The Dimensional Yale–Brown Obsessive–Compulsive Scale (DY-BOCS): an instrument for assessing obsessive–compulsive symptom dimensions. Mol Psychiatry 11(5):495–504CrossRefGoogle Scholar
  54. Rotge JY, Langbour N, Guehl D, Bioulac B, Jaafari N, Allard M, Aouizerate B, Burbaud P (2010) Gray matter alterations in obsessive–compulsive disorder: an anatomic likelihood estimation meta-analysis. Neuropsychopharmacology 35(3):686–691CrossRefGoogle Scholar
  55. Sanides F (1962) Die Architektonik des menschlichen Stirnhirns-Zugleich eine Darstellung der Prinzipien seiner Gestaltung als Spiegel der stammesgeschichtlichen Differenzierung der Grosshirnrinde. In: Müller M, Spatz H, Vogel P (eds) Monographien aus dem Gesamtgebiete der Neurologie und Psychiatrie. Springer, Berlin, pp 1–201Google Scholar
  56. Saxena S, Rauch SL (2000) Functional neuroimaging and the neuroanatomy of obsessive–compulsive disorder. Psychiatr Clin N Am 23(3):563–586CrossRefGoogle Scholar
  57. Schmitz C (1997) Towards more readily comprehensible procedures in disector stereology. J Neurocytol 26(10):707–710CrossRefGoogle Scholar
  58. Schmitz C (1998) Variation of fractionator estimates and its prediction. Anat Embryol (Berl) 198(5):371–397CrossRefGoogle Scholar
  59. Schmitz C (2000) Towards the use of state-of-the-art stereology in experimental gerontology. Exp Gerontol 35(3):429–431CrossRefGoogle Scholar
  60. Schmitz C, Hof PR (2000) Recommendations for straightforward and rigorous methods of counting neurons based on a computer simulation approach. J Chem Neuroanat 20(1):93–114CrossRefGoogle Scholar
  61. Schmitz C, Hof PR (2005) Design-based stereology in neuroscience. Neuroscience 130(4):813–831CrossRefGoogle Scholar
  62. Schmitz C, Korr H, Heinsen H (1999a) Design-based counting techniques: the real problems. Trends Neurosci 22(8):345–346CrossRefGoogle Scholar
  63. Schmitz C, Rüb U, Korr H, Heinsen H (1999b) Nerve cell loss in the thalamic mediodorsal nucleus in Huntington’s disease. II. Optimization of a stereological estimation procedure. Acta Neuropathol 97(6):623–628CrossRefGoogle Scholar
  64. Spitzer RL, Williams JB, Gibbon M, First MB (1992) The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry 49(8):624–629CrossRefGoogle Scholar
  65. Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA, Arnold PD, Evans PD, Gamazon ER, Davis LK, Osiecki L, McGrath L, Haddad S, Crane J, Hezel D, Illman C, Mayerfeld C, Konkashbaev A, Liu C, Pluzhnikov A, Tikhomirov A, Edlund CK, Rauch SL, Moessner R, Falkai P, Maier W, Ruhrmann S, Grabe HJ, Lennertz L, Wagner M, Bellodi L, Cavallini MC, Richter MA, Cook EH Jr, Kennedy JL, Rosenberg D, Stein DJ, Hemmings SM, Lochner C, Azzam A, Chavira DA, Fournier E, Garrido H, Sheppard B, Umana P, Murphy DL, Wendland JR, Veenstra-VanderWeele J, Denys D, Blom R, Deforce D, Van Nieuwerburgh F, Westenberg HG, Walitza S, Egberts K, Renner T, Miguel EC, Cappi C, Hounie AG, Conceicao do Rosario M, Sampaio AS, Vallada H, Nicolini H, Lanzagorta N, Camarena B, Delorme R, Leboyer M, Pato CN, Pato MT, Voyiaziakis E, Heutink P, Cath DC, Posthuma D, Smit JH, Samuels J, Bienvenu OJ, Cullen B, Fyer AJ, Grados MA, Greenberg BD, McCracken JT, Riddle MA, Wang Y, Coric V, Leckman JF, Bloch M, Pittenger C, Eapen V, Black DW, Ophoff RA, Strengman E, Cusi D, Turiel M, Frau F, Macciardi F, Gibbs JR, Cookson MR, Singleton A, Hardy J, Crenshaw AT, Parkin MA, Mirel DB, Conti DV, Purcell S, Nestadt G, Hanna GL, Jenike MA, Knowles JA, Cox N, Pauls DL (2013) Genome-wide association study of obsessive–compulsive disorder. Mol Psychiatry 18(7):788–798CrossRefGoogle Scholar
  66. Stockmeier CA, Mahajan GJ, Konick LC, Overholser JC, Jurjus GJ, Meltzer HY, Uylings HB, Friedman L, Rajkowska G (2004) Cellular changes in the postmortem hippocampus in major depression. Biol Psychiatry 56(9):640–650CrossRefGoogle Scholar
  67. Subira M, Cano M, de Wit SJ, Alonso P, Cardoner N, Hoexter MQ, Kwon JS, Nakamae T, Lochner C, Sato JR, Jung WH, Narumoto J, Stein DJ, Pujol J, Mataix-Cols D, Veltman DJ, Menchon JM, van den Heuvel OA, Soriano-Mas C (2016) Structural covariance of neostriatal and limbic regions in patients with obsessive–compulsive disorder. J Psychiatry Neurosci JPN 41(2):115–123CrossRefGoogle Scholar
  68. Szeszko PR, Robinson D, Alvir JM, Bilder RM, Lencz T, Ashtari M, Wu H, Bogerts B (1999) Orbital frontal and amygdala volume reductions in obsessive–compulsive disorder. Arch Gen Psychiatry 56(10):913–919CrossRefGoogle Scholar
  69. Teachman BA (2007) Linking obsessional beliefs to OCD symptoms in older and younger adults. Behav Res Ther 45(7):1671–1681CrossRefGoogle Scholar
  70. Todtenkopf MS, Vincent SL, Benes FM (2005) A cross-study meta-analysis and three-dimensional comparison of cell counting in the anterior cingulate cortex of schizophrenic and bipolar brain. Schizophr Res 73(1):79–89CrossRefGoogle Scholar
  71. Togao O, Yoshiura T, Nakao T, Nabeyama M, Sanematsu H, Nakagawa A, Noguchi T, Hiwatashi A, Yamashita K, Nagao E, Kanba S, Honda H (2010) Regional gray and white matter volume abnormalities in obsessive–compulsive disorder: a voxel-based morphometry study. Psychiatry Res 184(1):29–37CrossRefGoogle Scholar
  72. Torres AR, Fontenelle LF, Ferrao YA, do Rosario MC, Torresan RC, Miguel EC, Shavitt RG (2012) Clinical features of obsessive–compulsive disorder with hoarding symptoms: a multicenter study. J Psychiatr Res 46(6):724–732CrossRefGoogle Scholar
  73. Triarhou LC (2013) The cytoarchitectonic map of Constantin von Economo and Georg N. Koskinas. In: Geyer S, Turner R (eds) Microstructural parcellation of the human cerebral cortex. Springer, BerlinGoogle Scholar
  74. Uylings HB, Sanz-Arigita EJ, de VK, Pool, Evers CW, Rajkowska P G (2010) 3-D cytoarchitectonic parcellation of human orbitofrontal cortex correlation with postmortem MRI. Psychiatry Res 183(1):1–20CrossRefGoogle Scholar
  75. Valente AA Jr, Miguel EC, Castro CC, Amaro E Jr, Duran FL, Buchpiguel CA, Chitnis X, McGuire PK, Busatto GF (2005) Regional gray matter abnormalities in obsessive–compulsive disorder: a voxel-based morphometry study. Biol Psychiatry 58(6):479–487CrossRefGoogle Scholar
  76. van de Vondervoort I, Poelmans G, Aschrafi A, Pauls DL, Buitelaar JK, Glennon JC, Franke B (2016) An integrated molecular landscape implicates the regulation of dendritic spine formation through insulin-related signalling in obsessive–compulsive disorder. J Psychiatry Neurosci JPN 41(4):280–285CrossRefGoogle Scholar
  77. Vogt C, Vogt O (1919) Allgemeine Ergebnisse unserer Hirnforschung. Dritte Mitteilung. Die architektonische Rindenfelderung im Lichte unserer neuesten Forschungen. J Psychol Neurol (Lpz) 25(Ergänzungsheft 1):399–462Google Scholar
  78. Weibel ER (1979) Stereological methods. Academic Press, LondonGoogle Scholar
  79. West MJ (1999) Stereological methods for estimating the total number of neurons and synapses: issues of precision and bias. Trends Neurosci 22(2):51–61CrossRefGoogle Scholar
  80. Yoo SY, Roh MS, Choi JS, Kang DH, Ha TH, Lee JM, Kim IY, Kim SI, Kwon JS (2008) Voxel-based morphometry study of gray matter abnormalities in obsessive–compulsive disorder. J Korean Med Sci 23(1):24–30CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Katia Cristina de Oliveira
    • 1
    • 2
    • 3
    • 11
    • 13
  • Lea Tenenholz Grinberg
    • 1
    • 12
  • Marcelo Queiroz Hoexter
    • 2
  • Helena Brentani
    • 6
    • 8
    • 9
  • Claudia Kimie Suemoto
    • 1
    • 4
  • Fabiano Gonçalves Nery
    • 3
  • Luzia Carreira Lima
    • 1
  • Ana Tereza Di Lorenzo Alho
    • 1
    • 10
    • 11
  • José Marcelo Farfel
    • 1
    • 4
  • Renata Eloah de Lucena Ferretti-Rebustini
    • 1
    • 7
  • Renata Elaine Paraizo Leite
    • 1
    • 4
  • Ariane Cristine Moretto
    • 1
    • 3
  • Alexandre Valotta da Silva
    • 1
    • 10
  • Beny Lafer
    • 3
    • 9
  • Eurípedes Constantino Miguel
    • 2
    • 8
    • 9
  • Ricardo Nitrini
    • 1
    • 4
    • 5
  • Wilson Jacob-Filho
    • 1
    • 4
  • Helmut Heinsen
    • 1
    • 11
  • Carlos Augusto Pasqualucci
    • 1
    • 13
  1. 1.Brain Bank of the Brazilian Aging Brain Study Group and HCFMUSP-LIM 22University of São Paulo Medical SchoolSão PauloBrazil
  2. 2.Program Spectrum Disorders Obsessive-Compulsive Disorder (PROTOC), Department of PsychiatryUniversity of São Paulo Medical SchoolSão PauloBrazil
  3. 3.Bipolar Disorder Research Program (PROMAN), Department of PsychiatryUniversity of São Paulo Medical SchoolSão PauloBrazil
  4. 4.Discipline of GeriatricsUniversity of São Paulo Medical SchoolSão PauloBrazil
  5. 5.Department of NeurologyUniversity of São Paulo Medical SchoolSão PauloBrazil
  6. 6.LIM 23-Institute of PsychiatryUniversity of São Paulo Medical SchoolSão PauloBrazil
  7. 7.Medical-Surgical Nursing DepartmentUniversity of Sao Paulo School of NursingSão PauloBrazil
  8. 8.National Institute of Developmental Psychiatry for Children and Adolescents, CNPq São PauloSão PauloBrazil
  9. 9.Department of PsychiatryUniversity of São Paulo Medical SchoolSão PauloBrazil
  10. 10.Hospital Israelita Albert Einstein, Brain InstituteSão PauloBrazil
  11. 11.Department of Psychiatry, Psychosomatics and Psychotherapy, Mental Health CenterUniversity Hospital WuerzburgWürzburgGermany
  12. 12.Department of NeurologyMemory and Aging CenterSan FranciscoUSA
  13. 13.Departamento de PatologiaFaculdade de Medicina da Universidade de São PauloSão PauloBrazil

Personalised recommendations