Advertisement

Cingulate abnormalities in bipolar disorder relate to gender and outcome: a voxel-based morphometry study

  • Giuseppe Delvecchio
  • Valentina Ciappolino
  • Cinzia Perlini
  • Marco Barillari
  • Mirella Ruggeri
  • A. Carlo Altamura
  • Marcella Bellani
  • Paolo BrambillaEmail author
Original Paper
  • 219 Downloads

Abstract

Structural magnetic resonance imaging (MRI) studies reported gray matter (GM) loss in bipolar disorder (BD) in cingulate cortices, key regions subserving emotional regulation and cognitive functions in humans. The aim of this study was to further explore cingulate GM volumes in a sizeable group of BD patients with respect to healthy controls, particularly investigating the impact of gender and clinical variables. 39 BD patients (mean Age = 48.6 ± 9.7, 15 males and 24 females) and 39 demographically matched healthy subjects (mean Age = 47.9 ± 9.1, 15 males and 24 females) underwent a 1.5T MRI scan. GM volumes within the cingulate cortex were manually detected, including anterior and posterior regions. BD patients had decreased left anterior cingulate volumes compared with healthy controls (F = 6.7, p = 0.01). Additionally, a significant gender effect was observed, with male patients showing reduced left anterior cingulate cortex (ACC) volumes compared to healthy controls (F = 5.1, p = 0.03). Furthermore, a significant inverse correlation between right ACC volumes and number of hospitalizations were found in the whole group of BD patients (r = − 0.51, p = 0.04) and in male BD patients (r = − 0.88, p = 0.04). Finally, no statistically significant correlations were observed in female BD patients. Our findings further confirm the putative role of the ACC in the pathophysiology of BD. Interestingly, this study also suggested the presence of gender-specific GM volume reductions in ACC in BD, which may also be associated to poor outcome.

Keywords

Mood disorders Outcome Gray matter Illness severity Hospitalizations 

Notes

Acknowledgements

This study was partially supported by grants from the Italian Ministry of Health to PB and GD (RF-2011-02352308) and to MB (GR-2010-2319022). We thank Gianluca Rambaldelli for managing the dataset.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

References

  1. 1.
    Kessler RC, Chiu WT, Demler O et al (2005) Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the national comorbidity survey replication. Arch Gen Psychiatry 62:617CrossRefGoogle Scholar
  2. 2.
    Fagiolini A, Forgione R, Maccari M et al (2013) Prevalence, chronicity, burden and borders of bipolar disorder. J Affect Disord 148:161–169CrossRefGoogle Scholar
  3. 3.
    Maggioni E, Bellani M, Altamura AC, Brambilla P (2016) Neuroanatomical voxel-based profile of schizophrenia and bipolar disorder. Epidemiol Psychiatr Sci 25:312–316CrossRefGoogle Scholar
  4. 4.
    Houenou J, Perlini C, Brambilla P (2015) Epidemiological and clinical aspects will guide the neuroimaging research in bipolar disorder. Epidemiol Psychiatr Sci 24:117–120CrossRefGoogle Scholar
  5. 5.
    Bellani M, Boschello F, Delvecchio G et al (2016) DTI and myelin plasticity in bipolar disorder: integrating neuroimaging and neuropathological findings. Front psychiatry 7:21CrossRefGoogle Scholar
  6. 6.
    Hozer F, Houenou J (2016) Can neuroimaging disentangle bipolar disorder? J Affect Disord 195:199–214CrossRefGoogle Scholar
  7. 7.
    Wolfers T, Buitelaar JK, Beckmann CF et al (2015) From estimating activation locality to predicting disorder: a review of pattern recognition for neuroimaging-based psychiatric diagnostics. Neurosci Biobehav Rev 57:328–349CrossRefGoogle Scholar
  8. 8.
    Nery FG, Monkul ES, Lafer B (2013) Gray matter abnormalities as brain structural vulnerability factors for bipolar disorder: a review of neuroimaging studies of individuals at high genetic risk for bipolar disorder. Aust New Zeal J Psychiatry 47:1124–1135CrossRefGoogle Scholar
  9. 9.
    Fountoulakis KN, Giannakopoulos P, Kövari E, Bouras C (2008) Assessing the role of cingulate cortex in bipolar disorder: Neuropathological, structural and functional imaging data. Brain Res Rev 59:9–21CrossRefGoogle Scholar
  10. 10.
    Soares JC, Mann JJ (1997) The functional neuroanatomy of mood disorders. J Psychiatr Res 31:393–432CrossRefGoogle Scholar
  11. 11.
    Marlinge E, Bellivier F, Houenou J (2014) White matter alterations in bipolar disorder: potential for drug discovery and development. Bipolar Disord 16:97–112CrossRefGoogle Scholar
  12. 12.
    Vogt BA, Nimchinsky EA, Vogt LJ, Hof PR (1995) Human cingulate cortex: surface features, flat maps, and cytoarchitecture. J Comp Neurol 359:490–506CrossRefGoogle Scholar
  13. 13.
    Zimmerman ME, DelBello MP, Getz GE et al (2006) Anterior cingulate subregion volumes and executive function in bipolar disorder. Bipolar Disord 8:281–288CrossRefGoogle Scholar
  14. 14.
    Bruno SD, Barker GJ, Cercignani M et al (2004) A study of bipolar disorder using magnetization transfer imaging and voxel-based morphometry. Brain 127:2433–2440CrossRefGoogle Scholar
  15. 15.
    Farrow TFD, Whitford TJ, Williams LM et al (2005) Diagnosis-related regional gray matter loss over two years in first episode schizophrenia and bipolar disorder. Biol Psychiatry 58:713–723CrossRefGoogle Scholar
  16. 16.
    Sassi RB, Brambilla P, Hatch JP et al (2004) Reduced left anterior cingulate volumes in untreated bipolar patients. Biol Psychiatry 56:467–475CrossRefGoogle Scholar
  17. 17.
    Atmaca M, Ozdemir H, Cetinkaya S et al (2007) Cingulate gyrus volumetry in drug free bipolar patients and patients treated with valproate or valproate and quetiapine. J Psychiatr Res 41:821–827CrossRefGoogle Scholar
  18. 18.
    Kaur S, Sassi RB, Axelson D et al (2005) Cingulate cortex anatomical abnormalities in children and adolescents with bipolar disorder. Am J Psychiatry 162:1637–1643CrossRefGoogle Scholar
  19. 19.
    Lim KO, Rosenbloom MJ, Faustman WO et al (1999) Cortical gray matter deficit in patients with bipolar disorder. Schizophr Res 40:219–227CrossRefGoogle Scholar
  20. 20.
    Lochhead RA, Parsey RV, Oquendo MA, Mann JJ (2004) Regional brain gray matter volume differences in patients with bipolar disorder as assessed by optimized voxel-based morphometry. Biol Psychiatry 55:1154–1162CrossRefGoogle Scholar
  21. 21.
    Nugent AC, Milham MP, Bain EE et al (2006) Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry. Neuroimage 30:485–497CrossRefGoogle Scholar
  22. 22.
    Diflorio A, Jones I (2010) Is sex important? Gender differences in bipolar disorder. Int Rev Psychiatry 22:437–452CrossRefGoogle Scholar
  23. 23.
    Jogia J, Dima D, Frangou S (2012) Sex differences in bipolar disorder: a review of neuroimaging findings and new evidence. Bipolar Disord 14:461–471CrossRefGoogle Scholar
  24. 24.
    Altshuler LL, Kupka RW, Hellemann G et al (2010) Gender and depressive symptoms in 711 patients with bipolar disorder evaluated prospectively in the stanley foundation bipolar treatment outcome network. Am J Psychiatry 167:708–715CrossRefGoogle Scholar
  25. 25.
    Cosgrove KP, Mazure CM, Staley JK (2007) Evolving knowledge of sex differences in brain structure, function, and chemistry. Biol Psychiatry 62:847–855CrossRefGoogle Scholar
  26. 26.
    Fornito A, Yucel M, Wood SJ et al (2009) Anterior cingulate cortex abnormalities associated with a first psychotic episode in bipolar disorder. Br J Psychiatry 194:426–433CrossRefGoogle Scholar
  27. 27.
    Bora E, Fornito A, Yücel M, Pantelis C (2012) The effects of gender on grey matter abnormalities in major psychoses: a comparative voxelwise meta-analysis of schizophrenia and bipolar disorder. Psychol Med 42:295–307CrossRefGoogle Scholar
  28. 28.
    Crow TJ, Chance SA, Priddle TH et al (2013) Laterality interacts with sex across the schizophrenia/bipolarity continuum: an interpretation of meta-analyses of structural MRI. Psychiatry Res 210:1232–1244CrossRefGoogle Scholar
  29. 29.
    Doris A, Belton E, Ebmeier KP et al (2004) Reduction of cingulate gray matter density in poor outcome bipolar illness. Psychiatry Res 130:153–159CrossRefGoogle Scholar
  30. 30.
    Dazzan P, Soulsby B, Mechelli A et al (2012) Volumetric abnormalities predating the onset of schizophrenia and affective psychoses: an MRI study in subjects at ultrahigh risk of psychosis. Schizophr Bull 38:1083–1091CrossRefGoogle Scholar
  31. 31.
    MORGAN KD, DAZZAN P, ORR KG et al (2007) Grey matter abnormalities in first-episode schizophrenia and affective psychosis. Br J Psychiatry 191:s111–s116CrossRefGoogle Scholar
  32. 32.
    Gogtay N, Ordonez A, Herman DH et al (2007) Dynamic mapping of cortical development before and after the onset of pediatric bipolar illness. J Child Psychol Psychiatry 48:852–862CrossRefGoogle Scholar
  33. 33.
    Pina-Camacho L, Del Rey-Mejías Á, Janssen J et al (2016) Age at first episode modulates diagnosis-related structural brain abnormalities in psychosis. Schizophr Bull 42:344–357CrossRefGoogle Scholar
  34. 34.
    Tansella M, Burti L (2003) Integrating evaluative research and community-based mental health care in Verona, Italy. Br J Psychiatry 183:167–169CrossRefGoogle Scholar
  35. 35.
    Emsell L, McDonald C (2009) The structural neuroimaging of bipolar disorder. Int Rev Psychiatry 21:297–313CrossRefGoogle Scholar
  36. 36.
    Gasquoine PG (2013) Localization of function in anterior cingulate cortex: from psychosurgery to functional neuroimaging. Neurosci Biobehav Rev 37:340–348CrossRefGoogle Scholar
  37. 37.
    Rive MM, van Rooijen G, Veltman DJ et al (2013) Neural correlates of dysfunctional emotion regulation in major depressive disorder. a systematic review of neuroimaging studies. Neurosci Biobehav Rev 37:2529–2553CrossRefGoogle Scholar
  38. 38.
    Drevets WC, Price JL, Simpson JR et al (1997) Subgenual prefrontal cortex abnormalities in mood disorders. Nature 386:824–827CrossRefGoogle Scholar
  39. 39.
    Molina V, Galindo G, Cortés B et al (2011) Different gray matter patterns in chronic schizophrenia and chronic bipolar disorder patients identified using voxel-based morphometry. Eur Arch Psychiatry Clin Neurosci 261:313–322CrossRefGoogle Scholar
  40. 40.
    Fornito A, Malhi GS, Lagopoulos J et al (2008) Anatomical abnormalities of the anterior cingulate and paracingulate cortex in patients with bipolar I disorder. Psychiatry Res Neuroimaging 162:123–132CrossRefGoogle Scholar
  41. 41.
    Hirayasu Y, Shenton ME, Salisbury DF et al (1999) Subgenual cingulate cortex volume in first-episode psychosis. Am J Psychiatry 156:1091–1093Google Scholar
  42. 42.
    Adler CM, DelBello MP, Jarvis K et al (2007) Voxel-based study of structural changes in first-episode patients with bipolar disorder. Biol Psychiatry 61:776–781CrossRefGoogle Scholar
  43. 43.
    Kubicki M, Shenton ME, Salisbury DF et al (2002) Voxel-based morphometric analysis of gray matter in first episode schizophrenia. Neuroimage 17:1711–1719CrossRefGoogle Scholar
  44. 44.
    Lyoo IK, Kim MJ, Stoll AL et al (2004) Frontal lobe gray matter density decreases in bipolar I disorder. Biol Psychiatry 55:648–651CrossRefGoogle Scholar
  45. 45.
    Lyoo IK, Sung YH, Dager SR et al (2006) Regional cerebral cortical thinning in bipolar disorder. Bipolar Disord 8:65–74CrossRefGoogle Scholar
  46. 46.
    Wise T, Radua J, Via E et al (2016) Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis. Mol Psychiatry 22:1455–1463CrossRefGoogle Scholar
  47. 47.
    Lennox BR, Jacob R, Calder AJ et al (2004) Behavioural and neurocognitive responses to sad facial affect are attenuated in patients with mania. Psychol Med 34:795–802CrossRefGoogle Scholar
  48. 48.
    Gruber SA, Rogowska J, Yurgelun-Todd DA (2004) Decreased activation of the anterior cingulate in bipolar patients: an fMRI study. J Affect Disord 82:191–201CrossRefGoogle Scholar
  49. 49.
    Yoshimura Y, Okamoto Y, Onoda K et al (2014) Psychosocial functioning is correlated with activation in the anterior cingulate cortex and left lateral prefrontal cortex during a verbal fluency task in euthymic bipolar disorder: a preliminary fMRI study. Psychiatry Clin Neurosci 68:188–196CrossRefGoogle Scholar
  50. 50.
    Roland PE (1993) Brain activation. Wiley-Liss, New YorkGoogle Scholar
  51. 51.
    Monkul ES, Malhi GS, Soares JC (2005) Anatomical MRI abnormalities in bipolar disorder: do they exist and do they progress? Aust N Z J Psychiatry 39:222–226CrossRefGoogle Scholar
  52. 52.
    Brambilla P, Glahn DC, Balestrieri M, Soares JC (2005) Magnetic resonance findings in bipolar disorder. Psychiatr Clin North Am 28:443–467CrossRefGoogle Scholar
  53. 53.
    Mann SL, Hazlett EA, Byne W et al (2011) Anterior and posterior cingulate cortex volume in healthy adults: effects of aging and gender differences. Brain Res 1401:18–29CrossRefGoogle Scholar
  54. 54.
    Kawa I, Carter JD, Joyce PR et al (2005) Gender differences in bipolar disorder: age of onset, course, comorbidity, and symptom presentation. Bipolar Disord 7:119–125CrossRefGoogle Scholar
  55. 55.
    Arnold LM (2003) Gender differences in bipolar disorder. Psychiatr Clin North Am 26:595–620CrossRefGoogle Scholar
  56. 56.
    Hochman E, Valevski A, Onn R et al (2016) Seasonal pattern of manic episode admissions among bipolar I disorder patients is associated with male gender and presence of psychotic features. J Affect Disord 190:123–127CrossRefGoogle Scholar
  57. 57.
    DelBello M, Strakowski SM, Zimmerman ME et al (1999) MRI analysis of the cerebellum in bipolar disorder a pilot study. Neuropsychopharmacology 21:63–68CrossRefGoogle Scholar
  58. 58.
    Brambilla P, Harenski K, Nicoletti M et al (2001) Differential effects of age on brain gray matter in bipolar patients and healthy individuals. Neuropsychobiology 43:242–247CrossRefGoogle Scholar
  59. 59.
    Mills NP, DelBello MP, Adler CM, Strakowski SM (2005) MRI analysis of cerebellar vermal abnormalities in bipolar disorder. Am J Psychiatry 162:1530–1533CrossRefGoogle Scholar
  60. 60.
    Robinson LJ, Thompson JM, Gallagher P et al (2006) A meta-analysis of cognitive deficits in euthymic patients with bipolar disorder. J Affect Disord 93:105–115CrossRefGoogle Scholar
  61. 61.
    Moorhead TWJ, McKirdy J, Sussmann JED et al (2007) Progressive gray matter loss in patients with bipolar disorder. Biol Psychiatry 62:894–900CrossRefGoogle Scholar
  62. 62.
    Silverstone PH, Wu RH, O’Donnell T, U et al (2003) Chronic treatment with lithium, but not sodium valproate, increases cortical N-acetyl-aspartate concentrations in euthymic bipolar patients. Int Clin Psychopharmacol 18(2):73–79CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Giuseppe Delvecchio
    • 1
  • Valentina Ciappolino
    • 2
  • Cinzia Perlini
    • 3
    • 4
  • Marco Barillari
    • 5
  • Mirella Ruggeri
    • 4
    • 6
  • A. Carlo Altamura
    • 2
  • Marcella Bellani
    • 4
    • 6
  • Paolo Brambilla
    • 2
    • 7
    Email author
  1. 1.IRCCS “E. Medea” Scientific InstituteSan Vito al TagliamentoItaly
  2. 2.Department of Neurosciences and Mental Health, Fondazione IRCCS Ca’ Granda Ospedale Maggiore PoliclinicoUniversity of MilanMilanItaly
  3. 3.Section of Clinical Psychology, Department of Neurosciences, Biomedicine and Movement SciencesUniversity of VeronaVeronaItaly
  4. 4.Interuniversity Centre for Behavioural NeurosciencesAOUI VeronaVeronaItaly
  5. 5.Section of Radiology, Department of Neurological and Movement SciencesUniversity Hospital of VeronaVeronaItaly
  6. 6.Section of Psychiatry, Department of Neurosciences, Biomedicine and Movement SciencesUniversity of VeronaVeronaItaly
  7. 7.Department of Psychiatry and Behavioural NeurosciencesUniversity of Texas at HoustonHoustonUSA

Personalised recommendations