Skip to main content

Brain structure and function in borderline personality disorder

Abstract

The spotlight on borderline personality disorder (BPD) has been growing in recent years, with the number of papers discussing potential causes and triggers of the disorder rapidly on the increase. Also on the increase, though still lacking sufficient numbers to produce well-supported hypotheses, are studies employing neuroimaging techniques as investigative tools in BPD. In this review, we investigate the current state and findings of neuroimaging studies in BPD, focusing in particular, on the studies examining structural, functional, and neurometabolic abnormalities in the disorder. Some suspected trends in the data are highlighted, including reductions in the hippocampi and amygdalae of BPD patients compared to healthy controls, exaggerated amygdala activity in BPD patients when confronted with emotion-related stimulus, and negative correlations between increases in left amygdalar creatine and reductions in amygdalar volume, reductions in absolute N-acetylaspartate concentration in the dorsolateral prefrontal cortex of BPD patients, and increases in glutamate concentration in the anterior cingulate cortices of BPD patients. We also discuss the limitations of some of the current studies including hindrances due to sample effects and techniques used and the potential of future neuroimaging research in BPD.

This is a preview of subscription content, access via your institution.

References

  1. Asnaani A, Chelminski I, Young D, Zimmerman M (2007) Heterogeneity of borderline personality disorder: do the number of criteria met make a difference? J Pers Disord 21(6):615–625. doi:10.1521/pedi.2007.21.6.615

    PubMed  Article  Google Scholar 

  2. Brambilla P, Soloff PH, Sala M, Nicoletti MA, Keshavan MS, Soares JC (2004) Anatomical MRI study of borderline personality disorder patients. Psychiatry Res 131(2):125–133. doi:10.1016/j.pscychresns.2004.04.003

    PubMed  Article  Google Scholar 

  3. Bremne JD, Vermetten E (2001) Stress and development: behavioral and biological consequences. Dev Psychopathol 13(3):473–489

    PubMed  Article  CAS  Google Scholar 

  4. Bremner JD (1999) Does stress damage the brain? Biol Psychiatry 45(7):797–805. doi:10.1016/s0006-3223(99)00009-8

    PubMed  Article  CAS  Google Scholar 

  5. Brunner R, Henze R, Parzer P, Kramer J, Feigl N, Lutz K, Essig M, Resch F, Stieltjes B (2010) Reduced prefrontal and orbitofrontal gray matter in female adolescents with borderline personality disorder: Is it disorder specific? Neuroimage 49(1):114–120. doi:10.1016/j.neuroimage.2009.07.070

    PubMed  Article  Google Scholar 

  6. Chanen AM, Velakoulis D, Carison K, Gaunson K, Wood SJ, Yuen HP, Yucel M, Jackson HJ, McGorry PD, Pantelis C (2008) Orbitofrontal, amygdala and hippocampal volumes in teenagers with first-presentation borderline personality disorder. Psychiatry Res 163(2):116–125. doi:10.1016/j.pscychresns.2007.08.007

    PubMed  Article  Google Scholar 

  7. Cohen RA, Grieve S, Hoth KF, Paul RH, Sweet L, Tate D, Gunstad J, Stroud L, McCaffery J, Hitsman B, Niaura R, Clark CR, McFarlane A, Bryant R, Gordon E, Williams LM (2006) Early life stress and morphometry of the adult anterior cingulate cortex and caudate nuclei. Biol Psychiatry 59(10):975–982. doi:10.1016/j.biopsych.2005.12.016

    PubMed  Article  Google Scholar 

  8. Congdon E, Canli T (2008) A neurogenetic approach to impulsivity. J Pers 76(6):1447–1484. doi:10.1111/j.1467-6494.2008.00528.x

    PubMed  Google Scholar 

  9. De la Fuente J, Goldman S, Stanus E, Vizuete C, Morlán I, Bobes J, Mendlewicz J (1997) Brain glucose metabolism in borderline personality disorder. J Psychiatr Res 31(5):531–541. doi:10.1016/s0022-3956(97)00001-0

    Article  Google Scholar 

  10. Donegan NH, Sanislow CA, Blumberg HP, Fulbright RK, Lacadie C, Skudlarski P, Gore JC, Olson IR, McGlashan TH, Wexler BE (2003) Amygdala hyperreactivity in borderline personality disorder: implications for emotional dysregulation. Biol Psychiatry 54(11):1284–1293. doi:10.1016/s0006-3223(03)00636-x

    PubMed  Article  Google Scholar 

  11. Driessen M, Herrmann J, Stahl K, Zwaan M, Meier S, Hill A, Osterheider M, Petersen D (2000) Magnetic resonance imaging volumes of the hippocampus and the amygdala in women with borderline personality disorder and early traumatization. Arch Gen Psychiatry 57(12):1115–1122 (pii:yoa9416)

    PubMed  Article  CAS  Google Scholar 

  12. Duman RS (2002) Pathophysiology of depression: the concept of synaptic plasticity. Eur Psychiatry 17(Suppl 3):306–310 (pii:S0924933802006545)

    PubMed  Article  Google Scholar 

  13. Fossati A, Novella L, Donati D, Donini M, Maffei C (2002) History of childhood attention deficit/hyperactivity disorder symptoms and borderline personality disorder: a controlled study. Compr Psychiatry 43(5):369–377 (pii:S0010440X02000159)

    PubMed  Article  Google Scholar 

  14. Foti ME, Geller J, Guy LS, Gunderson JG, Palmer BA, Smith LM (2010) Borderline personality disorder: considerations for inclusion in the Massachusetts parity list of “biologically-based” disorders. Psychiatr Q. doi:10.1007/s11126-010-9154-y

    Google Scholar 

  15. Friedel RO (2004) Dopamine dysfunction in borderline personality disorder: a hypothesis. Neuropsychopharmacology 29(6):1029–1039. doi:10.1038/sj.npp.1300424

    PubMed  Article  CAS  Google Scholar 

  16. Giedd JN, Blumenthal J, Jeffries NO, Castellanos FX, Liu H, Zijdenbos A, Paus T, Evans AC, Rapoport JL (1999) Brain development during childhood and adolescence: a longitudinal MRI study. Nat Neurosci 2(10):861–863. doi:10.1038/13158

    PubMed  Article  CAS  Google Scholar 

  17. Goodman M, New A, Siever L (2004) Trauma, genes, and the neurobiology of personality disorders. Ann N Y Acad Sci 1032:104–116. doi:10.1196/annals.1314.008

    PubMed  Article  CAS  Google Scholar 

  18. Hall J, Olabi B, Lawrie SM, McIntosh AM (2010) Hippocampal and amygdala volumes in borderline personality disorder: A meta-analysis of magnetic resonance imaging studies. Pers Ment Health 4(3):172–179. doi:10.1002/pmh.128

    Article  Google Scholar 

  19. Hazlett EA, New AS, Newmark R, Haznedar MM, Lo JN, Speiser LJ, Chen AD, Mitropoulou V, Minzenberg M, Siever LJ, Buchsbaum MS (2005) Reduced anterior and posterior cingulate gray matter in borderline personality disorder. Biol Psychiatry 58(8):614–623. doi:10.1016/j.biopsych.2005.04.029

    PubMed  Article  Google Scholar 

  20. Herpertz SC, Dietrich TM, Wenning B, Krings T, Erberich SG, Willmes K, Thron A, Sass H (2001) Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study. Biol Psychiatry 50(4):292–298. doi:10.1016/s0006-3223(01)01075-7

    PubMed  Article  CAS  Google Scholar 

  21. Hoerst M, Weber-Fahr W, Tunc-Skarka N, Ruf M, Bohus M, Schmahl C, Ende G (2010a) Correlation of glutamate levels in the anterior cingulate cortex with self-reported impulsivity in patients with borderline personality disorder and healthy controls. Arch Gen Psychiatry 67(9):946–954. doi:10.1001/archgenpsychiatry.2010.93

    PubMed  Article  CAS  Google Scholar 

  22. Hoerst M, Weber-Fahr W, Tunc-Skarka N, Ruf M, Bohus M, Schmahl C, Ende G (2010b) Metabolic alterations in the amygdala in borderline personality disorder: a proton magnetic resonance spectroscopy study. Biol Psychiatry 67(5):399–405. doi:10.1016/j.biopsych.2009.09.030

    PubMed  Article  CAS  Google Scholar 

  23. Insel TR (2010) Faulty circuits. Sci Am 302(4):44–51

    PubMed  Article  Google Scholar 

  24. Irle E, Lange C, Sachsse U (2005) Reduced size and abnormal asymmetry of parietal cortex in women with borderline personality disorder. Biol Psychiatry 57(2):173–182. doi:10.1016/j.biopsych.2004.10.004

    PubMed  Article  Google Scholar 

  25. Jacob GA, Gutz L, Bader K, Lieb K, Tuscher O, Stahl C (2010) Impulsivity in borderline personality disorder: impairment in self-report measures, but not behavioral inhibition. Psychopathology 43(3):180–188. doi:10.1159/000304174

    PubMed  Article  Google Scholar 

  26. Juengling FD, Schmahl C, Hesslinger B, Ebert D, Bremner JD, Gostomzyk J, Bohus M, Lieb K (2003) Positron emission tomography in female patients with borderline personality disorder. J Psychiatr Res 37(2):109–115 (pii:S0022395602000845)

    PubMed  Article  CAS  Google Scholar 

  27. Jung RE, Yeo RA, Love TM, Petropoulos H, Sibbitt WL Jr, Brooks WM (2002) Biochemical markers of mood: a proton magnetic resonance spectroscopy study of normal human brain. Biol Psychiatry 51(3):224–229 (pii:S0006322301012240)

    PubMed  Article  CAS  Google Scholar 

  28. Karl A, Schaefer M, Malta LS, Dorfel D, Rohleder N, Werner A (2006) A meta-analysis of structural brain abnormalities in PTSD. Neurosci Biobehav Rev 30(7):1004–1031. doi:10.1016/j.neubiorev.2006.03.004

    PubMed  Article  Google Scholar 

  29. Kaufman J, Charney D (2001) Effects of early stress on brain structure and function: implications for understanding the relationship between child maltreatment and depression. Dev Psychopathol 13(3):451–471

    PubMed  Article  CAS  Google Scholar 

  30. Koenigsberg HW, Fan J, Ochsner KN, Liu X, Guise KG, Pizzarello S, Dorantes C, Guerreri S, Tecuta L, Goodman M, New A, Siever LJ (2009a) Neural correlates of the use of psychological distancing to regulate responses to negative social cues: a study of patients with borderline personality disorder. Biol Psychiatry 66(9):854–863. doi:10.1016/j.biopsych.2009.06.010

    PubMed  Article  Google Scholar 

  31. Koenigsberg HW, Siever LJ, Lee H, Pizzarello S, New AS, Goodman M, Cheng H, Flory J, Prohovnik I (2009b) Neural correlates of emotion processing in borderline personality disorder. Psychiatry Res 172(3):192–199. doi:10.1016/j.pscychresns.2008.07.010

    PubMed  Article  Google Scholar 

  32. Macqueen G, Frodl T (2010) The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research? Mol Psychiatry 1-13. doi:10.1038/mp.2010.80

  33. Mathew SJ, Shungu DC, Mao X, Smith EL, Perera GM, Kegeles LS, Perera T, Lisanby SH, Rosenblum LA, Gorman JM, Coplan JD (2003) A magnetic resonance spectroscopic imaging study of adult nonhuman primates exposed to early-life stressors. Biol Psychiatry 54(7):727–735 (pii:S0006322303000040)

    PubMed  Article  CAS  Google Scholar 

  34. Mechelli A, Price CJ, Friston KJ, Ashburner J (2005) Voxel-based morphometry of the human brain: methods and applications. Current Medical Imaging Reviews 1:105–113

    Article  Google Scholar 

  35. Minzenberg MJ, Fan J, New AS, Tang CY, Siever LJ (2007a) Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study. Psychiatry Res 155(3):231–243. doi:10.1016/j.pscychresns.2007.03.006

    PubMed  Article  Google Scholar 

  36. Minzenberg MJ, Fan J, New AS, Tang CY, Siever LJ (2007b) Fronto-limbic dysfunction in response to facial emotion in borderline personality disorder: an event-related fMRI study. Psychiatry Res Neuroimaging 155(3):231–243. doi:10.1016/j.pscychresns.2007.03.006

    Article  Google Scholar 

  37. Minzenberg MJ, Fan J, New AS, Tang CY, Siever LJ (2008) Frontolimbic structural changes in borderline personality disorder. J Psychiatr Res 42(9):727–733. doi:10.1016/j.jpsychires.2007.07.015

    PubMed  Article  Google Scholar 

  38. New AS, Hazlett EA, Buchsbaum MS, Goodman M, Mitelman SA, Newmark R, Trisdorfer R, Haznedar MM, Koenigsberg HW, Flory J, Siever LJ (2007) Amygdala-prefrontal disconnection in borderline personality disorder. Neuropsychopharmacology 32(7):1629–1640. doi:10.1038/sj.npp.1301283

    PubMed  Article  CAS  Google Scholar 

  39. New AS, Hazlett EA, Newmark RE, Zhang J, Triebwasser J, Meyerson D, Lazarus S, Trisdorfer R, Goldstein KE, Goodman M, Koenigsberg HW, Flory JD, Siever LJ, Buchsbaum MS (2009) Laboratory induced aggression: a positron emission tomography study of aggressive individuals with borderline personality disorder. Biol Psychiatry 66(12):1107–1114. doi:10.1016/j.biopsych.2009.07.015

    PubMed  Article  Google Scholar 

  40. Nunes PM, Wenzel A, Borges KT, Porto CR, Caminha RM, de Oliveira IR (2009) Volumes of the hippocampus and amygdala in patients with borderline personality disorder: a meta-analysis. J Pers Disord 23(4):333–345. doi:10.1521/pedi.2009.23.4.333

    PubMed  Article  Google Scholar 

  41. Paus T (2005) Mapping brain maturation and cognitive development during adolescence. Trends Cogn Sci 9(2):60–68. doi:10.1016/j.tics.2004.12.008

    PubMed  Article  Google Scholar 

  42. Rusch N, van Elst LT, Ludaescher P, Wilke M, Huppertz HJ, Thiel T, Schmahl C, Bohus M, Lieb K, Hesslinger B, Hennig J, Ebert D (2003) A voxel-based morphometric MRI study in female patients with borderline personality disorder. Neuroimage 20(1):385–392 (pii:S1053811903002970)

    PubMed  Article  CAS  Google Scholar 

  43. Salavert J, Gasol M, Vieta E, Cervantes A, Trampal C, Gispert JD (2011) Fronto-limbic dysfunction in borderline personality disorder: a 18F-FDG positron emission tomography study. J Affect Disord 131(1–3):260–267. doi:10.1016/j.jad.2011.01.001

    PubMed  Article  Google Scholar 

  44. Schmahl C, Bremner JD (2006) Neuroimaging in borderline personality disorder. J Psychiatr Res 40(5):419–427. doi:10.1016/j.jpsychires.2005.08.011

    PubMed  Article  Google Scholar 

  45. Schmahl CG, Vermetten E, Elzinga BM, Bremner JD (2003) Magnetic resonance imaging of hippocampal and amygdala volume in women with childhood abuse and borderline personality disorder. Psychiatry Res 122(3):193–198 (pii:S0925492703000234)

    PubMed  Article  Google Scholar 

  46. Schmahl C, Berne K, Krause A, Kleindienst N, Valerius G, Vermetten E, Bohus M (2009) Hippocampus and amygdala volumes in patients with borderline personality disorder with or without posttraumatic stress disorder. J Psychiatry Neurosci 34(4):289–295

    PubMed  Google Scholar 

  47. Silbersweig D, Clarkin JF, Goldstein M, Kernberg OF, Tuescher O, Levy KN, Brendel G, Pan H, Beutel M, Pavony MT, Epstein J, Lenzenweger MF, Thomas KM, Posner MI, Stern E (2007) Failure of frontolimbic inhibitory function in the context of negative emotion in borderline personality disorder. Am J Psychiatry 164(12):1832–1841. doi:10.1176/appi.ajp.2007.06010126

    PubMed  Article  Google Scholar 

  48. Soloff P, Nutche J, Goradia D, Diwadkar V (2008) Structural brain abnormalities in borderline personality disorder: a voxel-based morphometry study. Psychiatry Res 164(3):223–236. doi:10.1016/j.pscychresns.2008.02.003

    PubMed  Article  Google Scholar 

  49. Steele H, Siever L (2010) An attachment perspective on borderline personality disorder: advances in gene-environment considerations. Curr Psychiatry Rep 12(1):61–67. doi:10.1007/s11920-009-0091-0

    PubMed  Article  Google Scholar 

  50. Takahashi T, Chanen AM, Wood SJ, Walterfang M, Harding IH, Yucel M, Nakamura K, McGorry PD, Suzuki M, Velakoulis D, Pantelis C (2009a) Midline brain structures in teenagers with first-presentation borderline personality disorder. Prog Neuropsychopharmacol Biol Psychiatry 33(5):842–846. doi:10.1016/j.pnpbp.2009.03.035

    PubMed  Article  Google Scholar 

  51. Takahashi T, Chanen AM, Wood SJ, Yucel M, Tanino R, Suzuki M, Velakoulis D, Pantelis C, McGorry PD (2009b) Insular cortex volume and impulsivity in teenagers with first-presentation borderline personality disorder. Prog Neuropsychopharmacol Biol Psychiatry 33(8):1395–1400. doi:10.1016/j.pnpbp.2009.07.017

    PubMed  Article  Google Scholar 

  52. Tebartz van Elst L, Thiel T, Hesslinger B, Lieb K, Bohus M, Hennig J, Ebert D (2001) Subtle prefrontal neuropathology in a pilot magnetic resonance spectroscopy study in patients with borderline personality disorder. J Neuropsychiatry Clin Neurosci 13(4):511–514

    Article  Google Scholar 

  53. Tebartz van Elst L, Hesslinger B, Thiel T, Geiger E, Haegele K, Lemieux L, Lieb K, Bohus M, Hennig J, Ebert D (2003) Frontolimbic brain abnormalities in patients with borderline personality disorder: a volumetric magnetic resonance imaging study. Biol Psychiatry 54(2):163–171 (pii:S0006322302017432)

    PubMed  Article  Google Scholar 

  54. Tebartz van Elst L, Ludaescher P, Thiel T, Buchert M, Hesslinger B, Bohus M, Rusch N, Hennig J, Ebert D, Lieb K (2007) Evidence of disturbed amygdalar energy metabolism in patients with borderline personality disorder. Neurosci Lett 417(1):36–41. doi:10.1016/j.neulet.2007.02.071

    PubMed  Article  CAS  Google Scholar 

  55. Vollm BA, Zhao L, Richardson P, Clark L, Deakin JF, Williams S, Dolan MC (2009) A voxel-based morphometric MRI study in men with borderline personality disorder: preliminary findings. Crim Behav Ment Health 19(1):64–72. doi:10.1002/cbm.716

    PubMed  Article  Google Scholar 

  56. Weniger G, Lange C, Sachsse U, Irle E (2009) Reduced amygdala and hippocampus size in trauma-exposed women with borderline personality disorder and without posttraumatic stress disorder. J Psychiatry Neurosci 34(5):383–388

    PubMed  Google Scholar 

  57. Whittle S, Chanen AM, Fornito A, McGorry PD, Pantelis C, Yucel M (2009) Anterior cingulate volume in adolescents with first-presentation borderline personality disorder. Psychiatry Res 172(2):155–160. doi:10.1016/j.pscychresns.2008.12.004

    PubMed  Article  Google Scholar 

  58. Whitwell JL (2009) Voxel-based morphometry: an automated technique for assessing structural changes in the brain. J Neurosci 29(31):9661–9664. doi:10.1523/JNEUROSCI.2160-09.2009

    PubMed  Article  CAS  Google Scholar 

  59. Williamson A (2007) Using self-report measures in neurobehavioural toxicology: can they be trusted? Neurotoxicology 28(2):227–234. doi:10.1016/j.neuro.2006.03.009

    PubMed  Article  Google Scholar 

  60. Wingenfeld K, Spitzer C, Rullkotter N, Lowe B (2010) Borderline personality disorder: hypothalamus pituitary adrenal axis and findings from neuroimaging studies. Psychoneuroendocrinology 35(1):154–170. doi:10.1016/j.psyneuen.2009.09.014

    PubMed  Article  CAS  Google Scholar 

  61. Wiseman RM, Saxby BK, Burton EJ, Barber R, Ford GA, O’Brien JT (2004) Hippocampal atrophy, whole brain volume, and white matter lesions in older hypertensive subjects. Neurology 63(10):1892–1897

    PubMed  Article  CAS  Google Scholar 

  62. Zanarini MC, Williams AA, Lewis RE, Reich RB, Vera SC, Marino MF, Levin A, Yong L, Frankenburg FR (1997) Reported pathological childhood experiences associated with the development of borderline personality disorder. Am J Psychiatry 154(8):1101–1106

    PubMed  CAS  Google Scholar 

  63. Zanarini MC, Yong L, Frankenburg FR, Hennen J, Reich DB, Marino MF, Vujanovic AA (2002) Severity of reported childhood sexual abuse and its relationship to severity of borderline psychopathology and psychosocial impairment among borderline inpatients. J Nerv Ment Dis 190(6):381–387

    PubMed  Article  Google Scholar 

  64. Zetzsche T, Frodl T, Preuss UW, Schmitt G, Seifert D, Leinsinger G, Born C, Reiser M, Moller HJ, Meisenzahl EM (2006) Amygdala volume and depressive symptoms in patients with borderline personality disorder. Biol Psychiatry 60(3):302–310. doi:10.1016/j.biopsych.2005.11.020

    PubMed  Article  Google Scholar 

  65. Zetzsche T, Preuss UW, Frodl T, Schmitt G, Seifert D, Munchhausen E, Tabrizi S, Leinsinger G, Born C, Reiser M, Moller HJ, Meisenzahl EM (2007) Hippocampal volume reduction and history of aggressive behaviour in patients with borderline personality disorder. Psychiatry Res 154(2):157–170. doi:10.1016/j.pscychresns.2006.05.010

    PubMed  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Thomas Frodl.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

O’Neill, A., Frodl, T. Brain structure and function in borderline personality disorder. Brain Struct Funct 217, 767–782 (2012). https://doi.org/10.1007/s00429-012-0379-4

Download citation

Keywords

  • Borderline personality disorder
  • Neuroimaging
  • Structural
  • PET
  • fMRI
  • Neurometabolite
  • Hippocampus
  • Amygdala