Brain Structure and Function

, Volume 217, Issue 4, pp 767–782 | Cite as

Brain structure and function in borderline personality disorder

Review

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.

Keywords

Borderline personality disorder Neuroimaging Structural PET fMRI Neurometabolite Hippocampus Amygdala 

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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle Scholar
  3. Bremne JD, Vermetten E (2001) Stress and development: behavioral and biological consequences. Dev Psychopathol 13(3):473–489PubMedCrossRefGoogle Scholar
  4. Bremner JD (1999) Does stress damage the brain? Biol Psychiatry 45(7):797–805. doi:10.1016/s0006-3223(99)00009-8 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedGoogle 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 CrossRefGoogle 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 PubMedCrossRefGoogle 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)PubMedCrossRefGoogle Scholar
  12. Duman RS (2002) Pathophysiology of depression: the concept of synaptic plasticity. Eur Psychiatry 17(Suppl 3):306–310 (pii:S0924933802006545)PubMedCrossRefGoogle 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)PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 CrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle Scholar
  23. Insel TR (2010) Faulty circuits. Sci Am 302(4):44–51PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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)PubMedCrossRefGoogle 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)PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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):451–471PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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)PubMedCrossRefGoogle 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 1:105–113CrossRefGoogle 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 PubMedCrossRefGoogle 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 CrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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)PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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)PubMedCrossRefGoogle 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):289–295PubMedGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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):511–514CrossRefGoogle 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)PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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):383–388PubMedGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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):1892–1897PubMedCrossRefGoogle 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):1101–1106PubMedGoogle 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):381–387PubMedCrossRefGoogle 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 PubMedCrossRefGoogle 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 PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Department of Psychiatry, Institute of NeuroscienceTrinity CollegeDublin 2Ireland
  2. 2.Department of PsychiatryAdelaide and Meath Hospital Incorporating the National Children Hospital (AMNCH) and St. James’s HospitalDublinIreland

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