Hostname: page-component-8448b6f56d-cfpbc Total loading time: 0 Render date: 2024-04-24T07:05:26.465Z Has data issue: false hasContentIssue false
  • English
  • Français

Structural alterations in white-matter tracts connecting (para-)limbic and prefrontal brain regions in borderline personality disorder

Published online by Cambridge University Press:  19 June 2015

A. Lischke ,
M. Domin ,
H. J. Freyberger ,
H. J. Grabe ,
R. Mentel ,
D. Bernheim  and
M. Lotze
A. Lischke*
Affiliation:
Department of Psychiatry and Psychotherapy, University of Greifswald, Germany Department of Psychology, University of Greifswald, Germany Functional Imaging, Center for Diagnostic Radiology and Neuroradiology, University of Greifswald, Germany
M. Domin
Affiliation:
Functional Imaging, Center for Diagnostic Radiology and Neuroradiology, University of Greifswald, Germany
H. J. Freyberger
Affiliation:
Department of Psychiatry and Psychotherapy, University of Greifswald, Germany Helios Hospital, Stralsund, Germany
H. J. Grabe
Affiliation:
Department of Psychiatry and Psychotherapy, University of Greifswald, Germany Helios Hospital, Stralsund, Germany
R. Mentel
Affiliation:
Department of Psychiatry and Psychotherapy, University of Greifswald, Germany
D. Bernheim
Affiliation:
Department of Child and Adolescent Psychiatry and Psychotherapy, University of Ulm, Germany
M. Lotze
Affiliation:
Functional Imaging, Center for Diagnostic Radiology and Neuroradiology, University of Greifswald, Germany
*
*Address for correspondence: A. Lischke, Ph.D., Department of Psychology, University of Greifswald, Franz-Mehring-Str. 47, 17489, Germany. (Email: alexander.lischke@uni-greifswald.de)
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

A dysfunctional network of prefrontal and (para-)limbic brain region has been suggested to underlie emotional dysregulation in borderline personality disorder (BPD). Abnormal activity in this network may be due to structural alterations in white-matter tracts connecting prefrontal and (para-)limbic brain regions. To test this hypothesis, we investigated the structural integrity of major white-matter tracts connecting these regions in BPD.

Method

Using diffusion tensor imaging, we investigated fractional anisotropy (FA), axonal anisotropy (AD) and radial diffusivity (RD) in the uncinate fasciculus, the major white-matter tract connecting (para-)limbic and prefrontal brain regions, in 26 healthy controls (HC) and 26 BPD participants. To clarify the specificity of possible white-matter alterations among HC and BPD participants, FA, AD and RD were also investigated in the cingulum.

Results

We found distinct structural alterations in the uncinate fasciculus but not in the cingulum of BPD participants. Compared to HC participants, BPD participants showed lower FA and higher RD in the uncinate fasciculus. By contrast, AD did not differ in the uncinate fasciculus of HC and BPD participants.

Conclusions

Our finding of abnormal FA and RD in the uncinate fasciculus indicates distinct white-matter alterations in BPD, presumably due to stress-induced myelin degeneration in the aftermath of stressful life events. Although these alterations may account for abnormal activity in brain regions implicated in emotion dysregulation, such as the amygdala, anterior cingulate cortex and prefrontal cortex, it remains to be determined whether these alterations are specific for BPD.

Keywords

Amygdalaanterior cingulate cortexborderline personality disorderdiffusion tensor imagingprefrontal cortexuncinate fasciculuswhite matter
Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 15 , November 2015 , pp. 3171 - 3180
Copyright
Copyright © Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bohus, M, Kleindienst, N, Limberger, MF, Stieglitz, RD, Domsalla, M, Chapman, AL, Steil, R, Philipsen, A, Wolf, M (2009). The short version of the Borderline Symptom List (BSL-23): development and initial data on psychometric properties. Psychopathology 42, 32–39.CrossRefGoogle ScholarPubMed
Bohus, M, Limberger, MF, Frank, U, Chapman, AL, Kuhler, T, Stieglitz, RD (2007). Psychometric properties of the Borderline Symptom List (BSL). Psychopathology 40, 126–132.Google Scholar
Bruehl, H, Preissler, S, Heuser, I, Heekeren, HR, Roepke, S, Dziobek, I (2013). Increased prefrontal cortical thickness is associated with enhanced abilities to regulate emotions in PTSD-free women with borderline personality disorder. PLoS One 8, e65584.CrossRefGoogle ScholarPubMed
Carrasco, JL, Tajima-Pozo, K, Diaz-Marsa, M, Casado, A, Lopez-Ibor, JJ, Arrazola, J, Yus, M (2012). Microstructural white matter damage at orbitofrontal areas in borderline personality disorder. Journal of Affective Disorders 139, 149–153.Google Scholar
Crowell, SE, Beauchaine, TP, Linehan, MM (2009). A biosocial developmental model of borderline personality: elaborating and extending Linehan's theory. Psychological Bulletin 135, 495–510.Google Scholar
Diaz-Marsa, M, Macdowell, KS, Guemes, I, Rubio, V, Carrasco, JL, Leza, JC (2012). Activation of the cholinergic anti-inflammatory system in peripheral blood mononuclear cells from patients with borderline personality disorder. Journal of Psychiatric Research 46, 1610–1617.Google Scholar
Domin, M, Langner, S, Hosten, N, Lotze, M (2014). Comparison of parameter threshold combinations for diffusion tensor tractography in chronic stroke patients and healthy subjects. PLoS ONE 9, e98211.Google Scholar
Fani, N, King, TZ, Jovanovic, T, Glover, EM, Bradley, B, Choi, K, Ely, T, Gutman, DA, Ressler, KJ (2012). White matter integrity in highly traumatized adults with and without post-traumatic stress disorder. Neuropsychopharmacology 37, 2740–2746.CrossRefGoogle ScholarPubMed
Fydrich, T, Renneberg, B, Schmitz, B, Wittchen, HU (1997). SKID-II - Strukturiertes Klinisches Interview für DSM-IV Achse II: Persönlichkeitsstörungen. Hogrefe: Göttingen.Google Scholar
Garcia-Bueno, B, Caso, JR, Leza, JC (2008). Stress as a neuroinflammatory condition in brain: damaging and protective mechanisms. Neuroscience & Biobehavioral Reviews 32, 1136–1151.Google Scholar
Goldin, PR, Manber, T, Hakimi, S, Canli, T, Gross, JJ (2009). Neural bases of social anxiety disorder: emotional reactivity and cognitive regulation during social and physical threat. Archives of General Psychiatry 66, 170–180.CrossRefGoogle ScholarPubMed
Grant, JE, Correia, S, Brennan-Krohn, T, Malloy, PF, Laidlaw, DH, Schulz, SC (2007). Frontal white matter integrity in borderline personality disorder with self-injurious behavior. Journal of Neuropsychiatry & Clinical Neurosciences 19, 383–390.Google Scholar
Hautzinger, M, Bailer, M, Worall, H, Keller, F (1995). Beck-Depressions-Inventar (BDI). Testhandbuch. Huber: Bern.Google Scholar
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. Biological Psychiatry 58, 614–623.Google Scholar
Hazlett, EA, Zhang, J, New, AS, Zelmanova, Y, Goldstein, KE, Haznedar, MM, Meyerson, D, Goodman, M, Siever, LJ, Chu, KW (2012). Potentiated amygdala response to repeated emotional pictures in borderline personality disorder. Biological Psychiatry 72, 448–456.Google Scholar
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. Biological Psychiatry 50, 292–298.Google Scholar
Kahl, KG, Bens, S, Ziegler, K, Rudolf, S, Dibbelt, L, Kordon, A, Schweiger, U (2006). Cortisol, the cortisol-dehydroepiandrosterone ratio, and pro-inflammatory cytokines in patients with current major depressive disorder comorbid with borderline personality disorder. Biological Psychiatry 59, 667–671.Google Scholar
Koenigsberg, HW, Fan, J, Ochsner, KN, Liu, X, Guise, KG, Pizzarello, S, Dorantes, C, Guerreri, S, Tecuta, L, Goodman, M, New, A, Siever, LJ (2009 a). Neural correlates of the use of psychological distancing to regulate responses to negative social cues: a study of patients with borderline personality disorder. Biological Psychiatry 66, 854–863.CrossRefGoogle ScholarPubMed
Koenigsberg, HW, Siever, LJ, Lee, H, Pizzarello, S, New, AS, Goodman, M, Cheng, H, Flory, J, Prohovnik, I (2009 b). Neural correlates of emotion processing in borderline personality disorder. Psychiatry Research 172, 192–199.Google Scholar
Krause-Utz, A, Winter, D, Niedtfeld, I, Schmahl, C (2014). The latest neuroimaging findings in borderline personality disorder. Current Psychiatry Reports 16, 438.Google Scholar
Laux, L, Glanzmann, P, Schaffner, P, Spielberger, CD (1981). Das State-Trait-Angstinventar. Beltz: Weinheim.Google Scholar
Lehrl, S, Triebig, G, Fischer, B (1995). Multiple choice vocabulary test MWT as a valid and short test to estimate premorbid intelligence. Acta Neurologica Scandinavica 91, 335–345.Google Scholar
Lobbestael, J, Arntz, A, Bernstein, DP (2010). Disentangling the relationship between different types of childhood maltreatment and personality disorders. Journal of Personality Disorders 24, 285–295.Google Scholar
Mauchnik, J, Schmahl, C (2010). The latest neuroimaging findings in borderline personality disorder. Current Psychiatry Reports 12, 46–55.Google Scholar
McGlashan, TH, Grilo, CM, Skodol, AE, Gunderson, JG, Shea, MT, Morey, LC, Zanarini, MC, Stout, RL (2000). The Collaborative Longitudinal Personality Disorders Study: baseline Axis I/II and II/II diagnostic co-occurrence. Acta Psychiatrica Scandinavica 102, 256–264.Google Scholar
McGowan, A, King, H, Frankenburg, FR, Fitzmaurice, G, Zanarini, MC (2012). The course of adult experiences of abuse in patients with borderline personality disorder and Axis II comparison subjects: a 10-year follow-up study. Journal of Personality Disorders 26, 192–202.CrossRefGoogle ScholarPubMed
Merrill, JE, Benveniste, EN (1996). Cytokines in inflammatory brain lesions: helpful and harmful. Trends in Neurosciences 19, 331–338.Google Scholar
Mori, S, Oishi, K, Jiang, H, Jiang, L, Li, X, Akhter, K, Hua, K, Faria, AV, Mahmood, A, Woods, R, Toga, AW, Pike, GB, Neto, PR, Evans, A, Zhang, J, Huang, H, Miller, MI, van Zijl, P, Mazziotta, J (2008). Stereotaxic white matter atlas based on diffusion tensor imaging in an ICBM template. Neuroimage 40, 570–582.Google Scholar
Mori, S, Zhang, J (2006). Principles of diffusion tensor imaging and its applications to basic neuroscience research. Neuron 51, 527–539.Google Scholar
New, AS, Carpenter, DM, Perez-Rodriguez, MM, Ripoll, LH, Avedon, J, Patil, U, Hazlett, EA, Goodman, M (2013). Developmental differences in diffusion tensor imaging parameters in borderline personality disorder. Journal of Psychiatric Research 47, 1101–1109.Google Scholar
New, AS, Fan, J, Murrough, JW, Liu, X, Liebman, RE, Guise, KG, Tang, CY, Charney, DS (2009). A functional magnetic resonance imaging study of deliberate emotion regulation in resilience and posttraumatic stress disorder. Biological Psychiatry 66, 656–664.Google Scholar
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, 1629–1640.Google Scholar
Niedtfeld, I, Kirsch, P, Schulze, L, Herpertz, SC, Bohus, M, Schmahl, C (2012). Functional connectivity of pain-mediated affect regulation in Borderline Personality Disorder. PLoS ONE 7, e33293.Google Scholar
Niedtfeld, I, Schulze, L, Kirsch, P, Herpertz, SC, Bohus, M, Schmahl, C (2010). Affect regulation and pain in borderline personality disorder: a possible link to the understanding of self-injury. Biological Psychiatry 68, 383–391.Google Scholar
Niedtfeld, I, Schulze, L, Krause-Utz, A, Demirakca, T, Bohus, M, Schmahl, C (2013). Voxel-based morphometry in women with borderline personality disorder with and without comorbid posttraumatic stress disorder. PLoS ONE 8, e65824.Google Scholar
Ochsner, KN, Silvers, JA, Buhle, JT (2012). Functional imaging studies of emotion regulation: a synthetic review and evolving model of the cognitive control of emotion. Annals of the New York Academy of Sciences 1251, E1–E24.Google Scholar
Oishi, K, Zilles, K, Amunts, K, Faria, A, Jiang, H, Li, X, Akhter, K, Hua, K, Woods, R, Toga, AW, Pike, GB, Rosa-Neto, P, Evans, A, Zhang, J, Huang, H, Miller, MI, van Zijl, PC, Mazziotta, J, Mori, S (2008). Human brain white matter atlas: identification and assignment of common anatomical structures in superficial white matter. Neuroimage 43, 447–457.Google Scholar
Pagano, ME, Skodol, AE, Stout, RL, Shea, MT, Yen, S, Grilo, CM, Sanislow, CA, Bender, DS, McGlashan, TH, Zanarini, MC, Gunderson, JG (2004). Stressful life events as predictors of functioning: findings from the collaborative longitudinal personality disorders study. Acta Psychiatrica Scandinavica 110, 421–429.Google Scholar
Phan, KL, Orlichenko, A, Boyd, E, Angstadt, M, Coccaro, EF, Liberzon, I, Arfanakis, K (2009). Preliminary evidence of white matter abnormality in the uncinate fasciculus in generalized social anxiety disorder. Biological Psychiatry 66, 691–694.Google Scholar
Rusch, N, Luders, E, Lieb, K, Zahn, R, Ebert, D, Thompson, PM, Toga, AW, van Elst, LT (2007 a). Corpus callosum abnormalities in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder. Journal of Psychiatry & Neuroscience 32, 417–422.Google Scholar
Rusch, N, Weber, M, Il'yasov, KA, Lieb, K, Ebert, D, Hennig, J, van Elst, LT (2007 b). Inferior frontal white matter microstructure and patterns of psychopathology in women with borderline personality disorder and comorbid attention-deficit hyperactivity disorder. Neuroimage 35, 738–747.Google Scholar
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 Research 122, 193–198.Google Scholar
Schulze, L, Domes, G, Kruger, A, Berger, C, Fleischer, M, Prehn, K, Schmahl, C, Grossmann, A, Hauenstein, K, Herpertz, SC (2011). Neuronal correlates of cognitive reappraisal in borderline patients with affective instability. Biological Psychiatry 69, 564–573.Google Scholar
Shea, MT, Stout, RL, Yen, S, Pagano, ME, Skodol, AE, Morey, LC, Gunderson, JG, McGlashan, TH, Grilo, CM, Sanislow, CA, Bender, DS, Zanarini, MC (2004). Associations in the course of personality disorders and Axis I disorders over time. Journal of Abnormal Psychology 113, 499–508.Google Scholar
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. American Journal of Psychiatry 164, 1832–1841.Google Scholar
Song, SK, Sun, SW, Ju, WK, Lin, SJ, Cross, AH, Neufeld, AH (2003). Diffusion tensor imaging detects and differentiates axon and myelin degeneration in mouse optic nerve after retinal ischemia. Neuroimage 20, 1714–1722.Google Scholar
Song, SK, Sun, SW, Ramsbottom, MJ, Chang, C, Russell, J, Cross, AH (2002). Dysmyelination revealed through MRI as increased radial (but unchanged axial) diffusion of water. Neuroimage 17, 1429–1436.Google Scholar
Sun, SW, Liang, HF, Trinkaus, K, Cross, AH, Armstrong, RC, Song, SK (2006). Noninvasive detection of cuprizone induced axonal damage and demyelination in the mouse corpus callosum. Magnetic Resonance in Medicine 55, 302–308.Google Scholar
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. Biological Psychiatry 54, 163–171.Google Scholar
Townsend, JD, Torrisi, SJ, Lieberman, MD, Sugar, CA, Bookheimer, SY, Altshuler, LL (2013). Frontal-amygdala connectivity alterations during emotion downregulation in bipolar I disorder. Biological Psychiatry 73, 127–135.Google Scholar
Tromp, DP, Grupe, DW, Oathes, DJ, McFarlin, DR, Hernandez, PJ, Kral, TR, Lee, JE, Adams, M, Alexander, AL, Nitschke, JB (2012). Reduced structural connectivity of a major frontolimbic pathway in generalized anxiety disorder. Archives of General Psychiatry 69, 925–934.Google Scholar
Versace, A, Almeida, JR, Hassel, S, Walsh, ND, Novelli, M, Klein, CR, Kupfer, DJ, Phillips, ML (2008). Elevated left and reduced right orbitomedial prefrontal fractional anisotropy in adults with bipolar disorder revealed by tract-based spatial statistics. Archives of General Psychiatry 65, 1041–1052.Google Scholar
Wakana, S, Jiang, H, Nagae-Poetscher, LM, van Zijl, PC, Mori, S (2004). Fiber tract-based atlas of human white matter anatomy. Radiology 230, 77–87.Google Scholar
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. Journal of Psychiatry, Neuroscience 34, 383–388.Google Scholar
Wingenfeld, K, Spitzer, C, Rullkotter, N, Lowe, B (2009). Borderline personality disorder: hypothalamus pituitary adrenal axis and findings from neuroimaging studies. Psychoneuroendocrinology 35, 154–170.Google Scholar
Wittchen, HU, Pflister, H (1997). Diagnostisches Expertensystem für psychische Störungen. Swets, Zeitlinge: Frankfurt.Google Scholar
Zanarini, MC, Frankenburg, FR, Dubo, ED, Sickel, AE, Trikha, A, Levin, A, Reynolds, V (1998). Axis I comorbidity of borderline personality disorder. American Journal of Psychiatry 155, 1733–1739.Google Scholar
Zanarini, MC, Frankenburg, FR, Hennen, J, Reich, DB, Silk, KR (2004). Axis I comorbidity in patients with borderline personality disorder: 6-year follow-up and prediction of time to remission. American Journal of Psychiatry 161, 2108–2114.Google Scholar
Zanarini, MC, Horz, S, Frankenburg, FR, Weingeroff, J, Reich, DB, Fitzmaurice, G (2011). The 10-year course of PTSD in borderline patients and axis II comparison subjects. Acta Psychiatrica Scandinavica 124, 349–356.Google Scholar
Zhang, A, Leow, A, Ajilore, O, Lamar, M, Yang, S, Joseph, J, Medina, J, Zhan, L, Kumar, A (2012). Quantitative tract-specific measures of uncinate and cingulum in major depression using diffusion tensor imaging. Neuropsychopharmacology 37, 959–967.Google Scholar
Supplementary material: File

Lischke supplementary material

Supplementary Material S1

Download Lischke supplementary material(File)
File 2.5 MB