Neuroimaging in borderline personality disorder

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Abstract

Neuroimaging has become one of the most important methods in the investigation of the neurobiological underpinnings of borderline personality disorder. Structural and functional imaging studies have revealed dysfunction in different brain regions which seem to contribute to borderline symptomatology. This review presents relevant studies using different methodologies: volumetry of limbic and prefrontal regions, investigations of brain metabolism under resting conditions, studies of serotonergic neurotransmission, and challenge studies using emotional, stressful, and sensory stimuli. Dysfunction in a frontolimbic network is suggested to mediate much, if not all of the borderline symptomatology.

Introduction

The past few years have seen a rapidly growing body of research in the field of neurobiological correlates of borderline personality disorder (BPD) (Lieb et al., 2004, Schmahl et al., 2002, Skodol et al., 2002). In addition to research on the genetic basis of the disorder (Jang et al., 1996, Torgersen et al., 2000), psychopharmacological treatment (Soloff, 2000), and neuroendocrinology (Rinne et al., 2002), progress in neuroimaging has been fruitful in the elucidation of the underlying neurobiology of this severe and chronic disorder.

Affective dysregulation has been suggested to represent the core of borderline symptomatology and to underlie most if not all of the characteristic features of the disorder, such as instable self image, disturbed interpersonal relationships, and self-injurious behavior. Animal studies as well as investigations in healthy human subjects suggest that limbic as well as prefrontal regions play a decisive role in emotion regulation (Davidson and Irwin, 1999). Thus, it can be hypothesized that frontolimbic dysfunction underlies affective dysregulation as well as other closely connected symptoms of BPD. Consequently, structural as well as functional neuroimaging investigations have focussed on alterations in these brain regions.

This review on neuroimaging in BPD is arranged according to the different imaging methods used. It will start with studies using volumetrics and spectroscopy of different brain regions, such as hippocampus, amygdala, and prefrontal regions. An overview of functional neuroimaging will begin with studies of brain metabolism under resting conditions using FDG-PET. Imaging of the serotonergic neurotransmission system using serotonergic agents will then be reviewed, followed by challenge studies that investigate reactivity of brain areas to stimuli such as emotional pictures, stressful memories, or sensory challenges with the aid of PET or functional MRI. Finally, conclusions from the literature reviewed will be drawn and an outlook on future studies will be given.

Section snippets

Volumetrics and spectroscopy

Neuroimaging research in the field of BPD began in the early 1980s with the use of computed tomography (CT). Similar to research on brain alterations in schizophrenic patients, whole brain volumes and ventricle sizes were investigated. In contrast to findings in schizophrenia, studies in BPD did not show ventricular enlargement (Schulz et al., 1983, Snyder et al., 1983), or changes in ventricle–brain ratio (Lucas et al., 1989) in patients with BPD. With the advent of Magnetic Resonance Imaging,

Brain metabolism under resting conditions assessed with FDG-PET

[18F]Deoxyglucose positron emission tomography (FDG-PET) can be used to assess baseline brain metabolism under resting conditions. The first study using FDG-PET in BPD was conducted by Goyer and coworkers (1994). Their investigation comprised 17 patients with DSM III-R personality disorders, six of which (four women and two men) were clinically diagnosed with BPD. However, the average score on the diagnostic interview for borderlines (DIB; Zanarini et al., 1989) in the BPD group was only 3.7,

Imaging of the serotonergic system

Impulsive aggression is part of the BPD phenotype and yet little is known about its neurobiology. Reduced serotonergic activity has been associated with impulsive aggression in metabolite and pharmacologic challenge studies, e.g. hormone responses to fenfluramine that increases serotonergic activity were shown to be abnormal in personality disordered patients with impulsive aggression (Coccaro et al., 1989). However, the neuroanatomical locus of this serotonergic dysfunction is still unclear.

Functional imaging studies with emotional, stressful, and sensory challenges

BPD was suggested to be part of a spectrum of stress-associated disorders together with PTSD, depression and dissociative disorders (Bremner, 2002) and reactivity to stress and stressful reminders appear to underlie affective dysregulation characteristic of patients with BPD. One method to test this reactivity is to expose subjects to emotional challenges or to stressful memories. Challenge studies are using either standardized materials such as emotional slides, or personalized material such

Summary, conclusions, and outlook

Neuroimaging research in BPD started about 20 years ago, and the last decade has brought an enormous increase in structural as well as functional imaging research. This research has been stimulated by neuroimaging investigations in Posttraumatic Stress Disorder and methodologies have been transferred from neuroimaging research in PTSD, e.g., volumetry of hippocampus and amygdala, or challenge studies with stressful autobiographical scripts. Since PTSD and BPD are both characterized by stressful

References (67)

  • T.V. Gurvits et al.

    Magnetic resonance imaging study of hippocampal volume in chronic, combat-related posttraumatic stress disorder

    Biological Psychiatry

    (1996)
  • S.C. Herpertz et al.

    Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study

    Biological Psychiatry

    (2001)
  • F.D. Juengling et al.

    Positron emission tomography in female patients with Borderline Personality Disorder

    Journal of Psychiatric Research

    (2003)
  • T.A. Kimbrell et al.

    Regional brain activity during transient self-induced anxiety and anger in healthy adults

    Biological Psychiatry

    (1999)
  • R.A. Lanius et al.

    Recall of emotional states in posttraumatic stress disorder: an fMRI investigation

    Biological Psychiatry

    (2003)
  • K. Lieb et al.

    Borderline personality disorder

    Lancet

    (2004)
  • P.B. Lucas et al.

    Cerebral structure in borderline personality disorder

    Psychiatry Research

    (1989)
  • I.K. Lyoo

    A brain MRI study in subjects with borderline personality disorder

    Journal of Affective Disorders

    (1998)
  • R. Peyron et al.

    Functional imaging of brain responses to pain

    Clinical Neurophysiology

    (2000)
  • S.L. Rauch et al.

    Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study

    Biological Psychiatry

    (2000)
  • T. Rinne et al.

    Hyperresponsiveness of hypothalamic-pituitary-adrenal axis to combined dexamethasone/corticotropin-releasing hormaone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse

    Biological Psychiatry

    (2002)
  • C.G. Schmahl et al.

    Neural correlates of memories of abandonment in women with and without borderline personality disorder

    Biological Psychiatry

    (2003)
  • C.G. Schmahl et al.

    A PET study of memories of childhood abuse in Borderline Personality Disorder

    Biological Psychiatry

    (2004)
  • L.J. Siever et al.

    d,l-fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoyglucose positron emission tomography

    Neuropsychopharmacology

    (1999)
  • A. Skodol et al.

    The borderline diagnosis II: biology, genetics, and clinical course

    Biological Psychiatry

    (2002)
  • P.H. Soloff

    Borderline personality disorder: psychopharmacology of borderline personality disorder

    Psychiatric Clinics of North America

    (2000)
  • P.H. Soloff et al.

    A fenfluramine-activated FDG-PET study of borderline personality disorder

    Biological Psychiatry

    (2000)
  • P.H. Soloff et al.

    Impulsivity and prefrontal hypometabolism in borderline personality disorder

    Psychiatry Res: Neuroimaging

    (2003)
  • L. Tebartz van Elst et al.

    Frontolimbic brain abnormalities in patients with borderline personality disorder. A volumetric MRI study

    Biological Psychiatry

    (2003)
  • S. Torgersen et al.

    A twin study of personality disorders

    Comprehensive Psychiatry

    (2000)
  • R.-D. Treede et al.

    The cortical representation of pain

    Pain

    (1999)
  • O. Bonne et al.

    Longitudinal MRI study of hippocampal volume in trauma survivors with PTSD

    American Journal of Psychiatry

    (2001)
  • K. Bornhoevd et al.

    Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study

    Brain

    (2002)
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