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

Department of Psychiatry and Psychotherapy, Medical Faculty of Aachen Technical University-RWTH, Aachen, Germany.
Biological Psychiatry (Impact Factor: 10.26). 09/2001; 50(4):292-8. DOI: 10.1016/S0006-3223(01)01075-7
Source: PubMed

ABSTRACT Intense and rapidly changing mood states are a major feature of borderline personality disorder (BPD); however, there have only been a few studies investigating affective processing in BPD, and in particular no neurofunctional correlates of abnormal emotional processing have been identified so far.
Six female BPD patients without additional major psychiatric disorder and six age-matched female control subjects underwent functional magnetic resonance imaging (fMRI) to measure regional cerebral hemodynamic changes following brain activity when viewing 12 standardized emotionally aversive slides compared to 12 neutral slides, which were presented in random order.
Our main finding was that BPD subjects but not control subjects were characterized by an elevated blood oxygenation level dependent fMRI signal in the amygdala on both sides. In addition, activation of the medial and inferolateral prefrontal cortex was seen in BPD patients. Both groups showed activation in the temporo-occipital cortex including the fusiform gyrus in BPD subjects but not in control subjects.
Enhanced amygdala activation in BPD is suggested to reflect the intense and slowly subsiding emotions commonly observed in response to even low-level stressors. Borderline subjects' perceptual cortex may be modulated through the amygdala leading to increased attention to emotionally relevant environmental stimuli.

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    • "Contents lists available at ScienceDirect NeuroImage: Clinical Brambilla et al., 2004; Zetzsche et al., 2007; O3Neill and Frodl, 2012; Richter et al., 2014). Functional imaging studies have also reported altered activation of amygdala to emotional stimuli (Herpertz et al., 2001; Donegan et al., 2003; Minzenberg et al., 2007; Hazlett et al., 2012), along with abnormal activation of regulatory regions in the prefrontal cortex (Silbersweig et al., 2007; O3Neill and Frodl, 2012; Kamphausen et al., 2013; Koenigsberg et al., 2014). There have, however, been fewer neuroimaging studies directly examining the integrity of white matter tracts within fronto-limbic circuits in BPD (Rusch et al., 2010; Carrasco et al., 2012; Maier-Hein et al., 2014). "
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    ABSTRACT: Borderline personality disorder (BPD) is a severe psychiatric disorder involving a range of symptoms including marked affective instability and disturbances in interpersonal interactions. Neuroimaging studies are beginning to provide evidence of altered processing in fronto-limbic network deficits in the disorder, however, few studies directly examine structural connections within this circuitry together with their relation to proposed causative processes and clinical features. In the current study, we investigated whether individuals with BPD (n = 20) have deficits in white matter integrity compared to a matched group of healthy controls (n = 18) using diffusion tensor MRI (DTI). We hypothesized that the BPD group would have decreased fractional anisotropy (FA), a measure of white matter integrity, compared to the controls in white matter tracts connecting frontal and limbic regions, primarily the cingulum, fornix and uncinate fasciculus. We also investigated the extent to which any such deficits related to childhood adversity, as measured by the childhood trauma questionnaire, and symptom severity as measured by the Zanarini rating scale for BPD. We report decreased white matter integrity in BPD versus controls in the cingulum and fornix. There were no significant relationships between FA and measures of childhood trauma. There were, however, significant associations between FA in the cingulum and clinical symptoms of anger, and in the fornix with affective instability, and measures of avoidance of abandonment from the Zanarini rating scale. We report deficits within fronto-limbic connections in individuals with BPD. Abnormalities within the fornix and cingulum were related to severity of symptoms and highlight the importance of these tracts in the pathogenesis of the disorder.
    Clinical neuroimaging 02/2015; 7. DOI:10.1016/j.nicl.2015.01.016 · 2.53 Impact Factor
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    • "The findings of some studies were dependent on the stimuli and revealed effects for BPD-specific stimuli but not for neutral stimuli (Hazlett et al., 2007; Limberg, Barnow, Freyberger, & Hamm, 2011) or effects of specific emotions such as fear but not anger (Minzenberg, Fan, New, Tang, & Siever, 2007). Additionally, a dissociation between physiological measures and subjective reports has been reported (Hazlett et al., 2007; Herpertz et al., 2001; Koenigsberg et al., 2009; Limberg et al., 2011). The findings of psychophysiological studies that have used standardized film clips are also mixed; some of these studies have reported higher baseline values and unchanged reactivity (Kuo & Linehan, 2009), whereas other studies have reported the opposite pattern (Austin, Riniolo, & Porges, 2007). "
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    ABSTRACT: Although emotion dysregulation has consistently been conceptualized as a core problem of borderline personality disorder (BPD), a comprehensive, and empirically and ecologically validated model that captures the exact types of dysregulation remains absent. In the present article, we combine insights from basic affective science and the biosocial theory of BPD to present a theoretical model that captures the most fundamental affective dynamical processes that underlie BPD and stipulates that individuals with BPD are characterized by more negative affective homebases, higher levels of affective variability, and lower levels of attractor strength or return to baseline. Next, we empirically validate this proposal by statistically modeling data from three electronic diary studies on emotional responses to personally relevant stimuli in personally relevant environments that were collected both from patients with BPD (N = 50, 42, and 43) and from healthy subjects (N = 50, 24, and 28). The results regarding negative affective homebases and heightened affective variabilities consistently confirmed our hypotheses across all three datasets. The findings regarding attractor strengths (i.e., return to baseline) were less consistent and of smaller magnitude. The transdiagnostic nature of our approach may help to elucidate the common and distinctive mechanisms that underlie several different disorders that are characterized by affective dysregulation. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    Journal of Abnormal Psychology 01/2015; 124(1). DOI:10.1037/abn0000021 · 4.86 Impact Factor
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    • "Building on the substantial literature in both animals and humans that implicates amygdala in emotional processes, including the perception and production of emotion (Davidson et al., 1999), there is growing evidence supporting the role of amygdala in the emotion processing disturbances observed in BPD. Functional magnetic resonance imaging (fMRI) studies in BPD show increased amygdala activity to specific types of stimuli, e.g., " unresolved " life events (Schmahl et al., 2006), emotional faces (Donegan et al., 2003), positive and negative emotional pictures (Herpertz et al., 2001) and emotionally-triggering scripts (Beblo et al., 2006). More recently, our group has demonstrated exaggerated amygdala response to repeated emotional pictures in two separate BPD studies. "
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    ABSTRACT: Objective: Siever and Davis' (1991) psychobiological framework of borderline personality disorder (BPD) identifies affective instability (AI) as a core dimension characterized by prolonged and intense emotional reactivity. Recently, deficient amygdala habituation, defined as a change in response to repeated relative to novel unpleasant pictures within a session, has emerged as a biological correlate of AI in BPD. Dialectical behavior therapy (DBT), an evidence-based treatment, targets AI by teaching emotion-regulation skills. This study tested the hypothesis that BPD patients would exhibit decreased amygdala activation and improved habituation, as well as improved emotion regulation with standard 12-month DBT. Methods: Event-related fMRI was obtained pre- and post-12-months of standard-DBT in unmedicated BPD patients. Healthy controls (HCs) were studied as a benchmark for normal amygdala activity and change over time (n = 11 per diagnostic-group). During each scan, participants viewed an intermixed series of unpleasant, neutral and pleasant pictures presented twice (novel, repeat). Change in emotion regulation was measured with the Difficulty in Emotion Regulation (DERS) scale. Results: fMRI results showed the predicted Group × Time interaction: compared with HCs, BPD patients exhibited decreased amygdala activation with treatment. This post-treatment amygdala reduction in BPD was observed for all three pictures types, but particularly marked in the left hemisphere and during repeated-emotional pictures. Emotion regulation measured with the DERS significantly improved with DBT in BPD patients. Improved amygdala habituation to repeated-unpleasant pictures in patients was associated with improved overall emotional regulation measured by the DERS (total score and emotion regulation strategy use subscale). Conclusion: These findings have promising treatment implications and support the notion that DBT targets amygdala hyperactivity-part of the disturbed neural circuitry underlying emotional dysregulation in BPD. Future work includes examining how DBT-induced amygdala changes interact with frontal-lobe regions implicated in emotion regulation.
    Journal of Psychiatric Research 10/2014; 57(1). DOI:10.1016/j.jpsychires.2014.06.020 · 3.96 Impact Factor
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