Amygdala–Prefrontal Disconnection in Borderline Personality Disorder

Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10029, USA.
Neuropsychopharmacology (Impact Factor: 7.05). 08/2007; 32(7):1629-40. DOI: 10.1038/sj.npp.1301283
Source: PubMed


Abnormal fronto-amygdala circuitry has been implicated in impulsive aggression, a core symptom of borderline personality disorder (BPD). We examined relative glucose metabolic rate (rGMR) at rest and after m-CPP (meta-chloropiperazine) with (18)fluorodeoxyglucose (FDG) with positron emission tomography (PET) in 26 impulsive aggressive (IED)-BPD patients and 24 controls. Brain edges/amygdala were visually traced on MRI scans co-registered to PET scans; rGMR was obtained for ventral and dorsal regions of the amygdala and Brodmann areas within the prefrontal cortex (PFC). Correlation coefficients were calculated between rGMR for dorsal/ventral amygdala regions and PFC. Additionally, amygdala volumes and rGMR were examined in BPD and controls. Correlations PFC/amygdala Placebo: Controls showed significant positive correlations between right orbitofrontal (OFC) and ventral, but not dorsal, amygdala. Patients showed only weak correlations between amygdala and the anterior PFC, with no distinction between dorsal and ventral amygdala. Correlations PFC/amygdala: m-CPP response: Controls showed positive correlations between OFC and amygdala regions, whereas patients showed positive correlations between dorsolateral PFC and amygdala. Group differences between interregional correlational matrices were highly significant. Amygdala volume/metabolism: No group differences were found for amygdala volume, or metabolism in the placebo condition or in response to meta-chloropiperazine (m-CPP). We demonstrated a tight coupling of metabolic activity between right OFC and ventral amygdala in healthy subjects with dorsoventral differences in amygdala circuitry, not present in IED-BPD. We demonstrated no significant differences in amygdala volumes or metabolism between BPD patients and controls.

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Available from: Larry J Siever, Oct 05, 2015
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    • "Consistent with the assumption of prefrontal-limbic imbalance involved in affective dysregulation, functional neuroimaging studies have revealed increased and prolonged amygdala activity in response to (negative) emotional stimuli in BPD patients compared with healthy controls, as well as reduced activity in prefrontal regions involved in regulatory processes such as the anterior cingulate cortex, the medial frontal cortex, the orbitofrontal cortex, and the dorsolateral prefrontal cortex (see, e.g., O'Neill & Frodl, 2012, for a review). In addition, compared with healthy controls, individuals with BPD and comorbid intermittent explosive disorder (BPD-IED) showed impaired functional connectivity between prefrontal and amygdala regions (New et al., 2007). "
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    ABSTRACT: This article proposes a multidimensional model of aggression in borderline personality disorder (BPD) from the perspective of the biobehavioral dimensions of affective dysregulation, impulsivity, threat hypersensitivity, and empathic functioning. It summarizes data from studies that investigated these biobehavioral dimensions using self-reports, behavioral tasks, neuroimaging, neurochemistry as well as psychophysiology, and identifies the following alterations: (a) affective dysregulation associated with prefrontal-limbic imbalance, enhanced heart rate reactivity, skin conductance, and startle response; (b) impulsivity also associated with prefrontal-limbic imbalance, central serotonergic dysfunction, more electroencephalographic slow wave activity, and reduced P300 amplitude in a 2-tone discrimination task; (c) threat hypersensitivity associated with enhanced perception of anger in ambiguous facial expressions, greater speed and number of reflexive eye movements to angry eyes (shown to be compensated by exogenous oxytocin), enhanced P100 amplitude in response to blends of happy versus angry facial expressions, and prefrontal-limbic imbalance; (d) reduced cognitive empathy associated with reduced activity in the superior temporal sulcus/gyrus and preliminary findings of lower oxytocinergic and higher vasopressinergic activity; and (e) reduced self-other differentiation associated with greater emotional simulation and hyperactivation of the somatosensory cortex. These biobehavioral dimensions can be nicely linked to conceptual terms of the alternative Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) model of BPD, and thus to a multidimensional rather than a traditional categorical approach. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    Personality Disorders: Theory, Research, and Treatment 07/2015; 6(3):278-291. DOI:10.1037/per0000098 · 3.54 Impact Factor
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    • "However, we observed the converse. Based on previous work in populations with alcohol dependence alone or with comorbid DSM Axis II disorders, greater BOLD activation would be expected in the limbic regions, with diminished activation in prefrontal cortex corresponding to dysfunctional circuitry, lack of top-down control, and overexpression of anger/emotion (Courtney, Ghahremani, & Ray, 2013; New et al., 2007; Siever, 2008). Chronic alcohol use may disrupt activation of the collective emotional/inhibitory circuitry and manifest as a general inhibitory control deficit (Endres et al., 2014; Fillmore et al., 2005; Li et al., Table 3 "
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    ABSTRACT: Alcohol-related aggression is a complex and problematic phenomenon with profound public health consequences. We examined neural correlates potentially moderating the relationship between human aggressive behavior and chronic alcohol use. Thirteen subjects meeting DSM-IV criteria for past alcohol-dependence in remission (AD) and 13 matched healthy controls (CONT) participated in an fMRI study adapted from a laboratory model of human aggressive behavior (Point Subtraction Aggression Paradigm, or PSAP). Blood oxygen level dependent (BOLD) activation was measured during bouts of operationally defined aggressive behavior, during postprovocation periods, and during monetary-reinforced behavior. Whole brain voxelwise random-effects analyses found group differences in brain regions relevant to chronic alcohol use and aggressive behavior (e.g., emotional and behavioral control). Behaviorally, AD subjects responded on both the aggressive response and monetary response options at significantly higher rates than CONT. Whole brain voxelwise random-effects analyses revealed significant group differences in response to provocation (monetary subtractions), with CONT subjects showing greater activation in frontal and prefrontal cortex, thalamus, and hippocampus. Collapsing data across all subjects, regression analyses of postprovocation brain activation on aggressive response rate revealed significant positive regression slopes in precentral gyrus and parietal cortex; and significant negative regression slopes in orbitofrontal cortex, prefrontal cortex, caudate, thalamus, and middle temporal gyrus. In these collapsed analyses, response to provocation and aggressive behavior were associated with activation in brain regions subserving inhibitory and emotional control, sensorimotor integration, and goal directed motor activity. (PsycINFO Database Record (c) 2015 APA, all rights reserved).
    Behavioral Neuroscience 02/2015; 129(2). DOI:10.1037/bne0000038 · 2.73 Impact Factor
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    • "More recently, the use of objective psychophysiological parameters including affective startle modulation, skin conductance, and heart rate measures of emotional arousal have been employed, also revealing heightened responsivity in BPD, e.g., (Hazlett et al., 2007; Herpertz and Koetting, 2005). The second part of Linehan's Biosocial Theory focusing on difficulties in effortful modulation of negative affect is supported by neuroimaging data demonstrating inefficient regulatory control of the amygdala by prefrontal cortex (PFC) regions (Lis et al., 2007; Minzenberg et al., 2007; Wingenfeld et al., 2009; Silbersweig et al., 2007) and dysfunctional coupling of frontolimbic structures (New et al., 2007). 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. "
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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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