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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    • "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).
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    • "Herpertz et al. 2001; Koenigsberg et al. 2009a, b; Niedtfeld et al. 2010; Schulze et al. 2011; Hazlett et al. 2012) and abnormal connectivity (e.g. New et al. 2007; Silbersweig et al. 2007; Niedtfeld et al. 2012) in these regions, indicating a dysfunctional interplay between (para-)limbic and prefrontal brain regions in BPD (Mauchnik & Schmahl, 2010; Krause-Utz et al. 2014). Since these regions are implicated in the experience and regulation of emotions (Ochsner et al. 2012), emotion dysregulation may be due to structural and functional alterations in these regions (Mauchnik & Schmahl, 2010; Krause-Utz et al. 2014). "
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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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