Dysregulation of Regional Endogenous Opioid Function in Borderline Personality Disorder

Department of Psychiatry, Molecular and Behavioral Neuroscience Institute, University of Michigan, 4250 Plymouth Rd., Ann Arbor, MI 48109-2700, USA.
American Journal of Psychiatry (Impact Factor: 12.3). 05/2010; 167(8):925-33. DOI: 10.1176/appi.ajp.2010.09091348
Source: PubMed


Borderline personality disorder is characterized by a lack of effective regulation of emotional responses. The authors investigated the role of the endogenous opioid system and mu-opioid receptors in emotion regulation in borderline personality disorder.
Mu-opioid receptor availability in vivo (nondisplaceable binding potential, or BP(ND)) was measured with positron emission tomography and the selective radiotracer [(11)C]carfentanil during neutral and sustained sadness states in 18 unmedicated female patients with borderline personality disorder and 14 healthy female comparison subjects.
Patients showed greater regional mu-opioid BP(ND) than did comparison subjects at baseline (neutral state) bilaterally in the orbitofrontal cortex, caudate, and nucleus accumbens and in the left amygdala, but lower BP(ND) in the posterior thalamus. Sadness induction was associated with greater reductions in BP(ND) (endogenous opioid system activation) in the patient group than in the comparison group in the pregenual anterior cingulate, left orbitofrontal cortex, left ventral pallidum, left amygdala, and left inferior temporal cortex. Patients showed evidence of endogenous opioid system deactivation in the left nucleus accumbens, the hypothalamus, and the right hippocampus/parahippocampus relative to comparison subjects. Correlations of baseline measures with the Dissociative Experiences Scale and endogenous opioid system activation with the Barratt Impulsiveness Scale did not remain significant after correction for multiple comparisons.
Differences exist between patients with borderline personality disorder and comparison subjects in baseline in vivo mu-opioid receptor concentrations and in the endogenous opioid system response to a negative emotional challenge that can be related to some of the clinical characteristics of patients with borderline personality disorder. The regional network involved is implicated in the representation and regulation of emotion and stress responses.

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Available from: Alan Rodney Prossin, Jan 01, 2016
    • "Imaging studies using the selective μ-opioid receptor agonist [ 11 C]carfentanyl, or nonselective opioid antagonist naloxone, identified a critical role of the EOS in control of these processes in the pgACC (Kennedy et al. 2006; Wager et al. 2007; Eippert et al. 2009). Analysis of the mechanisms underlying the neurochemical basis of lateralized function in the pgACC is clinically important, because abnormalities in this area are associated with depression, schizophrenia , borderline personality, and anxiety disorders (Fahim et al. 2005; Walter et al. 2009; Prossin et al. 2010; Pizzagalli 2011), and autism spectrum disorder including Asperger syndrome (Oner et al. 2007). Thus, an aberrant neuronal activation of the pgACC may contribute to anhedonia in major depression (Walter et al. 2009). "
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    ABSTRACT: Lateralization of the processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria, and pain, the μ-, δ-, and κ-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and 5 "classical" neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg (LER) and Met-enkephalin-Arg-Phe, preferential δ-/μ- and κ-/μ-opioid agonists, demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B (Dyn B) strongly correlated with LER in the left, but not in the right ACC suggesting different mechanisms of the conversion of this κ-opioid agonist to δ-/μ-opioid ligand in the 2 hemispheres; in the right ACC, Dyn B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlies in part lateralization of higher functions, including positive and negative emotions and pain in the human brain.
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    • "Hirvonen et al., 2009; Prossin et al., 2010; Tuominen et al., 2012), employing the radioligand [ 11 C] carfentanil, which selectively binds to ␮-opioid receptors; a high-affinity binding site for ␤-endorphin (McDonald and Lambert, 2005). This technique has yielded promising results when investigating dynamic levels of endogenous opioids in response to peripherally applied noxious stimuli, such as topical capsaicin (Bencherif et al., 2002) and also in response to affective manipulation (Prossin et al., 2010). Imaging techniques allow us a valuable window into central basal and crucially, dynamic endogenous opioid activity; the latter being problematic to assess with CSF and to some extent, also with plasma measures. "
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    • "Other relevant neuropeptides include vasopressin and neuropeptide Y. Recent neurobiological research has suggested endogenous opioid modulation as a potential avenue for treatment of BPD.115-116 Endogenous opioid signaling is involved in consummatory reward processing, pain modulation, social affiliation,117 rejection sensitivity, and maternal-infant attachment,118-119 which may have implications for impulsivity, self-injurious behavior, and interpersonal dysfunction in BPD. Dysregulated opioid signaling is also associated with affective instability in BPD.120 Despite promise in terms of potential implications in the developmental psychopathology of BPD, opioid medications have not demonstrated consistent therapeutic benefit. "
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