Nathan J Kolla1, Lina Chiuccariello2, Alan A Wilson2, Sylvain Houle2, Paul Links3, R Michael Bagby4, Shelley McMain2, Charis Kellow2, Jalpa Patel2, Paraskevi V Rekkas2, Suvercha Pasricha2, Jeffrey H Meyer5. 1. Centre for Addiction and Mental Health Research Imaging Centre, Campbell Family Mental Health Research Institute at Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto; Institute of Medical Science, University of Toronto, Toronto, Canada. 2. Centre for Addiction and Mental Health Research Imaging Centre, Campbell Family Mental Health Research Institute at Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto. 3. Department of Psychiatry, University of Western Ontario; Institute of Medical Science, University of Toronto, Toronto, Canada. 4. Centre for Addiction and Mental Health Research Imaging Centre, Campbell Family Mental Health Research Institute at Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto; Department of Psychology; Institute of Medical Science, University of Toronto, Toronto, Canada. 5. Centre for Addiction and Mental Health Research Imaging Centre, Campbell Family Mental Health Research Institute at Centre for Addiction and Mental Health, and Department of Psychiatry, University of Toronto; Institute of Medical Science, University of Toronto, Toronto, Canada.. Electronic address: jeff.meyer@camhpet.ca.
Abstract
BACKGROUND: Monoamine oxidase-A (MAO-A) is a treatment target in neurodegenerative illness and mood disorders that increases oxidative stress and predisposition toward apoptosis. Increased MAO-A levels in prefrontal cortex (PFC) and anterior cingulate cortex (ACC) occur in rodent models of depressive behavior and human studies of depressed moods. Extreme dysphoria is common in borderline personality disorder (BPD), especially when severe, and the molecular underpinnings of severe BPD are largely unknown. We hypothesized that MAO-A levels in PFC and ACC would be highest in severe BPD and would correlate with symptom magnitude. METHODS: [(11)C] Harmine positron emission tomography measured MAO-A total distribution volume (MAO-A VT), an index of MAO-A density, in severe BPD subjects (n = 14), moderate BPD subjects (n = 14), subjects with a major depressive episode (MDE) only (n = 14), and healthy control subjects (n = 14). All subjects were female. RESULTS: Severe BPD was associated with greater PFC and ACC MAO-A VT compared with moderate BPD, MDE, and healthy control subjects (multivariate analysis of variance group effect: F6,102 = 5.6, p < .001). In BPD, PFC and ACC MAO-A VT were positively correlated with mood symptoms (PFC: r = .52, p = .005; ACC: r = .53, p = .004) and suicidality (PFC: r = .40, p = .037; ACC: r = .38, p = .046), while hippocampus MAO-A VT was negatively correlated with verbal memory (r = -.44, p = .023). CONCLUSIONS: These results suggest that elevated MAO-A VT is associated with multiple indicators of BPD severity, including BPD symptomatology, mood symptoms, suicidality, and neurocognitive impairment.
BACKGROUND:Monoamine oxidase-A (MAO-A) is a treatment target in neurodegenerative illness and mood disorders that increases oxidative stress and predisposition toward apoptosis. Increased MAO-A levels in prefrontal cortex (PFC) and anterior cingulate cortex (ACC) occur in rodent models of depressive behavior and human studies of depressed moods. Extreme dysphoria is common in borderline personality disorder (BPD), especially when severe, and the molecular underpinnings of severe BPD are largely unknown. We hypothesized that MAO-A levels in PFC and ACC would be highest in severe BPD and would correlate with symptom magnitude. METHODS: [(11)C] Harmine positron emission tomography measured MAO-A total distribution volume (MAO-AVT), an index of MAO-A density, in severe BPD subjects (n = 14), moderate BPD subjects (n = 14), subjects with a major depressive episode (MDE) only (n = 14), and healthy control subjects (n = 14). All subjects were female. RESULTS: Severe BPD was associated with greater PFC and ACC MAO-AVT compared with moderate BPD, MDE, and healthy control subjects (multivariate analysis of variance group effect: F6,102 = 5.6, p < .001). In BPD, PFC and ACC MAO-AVT were positively correlated with mood symptoms (PFC: r = .52, p = .005; ACC: r = .53, p = .004) and suicidality (PFC: r = .40, p = .037; ACC: r = .38, p = .046), while hippocampus MAO-AVT was negatively correlated with verbal memory (r = -.44, p = .023). CONCLUSIONS: These results suggest that elevated MAO-AVT is associated with multiple indicators of BPD severity, including BPD symptomatology, mood symptoms, suicidality, and neurocognitive impairment.
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