Kolla Nathan J, Chiuccariello Lina, Wilson Alan A, Houle Sylvain, Links Paul, Bagby R Michael, McMain Shelley, Kellow Charis, Patel Jalpa, Rekkas Paraskevi V, Pasricha Suvercha, Meyer Jeffrey H
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.
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.
Biol Psychiatry. 2016 Jan 15;79(2):117-26. doi: 10.1016/j.biopsych.2014.11.024. Epub 2014 Dec 16.
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.
[(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.
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).
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.
单胺氧化酶A(MAO-A)是神经退行性疾病和情绪障碍的治疗靶点,它会增加氧化应激并导致细胞凋亡倾向。在抑郁行为的啮齿动物模型以及人类抑郁情绪研究中,前额叶皮质(PFC)和前扣带回皮质(ACC)中的MAO-A水平会升高。极端烦躁不安在边缘型人格障碍(BPD)中很常见,尤其是在病情严重时,而重度BPD的分子基础在很大程度上尚不清楚。我们假设,PFC和ACC中的MAO-A水平在重度BPD中最高,并且与症状严重程度相关。
采用[(11)C]哈米因正电子发射断层扫描测量重度BPD患者(n = 14)、中度BPD患者(n = 14)、仅患有重度抑郁发作(MDE)的患者(n = 14)和健康对照者(n = 14)的MAO-A总分布容积(MAO-A VT),这是MAO-A密度的一个指标。所有受试者均为女性。
与中度BPD、MDE和健康对照者相比,重度BPD与更高的PFC和ACC的MAO-A VT相关(多变量方差分析组效应:F6,102 = 5.6,p <.001)。在BPD中,PFC和ACC的MAO-A VT与情绪症状呈正相关(PFC:r =.52,p =.005;ACC:r =.53,p =.004)以及与自杀倾向呈正相关(PFC:r =.40,p =.037;ACC:r =.38,p =.046),而海马体的MAO-A VT与言语记忆呈负相关(r = -.44,p =.023)。
这些结果表明,升高的MAO-A VT与BPD严重程度的多个指标相关,包括BPD症状、情绪症状、自杀倾向和神经认知障碍。