McGill University, Department of Psychiatry & Douglas Mental Health University Institute, McGill Group for Suicide Studies, Montréal, Québec, Canada; Université de Paris (ex-Université Paris-Descartes), Paris, France; Clinique des Maladies Mentales et de l'Encéphale (CMME), CH Sainte-Anne, GHU Paris Psychiatrie et Neurosciences, Paris, France; Nîmes Academic Hospital (CHU), Nîmes, France.
Nîmes Academic Hospital (CHU), Nîmes, France.
Prog Neuropsychopharmacol Biol Psychiatry. 2020 Jun 8;100:109909. doi: 10.1016/j.pnpbp.2020.109909. Epub 2020 Mar 4.
Psychological pain increases the risk of suicidal ideas and acts, and represents a potential therapeutic target. However, the mechanisms of mental pain remain unclear. Here, we assessed the peripheral transcriptomic and central neural correlates of mental pain during a depressive episode.
172 adult un-medicated depressed patients were recruited. Leucocytes were extracted for RNA quantification at baseline (T0) and after 8 weeks (T8) of an antidepressant treatment. Ninety-nine genes of the cortisol, immune, opioid, serotonergic, and kynurenine systems were a priori selected, and 41 were sufficiently expressed to be analyzed. At both T0 and T8, mean level of mental pain over the last 15 days was measured with a visual analog scale. A subset of 38 patients was additionally scanned with Magnetic Resonance Imaging at T0. Resting-state sequences of 4 networks (default-mode, basal ganglia, central executive, salience) were examined.
Mean psychological pain scores significantly decreased between T0 and T8. At conservative p-corrected levels, T0 mental pain was significantly correlated with 11 brain clusters encompassing the prefrontal, parietal, and temporal cortices, the striatum, and the cerebellum. There was no direct association between peripheral gene expression and mean mental pain at any time points or in terms of temporal changes. However, expressions of 5HTR2B at p-corrected levels, and 5HTR3A, TPH1, and OPRL1 were correlated with the activity of several identified brain clusters at T0. Finally, while suicidal ideas and mental pain were correlated, the neural and molecular correlates of suicidal ideas were not the same.
Our study suggests that the serotonergic and nociceptin systems are associated with the activity of a cortico-subcortical brain network underlying the perception of mental pain during depression. Mental pain may be a necessary but insufficient condition for the emergence of suicidal ideation during depression.
心理痛苦会增加自杀意念和行为的风险，是潜在的治疗靶点。然而，精神痛苦的机制尚不清楚。本研究旨在评估抑郁发作期间心理痛苦的外周转录组学和中枢神经相关性。
招募了 172 名未经药物治疗的成年抑郁症患者。在抗抑郁治疗 8 周后（T8），提取白细胞进行 RNA 定量。皮质醇、免疫、阿片、5-羟色胺能和犬尿氨酸系统的 172 个基因被预先选择，并对 41 个充分表达的基因进行了分析。在 T0 和 T8 时，使用视觉模拟量表评估过去 15 天内心理痛苦的平均水平。38 名患者的亚组在 T0 时还进行了磁共振成像扫描。检测了 4 个网络（默认模式、基底神经节、中央执行、突显）的静息状态序列。
心理痛苦评分从 T0 到 T8 显著降低。在保守的 p 校正水平下，T0 心理痛苦与包括前额叶、顶叶和颞叶皮质、纹状体和小脑在内的 11 个脑区显著相关。在任何时间点或时间变化方面，外周基因表达与平均心理痛苦之间均无直接关联。然而，5HTR2B 的表达在 p 校正水平，以及 5HTR3A、TPH1 和 OPRL1 的表达与 T0 时几个识别出的脑区的活动相关。最后，尽管自杀意念和心理痛苦相关，但自杀意念的神经和分子相关性并不相同。
本研究表明，5-羟色胺能和阿片样物质系统与抑郁期间心理痛苦感知的皮质-皮质下脑网络的活动相关。心理痛苦可能是抑郁期间出现自杀意念的必要但不充分条件。
