Neuropsychopharmacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
Center for Addictive Disorders, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry Zurich, Lenggstr. 31, 8032 Zurich, Switzerland.
Curr Biol. 2017 Feb 6;27(3):451-457. doi: 10.1016/j.cub.2016.12.030. Epub 2017 Jan 26.
A core aspect of the human self is the attribution of personal relevance to everyday stimuli enabling us to experience our environment as meaningful [1]. However, abnormalities in the attribution of personal relevance to sensory experiences are also critical features of many psychiatric disorders [2, 3]. Despite their clinical relevance, the neurochemical and anatomical substrates enabling meaningful experiences are largely unknown. Therefore, we investigated the neuropharmacology of personal relevance processing in humans by combining fMRI and the administration of the mixed serotonin (5-HT) and dopamine receptor (R) agonist lysergic acid diethylamide (LSD), well known to alter the subjective meaning of percepts, with and without pretreatment with the 5-HTR antagonist ketanserin. General subjective LSD effects were fully blocked by ketanserin. In addition, ketanserin inhibited the LSD-induced attribution of personal relevance to previously meaningless stimuli and modulated the processing of meaningful stimuli in cortical midline structures. These findings point to the crucial role of the 5-HTR subtype and cortical midline regions in the generation and attribution of personal relevance. Our results thus increase our mechanistic understanding of personal relevance processing and reveal potential targets for the treatment of psychiatric illnesses characterized by alterations in personal relevance attribution.
人类自我的一个核心方面是将个人相关性归因于日常刺激，使我们能够将环境体验为有意义的[1]。然而，对感官体验的个人相关性的异常归因也是许多精神疾病的关键特征[2,3]。尽管具有临床相关性，但使体验有意义的神经化学和解剖学基础在很大程度上仍是未知的。因此，我们通过结合 fMRI 和混合 5-羟色胺（5-HT）和多巴胺受体（R）激动剂麦角酸二乙酰胺（LSD）的给药，研究了人类个人相关性处理的神经药理学，LSD 众所周知会改变感知的主观意义，有无 5-HT 受体拮抗剂酮色林预处理。酮色林完全阻断了 LSD 的一般主观效应。此外，酮色林抑制了 LSD 对先前无意义刺激的个人相关性的归因，并调节了皮质中线结构中有意义刺激的处理。这些发现表明 5-HT 受体亚型和皮质中线区域在个人相关性的产生和归因中起着关键作用。我们的研究结果增加了我们对个人相关性处理的机制理解，并揭示了治疗以个人相关性归因改变为特征的精神疾病的潜在靶点。
