Myin-Germeys Inez, Marcelis Machteld, Krabbendam Lydia, Delespaul Philippe, van Os Jim
Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands.
Biol Psychiatry. 2005 Jul 15;58(2):105-10. doi: 10.1016/j.biopsych.2005.02.012.
Subjects at increased risk for psychosis experience continuous variation in the intensity of subtle psychotic experiences in response to minor stressors. It was investigated whether this psychotic reactivity in individuals at risk for psychosis is the exophenotypic expression of an underlying endophenotype characterized by a hyperreactive dopamine (DA) system.
First-degree relatives (n = 47) and control subjects (n = 49) were studied with the Experience Sampling Method (ESM), a structured diary technique assessing current context and psychopathology in daily life, to assess psychotic experiences in response to stress. A metabolic perturbation paradigm (administration of 2-deoxy-D-glucose inducing a mild state of glucoprivation) causing plasma elevation of homovanillic acid (HVA) was used as a proxy of DA reactivity.
Multilevel regression analyses revealed that the interaction between HVA reactivity and daily stress in their effect on psychotic experiences differed according to underlying vulnerability. In the first-degree relatives, underlying HVA reactivity modified the psychotic experiences to daily stress, whereas no such effect was found in control subjects.
These results suggest that psychotic experiences in response to minor stresses in the flow of daily life may be functional states of an underlying abnormal DA reactivity in subjects at risk to develop psychosis. The results add credence to the suggestion that abnormal DA reactivity may be part of the substrate that increases risk for psychotic symptoms in individuals at risk.
精神病风险增加的个体在面对轻微应激源时，其细微精神病体验的强度会持续变化。本研究旨在探讨精神病风险个体的这种精神病反应性是否是以多巴胺（DA）系统反应过度为特征的潜在内表型的外在表现。
采用经验取样法（ESM）对一级亲属（n = 47）和对照受试者（n = 49）进行研究，ESM是一种结构化日记技术，用于评估日常生活中的当前情境和精神病理学，以评估对应激的精神病体验。使用代谢扰动范式（给予2-脱氧-D-葡萄糖诱导轻度糖剥夺状态）导致高香草酸（HVA）血浆升高作为DA反应性的指标。
多层次回归分析显示，HVA反应性与日常应激对精神病体验的交互作用因潜在易感性而异。在一级亲属中，潜在的HVA反应性改变了对应激的精神病体验，而在对照受试者中未发现此类效应。
这些结果表明，日常生活中对轻微应激的精神病体验可能是有精神病发作风险个体潜在异常DA反应性的功能状态。这些结果进一步支持了异常DA反应性可能是增加有风险个体出现精神病症状风险的部分基础这一观点。
