Bell I R
Department of Psychiatry, University of Arizona Health Sciences Center, USA.
Toxicol Ind Health. 1994 Jul-Oct;10(4-5):277-312.
The present paper summarizes the proposed time-dependent sensitization (TDS) and partial limbic kindling model for illness from low-level chemicals; reviews and critiques prior studies on CNS aspects of multiple chemical sensitivity (MCS); and outlines possible experimental approaches to future studies. TDS is the progressive and persistent amplification of behavioral, neurochemical, endocrine, and/or immunological responses to repeated intermittent stimuli over time. Partial limbic kindling is a progressive and persistent lowering of the threshold for eliciting electrical afterdischarges, but not motor seizures, in certain brain structures such as amygdala and hippocampus; behavioral consequences include increased avoidant behaviors. The focus of the paper is the controversial claim of altered sense of smell and illness from low levels of environmental chemicals (i.e., "cacosmia"), levels that should not have any biologically harmful effects by the rules of classical neurotoxicology. A major perspective of this paper is that the phenomenology of MCS is similar to that of time-dependent sensitization (reverse tolerance) and tolerance as studied in the substance abuse literature. The TDS model for MCS proposes that neurobiological amplification underlies the symptoms and phenomenology of these patients, including their behavioral features of heightened affective and somatic distress. It is hypothesized that MCS patients, who are mostly women, may be individuals who sensitize to substances rapidly and to the extreme, to the point of aversive symptomatology with less complete capacity for development of tolerance. Possible parallels between MCS and TDS include: (a) initiation by single or multiple intermittent stimuli; (b) lasting changes in subsequent reactivity to low levels of chemically unrelated substances; (c) cross-sensitization between the stressors and pharmacological agents; (d) greater vulnerability of individuals who are female, who have certain genetic characteristics, and/or who may be hyperreactive to novelty (cf. trait shyness); (e) lack of obvious differences between sensitized and unsensitized individuals at baseline without eliciting exposures; (f) bidirectionality (bipolarity) of sensitized responses; (g) both context-dependent (conditioned) and context-independent (unconditioned) amplification of responses. To minimize variability between studies, research in this area needs (a) consensus on a working case definition of MCS or at least of cacosmia as a specific symptom in a subset of well-defined medical and psychiatric disorders; and (b) proper design of chemical challenge studies in MCS, controlling for individual differences in sensitizability and for the properties of sensitization (e.g., repeated intermittent exposure tests) and tolerance (e.g., removal from customary ambient air exposures prior to testing).
本文总结了针对低水平化学物质引发疾病所提出的时间依赖性致敏（TDS）和部分边缘点燃模型；回顾并批判了先前关于多重化学敏感性（MCS）中枢神经系统方面的研究；并概述了未来研究可能采用的实验方法。TDS是行为、神经化学、内分泌和/或免疫反应随着时间对重复间歇性刺激的渐进性和持续性放大。部分边缘点燃是指在某些脑结构（如杏仁核和海马体）中引发电后放电（而非运动性癫痫发作）的阈值的渐进性和持续性降低；行为后果包括回避行为增加。本文的重点是关于低水平环境化学物质导致嗅觉改变和疾病（即“嗅觉倒错”）这一有争议的说法，按照经典神经毒理学的规则，这些化学物质水平不应产生任何生物有害影响。本文的一个主要观点是，MCS的现象学与物质滥用文献中所研究的时间依赖性致敏（反向耐受）和耐受相似。MCS的TDS模型提出，神经生物学放大是这些患者症状和现象学的基础，包括他们情感和躯体痛苦加剧的行为特征。据推测，MCS患者大多为女性，可能是对物质快速且极端敏感的个体，以至于出现厌恶症状，且耐受发展能力不完整。MCS与TDS之间可能的相似之处包括：（a）由单一或多个间歇性刺激引发；（b）随后对低水平化学性质不相关物质的反应性持续变化；（c）应激源与药物之间的交叉致敏；（d）女性、具有某些遗传特征和/或可能对新事物反应过度的个体（参见特质性害羞）更易患病；（e）在未引发暴露的基线时，致敏个体和未致敏个体之间缺乏明显差异；（f）致敏反应的双向性（双极性）；（g）反应的情境依赖性（条件性）和情境独立性（非条件性）放大。为尽量减少研究之间的变异性，该领域的研究需要：（a）就MCS的工作病例定义达成共识，或者至少就嗅觉倒错作为一组明确界定的医学和精神疾病子集中的特定症状达成共识；（b）对MCS化学激发研究进行恰当设计，控制个体致敏性差异以及致敏（如重复间歇性暴露试验）和耐受（如在测试前脱离常规环境空气暴露）的特性。
