Sensitization as a mechanism for multiple chemical sensitivity
Relationship to evolutionary theory
Barbara A. Sorg, David B. Newlin. Scandinavian Journal of Psychology, 43, 161-167. 2002
The following is excerpted from the original 11 page article.
As a first step toward testing some of the hypotheses put forth for MCS, we have developed an animal model of MCS in rats based upon three behavioral endpoints for which the underlying neural circuitry is relatively well described. This circuitry appears to mediate the motivational aspects of approach and avoidance responses to potentially life-threatening stimuli, and is therefore highly relevant to evolutionary theory.
Hypothesis And Multiple Chemical Sensitivity
Like sensitization, the development of MCS has been described as a dual-phase process. The initiation phase is thought to be the stage during which either repeated exposure to chemicals or high-level chemical exposure (such as that occurring during a chemical spill) initiates the process of later sensitivity to chemicals. Thus, initiation events appear to set the individual on a course during which very low levels of subsequent encounters with chemicals or foods elicit the symptoms described above. The experience of symptoms is described as the elicitation phase; it is during this phase that individuals report extreme sensitivity to odors and feelings of illness from chemical exposures encountered at the home and workplace. Another term used for the elicitation phase is triggering.
Our studies have used a rat model to explore the notion that repeated chemical exposure may produce amplified responding (cross-sensitivity) to later presentation of chemicals. For the studies described below, formaldehyde (Form) was chosen for study because it is among the most ubiquitous volatile organic compounds found in indoor air, present in hundreds of common products, such as paper, insulation, wood products, and resins, and appears to produce illness in many humans with sensitivity to chemicals. It is an upper airway irritant in rodents as well, and our recent studies have indicated that Form exposure produces an elevation in basal corticosterone (CORT) levels when given repeatedly at low levels (0.7 ppm), and increased responsiveness to subsequent Form exposure in rats given repeated exposure to higher levels (2.4 ppm).
Relevant to altered activation of the CORT response regarding either basal levels or CORT levels after Form challenge is that such alterations can perturb normal CNS functioning. Chronic elevation of CORT levels has been linked to alterations in corticotropin-releasing hormone (CRH) in the central nucleus of the amygdala and bed nucleus of the stria terminalis. These brain regions have been implicated in fear and anxiety and may increase anticipatory angst in individuals. Increased fear and anxiety and altered cortisol levels in humans have been associated with clinical syndromes, such as PTSD and depression. Interestingly, both of these disorders have been associated with the profile of subpopulations of MCS patients. While fearful depressed patients exhibit increased basal plasma cortisol levels, recent studies in PTSD individuals indicate lower basal cortisol levels but enhanced reactivity of the HPA axis to subsequent stimuli in PTSD. Posttraumatic stress disorder is often described as a sensitization disorder, and it has been suggested that certain individuals may be predisposed to become sensitized to traumatic stressors. If there are similarities between MCS and PTSD, MCS may also be an endpoint reached by those predisposed to sensitization to environmental stimuli in the form of chemicals/foods.
Are MCS And Drug
Abuse Polar Opposites?
One investigator has pointed out the possibility that those who seek out solvent intoxication may differ from those who become aversive to solvent odors in their individual sensitivities. For example, an anxiety response may be initiated in the MCS patient while, for unknown reasons, inhalant abusers may not activate these systems. In Trichloroethylene, a commonly abused inhalant, the chemical produces many of the same symptoms as MCS, such as headache, fatigue, irritability, depression, and alcohol intolerance, but individuals who abuse this inhalant nevertheless find the intoxicating effects pleasurable.
Fig. 1. Neural circuitry mediating approach/avoidance responses to environmental stimuli, individuals with MCS manifest extreme avoidance behavior, whereas in drug abusers, extreme approach behavior toward drugs of abuse is observed. Sensitization is represented by increased gain of the mesolimbic dopamine related circuitry and/or projections from the amygdala, hippocampus (hippo) or prefrontal cortex (PFC) after repeated exposure to environmental chemicals in MCS patients, and to drugs of abuse in drug abusers. Gonadal hormones appear to play a critical role in the altered approach/avoidance behavior observed when repeated cocaine is used as the environmental stimulus (see text).
In humans, the construct of SPFit (self-perceived survival ability and reproductive fitness) describes the inherent capacity of humans to conceptualize and self-perceive their "fitness" (in an evolutionary sense). SPFit is highly adaptable and is strongly influenced by cultural and psychological factors, but reflects the operation of survival and reproductive motivation that is controlled by mesolimbic structures. In this model, the drug abuser is attempting to artificially enhance his/her SPFit by taking drugs of abuse, and the MCS patient is seeking to protect SPFit by avoiding environmental chemicals. In MCS, environmental chemicals, even at very low levels, are perceived as serious threats to survival (or to SPFit). This threat is magnified by prior exposure and the resulting sensitization of mesolimbic circuitry, leading to extreme defensive behavior that we label clinically as MCS.
Evolutionary theory in the context of MCS suggests that the perception of threat, as opposed to the adverse consequences of the chemical itself, may be just as important from a physiological and behavioral standpoint. In humans, this perception of threat may be controlled by SPFit, a psychological structure concerning biological fitness that has roots in the mesocorticolimbic dopamine system.
Contact: Barbara A. Sorg, Alcohol and Drug Abuse Program and Program in Neuroscience, Department of VCPP. Washington State University, Pullman, WA 99164-6520, USA.
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