Psychophysiological Hypotheses RegardingMultiple Chemical Sensitivity SyndromePaul M. LehrerDepartment of Psychiatry, University of Medicine and Dentistry of NewJersey-Robert Wood Johnson Medical School, Piscataway, New JerseyThis paper proposes several hypotheses and research strategies for exploring possiblepsychological factors contributing to multiple chemical sensitivity (MCS). The hypotheses are basedon concepts of individual response stereotypy, situational response specificity, classical conditioningof chemical-induced responses, and psychophysiological reactions to active and passive copingorientations. Hypotheses regarding hypersensitivity to perception and/or aversiveness ofchemical stimulation also are presented. Strategies for evaluating these hypotheses are

described based on experimental literature on psychophysiology and psychophysics. EnvironHealth Perspect 105(Suppl 2):479-483 (1997)

Key words: multiple chemical sensitivity, psychophysiology, individual response stereotypy,situational response specificity, active and passive coping, perception, psychophysics,suggestion, conditioning, panic

IntroductionThe topic of psychological aspects ofmultiple chemical sensitivity syndrome(MCS) raises some political issues, particu-larly with individuals who have the disorderand resent being treated as if the problemwere imaginary. Therefore, before thetopic can be addressed scientifically, somejustification sensitive to these concernsmust be made for undertaking this avenueof investigation. I propose the following.

First, conducting research on possiblepsychological or psychophysiological con-tributions to MCS does not imply thatMCS is entirely or primarily psychological.Scientific investigation is neutral on thetopic. If psychological factors play no roleor a minimal role in MCS, a program ofgood research will be able to establish thisfirmly. If psychological factors do play apart, then understanding them can only

This paper is based on a presentation at theConference on Experimental Approaches to ChemicalSensitivity held 20-22 September 1995 in Princeton,New Jersey. Manuscript received at EHP 6 March1996; manuscript accepted 4 September 1996.

The author is grateful to R. Carr, N. Giardino,and H. Kipen for comments on earlier drafts of thispaper.

Address correspondence to Dr. P.M. Lehrer,Department of Psychiatry, Robert Wood JohnsonMedical School, 671 Hoes Lane, Piscataway, NJ08854. Telephone: (908) 235-4413. Fax: (908) 235-5158. E-mail: lehrer@umdnj.edu

Abbreviations used: CNS, central nervous system;HR, heart rate; MCS, multiple chemical sensitivity.

help in the prevention and treatment ofthis debilitating problem.

Second, if psychological factors are foundto play an important role in MCS, this doesnot necessarily imply that the problem isimaginary. The distinction between psycho-logical and somatic disorders has becomeblurred in recent years. It is well knownthat psychological factors can exacerbate avariety of somatic diseases, includingheadache (1-3), ischemic heart disease (4),cancer (5,6), Raynaud's disease (7),rheumatoid arthritis (8), asthma (9), irrita-ble bowel syndrome (10), chronic pain(11), and even some infectious diseases(12). The role of psychological factors inexacerbation of these diseases has beenfirmly established. Some evidence also existsfor a possible contributing role in diathesis.

Conversely, some psychological disordersare known to be triggered by physical ail-ments that produce similar symptoms. Forexample, panic disorder and other anxietydisorders have a statistical relationship withthe presence ofsuch disorders as mitral valveprolapse (13), hyperthyroidism (14), irrita-ble bowel syndrome (15,16), and asthma(17,18). Although no firm evidence existsregarding the direction of causality, severaltheories have been proposed implicatingthese physical disorders as causal factors inpanic disorder. Also, psychological disordersincluding anxiety and depression have beenlinked to particular kinds of brain pathology,such as depressed levels of serotonin and

various structural abnormalities (19,20). Soeven some purely psychological disordershave physiological bases. If a chemical expo-sure adversely affects the central nervous sys-tem, some of the resulting symptoms maylook like mental disorders.

Third, finding an important role forpsychological procedures in treating MCSdoes not necessarily exclude the possibilitythat the disorder is organic in origin. Thisis true even if these psychological proce-dures are as effective or more effective thanvarious medical interventions. For exam-ple, this is the case for muscle contraction(21) and migraine headaches (22,23), irrita-ble bowel syndrome (24,25), and Raynaud'sdisease (26). Psychological components intreatment programs have proven effectivefor hypertension (27), cancer (28,29), andepilepsy (30), to name a few. If exposure tochemicals is a psychological stressor amongMCS patients (probably in addition tobeing a physical trigger of symptoms), astress-related autonomic reaction also mayoccur, perhaps superimposed on otherphysical reactions.

This paper reviews some of the psy-chophysiological research paradigms thathave been used to describe human psy-chophysiological response to various kindsof stimulation. If neuropsychological fac-tors play any role in MCS, their influencemay be measured by research using someof these paradigms.

Psychophysiological ConceptsAs Applied to MCSIndiidual Response StereotypyResearch from the 1950s to the 1970sshows that some individuals tend to pro-duce highly specific physiological responsesto many stressors whereas others apparentlydo not. This tendency has been called indi-vidual response stereotypy (31). Thus, somepeople respond primarily with heart rate(HR) variability, or just with skin conduc-tance responses, to a variety of psychologicalchallenges, from mental arithmetic to scarymovies to reaction time tasks. Individualswho respond in one physiological systemmay not respond in another.

Not everyone shows individual responsestereotypy, but some do to a marked extent.It has been hypothesized that in some casesstereotypy may predispose an individual topsychosomatic disease (32). Consistentwith this, individuals with family historiesof hypertension (and who therefore may

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have a physiological predisposition tohypertension) tend to show greater cardio-vascular reactivity to a variety of laboratorystressors (33). Similarly, asthmatics havebeen found to react to a variety of stressorswith bronchoconstriction (34) and musclecontraction headache patients react withtension in the skeletal muscles of the faceand shoulders, etc. (35). It is possible thatsevere chemical exposure may act as anunconditional stimulus, producing one-triallearning of a conditioned neuropsychologi-cal response. It may have a particular sensi-tizing effect upon individuals who arepredisposed to stereotypic psychophysio-logical responsiveness (e.g., in the lung orthe nose) even before exposure. Later thissame physiological response may generalizeand be elicited by other substances. In thisstage it may also be elicited in response topsychological stressors.

In some people response to chemicalexposure may be in the cardiovascular sys-tem (palpitations, faintness), in some casesin the respiratory system (wheezing ormucous secretions), and in some casessuch chemical exposure may cause nausea,inflammation, fever, fatigue, muscularaches and pains, weakness, or perhaps psy-chological symptoms such as confusion,anxiety, or depression. After chemical expo-sure, it is possible that the body's self-regu-latory system is compromised, so exposureto various kinds of stressors, particularlychemical ones, produces a stereotypedphysiological stress response in this subpop-ulation. To the extent that this responsemay be mediated in part by the central ner-vous system(CNS), psychological factorsmay be involved.

Situatonal Response SpecificitySome tasks elicit characteristic physiologicalresponses (31). For example, tasks elicitingan attitude of active coping tend to producea particular response characterized by betasympathetic activation: increased heart rateand systolic blood pressure, bronchodila-tion, and increased ventilation (36-39).Aversive tasks associated with a more passiveresponse (e.g., watching a scary film) tend toelicit responses such as alpha sympatheticactivation (peripheral vasoconstriction),increased cardiotropic parasympatheticactivity, and bronchoconstriction (40-42).

If exposure to chemicals is a psychologi-cal stressor among MCS patients (in addi-tion to possibly being a physical trigger ofsymptoms), a stress-related autonomic reac-tion also may occur, perhaps superimposedon other physical reactions. If exposure

cannot be avoided, we might expect thepsychological component of the responseto be similar to the passive coping profile:faintness, increased vagal tone, and asthma-like symptoms. On the other hand, if theindividual finds the exposure situationaversive and can avoid it, the response mayinclude rapid heartbeat and perhaps palpi-tations, bronchodilation, and increasedventilation. These all are common symp-toms in MCS. According to this theory,however, if the situation is not perceived tobe aversive, no observable autonomicresponse is expected except that directlyproduced by the chemical (which shouldbe observable in people without MCS andin lower animals).

There is also evidence that exposure tostimuli previously associated with chemicalexposure can produce a strong conditionedpsychophysiologial response specific tothe particular chemical (43). Siegel hashypothesized that this response is adaptivein that it may prepare the body for dealingwith oncoming chemical exposure moreeffectively (43). Thus, as observed ineveryday situations, the sight and smell offood elicits various changes in the gastroin-testinal tract. Aromas, sights, and soundsassociated with a particular place immedi-ately elicit thoughts and often feelings anddesires. Perfume elicits such powerful emo-tional responses that major industries havebeen capitalizing for centuries on pro-nounced psychophysiologial effects ofchemicals in the air. It is possible thatthrough psychological conditioning suchexposures might also elicit physiologicalreactions that could explain at least some ofthe symptoms ofMCS.

Some specific symptoms of disease caneven be triggered by suggestion. In theasthma literature a number of studies haveprovided evidence that psychogenic asthmaattacks can occur even when a person sim-ply thinks that exposure to an asthma trig-ger has occurred. The typical experimentalparadigm here involves telling the asth-matic subject that (s)he is being exposed toan asthma trigger (an allergen or a bron-choconstrictor), and then subjecting theperson to a convincing exposure of an inertsubstance (e.g., nebulized saline or justroom air); the subject believes that (s)hehas been exposed to a nebulized bron-choconstrictor. Among some asthmatics(between 1 in 4 and 1 in 20, depending onthe study), a clinically significant broncho-constriction occurs (34). Similarly, bron-chodilation may occur in some subjectswhen they believe they are being exposed

to a bronchodilator (44). Clinically signi-ficant bronchoconstriction responses tendnot to occur in nonasthmatics, althoughbrief and small but statistically significantresponses sometimes occur in this groupas well. (45).

Relationship between IndividualResponse Stereotypy, StimulusResponse Specificity, andPsychosomatic DiseaseIt is possible that psychosomatic diseasemay occur when a person with a tendencytoward individual response stereotypy isrepeatedly exposed over long periods oftime to situations that also specificallyevoke that person's characteristic response.Under such circumstances, the body maychange its homeostatic set point, or it maycontinually return to a level of physiologi-cal arousal that may be maladaptive inother respects. Alternatively, the organismmay become overly sensitized to particulartypes of stimulation and thus may over-react to stimulation that ordinarily wouldevoke no response. Such sensitization mayoccur either after repetitive stimulation oreven after a single mass exposure, as intraumatic conditioning, particularly wherethe organism is preprogrammed to developsuch a response. The concept of biologicalprepotency or preparedness has been usedto describe the tendency for certain biolog-ically relevant stimuli to be more powerfulthan others as nonhabituating and/or con-ditional stimuli (46). Although biologicalprepotency does not explain much variancein development of human phobias, as orig-inally hypothesized (47) it is possible thatcertain types of chemical stimulation maybe found to be prepotent in this way. Thus,we might hypothesize that MCS patients,whose systems are highly attuned to cues ofchemical exposure, show a similar psy-chophysiologial sensitization to olfactorycues of chemical exposure after repeated ortraumatic exposure. The critical factor dis-tinguishing such reactions from nonpsy-chological sensitization reactions (e.g., asmay occur in allergies) is the role of thecentral nervous system and psychologicalexperience in producing the effects.

Eflf s of Cognitive StyleResearch on coping with stress suggeststhat the cognitive orientation of the indi-vidual toward stressful stimulation has ameasurable and reliable effect on physio-logical response (48). It is reasonable,therefore, to hypothesize that this is alsotrue when stimulation is in the form of

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aversive chemical exposure. Some individualsmay interpret chemical exposure as aver-sive, unavoidable, and inescapable, andthus exhibit a passive coping response. Insuch cases, symptoms of faintness and dys-pnea may prevail because of increased vagaltone and bronchoconstriction. Others mayexperience palpitations and discomfortassociated with muscle tension, becausethey experience the stimulation as a "call toaction." Still others may not consider expo-sure aversive, and so exhibit no emotionallyinduced physiological response.

Differences in PerceptualSensitivity for OlfactoryStimulationBecause the presence and severity of MCSare determined primarily by self-reportingof symptoms, it is possible that sensitivityand ability (or willingness) to reportunpleasant sensations are important com-ponents of the clinical presentation of thedisease. Therefore it is important to studythe sensitivity of MCS patients to variouskinds of body stimulation and compare itto the sensitivity of individuals without thisproblem. Greater perceptual sensitivity tothe magnitude or aversiveness of chemicalstimulation would be consistent with thepossibility that MCS is mediated, in part,by psychophysiologial processes, althoughthis would not prove definitively that suchprocesses have a causal role. The keennessof perception of olfactory stimulation maybe a particularly important variable. Thismay be measurable using any of severalparadigms in psychophysics (49).

Mgnitude EstimatonMagnitude estimation would involveexposing MCS patients to various quanti-ties of inhaled chemicals and then askingthem to rate the relative magnitude of theexposures. This can be done by askingpatients to give a number proportional tothe amount of exposure relative to a stan-dard stimulus of exposure. The usual metricassociated with this method is the slope ofthe gain in perception of intensity relativeto the gain in actual exposure. Individualswho are more sensitive to stimulationwould have higher slopes, usually after dataare converted to a log-log function, toaccount for the expected curviinearity in allmodes of perception.

In addition, the aversiveness associatedwith exposure can be quantified. Based onprevious research on pain and on asthma, itwould be useful to measure relevant dimen-sions of the chemical-induced symptoms.

It is known that most physical symptomshave two independent dimensions: inten-sity and unpleasantness. Of these, theintensity dimension tends to be moreclosely related to physical intensity of stim-ulation, whereas unpleasantness is related tothe subject's emotional reaction to the stim-ulation. These two dimensions have beendocumented in laboratory studies of experi-mentally induced pain (50) and dyspnea(51). Tursky et al. (50) developed the PainPerception Profile, a verbal rating scale forpsychophysical estimate of pain. We haveadapted it for assessment of dyspnea inasthma (51). If MCS individuals experi-ence greater discomfort than others butsimilar levels of perception, this providessome evidence that central nervous systemcenters involving emotional reactivity (e.g.,limbic centers) are sensitized in this popu-lation or perhaps that endorphin levels,which may mitigate feelings of discomfort,are particularly low in this population. Ifsensitivity to the magnitude of the stimula-tion is elevated among MCS patients, it ispossible that sensory nerves and reflexesassociated with sensation may be moreactive among MCS patients. Data fromour laboratory suggest that psychologicalfactors may have a greater impact on per-ception of the unpleasantness of a stimula-tion than in perception of the magnitudeor intensity of the stimulus (52).

Threshold DetectionAnother method for quantifying perceptualsensitivity to stimulation is thresholddetection. In this procedure the intensityof exposure in gradually increased to thepoint at which the individual first feelssomething. This point is the threshold ofdetection. Threshold detection studies alsocan determine the threshold for detecting a"just noticeable difference" in exposure. IfMCS patients have lower absolute and dif-ference thresholds than other subjects, it ispossible that they are more tuned to react-ing to this type of stimulation. Differencesin sensitivity may reflect either physiologi-cal processes (e.g., greater sensory receptorsensitivity) or psychological processes (e.g.,greater alertness to chemical stimulation).A single study by Doty et al. (53) found nodifferences between MCS patients andnormal individuals in the threshold fordetecting the odor of phenyl ethyl alcoholand methyl ethyl ketone, but throughoutthe testing session MCS patients werefound to have higher nasal resistances, res-piration rates, and Beck Depression inven-tory scores. These data suggest that MCS

patients may not be perceptually moresensitive to odors than other subjects, butthey generally exhibit greater depressionand decreased nasal patency.

Method ofProductionInstead of responding verbally in thresholddetection tasks, individuals can self-admin-ister stimulation and stop the stimulationwhen they have reached a threshold ofdetection. This method can be used inconjunction with the magnitude estima-tion method; i.e., subjects can estimate themagnitude of discomfort. In one study, ourlaboratory used this method with patientssuffering from muscle contraction head-aches (54). A tourniquet was tied aroundtheir upper arms and subjects were askedto pump a ball until they began to feel dis-comfort, then pain, then pain sufficient tomake them want to stop pumping. (Toprevent subjects from harming themselvesthey were not permitted to do this task formore than 1.5 min.) We found that head-ache patients detected discomfort and painwithin shorter time periods than other sub-jects but reported the pain to be moreintense than did the other subjects. Thissuggested that headache pain patients weremore sensitive than others to forms ofischemic pain in areas other than the head.

Hyperventilation as a PossibleIntervening Variable in MCSMany physical and emotional stressorsproduce hyperventilation, as do some dis-ease states involving pulmonary or renaldysfunction. Symptoms of hyperventila-tion are extraordinarily varied, and caninclude some common symptoms of MCS.They can include headache, dyspnea, pal-pitations, tremor, pain, panic, and evenseizure activity (55). It would therefore beof interest to study the occurrence ofhyperventilation in this population, partic-ularly in response to chemical stimulation.If hyperventilation plays a role in MCS,then the respiratory responses of MCS vic-tims may be expected to differ from thoseof normal subjects and may be more simi-lar to those among people with known res-piratory abnormalities or panic disorder,both of which produce measurable effectson respiratory response to stress.A tendency to hyperventilate can be

measured noninvasively by measuring end-tidal C02, via a small tube placed at theend of the nostril. A decrease in petCO2might be expected after chemical exposureamong individuals who hyperventilate andmay indicate an emotional response to

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such stimulation. Although the existence ofsuch a response would not indicate that thesymptoms ofMCS are necessarily caused bya hyperventilation response (because corre-lation cannot prove causation), lack of cor-relation could rule out stimulus-inducedhyperventilation as a mediating variablein MCS.

In addition to petCO2, other respiratorymeasures may provide useful information.Measures of respiratory resistance canassess responses involving bronchodilationor bronchoconstriction. Bronchodilationmay predispose a person to hyperventilate,whereas bronchoconstriction may producesome asthmalike symptoms. IfMCS patientsreact bronchially more to psychologicalstress than other individuals, it is possiblethat this response may contribute to someof the symptoms ofMCS.

Assessing respiratory drive after exposureto various chemical stressors also wouldassess the possibility of an augmented

respiratory response. Asthmatics tend toshow a greater increase in inspiratory effortin response to breathing through externalresistors than do other individuals, andpanic disorder patients show greater inspi-ratory pressure responses in response tobreathing CO2. If MCS patients showgreater increases in respiratory drive thanothers when exposed to noxious chemicals,this would also suggest that some symptomsofMCS may result from hyperventilation.

ConclusionThis paper has presented some paradigmsthat have proven useful in the field of psy-chophysiology, and which have shed somelight on asthma and panic disorder. Similarresearch also has revealed informationabout the contribution of psychologicalfactors to hypertension and cardiovasculardisease as well as to a host of other ail-ments. Finding an association betweenMCS and psychophysiologial responsivity

does not necessarily prove a relationship,but it may produce useful informationabout the mechanisms of MCS that couldprove important in finding treatments forthe disorder. For example, if hyperventila-tion were associated with MCS, thenbreathing retraining programs may behelpful. If heightened perceptual sensitivityis involved, desensitization paradigms maybe helpful. If differences in interpretationof physical stimulation are involved, cogni-tive therapy may play a role, as may someantianxiety medication. If a passive copingorientation is implicated, alternative strate-gies might be explored that involve helpingindividuals develop more active strategiesto cope with various physical and emo-tional stressors. Psychophysiologial investi-gation ofMCS, therefore, holds promise ofdetecting factors that may help in psycho-logical control symptoms and consequentreduction in disability.

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