Neurobehavioral and Psychosocial Aspects of Multiple Chemical Sensitivity

Nancy Fiedler and Howard Kipen

Over the past decade an increasing number of patients have presented with a symptom complex that has been labeled multiple chemical sensitivities or environmental illness. These patients have been characterized to have persistent or recurrent somatic and psychological symptoms attributed to chemical exposures. The symptoms reported and their duration, however, are not consistent with the accepted toxicological properties of the chemicals. Schottenfeld and Cullen (1986), using DSM-III-R diagnostic criteria, initially described such patients to have one of three psychiatric disorders: 1) typical post-traumatic stress disorder; 2) atypical post-traumatic stress disorder; or 3) somatoform disorder. Commensurate with interest expressed in the lay and professional literature, further attempts have been made to characterize these individuals. Cullen (1987) edited an Occupational Medicine State of the Art Review in which he proposed the following relatively rigorous definition: 1) symptoms were acquired in relation to some initial identifiable environmental exposure(s); 2) the symptoms involve more than one organ system (e.g. respiratory and nervous system); 3) the symptoms recur and abate in response to predictable stimuli; 4) the symptoms are elicited by exposures to chemicals of diverse structural classes and toxicologic modes of action; 5) the exposures that elicit symptoms are very low, i.e. many standard deviations below the "TLV" and at levels not known to cause adverse human responses; 6) no single widely available test of organ system function can explain symptoms. This definition was proposed to differentiate MCS patients from patients with post-traumatic stress disorder and somatoform disorder.

Up to this point, subjects reported in the literature have not fully met this more rigorous definition (Brodsky, 1983; Terr, 1986; Bolla-Wilson, et al., 1968; Black et al., 1990; Rosenberg et al., 1990; Simon et al., 1990). For example, Simon et al. (1990) labeled a group of subjects who were currently in workers compensation litigation as chemically sensitive based solely on self-reported lifestyle modifications. Black et al. (1990) reported on psychological profiles of a group of subjects diagnosed as chemically sensitive by physicians practicing clinical ecology. The triggering event for these patients was not uniformly environmental (e.g. stress) nor was the associated diagnosis always chemical sensitivity. For example, some subjects were diagnosed as having chronic candidiasis. Because of the significant regulatory implications of "chemical" sensitivities a need exists to determine if a



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Multiple Chemical Sensitivities: A Workshop Neurobehavioral and Psychosocial Aspects of Multiple Chemical Sensitivity Nancy Fiedler and Howard Kipen Over the past decade an increasing number of patients have presented with a symptom complex that has been labeled multiple chemical sensitivities or environmental illness. These patients have been characterized to have persistent or recurrent somatic and psychological symptoms attributed to chemical exposures. The symptoms reported and their duration, however, are not consistent with the accepted toxicological properties of the chemicals. Schottenfeld and Cullen (1986), using DSM-III-R diagnostic criteria, initially described such patients to have one of three psychiatric disorders: 1) typical post-traumatic stress disorder; 2) atypical post-traumatic stress disorder; or 3) somatoform disorder. Commensurate with interest expressed in the lay and professional literature, further attempts have been made to characterize these individuals. Cullen (1987) edited an Occupational Medicine State of the Art Review in which he proposed the following relatively rigorous definition: 1) symptoms were acquired in relation to some initial identifiable environmental exposure(s); 2) the symptoms involve more than one organ system (e.g. respiratory and nervous system); 3) the symptoms recur and abate in response to predictable stimuli; 4) the symptoms are elicited by exposures to chemicals of diverse structural classes and toxicologic modes of action; 5) the exposures that elicit symptoms are very low, i.e. many standard deviations below the "TLV" and at levels not known to cause adverse human responses; 6) no single widely available test of organ system function can explain symptoms. This definition was proposed to differentiate MCS patients from patients with post-traumatic stress disorder and somatoform disorder. Up to this point, subjects reported in the literature have not fully met this more rigorous definition (Brodsky, 1983; Terr, 1986; Bolla-Wilson, et al., 1968; Black et al., 1990; Rosenberg et al., 1990; Simon et al., 1990). For example, Simon et al. (1990) labeled a group of subjects who were currently in workers compensation litigation as chemically sensitive based solely on self-reported lifestyle modifications. Black et al. (1990) reported on psychological profiles of a group of subjects diagnosed as chemically sensitive by physicians practicing clinical ecology. The triggering event for these patients was not uniformly environmental (e.g. stress) nor was the associated diagnosis always chemical sensitivity. For example, some subjects were diagnosed as having chronic candidiasis. Because of the significant regulatory implications of "chemical" sensitivities a need exists to determine if a

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Multiple Chemical Sensitivities: A Workshop subset of patients can be found who meet the more rigorous definition proposed by Cullen (1987). If such patients can be identified, it is also important to develop a standardized method for evaluating these patients. Therefore, the purpose of the present paper is to document that this relatively narrow group of patients can be identified and to describe the standardized battery of tests we have chosen to characterize these patients. CHARACTERISTICS OF MCS PATIENTS Over the past two years approximately 25 patients have presented at our Environmental and Occupational Health Clinical Center with symptoms suggestive of chemical sensitivity. That is, all patients reported becoming symptomatic to low levels of multiple chemicals/substances encountered in their daily lives. Each patient underwent a comprehensive medical examination by an occupational physician. This consisted of a lifetime and current medical history, review of previous medical records, brief psychiatric history, physical examination, and routine hematology, blood chemistry, thyroid and urine studies. Further testing such as spirometry or chest x-ray were done as needed to document organic conditions which might reasonably explain the symptomatology. While previous organic conditions were often present (e.g. asthma) patients were not excluded if these conditions did not explain the current symptoms. With regard to psychiatric history, patients who reported the following psychiatric diagnoses on their medical questionnaire or during a medical history were not included in the more narrowly defined group of MCS patients: Evidence of current psychosis, organic brain syndrome, mania, or major depression. History of treatment, within, 10 years of onset of symptoms attributed to toxic exposure, for psychosis, organic brain syndrome, hypomania, major depression, somatoform disorder, dissociative disorder, phobia, panic disorder, post-traumatic stress disorder, obsessive compulsive disorder, or personality disorder. Also, individuals were excluded from the rigorously defined subset of chemically sensitive patients if the following were present: 1) in litigation at the time of the evaluation; 2) in treatment with a clinical ecologist. While such patients may have chemical sensitivity, for various reasons these factors may confound the interpretion of the evaluation measures. For exit-pie, patients involved in litigation or being treated by a clinical ecologist may have altered symptom patterns based on these factors. That is, patients in litigation may have a vested interest in appearing more symptomatic while the treatments or information provided by a clinical ecologist could potentially change a patient's symptom profile. Based on the above criteria, eleven of the twenty-five patients qualified as presenting symptoms consistent with chemical sensitivity while not having other current or previous conditions or psychosocial factors that could account for their symptoms. Among those patients who did not qualify, eight did not strictly meet the Cullen (1987) criteria. That is, on careful consideration either they did not have symptoms that wax and wane with exposure or they could not identify a specific point in time or exposure event after which their symptoms began. Among the remaining six patients, two were involved in litigation, and one had a previous psychiatric history of major depression with electroconvulsive treatment. Three others were not available for further study due to logistic reasons, e.g. moved out of state. Thus, eleven patients met the full criteria proposed by Cullen (1987) and did not have the

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Multiple Chemical Sensitivities: A Workshop additional factors outlined previously which could confound an understanding of chemical sensitivity. Chemically sensitive patients were three men and eight women ranging in age from 28 to 57 with a mean age of 42 for men and 43 for women. Educational level ranged from 12 to 16 years with a mean of 15 years for men and 14 years for women. Two male patients had previously worked in the chemical industry while the third was currently working as a draftsman. Two of the eight women were currently working as secretaries and two were administrative assistants, while the remainder worked as a teacher, bus driver, health educator, and sales clerk. All patients were employed at the time their symptoms began. All of the male patients worked with significant chemical or solvent exposures and first experienced symptoms in response to a change in ventilation or in a process at work, although none experienced a particular episode associated with accidental release or acute intoxication. The identified precipitating exposures and subsequent symptoms for five of the eight women occurred at work. For the remaining female patients, precipitating exposures began outside of work. The nature of the identified precipitating exposures included laying new carpet (N=4), indoor air quality complaints in an office environment (N=2), an adverse reaction to a prescribed drug (N=1), and a home pesticide application (N=1). PSYCHOSOCIAL AND PSYCHIATRIC EVALUATION Neurobehavioral Assessment Measures: The primary neurobehavioral symptoms reported by MCS patients include impaired memory, concentration, and visuomotor speed and coordination. Standardized tests of these functions were selected to assess MCS patients and to compare their performance to a normative group of the same age and sex. Tests of Memory: California Verbal Learning Test (Delis, et al., 1987)-short and delayed recall of common words with an interference trial: This test assesses the strategies an individual employs to encode information as well as immediate recall. Therefore, it is sensitive not only to deficits in the amount remembered but also to the way in which material is remembered. It also provides an indicator of short-and long-term memory as well as memory following interference from other tasks. Thus, this test more closely approximates the kind of memory required in day-to-day functioning and the kind of memory deficits often cited among chemically exposed subjects. Digit Span (Wechsler, 1981)-short-term recall of an increasing string of digits: This test is a part of the World Health Organization's (WHO) core battery of tests recommended for assessment of neurobehavioral effects of toxic chemicals. It has age specific normative data and has been used widely in the psychological and exposure assessment literature. It provides an evaluation of immediate memory for digits which may

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Multiple Chemical Sensitivities: A Workshop require different skills from the California Verbal Learning Test which requires memory for common words. Wechsler Memory Scale, Visual Reproduction I & II (Wechsler, 1987) short-and long-term memory for designs: This task requires drawing visual designs from memory and, therefore, assesses the ability to reproduce rather than simply recognize designs. Tests of Concentration: Digit Span test to assess concentration: In addition to memory, this test also provides an assessment of the ability to concentrate. Stroop Color and Word Test (Trenerry et al. 1989)-determines the ability to concentrate with interference from outside stimuli: This task is more complex assessing the ability to concentrate when interfering stimuli are presented. As such, it provides a more realistic assessment of concentration. It has been successful in distinguishing patients with brain dysfunction and, therefore, should provide a useful addition to our assessment of dysfunction due to exposure. Visuomotor Coordination: Grooved Pegboard Test (Trites, 1981)-determines fine motor coordination in a timed situation: This task is used frequently as an indicator of fine motor coordination. Savage et al. (1988) as well as other investigators have found significant deficits on this task among exposed subjects. Digit Symbol (Wechsler, 1981)-requires sustained attention and coordination between eye and hand to record symbols associated with specific digits; This task is one of the World Health Organization's recommended tasks for the detection of brain dysfunction due w toxic exposure. It is particularly sensitive to brain dysfunction at a minimal level (Lezak, 1983). Performance on the above tests of neurobehavioral function can be confounded by difference in age, sex, race, and intelligence (Valciukas, 1985). That is, performance deficits may be due to these variables rather than due to exposures or trauma from exposures. Normative information for the tests cited above has taken into account differences in performance due to age and sex. However, the normative information available generally does not take into account differences in performance due to general intellectual ability. Therefore, a test of verbal ability is also administered as an estimate of overall intellectual ability. It is generally assumed that basic verbal abilities such as vocabulary and well-rehearsed general information will not be affected by acute or transient exposures to toxic substances (Hartman, 1988). Significant discrepancies in performance between a test of reading or vocabulary and those of concentration, memory, and visuomotor skills may help

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Multiple Chemical Sensitivities: A Workshop validate deficits reported by patients clinically. The reading portion of the Wide Range Achievement Test-Revised (Jastak and Wilkinson, 1984) was chosen to assess general word knowledge and as an estimate of overall intellectual ability. Psychiatric Assessment: Since many of the symptoms reported by MCS patients may also reflect psychological distress, several standard measures were selected to assess psychiatric symptomatology. The Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders-Third Edition-Revised (SCID-III-R -DSM-III-R) (Spitzer et al., 1990) is administered to assess current and previous psychiatric symptomatology and diagnoses. Questions are based on the criteria set forth in the DSM-III-R for the diagnosis of psychotic, mood, substance use, anxiety, somatoform, eating, and adjustment disorders. Evaluation of psychopathology prior to the development of MCS is also important since previous psychiatric status is often cited as a precursor to the development of MCS (e.g. Simon et al., 1990). To serve this purpose, the SCID-III-R interview was modified so that patients are specifically asked if their symptoms had existed prior to the development of chemical sensitivities. Where the SCID-III-R covers only current episodes, it was modified by asking patients if they had any occurrence of the symptoms prior to the development of their current chemically related symptomatology. Since previous history of somatization disorder is particularly important to consider among these patients, the Diagnostic Interview Schedule-III-A (DIS-III-A) section for somatization disorder is also separately administered to assess lifetime prevalence of somatization disorder (Robins & Helzer, 1985). The interview format for the DIS-III-A follows a strict set of procedures to ascertain whether physical symptoms reported could be explained medically or by the use of drugs or alcohol. Therefore, this interview format was chosen to be administered by an occupational health nurse with psychiatric experience. A physician then reviewed all medical explanations given by the patients to ascertain their medical plausibility. Based on this procedure, the number of medically explained and unexplained somatic symptoms, occurring before and after the development of MCS, can be determined. The Minnesota Multiphasic Personality Inventory MMPI) (Hathaway & McKinley, 1967) was given to assess current psychiatric symptoms. This self-report inventory has been in use for the past 47 years with a variety of clinical and non-clinical populations. Results from this inventory include validity scales to assess whether the patient responded with a particular response set such as under-or over-reporting of symptoms. H the validity scales are within acceptable limits, then one may proceed to interpret the clinical scales with some evidence that they truly represent the patient. Psychosocial Functioning: MCS has also been reported to have a major impact on patient's functioning in daily life (Cullen, 1987). Therefore, several standardized measures of social functioning were also selected. The Psychosocial Adjustment to Illness Survey Self-Report (PAIS-SR) (Derogatis

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Multiple Chemical Sensitivities: A Workshop & Lopez, 1983) was selected to assess the impact that MCS has on the following dimensions of a patient's life: health care orientation, vocational environment, domestic environment, sexual relationships, extended family relationships, social environment, and psychological distress. The scores of MCS patients may be compared to medically ill patients (i.e. diabetics) to contrast the level of social and life functioning. Other chronically ill groups are also available for comparison such as patients with severe coronary artery disease. The Social Adjustment Scale-Self Report (SAS-SR) (Weissman & Bothwell, 1976) was selected to assess social functioning compared to other psychiatric patients (e.g. depressed or alcoholic patients). This scale gives an overall adjustment score which is based on items covering social adjustment as it pertains to work in or out of home, social and leisure activities, family and marital relationships and economic issues. It has been shown to differentiate depressed patients from normals. RESULTS AND CONCLUSION Neurobehavioral Performance: Chemically sensitive patients did not reveal deficits in concentration or visuomotor skills although some memory tests suggested impairment. Psychosocial Function: Psychosocial functioning of MCS patients was impaired relative to diabetics on the PAIS-SR. That is, they had significant disruptions in their social, home and work lives as well as significant disillusionment with the medical care system. On the SAS-SR, they also revealed disruptions in their home and work functioning. These disruptions were comparable to depressed and alcoholic patients. CONCLUSION A subset of MCS patients who meet more rigid criteria can be identified and characterized using standardized neurobehavioral, psychiatric, and psychosocial measures of functioning. To make studies comparable, it is important to develop standard selection criteria for patient selection and standardized batteries for patient characterization.

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Multiple Chemical Sensitivities: A Workshop REFERENCES Black D.W., Rathe A., Goldstein R. Environmental Illness-A Controlled Study of Twenty-six Subjects with 20th Century Diseases. JAMA 1990;264: 3166-3170;#24. Bolla-Wilson K., Wilson R.J., Bleecher M.L. Conditioning of Physical Symptoms After Neurotoxic Exposure. J. Occup Med. 1988;30:684-686. Brodsky C.M. Psychological Factors Contributing to Somatoform Diseases Attributed to the Workplace. J Occup Med. 1983;25:459-464. Cullen M.R. The Worker With Multiple Chemical Sensitivities: An Overview. In: Cullen M, ed. Workers With Multiple Chemical Sensitivities. Philadelphia: Hanley & Belfus Inc; 1987:655-662. Dells D.C., Framer J.H., Kaplan E., Ober B.A. California Verbal Learning Test Manual. San Antonio: The Psychological Corporation; 1987. Derogatis L.R., Lopez M.C. The Psychosocial Adjustment to Illness Scale (PALS and PAIS-SR) Administration, Scoring and Procedures Manual-I., 1983. Hathaway S.R., McKinley J.C. Minnesota Multiphasic Personality Inventory Manual-Revised. New York: The Psychological Corporation, 1967. Hartman D.E. Neuropsychological Toxicology-Identification and Assessment of Human Neurotoxic Syndromes. New York: Pergamon Press; 1988. Jastak S., Wilkinson G.S. Wide Range Achievement Test Administration Manual. Wilmington: Jastak Associates Inc; 1984. Lezak M.D. Neuropsychological Assessment. New York: Oxford University Press; 1983. Robins L.N., Helzer J.E. Diagnostic Interview Schedule (DIS) Version III-A. St. Louis: Washington Univ. School of Medicine; 1985. Rosenberg S.J., Freedman M.R., Schmaling K.B., Rose C. Personality Styles of Patients Asserting Environmental Illness. J Occup Med. 1990; 32:678-681. Savage A.P., Keefe T.J., Mounce L.M., Heaton R.K., Lewis J.A., Burcar P.J. Chronic Neurological Sequelae of Acute Organophosphate Pesticide Poisoning. Arch of Env Health 1988;43:38-45. Schottenfeld P.S., Cullen M.R. Recognition of Occupational-Induced Post Traumatic Stress Disorders. J. Occup Med. 1986;28:365-369. Simon G.E., Katon W.J., Sparks P.J. Allergic to Life: Psychological Factors in Environmental Illness. Am J Psychiatry. 1990;147:901-906.

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Multiple Chemical Sensitivities: A Workshop Spitzer R.L., Williams J.B.W., Gibbon M., First M.B. User's Guide for the Structured Clinical Interview for DSM-III-R. Washington, DC: American Psychiatric Press, Inc.; 1990. Terr A.I. Environmental Illness: A Clinical Review of 50 Cases. Arch Int Med. 1986;146:145-149. Trenerry M.R., Crosson B., DeBoe J., Leber W.R. Stroop Neuropsychological Screening Test Manual. Odessa FL: Psychological Assessment Resources, Inc; 1989. Trites, R.L. Neuropsychological Test Manual. Montreal, Que: Technolab, 1981. Valciukas, J.A., Control of Confounding Demographic Factors in the Analysis of Neurotoxicological Data. In Environmental Health Document 3. Neurobehavioral Methods in Occupational and Environmental Health. Copenhagen: World Health Organization, 1985. Wechsler D. Wechsler Adult Intelligence Scale-Revised. New York: The Psychological Corporation; 1981. Wechsler D. Wechsler Memory Scale-Revised Manual. San Antonio: The Psychological Corporation; 1987. Weissman M.M., Bothwell S. Assessment of Social Adjustment by Patient Self-Report. Arch Gen Psychia 1976;33:1111-1115. Acknowledgments This project was supported by a grant from the Hazardous Substance Management Research Center, A National Science Foundation Industry/University Cooperative Center and A New Jersey Commission on Science and Technology Advanced Technology Center. We wish to acknowledge the contributions of Kathie Kelly-McNeil and Carol Natarelli, who have both been instrumental in providing the evaluation and care of our patients. We also appreciate the consultation of Bernard Goldstein, M.D. and Michael Gochfeld, M.D., Ph.D. in formulating this project Finally, we appreciate the support services of Joyce Kosmoski and Patricia Hutty in preparing this and other documents for this project.