Journal of Clinical and Experimental Neuropsychology
ISSN: 0168-8634 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ncen19
Psychosis following styrene exposure: A case report of neuropsychological sequelae David M. White , William E. Daniell , James K. Maxwell & Brenda D. Townes To cite this article: David M. White , William E. Daniell , James K. Maxwell & Brenda D. Townes (1990) Psychosis following styrene exposure: A case report of neuropsychological sequelae, Journal of Clinical and Experimental Neuropsychology, 12:5, 798-806, DOI: 10.1080/01688639008401020 To link to this article: http://dx.doi.org/10.1080/01688639008401020
Published online: 04 Jan 2008.
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Date: 06 November 2015, At: 01:15
Journal of Clinical and Experimental Netnopsychology 1990, Vol. 12, No.5, pp. 798-806
0 168-86M/90/1205-O798$3.OO Q Swets & Zeitlinger
Psychosis Following Styrene Exposure: A Case Report of Neuropsychological Sequelae"
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David M. White Department of Rehabilitation Medicine William E. Daniel1 Department of Occupational Medicine James K. Maxwell Department of Psychiatry and Behavioral Sciences Brenda D. Townes Department of Psychiatry and Behavioral Sciences University of Washington Medical Center
ABSTRACT A patient with a significant history of substance abuse was exposed to styrene and other solvents in the workplace. He became acutely psychotic, experiencing visual hallucinations. The psychosis was controlled with neuroleptic medications and avoidance of solvent exposure, but he continued to show significant deficits in visual-spatial and memory abilities. These deficits cleared with time away from the workplace. The case is of interest in terms of neuropsychological sequelae of solvent exposure and potential interaction of solvents with alcohol and recreational drugs.
Styrene i s an organic solvent which is used widely in the production of plastics and resins (Dick & Johnson, 1986). It may be absorbed by direct contact through the skin but, more typically, is inhaled as the substance evaporates. Experimental studies of the effects of styrene vapor have demonstrated that acute exposures can produce transient neurological symptoms including a sensation of drunkenness, headache, reduced manual dexterity, and incoordination (Stewart, Dodd, Baretta. & Schaffer, 1968). These acute effects generally are dose-related and have been produced by levels of exposure Comparable to those which can be found in inadequately ventilated work areas.
* Correspondence should be sent to David M. White, University of Washington Medical Center, Department of Rehabilitation Medicine, RJ-30. Seattle, Washington 98195, USA Accepted for publication: February 7, 1990.
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STYRENE EXPOSURE AND PSYCHOSIS
799
Epidemiologic studies have further examined the effects of long-term styrene exposure upon the central and peripheral nervous systems. Such studies have been complicated by the fact that the majority of workers exposed to styrene are exposed to other organic solvents as well. Data from neuropsychological studies indicate that chronic exposure to styrene in the workplace may result in mild impairment in visuomotor speed, visuomotor accuracy, visual memory, manual dexterity, and simple reaction time (Harkonen, Lindstrom, Seppalainen, Asp, & Hernberg, 1978; Lindstrom, Harkonen, & Hemberg, 1976). Verbal memory also may be mildly impaired, but verbal functions tend to be better preserved than visual-spatial abilities (Mutti et al. 1983). Chronic fatigue and depression are common sequelae of long-term styrene exposure (Axelson & Gustavson, 1978) and electroencephalogram (EEG) studies have shown a higher prevalence of abnormal EEGs among this group than the general population (Harkonen et al., 1978). Alcohol consumption also may be affected by styrene exposure. In one study of the effects of chronic styrene exposure upon workers, 28% reported significant changes in their consumption of alcohol (either increased or decreased), with 32% noting decreased alcohol tolerance (Lindstrom, Harkonen, & Mantere, 1978). The following case report presents a patient who had a significant history of substance abuse and who was exposed to organic solvents, primarily styrene, in the workplace. He developed pronounced cognitive and psychiatric problems, and it is believed that exposure to styrene played a major role in the disturbance of mental functioning. To our knowledge, there are no previous descriptions in the literature of such effects from styrene exposure.
CASE REPORT The patient was a 27-year-old, right-handed male who dropped out of school during the 11th grade. He earned a high school equivalency degree and worked at manual labor jobs during his twenties. He had a history of abuse of alcohol, marijuana, and barbiturates, with treatment for barbiturate addiction at age 17. He reported occasional intravenous use of heroin in the past. At age 24 the patient began working as a fiberglass laminator in a factory where he was exposed to a number of organic solvents. Within a poorly ventilated workplace and with limited access to protective equipment, he was forced to inhale styrene fumes on a daily basis while working with polyester resins. In addition, he was exposed to small amounts of acetone, toluene, and chlorinated hydrocarbons in the workplace. Two years after beginning the job he sought psychiatric treatment for depression and was prescribed doxepin (Sinequan). The psychiatrist noted that the patient had been experiencing back and joint pain, fatigue, and sleep disturbance, in general, as well as nausea, headaches, and “spacey feelings” while at work. He was referred to a neurologist whose evaluation included laboratory testing for organic solvents in blood. The patient was
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found to have a high level of styrene in his blood (0.20 mg/l more than 24 hours after his work shift ended).’ Testing also revealed minute amounts of toluene and trichloroethylene. The patient was regularly using marijuana and alcohol and, on the advice of his psychiatrist, was willing to take disulfiram (Antabuse) to treat the alcohol problem. One month later the patient became increasingly confused over the course of several days and experienced feelings of intoxication at work, although he denied recent alcohol ingestion and continued to take Antabuse. He was sent from work to an emergency room where he was described as disoriented, paranoid, and experiencing both auditory and visual hallucinations. The emergency room physician reported that the patient’s breath smelled like “airplane glue,” although the patient did not deliberately sniff glue or other solvent products. Drug testing revealed trace amounts of urinary tetrahydrocannabinol (THC), consistent with remote or minimal recent use of marijuana. At this time, there was no suspicion that his exposure to chemicals in the workplace might account for his psychosis, so the hospital did not order testing for presence of solvents in the blood. The patient, who had no previous history of a thought disorder, was diagnosed as having an atypical psychosis of unknown etiology. He was admitted to the state psychiatric hospital and prescribed haloperidol (Haldol). For 3 weeks he continued to experience sleep disturbance, depression, and difficulties in concentration and attention. He also continued to have hallucinations, mainly visual in nature. He could describe these in detail (e.g., a tree growing from the carpet) and with recognition that the hallucinations were not real. He would explain to the staff that he was not “crazy” but just “seeing things.” The patient’s paranoid ideation ended soon after his hospitalization, and he gradually stopped experiencing hallucinations. He was released from the hospital and, soon afterwards, stopped taking haloperidol. He began experiencing hallucinations again and was rehospitalized and prescribed thioridizine (Mellaril). During this hospitalization neurological evaluation revealed negative HIV serology, normal brainstem evoked response, normal thyroid function, normal lumbar puncture results, normal cranial MRI, and normal EEG. A drug and alcohol screen was not obtained during this second hospitalization. He was referred for neuropsychological evaluation. The patient was cooperative during neuropsychological evaluation and did not show evidence of a major affective or thought disorder. He seemed upset and embarrassed about experiencing psychiatric symptoms during the previous month. Test results indicated a significant split between verbal and visual-spatial abilities (see Table 1). On the Wechsler Adult Intelligence Scale-Revised The American Conference of Governmental Industrial Hygienists, a professional society which recommends limits for workplace chemical exposures, indicates that blood styrene levels over 0.55 mg/l at end of shift and 0.02 mg/l prior to next shift are consistent with styrene exposure at or above the recommended guidelines (American Conference of Governmental Industrial Hygienists, 1987).
801
STYRENE EXPOSURE AND PSYCHOSIS
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(WAIS-R; Wechsler, 1981) he obtained a Verbal IQ of 96 and a Performance IQ of 79. His poorest performance on the WAIS-R (subtest score of 5 ) was on Picture Completion, measuring visual discrimination and visual alertness. Academic skills, as measured with the Wide Range Achievement Test-Revised (WRAT-R; Jastak & Wilkinson, 1984) were consistent with his 1 1 years of education and did not appear to be reduced by the current problems in cognitive functioning.
Table 1. Neuropsychological Profile of a Patient with Styrene Exposure Area of functioning
Measure
Intellectual abilities
WAIS-R VIQ PIQ
Academic
1st testing (1 month postinitial psychosis)
2nd testing (10 months postinitial psychosis)
96 79
FSIQ
87
99 93 96
WRAT-R Reading Spelling Arithmetic
34th centile 25th centile 9th centile
42nd centile 18th centile 9th centile
89 64 78 106 71
110 96 109 110 115
78 errors 4 errors 29 correct 57 taps
34 errors
WMS-R Verbal Index Visual Index General Index AttentiodConcentration Delayed Memory
Memory abilities
Neuropsychological
HALSTEAD-REITAN BATTERY Category Speech Perception Seashore Rhythm Finger tapping (dominant hand) Tactual Performance Test Dominant hand Nondominant hand Both hands Total time Memory Localization
Motor
4.4 min. 5.1 min. 3.2 min. 12.7 min. 8 objects 3 objects
GROOVED PEGBOARD Dominant hand 84 seconds Nondominant hand 102 seconds
4 errors 29 correct 53 taps
3.0 min. 2.9 min. 1.3 min. 7.2 min. 7 objects 4 objects 57 seconds 59 seconds
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Impairment was shown in some areas of memory functioning. On the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987) he obtained a General Index of 78. Impairment was shown in visual memory (Visual Index of 69) while verbal memory was maintained in the low average range (Verbal Index of 89). On the Halstead-Reitan Neuropsychological Battery (Halstead, 1947) impairment was shown in complex problem solving (Category score of 78) and incidental memory for tactile-spatial relationships (Tactual Performance Test localization score of 3). Fine motor speed (Finger tapping) was above average bilaterally. However, on a test of fine motor dexterity, Grooved Pegboard (Klave, 1963), his scores were moderately impaired for both hands. The patient’s profile on the Minnesota Multiphasic Personality Inventory (MMPI; Hathaway & McKinley, 1951) was similar to that of individuals who present with a combination of characterological and somatic concerns (see Fig. 1). Depression, unusual sensory experiences, fear of losing mental control, and agitation were suggested by the profile. The patient’s neuropsychological profile indicated impairment in concentration, motor performance, and memory, all of which may be seen with exposure to industrial toxins (Feldman, Ricks, & Baker, 1980). The deficits in visual-spatial abilities and visual memory were striking, particularly in view of his visual
100 120\
c
2o
-II
x-x
1 month post-initial psychosls
o--a 10 months post-initial psychosls I
0 ‘
L
F
K
Hs
D
Hy
Pd
Mf
MMPI Scales Fig. 1. MMPI profile of a patient with styrene exposure.
Pa
Pt
Sc
I
t
Ma
Si
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STYRENE EXPOSURE AND PSYCHOSIS
803
hallucinations. Some generalized lowering of cognition was indicated, which likely was due to organic brain dysfunction and depression. The patient showed considerable recovery in cognitive and psychiatric functioning during :he subsequent month while taking thioridizine and remaining away from work. Gradually, he stopped taking his medication and then decided to return to work. After the patient became ill, the company had installed fans and fume hoods in the workplace. In addition, the patient now wore a charcoal filter respirator while working, although he continued to experience cutaneous exposure to solvents by handling chemical products with unprotected hands. He began to consume alcohol heavily and experienced several blackouts within a 1month period. He again began to experience visual hallucinations including the perception that he was viewing the floating heads of small children. The patient quit work and was admitted to an alcohol treatment center for 30 days. Hallucinations were controlled with thioridizine, and he was prescribed medications for control of depression and anxiety. Four months later he was administered neuropsychological tests by the same examiner. At that time, he was not experiencing hallucinations, depression and anxiety were reduced, and he denied recent usage of alcohol or recreational drugs. His only medication was arnitripyline (Elavil) for mild depression, During the second neuropsychological evaluation he showed significant improvement in cognitive functioning (see Table 1). On the WAIS-R his visualspatial abilities generally were average (PIQ = 93). Memory functioning was improved, and on the Halstead-Reitan Neuropsychological Battery his profile was within normal limits. Complex problem solving and tactile-spatial problem solving were improved beyond the level that would be expected simply due to practice effects. Finger tapping speed was within normal limits, and manual dexterity was improved on Grooved Pegboard. On the MMPI (see Figure 1) his profile continued to indicate some characterological problems but also showed substantial reduction in somatic concerns, depression, agitation, and unusual sensory experiences.
DISCUSSION This case illustrates an instance in which exposure to organic solvents in the workplace, primarily styrene, seems to have played a major role in the development of substantial cognitive and psychiatric impairment. The patient’s clinical picture is complicated by a significant history of substance abuse. However, it is unlikely that substance abuse alone could have resulted in his particular pattern of psychiatric and neuropsychological symptoms. His substance abuse had been more active in the past without any other psychiatric abnormality, and his symptoms fluctuated in response to solvent exposure in the workplace. It is reasonable to speculate that the alcohol and recreational drugs might have interacted with the organic solvents to impair brain functioning. A number of studies have shown
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DAVID M.WHITE ET AL.
that alcohol can interact with organic solvents in the body to have synergistic adverse effects (Baker, Smith, & Landrigan, 1985; Klockars, 1986), and many workers report changes in alcohol consumption after chronic styrene exposure (Lindstrom et al., 1978). The patient demonstrated recurrent symptoms at work consistent with acute styrene intoxication as well as paranoia and visual hallucinations. These symptoms cleared with avoidance of the workplace, psychiatric treatment, and abstinence from alcohol. However, he continued to demonstrate abnormalities on neuropsychological tests similar to those observed among workers with longterm exposure. In particular, he showed memory problems and disproportionate deficits in visual-spatial relative to verbal abilities. The patient had been exposed to styrene and other solvents for only two years and, with time away from the workplace, his neuropsychological deficits cleared. The pattern of deficits presented by this patient is intriguing with regard to how styrene and other solvents affect central nervous system functioning. A number of studies have shown that styrene can affect neurochemical processes within the brain. Rats exposed to styrene vapor show initial somnolence with pathologic study revealing a high concentration of styrene within brain tissue (Savolainen & Pfaffli, 1977). However, after a few weeks of regular exposure to styrene the organism appears to show partial metabolic adaptation; styrene levels in the brain tissue of rats were reduced. In humans, abnormalities in levels of doparnine and serotonin have been implicated in psychotic thought processes (McKenna, 1987), and abnormalities in levels of these neurotransmitters have been found following styrene exposure. In rodents styrene exposure has resulted in increased sensitivity of dopamine receptors as well as depletion of dopamine within the corpus striatum (Agrawal, Srivastava, & Seth, 1982; Mutti, Falzoi, Romanelli. & Franchini, 1985). It is hypothesized that styrene may affect dopaminergic activity by destroying dopamine neurons (Agrawal et al., 1982) or by being biotransformed into an active metabolite which competes with dopamine for vesicular storage capacity (Mutti et d.,1985). Husain, Srivastava, Mushtaq, and Seth (1980) did not find changes in quantities of dopamine in rat brains following styrene exposure, but instead found a significant increase of both serotonin and noradrenaline as well as depletion of monoamine oxidase. In humans occupationally exposed to styrene, results of neuroendocrine studies have suggested that this solvent affects dopaminergic activity (Mutti et al., 1984). Since the 19th century it has been known that exposure to certain industrial solvents (e.g., carbon disulphide) can result in dramatic neuropsychiatric symptoms (Hanninen, 1971). The above case illustrates an example in which a worker with a significant history of substance abuse was exposed to styrene and other organic solvents and experienced visual hallucinations, visual-spatial deficits, and memory problems. It is unclear why he displayed such profound symptoms when other workers did not. Analysis of the workplace indicated that the patient’s job duties were in some ways different from those of his co-workers and, at times, he was exposed to a greater concentration of styrene fumes than other
STYRENE EXPOSURE AND PSYCHOSIS
8t)5
i t l d i v t d d s . I n addition, €or most neurotoxins there is considerable variability ersons in terms of susceptibility t o heutopsychiatric symptonis (Hartnldn, 1 8 8 ) , and the patient may h a v e beeh relativefy sensitive to solvent exposure dbe to cofistitutional factors. Finally, h e had a history of substance abuse and, before his secodd psychotic episode, there is evidence that h e was consuming large quantities of alcohol. His symptom picture m a y represent a complex interaction between the effects of styrene, alcohol. and recreationaI drugs on brain f m c t l o n i n g , and styrene appears t o have played a critical role in this interaction. Approximately 9.8 million workers are exposed to potential neurotoxins in the workplace (Minter, 1087). W!ien workers are evaluated for neuropsychintric o r neuropsychological concerns, it is important t o nolc that neurotoxins r n a y simultaneously affect the patient's perceptual, emotional, and higher cognitive functions. It is necessary to appreciate that changes in brain functioning are likely to be multicausal and that all potential contributing factors need to be considered in planning treatment.
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REFERENCES Agrawal, A . K . , Srivastava, S. P.. & Seth, P. K . (1982). Effect of styrene on dopamine receptors. Bulletin of Environmental Contaniination and Toxicology, 2 0 , 400-403. American Conference of Governrncntal Industrial llygienists (1 987). Threshold h i t valrces and biological expoxurc indices for 1987-1988. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. Axelson, O., Rr Gustavson, J. (1978). Some hygenic and clinical observations on styrene exposure. Scandinavian Journal ($Work. Environnient and Health, 4 (suppl. 2). 21 S219.
Baker, E. L., Smith, T. J., & Landrigan, P. J. (1Y85). The neurotoxicity of solvents: A review of the literature. American Journal of Industrid Mctficine, 8 , 207-217. Dick, R. B., & Johnson, 13. I.. (1Y86). Iluman experimental studies. In Z. Aniiau (Ed.), Neurohehavioral toxicology (pp. 348-390). Baltimore: 'I'lie Johns Ilopkins University Press. Feldman, K. G., Ricks, N . L., & Baker, E. L. (1980). Neuropsychological erfects of ~ndustrialtoxins: A review. Anwrican Journal of Industrial Medicine, I , 2 I1-227. Halstead, W. C. (1947). Brain and intelligence. Chicago: Univcrsity of Chicago Press. Hanninen, t i . ( I 97 I ). Psychological picture of manifest and laterit carbon disulpliitlt. poisoning. British Journal of Industrial Medicine, 28, 17.1-381. Harkonen. H., Lindstrom, K., Seppalainen, A . M., Asp, S. & \!ernberg, S. (1978). Exposure-response relationship between styrene exposure and central nervous functions. Scandinavian Journal of Work, Environment und Jtcullh, 4 , 53-59. Ilartman, D. E. ( 1988). Neuro~~.sycholo~ical toxicology: Idrntificcition arid a.s,se.s.snicnt o/ human neurotoxic syndromes. New York: Pergamon Press. Mathaway, S . R., & McKinley. J. C. (1951). The Minncsirta Multiphuic Personality Inventory manual (revised). New York: Psychological Corporation. Hussain, R., Srivastava, S . P., Musthaq, M., & Seth, P. K . ( I Y X O ) . Effects of styrene oil levels of serotonin, noradrenaline, doparnine and activity of acetyl cholinesterase and rnonoainine oxidase iri rat brain. Toxicology Letfers. 7, 47-50.
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Jastak, S., & Wilkinson, G. S. (1984). The Wide Range Achievement Test-Revisedadministrarion manual. Wilmington. Delaware: Jastak Associates. Klockars, M. (1986). Solvents and the liver. In V. Riiiimaki & U. Ulfvarson (Us.), Safety and health aspects of organic solvents (pp. 139-154). New York: Alan R. Liss, Inc. Klprve, H. (1963). Clinical neuropsychology. In F. M. Forster (Ed.),The medical clinics of North America (pp. OOO-O00). New York: Saunders. Lindstrom. K.. Harkonen, H., & Hemberg. S. (1976). Disturbances in psychological functions of workers occupationally exposed to styrene. Scandinavian Journal of Work, Environment and Health, 3, 129-139. Lindstrom, K., Harkonen. H.. & Mantere, P. (1978). Alcohol consumption and tolerance of workers exposed to styrene in relation to level of exposure and psychological symptoms and signs. Scandinavian Journal of Work,Environment and Health, 4 (suppl 2). 129-139.
McKenna, P. J. (1987). Pathology, phenomenology and the dopamine hypothesis of schizophrenia. British Journal of Psychiatry, 151, 288-301. Minter, S. G. (1987). Solvents: New health data demands tighter controls. Occupational Hazards, 56, 125-128. Mutti, A.. Falzoi. M., Romanelli, A., & Franchini, I. (1985). Regional alterations of brain catecholamines by styrene exposure in rabbits. Archives of Toxicology, SS, 173-177. Mutti, A., Mazzucchi, A., Frigeri. G.. Falzoi, M., Arfimi. G.,& Franchini, I. (1983). Neuropsychological investigation of styrene exposed workers. In R. Gilioli. M. G. Cassitto, & V. Foa (Eds.), Neurobehavioral methodr in occupational health (pp. 271281). New York Pergamon Press. Mutti, A.. Vescovi. P. P., Falzoi. M., Arfini. G.. Valenti. G., & Franchini, I. (1984). Neuroendocrine effects of styrene on occupationally exposed workers. Scandinavian Journal of Work, Environment and Health, 10,225-228. Savolahen, H., & Pfaffli, P. (1977). Effects of chronic styrene inhalation on rat protein metabolism. Acta Neuropathologica, 40, 237-241. Stewart, R. D., Dodd. H. C., Baretta. E. D.. & Schaffer. B. S. (1968). Human exposure to styrene vapor. Archives of Environmental Health, 16.656-662. Wechsler, D. (1981). WAIS-R manual. New York: Psychological Corporation. Wechsler. D. (1 987). WMS-R manual. New York: Psychological Corporation.
ISSN: 0168-8634 (Print) (Online) Journal homepage: http://www.tandfonline.com/loi/ncen19
Psychosis following styrene exposure: A case report of neuropsychological sequelae David M. White , William E. Daniell , James K. Maxwell & Brenda D. Townes To cite this article: David M. White , William E. Daniell , James K. Maxwell & Brenda D. Townes (1990) Psychosis following styrene exposure: A case report of neuropsychological sequelae, Journal of Clinical and Experimental Neuropsychology, 12:5, 798-806, DOI: 10.1080/01688639008401020 To link to this article: http://dx.doi.org/10.1080/01688639008401020
Published online: 04 Jan 2008.
Submit your article to this journal
Article views: 6
View related articles
Citing articles: 7 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ncen20 Download by: [NUS National University of Singapore]
Date: 06 November 2015, At: 01:15
Journal of Clinical and Experimental Netnopsychology 1990, Vol. 12, No.5, pp. 798-806
0 168-86M/90/1205-O798$3.OO Q Swets & Zeitlinger
Psychosis Following Styrene Exposure: A Case Report of Neuropsychological Sequelae"
Downloaded by [NUS National University of Singapore] at 01:15 06 November 2015
David M. White Department of Rehabilitation Medicine William E. Daniel1 Department of Occupational Medicine James K. Maxwell Department of Psychiatry and Behavioral Sciences Brenda D. Townes Department of Psychiatry and Behavioral Sciences University of Washington Medical Center
ABSTRACT A patient with a significant history of substance abuse was exposed to styrene and other solvents in the workplace. He became acutely psychotic, experiencing visual hallucinations. The psychosis was controlled with neuroleptic medications and avoidance of solvent exposure, but he continued to show significant deficits in visual-spatial and memory abilities. These deficits cleared with time away from the workplace. The case is of interest in terms of neuropsychological sequelae of solvent exposure and potential interaction of solvents with alcohol and recreational drugs.
Styrene i s an organic solvent which is used widely in the production of plastics and resins (Dick & Johnson, 1986). It may be absorbed by direct contact through the skin but, more typically, is inhaled as the substance evaporates. Experimental studies of the effects of styrene vapor have demonstrated that acute exposures can produce transient neurological symptoms including a sensation of drunkenness, headache, reduced manual dexterity, and incoordination (Stewart, Dodd, Baretta. & Schaffer, 1968). These acute effects generally are dose-related and have been produced by levels of exposure Comparable to those which can be found in inadequately ventilated work areas.
* Correspondence should be sent to David M. White, University of Washington Medical Center, Department of Rehabilitation Medicine, RJ-30. Seattle, Washington 98195, USA Accepted for publication: February 7, 1990.
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STYRENE EXPOSURE AND PSYCHOSIS
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Epidemiologic studies have further examined the effects of long-term styrene exposure upon the central and peripheral nervous systems. Such studies have been complicated by the fact that the majority of workers exposed to styrene are exposed to other organic solvents as well. Data from neuropsychological studies indicate that chronic exposure to styrene in the workplace may result in mild impairment in visuomotor speed, visuomotor accuracy, visual memory, manual dexterity, and simple reaction time (Harkonen, Lindstrom, Seppalainen, Asp, & Hernberg, 1978; Lindstrom, Harkonen, & Hemberg, 1976). Verbal memory also may be mildly impaired, but verbal functions tend to be better preserved than visual-spatial abilities (Mutti et al. 1983). Chronic fatigue and depression are common sequelae of long-term styrene exposure (Axelson & Gustavson, 1978) and electroencephalogram (EEG) studies have shown a higher prevalence of abnormal EEGs among this group than the general population (Harkonen et al., 1978). Alcohol consumption also may be affected by styrene exposure. In one study of the effects of chronic styrene exposure upon workers, 28% reported significant changes in their consumption of alcohol (either increased or decreased), with 32% noting decreased alcohol tolerance (Lindstrom, Harkonen, & Mantere, 1978). The following case report presents a patient who had a significant history of substance abuse and who was exposed to organic solvents, primarily styrene, in the workplace. He developed pronounced cognitive and psychiatric problems, and it is believed that exposure to styrene played a major role in the disturbance of mental functioning. To our knowledge, there are no previous descriptions in the literature of such effects from styrene exposure.
CASE REPORT The patient was a 27-year-old, right-handed male who dropped out of school during the 11th grade. He earned a high school equivalency degree and worked at manual labor jobs during his twenties. He had a history of abuse of alcohol, marijuana, and barbiturates, with treatment for barbiturate addiction at age 17. He reported occasional intravenous use of heroin in the past. At age 24 the patient began working as a fiberglass laminator in a factory where he was exposed to a number of organic solvents. Within a poorly ventilated workplace and with limited access to protective equipment, he was forced to inhale styrene fumes on a daily basis while working with polyester resins. In addition, he was exposed to small amounts of acetone, toluene, and chlorinated hydrocarbons in the workplace. Two years after beginning the job he sought psychiatric treatment for depression and was prescribed doxepin (Sinequan). The psychiatrist noted that the patient had been experiencing back and joint pain, fatigue, and sleep disturbance, in general, as well as nausea, headaches, and “spacey feelings” while at work. He was referred to a neurologist whose evaluation included laboratory testing for organic solvents in blood. The patient was
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found to have a high level of styrene in his blood (0.20 mg/l more than 24 hours after his work shift ended).’ Testing also revealed minute amounts of toluene and trichloroethylene. The patient was regularly using marijuana and alcohol and, on the advice of his psychiatrist, was willing to take disulfiram (Antabuse) to treat the alcohol problem. One month later the patient became increasingly confused over the course of several days and experienced feelings of intoxication at work, although he denied recent alcohol ingestion and continued to take Antabuse. He was sent from work to an emergency room where he was described as disoriented, paranoid, and experiencing both auditory and visual hallucinations. The emergency room physician reported that the patient’s breath smelled like “airplane glue,” although the patient did not deliberately sniff glue or other solvent products. Drug testing revealed trace amounts of urinary tetrahydrocannabinol (THC), consistent with remote or minimal recent use of marijuana. At this time, there was no suspicion that his exposure to chemicals in the workplace might account for his psychosis, so the hospital did not order testing for presence of solvents in the blood. The patient, who had no previous history of a thought disorder, was diagnosed as having an atypical psychosis of unknown etiology. He was admitted to the state psychiatric hospital and prescribed haloperidol (Haldol). For 3 weeks he continued to experience sleep disturbance, depression, and difficulties in concentration and attention. He also continued to have hallucinations, mainly visual in nature. He could describe these in detail (e.g., a tree growing from the carpet) and with recognition that the hallucinations were not real. He would explain to the staff that he was not “crazy” but just “seeing things.” The patient’s paranoid ideation ended soon after his hospitalization, and he gradually stopped experiencing hallucinations. He was released from the hospital and, soon afterwards, stopped taking haloperidol. He began experiencing hallucinations again and was rehospitalized and prescribed thioridizine (Mellaril). During this hospitalization neurological evaluation revealed negative HIV serology, normal brainstem evoked response, normal thyroid function, normal lumbar puncture results, normal cranial MRI, and normal EEG. A drug and alcohol screen was not obtained during this second hospitalization. He was referred for neuropsychological evaluation. The patient was cooperative during neuropsychological evaluation and did not show evidence of a major affective or thought disorder. He seemed upset and embarrassed about experiencing psychiatric symptoms during the previous month. Test results indicated a significant split between verbal and visual-spatial abilities (see Table 1). On the Wechsler Adult Intelligence Scale-Revised The American Conference of Governmental Industrial Hygienists, a professional society which recommends limits for workplace chemical exposures, indicates that blood styrene levels over 0.55 mg/l at end of shift and 0.02 mg/l prior to next shift are consistent with styrene exposure at or above the recommended guidelines (American Conference of Governmental Industrial Hygienists, 1987).
801
STYRENE EXPOSURE AND PSYCHOSIS
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(WAIS-R; Wechsler, 1981) he obtained a Verbal IQ of 96 and a Performance IQ of 79. His poorest performance on the WAIS-R (subtest score of 5 ) was on Picture Completion, measuring visual discrimination and visual alertness. Academic skills, as measured with the Wide Range Achievement Test-Revised (WRAT-R; Jastak & Wilkinson, 1984) were consistent with his 1 1 years of education and did not appear to be reduced by the current problems in cognitive functioning.
Table 1. Neuropsychological Profile of a Patient with Styrene Exposure Area of functioning
Measure
Intellectual abilities
WAIS-R VIQ PIQ
Academic
1st testing (1 month postinitial psychosis)
2nd testing (10 months postinitial psychosis)
96 79
FSIQ
87
99 93 96
WRAT-R Reading Spelling Arithmetic
34th centile 25th centile 9th centile
42nd centile 18th centile 9th centile
89 64 78 106 71
110 96 109 110 115
78 errors 4 errors 29 correct 57 taps
34 errors
WMS-R Verbal Index Visual Index General Index AttentiodConcentration Delayed Memory
Memory abilities
Neuropsychological
HALSTEAD-REITAN BATTERY Category Speech Perception Seashore Rhythm Finger tapping (dominant hand) Tactual Performance Test Dominant hand Nondominant hand Both hands Total time Memory Localization
Motor
4.4 min. 5.1 min. 3.2 min. 12.7 min. 8 objects 3 objects
GROOVED PEGBOARD Dominant hand 84 seconds Nondominant hand 102 seconds
4 errors 29 correct 53 taps
3.0 min. 2.9 min. 1.3 min. 7.2 min. 7 objects 4 objects 57 seconds 59 seconds
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Impairment was shown in some areas of memory functioning. On the Wechsler Memory Scale-Revised (WMS-R; Wechsler, 1987) he obtained a General Index of 78. Impairment was shown in visual memory (Visual Index of 69) while verbal memory was maintained in the low average range (Verbal Index of 89). On the Halstead-Reitan Neuropsychological Battery (Halstead, 1947) impairment was shown in complex problem solving (Category score of 78) and incidental memory for tactile-spatial relationships (Tactual Performance Test localization score of 3). Fine motor speed (Finger tapping) was above average bilaterally. However, on a test of fine motor dexterity, Grooved Pegboard (Klave, 1963), his scores were moderately impaired for both hands. The patient’s profile on the Minnesota Multiphasic Personality Inventory (MMPI; Hathaway & McKinley, 1951) was similar to that of individuals who present with a combination of characterological and somatic concerns (see Fig. 1). Depression, unusual sensory experiences, fear of losing mental control, and agitation were suggested by the profile. The patient’s neuropsychological profile indicated impairment in concentration, motor performance, and memory, all of which may be seen with exposure to industrial toxins (Feldman, Ricks, & Baker, 1980). The deficits in visual-spatial abilities and visual memory were striking, particularly in view of his visual
100 120\
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2o
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x-x
1 month post-initial psychosls
o--a 10 months post-initial psychosls I
0 ‘
L
F
K
Hs
D
Hy
Pd
Mf
MMPI Scales Fig. 1. MMPI profile of a patient with styrene exposure.
Pa
Pt
Sc
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Ma
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hallucinations. Some generalized lowering of cognition was indicated, which likely was due to organic brain dysfunction and depression. The patient showed considerable recovery in cognitive and psychiatric functioning during :he subsequent month while taking thioridizine and remaining away from work. Gradually, he stopped taking his medication and then decided to return to work. After the patient became ill, the company had installed fans and fume hoods in the workplace. In addition, the patient now wore a charcoal filter respirator while working, although he continued to experience cutaneous exposure to solvents by handling chemical products with unprotected hands. He began to consume alcohol heavily and experienced several blackouts within a 1month period. He again began to experience visual hallucinations including the perception that he was viewing the floating heads of small children. The patient quit work and was admitted to an alcohol treatment center for 30 days. Hallucinations were controlled with thioridizine, and he was prescribed medications for control of depression and anxiety. Four months later he was administered neuropsychological tests by the same examiner. At that time, he was not experiencing hallucinations, depression and anxiety were reduced, and he denied recent usage of alcohol or recreational drugs. His only medication was arnitripyline (Elavil) for mild depression, During the second neuropsychological evaluation he showed significant improvement in cognitive functioning (see Table 1). On the WAIS-R his visualspatial abilities generally were average (PIQ = 93). Memory functioning was improved, and on the Halstead-Reitan Neuropsychological Battery his profile was within normal limits. Complex problem solving and tactile-spatial problem solving were improved beyond the level that would be expected simply due to practice effects. Finger tapping speed was within normal limits, and manual dexterity was improved on Grooved Pegboard. On the MMPI (see Figure 1) his profile continued to indicate some characterological problems but also showed substantial reduction in somatic concerns, depression, agitation, and unusual sensory experiences.
DISCUSSION This case illustrates an instance in which exposure to organic solvents in the workplace, primarily styrene, seems to have played a major role in the development of substantial cognitive and psychiatric impairment. The patient’s clinical picture is complicated by a significant history of substance abuse. However, it is unlikely that substance abuse alone could have resulted in his particular pattern of psychiatric and neuropsychological symptoms. His substance abuse had been more active in the past without any other psychiatric abnormality, and his symptoms fluctuated in response to solvent exposure in the workplace. It is reasonable to speculate that the alcohol and recreational drugs might have interacted with the organic solvents to impair brain functioning. A number of studies have shown
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that alcohol can interact with organic solvents in the body to have synergistic adverse effects (Baker, Smith, & Landrigan, 1985; Klockars, 1986), and many workers report changes in alcohol consumption after chronic styrene exposure (Lindstrom et al., 1978). The patient demonstrated recurrent symptoms at work consistent with acute styrene intoxication as well as paranoia and visual hallucinations. These symptoms cleared with avoidance of the workplace, psychiatric treatment, and abstinence from alcohol. However, he continued to demonstrate abnormalities on neuropsychological tests similar to those observed among workers with longterm exposure. In particular, he showed memory problems and disproportionate deficits in visual-spatial relative to verbal abilities. The patient had been exposed to styrene and other solvents for only two years and, with time away from the workplace, his neuropsychological deficits cleared. The pattern of deficits presented by this patient is intriguing with regard to how styrene and other solvents affect central nervous system functioning. A number of studies have shown that styrene can affect neurochemical processes within the brain. Rats exposed to styrene vapor show initial somnolence with pathologic study revealing a high concentration of styrene within brain tissue (Savolainen & Pfaffli, 1977). However, after a few weeks of regular exposure to styrene the organism appears to show partial metabolic adaptation; styrene levels in the brain tissue of rats were reduced. In humans, abnormalities in levels of doparnine and serotonin have been implicated in psychotic thought processes (McKenna, 1987), and abnormalities in levels of these neurotransmitters have been found following styrene exposure. In rodents styrene exposure has resulted in increased sensitivity of dopamine receptors as well as depletion of dopamine within the corpus striatum (Agrawal, Srivastava, & Seth, 1982; Mutti, Falzoi, Romanelli. & Franchini, 1985). It is hypothesized that styrene may affect dopaminergic activity by destroying dopamine neurons (Agrawal et al., 1982) or by being biotransformed into an active metabolite which competes with dopamine for vesicular storage capacity (Mutti et d.,1985). Husain, Srivastava, Mushtaq, and Seth (1980) did not find changes in quantities of dopamine in rat brains following styrene exposure, but instead found a significant increase of both serotonin and noradrenaline as well as depletion of monoamine oxidase. In humans occupationally exposed to styrene, results of neuroendocrine studies have suggested that this solvent affects dopaminergic activity (Mutti et al., 1984). Since the 19th century it has been known that exposure to certain industrial solvents (e.g., carbon disulphide) can result in dramatic neuropsychiatric symptoms (Hanninen, 1971). The above case illustrates an example in which a worker with a significant history of substance abuse was exposed to styrene and other organic solvents and experienced visual hallucinations, visual-spatial deficits, and memory problems. It is unclear why he displayed such profound symptoms when other workers did not. Analysis of the workplace indicated that the patient’s job duties were in some ways different from those of his co-workers and, at times, he was exposed to a greater concentration of styrene fumes than other
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i t l d i v t d d s . I n addition, €or most neurotoxins there is considerable variability ersons in terms of susceptibility t o heutopsychiatric symptonis (Hartnldn, 1 8 8 ) , and the patient may h a v e beeh relativefy sensitive to solvent exposure dbe to cofistitutional factors. Finally, h e had a history of substance abuse and, before his secodd psychotic episode, there is evidence that h e was consuming large quantities of alcohol. His symptom picture m a y represent a complex interaction between the effects of styrene, alcohol. and recreationaI drugs on brain f m c t l o n i n g , and styrene appears t o have played a critical role in this interaction. Approximately 9.8 million workers are exposed to potential neurotoxins in the workplace (Minter, 1087). W!ien workers are evaluated for neuropsychintric o r neuropsychological concerns, it is important t o nolc that neurotoxins r n a y simultaneously affect the patient's perceptual, emotional, and higher cognitive functions. It is necessary to appreciate that changes in brain functioning are likely to be multicausal and that all potential contributing factors need to be considered in planning treatment.
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REFERENCES Agrawal, A . K . , Srivastava, S. P.. & Seth, P. K . (1982). Effect of styrene on dopamine receptors. Bulletin of Environmental Contaniination and Toxicology, 2 0 , 400-403. American Conference of Governrncntal Industrial llygienists (1 987). Threshold h i t valrces and biological expoxurc indices for 1987-1988. Cincinnati, OH: American Conference of Governmental Industrial Hygienists. Axelson, O., Rr Gustavson, J. (1978). Some hygenic and clinical observations on styrene exposure. Scandinavian Journal ($Work. Environnient and Health, 4 (suppl. 2). 21 S219.
Baker, E. L., Smith, T. J., & Landrigan, P. J. (1Y85). The neurotoxicity of solvents: A review of the literature. American Journal of Industrid Mctficine, 8 , 207-217. Dick, R. B., & Johnson, 13. I.. (1Y86). Iluman experimental studies. In Z. Aniiau (Ed.), Neurohehavioral toxicology (pp. 348-390). Baltimore: 'I'lie Johns Ilopkins University Press. Feldman, K. G., Ricks, N . L., & Baker, E. L. (1980). Neuropsychological erfects of ~ndustrialtoxins: A review. Anwrican Journal of Industrial Medicine, I , 2 I1-227. Halstead, W. C. (1947). Brain and intelligence. Chicago: Univcrsity of Chicago Press. Hanninen, t i . ( I 97 I ). Psychological picture of manifest and laterit carbon disulpliitlt. poisoning. British Journal of Industrial Medicine, 28, 17.1-381. Harkonen. H., Lindstrom, K., Seppalainen, A . M., Asp, S. & \!ernberg, S. (1978). Exposure-response relationship between styrene exposure and central nervous functions. Scandinavian Journal of Work, Environment und Jtcullh, 4 , 53-59. Ilartman, D. E. ( 1988). Neuro~~.sycholo~ical toxicology: Idrntificcition arid a.s,se.s.snicnt o/ human neurotoxic syndromes. New York: Pergamon Press. Mathaway, S . R., & McKinley. J. C. (1951). The Minncsirta Multiphuic Personality Inventory manual (revised). New York: Psychological Corporation. Hussain, R., Srivastava, S . P., Musthaq, M., & Seth, P. K . ( I Y X O ) . Effects of styrene oil levels of serotonin, noradrenaline, doparnine and activity of acetyl cholinesterase and rnonoainine oxidase iri rat brain. Toxicology Letfers. 7, 47-50.
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Jastak, S., & Wilkinson, G. S. (1984). The Wide Range Achievement Test-Revisedadministrarion manual. Wilmington. Delaware: Jastak Associates. Klockars, M. (1986). Solvents and the liver. In V. Riiiimaki & U. Ulfvarson (Us.), Safety and health aspects of organic solvents (pp. 139-154). New York: Alan R. Liss, Inc. Klprve, H. (1963). Clinical neuropsychology. In F. M. Forster (Ed.),The medical clinics of North America (pp. OOO-O00). New York: Saunders. Lindstrom. K.. Harkonen, H., & Hemberg. S. (1976). Disturbances in psychological functions of workers occupationally exposed to styrene. Scandinavian Journal of Work, Environment and Health, 3, 129-139. Lindstrom, K., Harkonen. H.. & Mantere, P. (1978). Alcohol consumption and tolerance of workers exposed to styrene in relation to level of exposure and psychological symptoms and signs. Scandinavian Journal of Work,Environment and Health, 4 (suppl 2). 129-139.
McKenna, P. J. (1987). Pathology, phenomenology and the dopamine hypothesis of schizophrenia. British Journal of Psychiatry, 151, 288-301. Minter, S. G. (1987). Solvents: New health data demands tighter controls. Occupational Hazards, 56, 125-128. Mutti, A.. Falzoi. M., Romanelli, A., & Franchini, I. (1985). Regional alterations of brain catecholamines by styrene exposure in rabbits. Archives of Toxicology, SS, 173-177. Mutti, A., Mazzucchi, A., Frigeri. G.. Falzoi, M., Arfimi. G.,& Franchini, I. (1983). Neuropsychological investigation of styrene exposed workers. In R. Gilioli. M. G. Cassitto, & V. Foa (Eds.), Neurobehavioral methodr in occupational health (pp. 271281). New York Pergamon Press. Mutti, A.. Vescovi. P. P., Falzoi. M., Arfini. G.. Valenti. G., & Franchini, I. (1984). Neuroendocrine effects of styrene on occupationally exposed workers. Scandinavian Journal of Work, Environment and Health, 10,225-228. Savolahen, H., & Pfaffli, P. (1977). Effects of chronic styrene inhalation on rat protein metabolism. Acta Neuropathologica, 40, 237-241. Stewart, R. D., Dodd. H. C., Baretta. E. D.. & Schaffer. B. S. (1968). Human exposure to styrene vapor. Archives of Environmental Health, 16.656-662. Wechsler, D. (1981). WAIS-R manual. New York: Psychological Corporation. Wechsler. D. (1 987). WMS-R manual. New York: Psychological Corporation.
