Chronic neurobehavioral effects of Tokyo subway sarin poisoning in relation to posttraumatic stress disorder

Chronic neurobehavioral effects of Tokyo subway sarin poisoning in relation to posttraumatic stress disorder

Kazuhito Yokoyama

SARIN (methyl phosphonofluoridic acid 1-methylethyl ester), an organophosphate compound known to be a chemical warfare nerve agent, is a strong acetylcholinesterase inhibitor. On June 27, 1994, approximately 600 residents in Matsumoto city, Japan–located about 150 km northwest of Tokyo–were poisoned during a presumed terrorist attack with sarin. All affected individuals recovered without abnormal findings on routine neurological and laboratory examinations, except for 1 patient who had severe anoxic encephalopathy from respiratory arrest.[1] On March 20, 1995, approximately 5 500 individuals were also poisoned with sarin in subways in Tokyo (Tokyo Subway Sarin Poisoning). According to the results of a follow-up study on the 640 cases,[2] 2 cases died immediately after admission to the hospital, and no clinical abnormalities persisted 3 mo after poisoning. Chronic neurological effects of acute sarin poisoning, therefore, were not reported in the two earlier studies.

Duffy et al.,[3] however, reported electroencephalogram (EEG) abnormalities in chemical plant workers that persisted more than 1 y after accidental exposure to sarin occurred.[3] Burchfeld et al.[4] observed EEG changes in monkeys 1 y after experimental sarin poisoning occurred. Recently, investigators[5-7] reported chronic neurological sequelae and decreased performance on neurobehavioral tests after acute organophosphate pesticide poisoning occurred.

In the present study, the authors assessed chronic neurobehavioral effects of acute sarin poisoning. The authors examined 18 patients who were exposed at the time of the Tokyo Subway Sarin Poisoning incident; they used nine neurobehavioral tests and the posttraumatic stress disorder (PTSD) checklist[8] 6-8 mo after the poisoning occurred. The authors directed special attention to the effects of PTSD on the occurrence of chronic effects.

Background

On March 20, 1995, 11 plastic bags containing an odorous chemical agent were placed in, and poisonous vapors released from, bags in five cars on three separate subway lines (i.e., Hibiya, Chiyoda, and Kasumigaseki lines), which were scheduled to converge from the north and west on the Kasumigaseki Station (located in the government district of Tokyo) between 8:09 A.M. and 8:13 A.M. As a result, approximately 5 500 people were poisoned in the subway cars and stations around 8:00 A.M.; 9 passengers and 2 station officers died. The Metropolitan Police Department and the Self-Defense Force quickly identified the chemical agent as sarin. Possible routes of exposure to sarin of all victims of the Tokyo Subway Sarin Poisoning were (a) inhalation through the lung, (b) absorption through mucosa (i.e., eye and nose) in vapor form, and (c) skin contact with the liquid form–all of which are major routes of absorption of the nerve agent.[9] Skin contact with liquid, however, was limited to station officers who touched the bags and who died from severe poisoning.[10]

The victims were transported to nearby hospitals, and they received emergency medical evaluations and treatments. St. Luke’s International Hospital, located 3 km from the affected subway stations, accepted a total of 640 patients (including subjects examined in the present study). This hospital treated the largest number of cases from the subway poisoning. Symptoms, signs, treatments, and clinical courses of all cases have been described elsewhere.[2] The Metropolitan Police Department and the Tokyo District Public Prosecutors suspected that the Aum Sinri Kyo cult released sarin during rush hour to create massive confusion in the Tokyo area, thus disturbing the police investigation of their murder crimes, including the poisoning in Matsumoto city.[10]

Method

Subjects. The nature of the procedure was explained fully to all subjects, and the study was conducted with their informed consent during September, October, and November of 1995 (i.e., 6-8 mo after the poisoning occurred). Hospital staffs contacted 150 victims of the poisoning and advised them to receive health checkups for possible neurological sequelae during this period; 9 males and 9 females consented readily to undergo the study. The 18 patients (sarin cases) examined included 1 plasterer, 1 kitchen maid, and 16 office clerks; all had been exposed to sarin vapor accidentally via the subway attack in Tokyo on March 20, 1995. The patients were admitted to St. Luke’s International Hospital, and their major signs and symptoms were miosis (n = 18), blurred vision (n = 13), dyspnea (n = 10), nausea and vomiting (n = 8), headache (n = 6), weakness (n = 6), chest oppression (n – 6), restlessness (n = 5), diarrhea (n = 4), cough (n = 4), muscle fasciculation (n = 4), and runny nose (n = 3). The patients were treated with injections of atropine and pralidoxim for 1-2 d. During interview, investigators surveyed age, level of education, amount and frequency of drinking, number of cigarettes smoked per day, past and present illnesses, and drug use. The authors calculated weekly ethanol consumption by using ethanol content in beverages (e.g., 15% for sake, 43% for whiskey, and 5% for beer).[11-13]

There were 8 male and 7 female control subjects, of whom 1 was a part-time lecturer, 2 were public health nurses, 6 were office clerks, and 6 were store clerks. None of the controls had been exposed in the sarin poisoning. In addition, none of the cases or controls had suffered from neurologic or psychiatric diseases. They consumed neither drugs nor alcohol on the day of testing, and none of them abused substances. Age, male-female ratio, education level, alcohol consumption, smoking habits in cases and controls, and serum cholinesterase activity (ChE) are shown in Table 1.

Table 1.–Differences in Age, Male-Female Ratio, Education Level, Alcohol Consumption, Smoking, and Serum Cholinesterase Activity (ChE) between 18 Sarin Cases and 15 Controls(*)

Variable Cases Controls

Age (y) 30.6 (19-58) 31.6 (20-59)

Males/Females 9/9 8/7

Education level 2.2 (1-4) 2.5 (1-4)

(score)([double dagger])

Alcohol consumption 78.3 (0-249) 140.0 (0-163)

(ml of 100% ethanol/wk)

Smoking (no. cigarettes/d) 1.7 (0-20) 1.8 (0-20)

ChE (IU/I)

Day of poisoning 72.1 –(#)

(13-131)([sections])

Day of study 157.7 (107-234)(//) –(#)

Variable Differences([dagger])

(p)

Age (y)

Males/Females >.05

Education level >.05

(score)([double dagger]) >.05

Alcohol consumption

(ml of 100% ethanol/wk) >.05

Smoking (no. cigarettes/d) >.05

ChE (IU/I)

Day of poisoning –(#)

Day of study –(#)

(*) Mean values with ranges in parentheses are shown; ratios are given for males/females.

([dagger]) Student’s t test or [chi square] test.

(double dagger]1) = Senior high school, 2 = technical school, 3 = college, and 4 = university or higher.

([sections]) Fifteen cases were below “normal” range (100-250 IU/I) on the day of poisoning.

(//) Measured in 13 cases and found to be within “normal” range.

(#) Not measured.

Neurobehavioral tests. Subjects underwent nine tests listed below (functional domain within parentheses). The first three tests (1-3) were subtests of the Japanese edition of the Wechsler Adult Intelligence Scale (WAIS).[11,12,14] The second three tests (4-6) were subtests of the Japanese version of the computer-administered testing (Neurobehavioral Evaluation System).[15,16] Test 7 was a subtest of the Japanese version of the Wechsler Memory Scale (WMA),[17,18] and the remaining two tests (8,9) were self-rating questionnaires.

1. Digit symbol (psychomotor performance). Investigators asked each subject to associate digits with symbols in accordance with a reference code in 90 s. Investigators then used the WAIS scoring, standardized for the Japanese version, to calculate the number of correct associations and to convert them to scaled scores. This test of psychomotor performance is relatively unaffected by intellectual prowess, memory, or learning. Motor persistence, sustained attention, response speed, and visuomotor coordination play important roles during the performance of this test.[19]

2. Picture completion (visual perception). Twenty pictures of objects and scores were presented, and the subject was asked to identify within 20 s what crucial part was missing. Investigators summed the number of correct responses and converted them to scaled scores as described earlier. Investigators used this test, which is related to general intellectual functioning,[19] to determine visual perception.

3. Digit span (attention and memory). The subject was instructed to recall digit series forward and backward immediately after hearing them. Maximal number of digits that the subject recalled exactly were converted to scaled scores as described earlier. This exercise tested auditory attention and memory.[19]

4. Finger tapping (psychomotor performance). The subject pressed a button as many times as possible during a 10-s interval. The speed of finger tapping is an index of the efficiency of nervous system processes that underlie psychomotor performance.[20]

5. Reaction time (psychomotor performance). The subject pressed a button when he or she observed a square on a video display of the microcomputer, and investigators calculated average reaction time over 60 stimuli. This exercise tested attention and motor response speed (activity rate). Slowing of mental activity manifests itself most clearly in delayed reaction times.[19,20]

6. Continuous performance test (sustained visual attention). The subject pressed a button upon seeing a large letter “S” projected onto a video display. Letters including “S” flashed briefly on the screen, and the session lasted for about 5 min. Number of errors (i.e., omissions and commission and reaction time for correct response were measured. This tested vigilance and information-processing capacity.[20]

7. Paired-associate learning (learning and memory). Ten pairs of words were presented orally, and the subject was then asked to answer the other word when one of the paired words was given. Three trials were conducted, and the number of correct answers was converted to the score in accordance with the scoring method of WMS.[17,18] This test is sensitive to learning (secondary memory) deficits that involve complex or novel information.[19]

8. General Health Questionnaire (GHQ) (psychiatric symptoms). This questionnaire contains 30 items used in the identification of current nonorganic nonpsychotic morbidity.[21] The Japanese version by Kitamura et al.[22] was used. Each item of the GHQ had four response codes (i.e., 1-4). Code 1 represented the most healthy code and 4 the most ill. The authors attributed zero point to codes 1 and 2, and I point to codes 3 and 4; the sum of the points was used as the score of the GHQ.

9. Profile of Mood States (POMS) (mood). A mood inventory contained 65 adjectives that describe six different moods.[23] Investigators asked the subject to indicate mood states during the most recent 1-wk period on a 5-point scale that ranged from “not-at-all” (0) to “extremely” (4). The Japanese version of the POMS, which was developed by the authors,[24,25] was used in this study.

Testing, which was conducted by the first author who had been trained by a psychologist, occurred in a quiet room during daylight hours of the weekdays.

Posttraumatic stress disorder (PTSD) checklist. A self-rating questionnaire that contained 17 problems and complaints related to PTSD (see Appendix) was administered on all subjects immediately before neurobehavioral testing occurred. This questionnaire was originally developed for PTSD, and it was based on DSM-III-R in veterans who had military experiences.[8] In the present study, the authors translated the list into Japanese, and the term military experience in the original questionnaire was substituted by the term subway sarin incident. The subject was asked to indicate how much he or she had been bothered by the incident (1 = not at all to 5 = extremely) and if they had related problems during the past month. The sum of the numbers was used as the score on the PTSD. In addition, the authors calculated the sums of 9 of 17 statements in which specific sarin questions (Nos. 1-5, 15-17 [Appendix]) were omitted, excluding statements directly related to the subway sarin incident.

Statistical analyses. The authors used Student’s t test or the chi-square test to analyze differences in the variables listed in Table 1 between the sarin cases and controls. Investigators used analysis of covariance to assess differences in performances on neurobehavioral testing and score on the PTSD checklist between the two groups; the factors were group (case or control) and gender (male or female), and covariates were age, level of education, alcohol consumption, and smoking. With respect to neurobehavioral tests, the analysis of covariance was also performed in which the score on the PTSD checklist was added to the covariates. The slope of the regression of the scores to the covariates was not significantly different between the cases and control subjects for any of the neurobehavioral tests and PTSD checklist (i.e., factor-by-covariate interaction was not significant [p [is less than] .05]).

The relationship between neurobehavioral tests and ChE and PTSD in 18 sarin cases was analyzed with Pearson’s product moment correlation or Spearman’s rank correlation and with stepwise multiple regression analysis. Serum cholinesterase activity on the day of poisoning and PTSD, together with one of the five variables (i.e., age, gender [male = 0, female = 1], level of education, alcohol consumption, and smoking [predictor variables]) were entered and removed at p [is less than] .05. Investigators performed statistical analyses with the SPSS version 6.0, which was loaded on a COMPAQ 9659 microcomputer.

Results

Results of the analysis of covariance for neurobehavioral tests and PTSD in 18 sarin cases and 15 controls are shown in Table 2. The mean score on the digit symbol test in the sarin cases was significantly lower than in the controls, and the scores on GHQ, fatigue (POMS), and PTSD (all 17 statements included) were significantly higher in the cases than controls (Fig. 1). Investigators added the PTSD score to the covariates, and they found that only the mean score on the digit symbol test for the sarin cases was significantly lower than in controls (Table 2). In contrast, the sum of 9 statements of the PTSD checklist, in which specific sarin questions were omitted, was not significantly different between the cases and controls. When investigators added this score to the covariates, scores on the digit symbol test, GHQ, fatigue (POMS), and PTSD remained significantly different between the two groups.

[Figure 1 ILLUSTRATION OMITTED]

Table 2.–Differences in Neurobehavioral Tests and Posttraumatic Stress Disorder (PTSD) between 18 Satin Cases and 15 Controls: Analysis of Covariance(*)

Cases

Test Mean Range

Digit Symbol (score) 15.9 11-19

Picture Completion (score) 9.7 7-13

Digit Span (score) 11.7 8-17

Finger Tapping (number/10 s) 47.6 34-62

Reaction time (msec) 257.2 196-375

Continuous Performance test

Latency (msec) 396.6 317-502

Errors (number) 0.1 0-1

Paired-Associate Learning 17.9 8.5-21

(score)

General Health 5.6 0-13

Questionnaires (score)(//)

Profile of Mood States (scores)

Tension-anxiety 11.3 2-19

Depression 10.8 1-24

Anger-hostility 12.1 2-24

Vigor 9.8 2-18

Fatigue 11.6 2-23

Confusion 9.4 3-16

PTSD (score)(#) 25.9 18-45

Controls

Test Mean Range

Digit Symbol (score) 17.5 14-19

Picture Completion (score) 9.4 6-13

Digit Span (score) 10.3 1-16

Finger Tapping (number/10 s) 47.7 33-69

Reaction time (msec) 261.4 191-374

Continuous Performance test

Latency (msec) 385.4 294-482

Errors (number) 0.3 0-2

Paired-Associate Learning 16.8 12.5-19.5

(score)

General Health 2.5 0-9

Questionnaires (score)(//)

Profile of Mood States (scores)

Tension-anxiety 10.3 1-16

Depression 8.1 0-19

Anger-hostility 8.7 1-19

Vigor 13.2 2-24

Fatigue 6.7 0-17

Confusion 7.1 3-11

PTSD (score)(#) 21.2 17-38

Differences([dagger])

Test F value

Digit Symbol (score) 7.41([double (8.98

dagger]) ([sections]))

Picture Completion (score) 0.96 (1.21)

Digit Span (score) 1.26 (1.17)

Finger Tapping (number/10 s) 0.03 (0.01)

Reaction time (msec) 0.21 (1.98)

Continuous Performance test

Latency (msec) 0.21 (0.64)

Errors (number) 1.07 (0.59)

Paired-Associate Learning 1.64 (1.39)

(score)

General Health 8.17([sections]) (3.14)

Questionnaires (score)(//)

Profile of Mood States (scores)

Tension-anxiety 0.51 (0.61)

Depression 1.13 (0.07)

Anger-hostility 1.95 (0.36)

Vigor 2.36 (0.91)

Fatigue 6.01([double (2.82)

dagger])

Confusion 3.10 (1.06)

PTSD (score)(#) 4.72([double –(**)

dagger])

(*) Factors are group (sarin case or are age, education level, alcohol consumption, and smoking.

([dagger]) The results of analysis of covariance after PTSD was added to the covariates are shown in parentheses.

([double dagger]) p < .05.

([sections]) p < .01.

(#) Score omitting specific subway sarin incident was not significantly different between the cases (mean = 13.9, range = 9-22) and controls (mean = 12.6, range = 9-26) (F = 0.83, p < .05). After we included this score in the covariates, no test–except for digit symbols, General Health Questionnaires, Fatigue, and PTSD–was significantly different between the two groups (F = 8.94, 9.25, 4.87, and 8.91, respectively; p < .05).

(//) No significant difference was found for each item between the cases and controls.

(**) Not measured.

In the stepwise multiple regression analysis, scores on paired-associate learning, GHQ, and four scales of POMS (i.e., tension-anxiety, depression, anger-hostility, and fatigue) were related significantly to PTSD scores in 18 sarin cases (Table 3). The relationships between PTSD and paired-associate learning, GHQ, and fatigue (POMS) are illustrated in Figure 2. In the multiple regression analysis, none of the neurobehavioral test scores for 18 sarin cases was significantly related to ChE on the day of sarin poisoning (Pearson’s product-moment correlation or Spearman’s rank correlation [n [is less than] .05].

[Figure 2 ILLUSTRATION OMITTED]

Table 3.–Regressions of Neurobehavioral Tests on Age, Gender, Education Level, Alcohol Consumption, Smoking, Serum Cholinesterase Activity, and Posttraumatic Stress Disorder (PTSD) in 18 Sarin Cases: Stepwise Multiple Regression Analysis(*)

Criterion variables R([dagger])

Paired-Associate Learning .738

.664(//)

General Health Questionnaires .822([sections])

.747([sections])

Profile of Mood States

Tension anxiety .849([sections])

Depression .696(//)

Anger-hostility .580(#)

Fatigue .471(#)

Criterion variables Set of independent variables

selected([dagger])

Paired-Associate Learning PTSD (-0.757([sections]),

Education Level (0.426(#))

PTSD (0.664(//))

General Health Questionnaires PTSD (1.050([sections])),

Age (-0.457(#))

PTSD (0.747([sections]))

Profile of Mood States

Tension anxiety PTSD (0.849([sections]))

Depression PTSD (0.696(//))

Anger-hostility PTSD (0.580(#))

Fatigue PTSD (0.471(#))

(*) Cholinesterase activity and PTSD together with one of the remaining variables were entered and removed at a significance level of p < .05.

([dagger]) Multiple regression coefficient.

([double dagger]) Standardized partial regression coefficients. Regression equations including PTSD or cholinesterase as significant predictor are shown.

([sections] p < .001.

(#) p < .05.

(//) p < .01.

Discussion

The mean score on the digit symbol test was decreased significantly in the cases 6-8 mo after acute satin poisoning occurred. The decrease was also significant when the effect of PTSD was controlled in the analysis of covariance. We therefore suggest that a chronic effect on psychomotor performance (i.e., motor persistence, sustained attention, response speed, and visuomotor coordination), as measured by the digit symbol test, is caused directly by acute sarin poisoning. This conclusion coincides with observations of chronic sequelae reported by others after acute organophosphate pesticide poisoning (i.e., significantly worse scores).[5-7]

Lesions in the brain (i.e., neuronal degeneration and necrosis) have been observed in rats that survive single subcutaneous injections of sarin or soman (0-[1,2,2-trimethylpropyl]–methylfluorophosphate-an organophosphate compound of potential wartime use).[26-28] In one of these studies,[28] the authors examined the histopathological changes up to 35 d after exposure and found that the changes remained present, suggesting that toxic organophosphate compounds (e.g., sarin, soman) can produce irreversible (or long-term) damage to the central nervous system. It is possible, therefore, that the significantly reduced scores on the digit symbol test in the cases in the present study were attributed to irreversible changes in the central nervous system caused by sarin.

The relationship between score on the digit symbol test and ChE on the day of the poisoning was not significant in the present study. Perhaps ChE is not a good predictor of the chronic effect of satin on psychomotor performance. This result may accord with the observations in rats that (a) ChE in the brain immediately after poisoning by sarin did not predict signs of encephalopathy 1-2 d after the poisoning,[26] and (b) behavioral abnormalities were not correlated with concurrent brain acetylcholinesterase activities 6 h and 24 h after poisoning by sarin, soman, or tabun (N-dimethylphosphoramide-cyanidate la toxic organophosphate compound]).[29] The mechanism of central nervous system toxicity of sarin and related organophosphate compounds, other than the inhibition of acetylcholinesterase activity, should be investigated.

The mean score on the PTSD (all 17 statements included) in satin cases was significantly higher than in controls–a finding that accords with the observations of the PTSD in the cases of the Tokyo Subway Sarin Poisoning.[2,30] The scores on GHQ and fatigue (POMS) were significantly increased in the cases when the authors did not use PTSD as a covariate in the analysis of covariance; conversely, the increases were not significant after PTSD was added to the covariates. In the multiple regression analysis, GHQ and fatigue were related positively to PTSD in sarin cases; therefore, psychiatric (GHQ) and mood (POMS) changes are likely the result of PTSD. In addition, tension-anxiety, depression, and anger-hostility (POMS) scores were related positively to PTSD in sarin cases; perhaps mood changes attributable to PTSD occurred in the cases. Given that psychological symptoms (e.g., complaints of physical distress, psychopathological profiles of Minnesota Multiphasic Personality Inventory) related to PTSD have been observed in Korean War veterans 30 y after the war,[31] the psychiatric and mood changes might have persisted in the cases subsequent to the Tokyo Subway Sarin Poisoning. The sum of the PTSD checklist–excluding the statements specifying subway sarin incident–was not significantly different between the two groups; inclusion of this variable as a covariate did not affect the results of the analysis of covariance. Apparently, psychiatric and mood changes were related specifically to the experience of the incident in sarin cases.

In a community in northern California, residents had been exposed to metam sodium (toxic pesticide) spilled in a railroad accident; increases in tension-anxiety, depression, anger-hostility, vigor, and fatigue–and a decrease in vigor of the POMS–were observed 3 mo after the spill occurred.[32] In addition, there were numerous complaints of depression and anxiety, somatic symptoms, environmental worry, and lower perceived social support.[32] These cases, therefore, demonstrated more profound mood changes than in the sarin cases in the present study who showed only a significant increase in fatigue of the POMS. It has been posited that Japanese respondents tend to suppress positive affect expression in self-administered questionnaires[33,34]; therefore, whether or not the results of POMS in the present study are unique to the Japanese when they experience chemical disasters relative to cross-cultural factors remains elusive. In the northern California cases, the inability of officers to provide accurate and timely information on the possible adverse health effects of metam sodium to the residents was reported as a major cause of their fears and worries.[32] In the sarin cases, we can speculate that the relationship between psychiatric mood changes and the subway sarin incident in the PTSD checklist reflects fear and worry of toxicity of sarin, although such fear and worry were not investigated directly. Accurate and timely information on health effects is potentially important in cases of chemical disaster.

Iwata and Suziki[35] reported that on the GHQ, the Japanese complained more about “loss of positive attitude” (e.g., not hopeful about own future, not feeling happy) than United Kingdom and Chinese populations. Similar complaints were reported in 9 (50%) and 9 (50%) sarin cases, respectively, and in 5 (33%) and 4 (27%) controls, respectively, in the present study (data not shown). Given that none of the 30 GHQ items revealed significant differences between the sarin cases and controls (Table 2), investigators need to conduct additional studies to determine which of the items is most sensitive to PTSD in Japanese and other populations.

Multiple regression analysis also revealed that the score on the paired-associate learning test was related inversely to PTSD in sarin cases. Given that the difference in score on the paired-associate learning test between cases and controls was not significant, the changes in this test seemed only minimum in the present study. Significantly decreased performance on learning and memory tests has been observed in veterans with clinically diagnosed PTSD[36,37] and in other populations with stress disorders[38]; therefore, the significant relationship between paired-associate learning and PTSD score may reflect a subclinical effect of PTSD in satin cases.

The present study, however, had some flaws in its design; additional well-designed studies are needed. In our study, there was a small sample size and a low number sarin cases; therefore, investigators must study many more victims of the Tokyo Subway Sarin Poisoning to confirm the observations of chronic neurobehavioral effects of sarin and PTSD. In addition, validation of the Japanese translation of the PTSD checklist will be necessary, although reliability and validity of its original version have been reported.[8] Electrophysiological studies may be important because chronic sequelae (e.g., decreases in nerve conduction velocity in organophosphate pesticide poisoning, EEG abnormalities) in sarin poisoning have been reported. Final[y, imaging techniques, such as magnetic resonance imaging, may be useful for the examination of structural changes in the brain relative to sarin exposure and/or PTSD.

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Appendix

PTSD Checklist

1. Repeated, disturbing memories of the Subway Sarin Incident? 2. Repeated, disturbing dreams of the Subway Sarin Incident? 3. Suddenly acting or feeling as if the Subway Satin Incident happened

again? 4. Feeling very upset when something happened that reminded you

of the Subway Sarin Incident? 5. Trouble remembering important parts of the Subway Sarin Incident? 6. Loss of interest in activity that you used to enjoy? 7. Feeling distant or cutoff from other people? 8. Feeling emotionally numb or being unable to have loving feelings

for those close to you? 9. Feeling as if your future will somehow be cut short? 10. Trouble falling or staying asleep? 11. Feeling irritable or having angry outbursts? 12. Having difficulty concentrating? 13. Being “super alert” or watchful or on guard? 14. Feeling jumpy or easily startled? 15. Having physical reactions when something reminds you of the

Subway Satin Incident? 16. Avoid thinking about the Subway Satin Incident or avoid having

feelings about it? 17. Avoid activities or situations because they remind you of the Subway

Sarin Incident?

KAZUHITO YOKOYAMA

SHUNICHI ARAKI

KATSUYUKI MU RATA

MARIKO NISHIKITANI

Department of Public Health

School of Medicine

University of Tokyo

Bunkyo-ku, Tokyo, Japan

TETSU OKUMURA

SHINICHI ISHIMATSU

NOBUKATSU TAKASU

Emergency Department

St. Luke’s International Hospital

Chuo-ku, Tokyo, Japan

ROBERTA F. WHITE

Department of Neurology

Boston University School of Medicine

Boston, Massachusetts

The authors thank Dr. Noboru Iwata, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, for his valuable suggestions.

Submitted for publication November 14, 1996; revised; accepted for publication October 6, 1997.

Requests for reprints should be sent to Shunichi Araki, M.D., Professor and Chairman, Department of Public Health, School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan

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