ARTICLE IN PRESS
Ecotoxicology and Environmental Safety 65 (2006) 288–291 www.elsevier.com/locate/ecoenv
Environmental exposure to natural sour gas containing sulfur compounds results in elevated depression and hopelessness scores Mostafa Saadata,, Zahra Zendeh-Boodia, Mohammad Ali Goodarzib a
Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran Department of Clinical Psychology, College of Education and Psychology, Shiraz University, Shiraz 71454, Iran
b
Received 19 February 2005; received in revised form 20 July 2005; accepted 25 July 2005 Available online 5 October 2005
Abstract Some parts of Masjid-i-Sulaiman (MIS) (Khozestan provinces, southwest of Iran) are contaminated with subsurface leakage of natural sour gas containing H2S. It is reported that the incidence of suicide by self-burning in MIS is very high. High endogenous H2S levels have been found in the brain and it is involved in the brain functions. Because there is no report about the effect(s) of natural sour gas containing sulfur compounds on the function(s) of human brain, the present study was done. The study was performed on 128 individuals exposed or unexposed to natural sour gas. The exposed group consisted of 64 persons (39 males, 25 females). Unexposed subjects were matched by sex, age, and educational levels. Depression and hopelessness were determined using Beck’s depression inventory (BDI) and Beck’s hopelessness (BHS) questionnaires. Using multiple linear regression models, the averages of BDI (t ¼ 2:637, P ¼ 0:009) and BHS (t ¼ 3:344, P ¼ 0:001) were significantly higher among the exposed subjects than among the control group. In Lali 57.8% and 14.1% of subjects had no depressed mood and moderate to severe depressed mood, respectively, while in MIS 31.3% and 35.9% of subjects had no depressed mood and moderate to severe depressed mood, respectively; the difference was significant (w2 ¼ 12:88, df ¼ 3, P ¼ 0:005). In Lali 35.9% and 12.5% of subjects had no hopelessness at all and moderate to severe hopelessness, respectively, while in MIS 17.2% and 32.8% of subjects had no hopelessness at all and moderate to severe hopelessness, respectively, the difference was significant (w2 ¼ 11:49, df ¼ 3, P ¼ 0:009). Replication is necessary and health implications are discussed. r 2005 Elsevier Inc. All rights reserved. Keywords: Hydrogen sulfide; Depression; Hopelessness; Natural sour gas; Iran
1. Introduction Hydrogen sulfide (H2S) has been best known for decades as the toxic gas dubbed ‘‘gas of rotten eggs.’’ Recently, however, it was found that H2S is a new gaseous messenger playing an important role in several physiological processes (Eto et al., 2002a, b; Abe and Kimura, 1996; Dello Russo et al., 2000). High endogenous levels of H2S have been found in the brain of rats, humans, and bovines. Endogenous H2S is responsive to neuronal excitation by Ca2+- and calmodulin-mediated pathways (Eto et al., 2002b), modifying long-term potentiation (Abe and Kimura, 1996) and Corresponding author. Fax: +98 711 2280926.
E-mail addresses:
[email protected],
[email protected] (M. Saadat). 0147-6513/$ - see front matter r 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ecoenv.2005.07.024
modulating hypothalamo–pitutary axis function (Eto et al., 2002a). Two pyridoxal-50 -phosphate-dependent enzymes— cystathionine b-synthase (CBS) and cystathionine g-lyase (CSE)—are responsible for the majority of the endogenous production of H2S in mammalian tissues using L-cysteine as the main substrate (Moore et al., 2003). Genetic polymorphisms of the CBS gene are significantly associated with overall cognitive function (Barbaux et al., 2000). The CBS activity is reduced in Alzheimer’s disease brains and the decrease in H2S may be involved in some aspects of the cognitive decline in Alzheimer’s disease (Eto et al., 2002a). The abnormal regulation of H2S production may cause neuronal dysfunction (Dello Russo et al., 2000). Masjid-i-Sulaiman (MIS) is located in the Khozestan province, southwest of Iran. Petroleum—whether gas, oil, or liquid asphalt—that exudes in the form of springs and
ARTICLE IN PRESS M. Saadat et al. / Ecotoxicology and Environmental Safety 65 (2006) 288–291
seepages may reach the surface. Active seepages of oil and gas overlie the MIS field. Unfortunately, some parts of the MIS are contaminated by subsurface leakage of natural gas containing H2S. The gas dissolved in the oil of the MIS oil field contains 40% H2S (Levirsen, 1967). The alterations of offspring sex ratio at birth (Saadat et al., 2002), hematological indices (Saadat and Bahaoddini, 2004), and blood pressure (Saadat et al., 2004b) of individuals resident in the contaminated areas of MIS were reported. Also, very recently, we reported the high incidence of suicide attempts, completed suicide, and suicide by self-burning in MIS and we showed that there is statistically significant positive correlation between mean values of all reactive sulfur compounds and seasonal frequency of self-burning (Saadat et al., 2004a). Because both depression and hopelessness are strongly associated with suicide and suicide attempts (Beck et al., 1989; Borges et al., 2000; Wetzel et al., 1980; Ranieri et al., 1987) we hypothesized that exposure to natural sour gas containing sulfur compounds such as H2S influences the depression and hopelessness levels of the chronically exposed individuals. Based on our knowledge there is no report about the depression and hopelessness scores in individuals living in areas that are contaminated with natural sour gas. Therefore, the present study was done. 2. Materials and methods 2.1. Subjects The study was performed on 128 individuals including those exposed and unexposed to natural sour gas. The exposed group consisted of 64 persons (39 males, 25 females). This group was from four polluted areas of MIS: Posht-e-Borj, Camp Brench, Bibian, and Naphton. Unexposed subjects from Lali (the nearest city to MIS) were
289
matched by age (73 years), sex, and educational level. Both groups belong to the same ethnic group, the Bakhtiyaries. Subjects were included only if they had no history of occupational exposure to benzene or alcohol consumption. None of the subjects worked in petroleum industries. None of the subjects had current illness, nor chemotherapy or exposure to radiation. Table 1 shows the sociodemographic characteristics of the study populations. There is no difference between the two study cohorts in age, sex, smoking status, educational levels, and employment status. There is no unrest in the study populations. In Lali and MIS the same recruitment method was used. Informed consent was obtained from each subject before the study. 2.2. Measurements The 21-item Beck depression inventory (BDI) is one of the most widely used and reliable questionnaires for detecting depression in normal populations and assessing its intensity. The 21-item BDI self-report questionnaire assesses depressive symptoms in the past week, rating their intensity on a scale from 0 to 3 (total score range 0–63). The higher the BDI score, the greater the indication of depressed mood, consistent with the following categories: 0–9, no depressed mood; 10–18, low depressed mood; 19–29, moderate depressed mood, and 30–63, severe depressed mood. Most items describe clinical symptoms of depression, specifically the presence and intensity of emotional, cognitive, and somatic aspects (Beck et al., 1975). The level of hopelessness was assessed by using the Beck hopelessness scale (BHS), which is a 20-item self-administered rating scale designed to measure the negative expectancies of adults with regard to themselves and their future life. The total score ranges from 0 to 20, and the
Table 1 Sociodemographic characteristics of the study cohorts Variables
Lali
MIS
Results of comparisons
Continuous variable Age Discontinuous variables Sex Females Males
28.3+8.1
26.0+9.0
t ¼ 1.48
P ¼ 0.139
25 39
25 39
0
P ¼ 1.0
Smoking status Nonsmokers Smokers
61 3
58 6
w2 ¼ 1:076 (df ¼ 1)
P ¼ 0.300
Educational level High school College
53 11
49 15
w2 ¼ 0:772 (df ¼ 1)
P ¼ 0.380
Employment status Unemployed Employed/student
4 60
6 58
w2 ¼ 0:430 (df ¼ 1)
P ¼ 0.512
ARTICLE IN PRESS 290
M. Saadat et al. / Ecotoxicology and Environmental Safety 65 (2006) 288–291
level of hopelessness increases with increasing score. Based on the original cutoff points, the subjects were classified into four groups: 0–3, no hopelessness at all; 4–8, mild hopelessness; 9–14, moderate hopelessness; and 15–20, severe hopelessness (Beck et al., 1974). The amount of all reactive sulfur compounds in the air of the contaminated areas of MIS and Lali that can produce sulfate using lead peroxide was estimated equal to 0.02370.002 (ppm of SO2) and 0.00, respectively. 2.3. Statistical analysis The multiple linear regression method was applied to detect differences among exposed and unexposed groups for scores of hopelessness and depression. Student’s t-test was performed for continuous variables between the two groups. w2 test was performed for categorical variables. Statistical analysis was performed using SPSS statistical software package (version 11.5). A probability of Po0:05 was considered statistically significant. All P values were two-tailed. 3. Results Table 2 shows the median, mean, and standard deviation of BDI and BHS scores according to sex of subjects in Lali and MIS. Statistical analysis showed that there are significant differences between the two study groups for both BDI and BHS. It is reported that BDI and BHS scores showed association with several factors such as age sex, smoking behavior, and education. Therefore the effects of living in contaminated areas on BDI and BHS scores after adjustment for possible confounding factors were investigated using multiple linear regression analysis. Based on the multiple linear regression models, the averages of BDI (t ¼ 2:637, P ¼ 0:009) and BHS (t ¼ 3:344, P ¼ 0:001) were significantly higher among the exposed subjects than among the control group. Overall, living in MIS, after adjustment for sex, age, smoking status, and education, results in increased averages of BDI and BHS of about 2.4 and 4.6 scores, respectively. Based on the original cutoff points, the subjects might be classified into four groups for hopelessness and depression as described undo Materials and methods. After classification, the study subjects were divided into two sex groups. Because there was no significant difference for levels of either BDI or BHS in Lali (for level of BDI, w2 ¼ 2:03, df ¼ 3, P ¼ 0:57; for level of BHS, w2 ¼ 2:57, df ¼ 2, P ¼ 0:28) and MIS (for level of BDI, w2 ¼ 4:24, df ¼ 3, P ¼ 0:24; for level of BHS, w2 ¼ 3:98, df ¼ 3, P ¼ 0:26), the sex groups were pooled (data not shown). Table 3 shows the distributions of hopelessness and depression levels in Lali and MIS. In Lali 57.8% and 14.1% of subjects had no depressed mood and moderate to severe depressed mood, respectively, while in MIS 31.3% and 35.9% of subjects had no depressed mood and moderate to severe depressed mood, respectively. There
Table 2 Median, mean, and standard deviation of BDI and DHS scores in Lali and MIS Lali Male
MIS Female
Total
Male
Female
Total
BDI score N Mean SD Median
39 8.67 7.1 6.0
25 9.67 8.7 8.0
64 9.06 7.70 7.0
39 16.41 10.39 14.0
25 14.72 9.55 12.0
64 15.75 10.03 13.5
BHS score N Mean SD Median
39 4.64 2.64 4.0
25 4.68 2.85 4.0
64 4.0 4.0 4.0
39 7.72 4.13 6.0
25 6.56 4.31 5.0
64 7.27 4.21 6.0
Comparison between Lali and MIS BDI score t 3.845 1.950 4.230 df 76 48 126 P value o0.001 0.057 o0.001 BHS score t df P value
3.920 76 o0.001
1.818 41 0.076
4.175 126 o0.001
Table 3 Levels of BDI and BHS in Lali and MIS Lali
MIS
w2 (df ¼ 3)
P value
Levels of BDI No depressed mood Low depressed mood Moderate depressed mood Severe depressed mood
37 18 8 1
20 21 15 8
12.88
0.005
Levels of BHS No hopelessness at all Mild hopelessness Moderate hopelessness Severe hopelessness
23 33 8 0
11 32 17 4
11.49
0.009
was significant difference between these populations for level of BDI (w2 ¼ 12:88, df ¼ 3, P ¼ 0:005). In Lali 35.9% and 12.5% of subjects had no hopelessness at all and moderate to severe hopelessness, respectively, while in MIS 17.2% and 32.8% of subjects had no hopelessness at all and moderate to severe hopelessness, respectively. There was significant difference between these populations for level of BHS (w2 ¼ 11:49, df ¼ 3, P ¼ 0:009). 4. Discussion The goal of this work was to clarify the association between chronic exposure to natural sour gas (containing sulfur compounds) and either depression or hopelessness
ARTICLE IN PRESS M. Saadat et al. / Ecotoxicology and Environmental Safety 65 (2006) 288–291
scores. The present findings indicate that MIS citizens are more at risk to be depressed and hopeless than are Lali citizens (Tables 2 and 3). These data support our previous findings of high levels of suicide attempts and suicide by self-burning in MIS and a positive correlation between seasonal variation of self-burning suicide and environmental contamination levels in the polluted areas of MIS (Saadat et al., 2004a). It should be mentioned that neurobehavioral effects in 16 subjects exposed to H2S have been reported. Psychological domains showed cognitive disability, reduced perceptual motor speed, impaired verbal recall and remote memory, and abnormal mood status (Kilburn, 1997). Our present findings support this report. However, behavioral effects associated with short-term exposure to hydrogen sulfide were controversial using Sprague–Dawley rats (Dorman et al., 2000; Struve et al., 2001). Significant reduction in motor activity of experimental animals was reported (Dorman et al., 2000). Considering that H2S is present in brain and is involved in the brain functions (Eto et al., 2002a, b; Abe and Kimura, 1996; Dello Russo et al., 2000), it is suggested that the environmental H2S disrupts some brain functions and subsequently higher scores of BDI and BHS were observed in MIS citizens. However, at present the mechanism(s) of this phenomenon is not understood. The potential importance of investigating the health impact of subclinical depressive symptoms has long been noted. Accumulating evidence indicates that subclinical levels of depressive symptoms can have major health implications (Kopp et al., 1995; Frasure-Smith et al., 1995; Lesperance et al., 2002; Bush et al., 2001). Indeed a largescale study with the vast majority of subjects below clinical cutoff points on the BDI suggested a dose–response association across a wide range of BDI scores and subsequent mortality following myocardial infraction. Even subjects with BDI scores of 5–9 had significantly increased health risk compared to participants scoring below 5 (Lesperance et al., 2002). Finally, these results suggest the need to (a) investigate the biological effect(s) of H2S on brain function, (b) develop some type of program or service within the MIS community able to influence the moods of citizens and modify their expectations with the aim of preventing suicide behavior, and (c) control of contamination.
Acknowledgments We are indebted to the MIS and Lali citizens who participated in this study. This study was supported by the Shiraz University.
References Abe, K., Kimura, H., 1996. The possible role of hydrogen sulfide as an endogenous neuromodulator. J. Neurosci. 16, 1066–1071.
291
Barbaux, S., Polmin, R., Whitehead, A.S., 2000. Polymorphisms of genes controlling homocysteine/folate metabolism and cognitive function. Neuro Rep. 11, 1133–1136. Beck, A.T., Beck, R., Kovacs, M., 1975. Classification of suicide behaviors: I. Quantifying intent and medical lethality. Am. J. Psychiatry 132, 285–287. Beck, A.T., Weissman, A., Lester, D., et al., 1974. The measurement of pessimism: the hopelessness scale. J. Consult. Clin. Psychol. 42, 861–865. Beck, A.T., Brown, G., Steer, R.A., 1989. Prediction of eventual suicide in psychiatric inpatients by clinical rating of hopelessness. J. Consult. Clin. Psychol. 57, 309–310. Borges, G., Saltijeral, M.T., Bimbela, A., et al., 2000. Suicide attempts in a sample of patients from a general hospital. Arch. Med. Res. 31, 366–372. Bush, D.E., Ziegelstein, R.C., Tayback. M., etal., 2001. Even minimal symptoms of depression increase mortality risk after acute myocardial infraction. Am. J. Cardiol. 88, 337–341. Dello Russo, C., Tringali, G., Ragazzoni, E., et al., 2000. Evidence that hydrogen sulfide can modulate hypothalamo–pituitary–adrenal axis function: in vitro and in vivo studies in the rat. J. Neuroendocrinol. 12, 225–233. Dorman, D.C., Brenneman, K.A., Struve, M.F., et al., 2000. Fertility and developmental neurotoxicity effects of inhaled hydrogen sulfide in Sprague–Dawley rats. Neutotoxicol. Teratol. 22, 71–84. Eto, K., Asada, T., Arima, K., et al., 2002a. Brain hydrogen sulfide is severely decreased in Alzheimer’s disease. Biochem. Biophys. Res. Commun. 293, 1485–1488. Eto, K., Ogasawara, M., Umemura, K., et al., 2002b. Hydrogen sulfide is produced in response to neural excitation. J. Neurosci. 22, 3386–3391. Frasure-Smith, N., Lesperance, F., Talajic, M., 1995. Depression and 18month prognosis after myocardial infraction. Circulation 91, 999–1005. Kilburn, K.H., 1997. Exposure to reduced sulfur gases impairs neurobehavioral function. South Med. J. 90, 997–1006. Kopp, M.S., Skrabski, A., Szedmak, S., 1995. Socioeconomic factors, severity of depressive symptommatology, and sickness absence rate in the Hungarian population. J. Psychosom. Res. 39, 1019–1029. Lesperance, F., Frasure-Smith, N., Talajic, M., et al., 2002. Five-year risk of cardiac mortality in relation to initial severity and one-year changes in depression symptoms after myocardial infraction. Circulation 105, 1049–1053. Levirsen, A.L., 1967. Geology of Petroleum. Freeman, San Francisco, pp. 15–19. Moore, P.K., Bhatia, M., Moochhala, S., 2003. Hydrogen sulfide: from the smell of the past to the mediator of the future? Trends Pharmacol. Sci. 24, 609–611. Ranieri, W.F., Steer, R.A., Lavrence, T.I., et al., 1987. Relationships of depression, hopelessness, and dysfunctional attitudes of suicide ideation in psychiatric patients. Psychol. Rep. 61, 967–975. Saadat, M., Bahaoddini, A., 2004. Hematological changes due to chronic exposure to natural gas leakage in polluted areas of Masjid-i-Sulaiman (Kozestan province, Iran). Ecotoxicol. Environ. Saf. 58, 273–276. Saadat, M., Ansari-Lari, M., Bahaoddini, A., 2002. Sex ratio at birth in Masjid-i-Sulaiman (Khozestan province, Iran). Occup. Environ. Med. 59, 853. Saadat, M., Bahaoddini, A., Mohabatkar, H., et al., 2004a. High incidence of suicide by self-burning in Masjid-i-Sulaiman (southwest of Iran), a polluted area with natural sour gas. Burns 30, 829–832. Saadat, M., Bahaoddini, A., Nazemi, S., 2004b. Alterations in blood pressure due to chronic exposure to natural sour gas leakage containing sulfur compounds. Biochem. Biophys. Res. Commun. 313, 568–569. Struve, M.F., Brisbois, J.N., James, R.A., et al., 2001. Neurotoxicological effects associated with short-term exposure of Sprague–Dawley rats to hydrogen sulfide. Neurotoxicology 22, 375–385. Wetzel, R.D., Margulies, T., Davis, R., et al., 1980. Hopelessness, depression, and suicide intent. J. Clin. Psychiatry 41, 159–160.