The Relationship between IMPS-Measured Stress Score and

The Relationship between IMPS-Measured Stress Score and Intraocular Pressure among Public School Workers Kazuhiko Yamamoto1), Yoko Sakamoto1), Masahiro Irie1), Susumu Ohmori2), Mototaka Yoshinari2) and Gazmend Kaçaniku3) 1) Institute of Health Science, Kyushu University 2) Kyushu Central Hospital 3) University Clinical Center of Kosova Eye Clinic, Pristina, UNMIK Kosovo

Abstract The aim of this study was to examine the relationship between psychosocial stress and intraocular pressure among apparently healthy subjects. Psychosocial stress among 1,461 public school workers (883 men and 578 women) was measured using the inventory to measure psychosocial stress (IMPS) and intraocular pressure was measured using a non-contact tonometer (Topcon CT-90). After controlling for the effects of likely confounding variables such as age, body mass index (BMI), glycosylated hemoglobin, systolic blood pressure, alcohol consumption, smoking status, and exercise, partial correlations and hierarchical multiple regression analysis were performed in order to test the hypothesis that IMPS-measured stress score was associated with intraocular pressure. IMPS-measured stress score was found to correlate positively with intraocular pressure in women after controlling for the effects of confounding variables, whereas this relationship was not found in men. Hierarchical multiple regression analysis indicated that IMPS-measured stress score was positively associated with intraocular pressure in women independent of confounding variables, but not in men. Perturbations of the hypothalamicpituitary-adrenal (HPA) axis associated with stress are considered to be partly responsible for an increase in intraocular pressure among people suffering from psychosocial stress. Further research is needed to elucidate the relationship between this stress-associated increase in intraocular pressure and open-angle glaucoma. J Physiol Anthropol 27(1): 43–50, 2008 http://www.jstage.jst.go.jp/browse/jpa2 [DOI: 10.2114/jpa2.27.43] Keywords: stress, intraocular pressure, IMPS, HPA axis, open-angle glaucoma

Introduction In addition to diabetic retinopathy, glaucoma is among the leading causes of blindness, both in Japan and in the Western world (Seddon et al., 1983; Shiose et al., 1991; Bonomi et al., 1998). The most common form of glaucoma is open-angle glaucoma, the prevalence of which is estimated to be high, ranging from 0.9% to 11.3% between studies, depending on race, age, and the area where the population-based survey was conducted (Bengtsson, 1981; Tielsch et al., 1991; Bonomi et al., 1998; Iwase et al., 2004). It is estimated that over 32 million people worldwide currently suffer from open-angle glaucoma (Quigley, 1996). While the pathophysiology of open-angle glaucoma, which may result in profound vision impairment if left untreated or if treated insufficiently, is not explicitly known, a number of risk factors, such as age, family history of glaucoma, diabetes mellitus, hypertension, myopia, cataracts, smoking, alcohol consumption, and stress, have been shown to be associated with open-angle glaucoma (Wilson et al., 1987; Katz and Sommer, 1988; Leske et al., 1995; Kaluza et al., 1996; Le et al., 2003; Suzuki et al., 2006). One of the most important risk factors for the development of open-angle glaucoma is elevated intraocular pressure (David et al., 1977; Seddon et al., 1983; Davanger et al., 1991; Sommer et al., 1991; Tielsch et al., 1991; Le et al., 2003; Suzuki et al., 2006), even though a considerable portion (30%) of patients with open-angle glaucoma have normal levels of intraocular pressure (Bonomi et al., 1998). Furthermore, in contrast to Western populations, the prevalence of open-angle glaucoma among patients with apparently normal intraocular pressure levels, i.e. low-tension glaucoma, was found to be exceptionally high among the Japanese population (Shiose et al., 1991; Iwase et al., 2004). Numerous factors have been reported to affect intraocular pressure, including age, systolic blood pressure, body mass index (BMI), serum glucose, hematocrit, glycosylated

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Psychosocial Stress and Intraocular Pressure

hemoglobin, water consumption, coffee intake, alcohol intake, smoking, exercise, time of day of measurement, and use of ocular corticosteroids (Bengtsson, 1972; Kass and Sears, 1977; Leske and Podgor, 1983; Carel et al., 1984; Poinoosawmy and Winder, 1984; Buckingham and Young, 1986; Klein et al., 1992; Wilensky et al., 1993; Qureshi, 1995). In addition to these factors, it has been shown that both physical and psychological stresses affect intraocular pressure (Buckingham and Young, 1986; Shily, 1987; Sauerborn et al., 1992; Kaluza et al., 1996; Brody et al., 1999; Leung and Yap, 1999). Several studies have investigated the effects of acute physical stress such as hard exercise and the Valsalva maneuver on intraocular pressure among healthy people (Buckingham and Young, 1986; Brody et al., 1999), and of acute psychological stress such as mental arithmetic tasks and noise among myopes (Sauerborn et al., 1992) and patients with open-angle glaucoma (Kaluza et al., 1996); however, few studies have explored the relationship between psychosocial stress and intraocular pressure among healthy subjects. Previously, we developed an inventory to measure psychosocial stress (IMPS) and reported that the IMPS was a valid method for the evaluation of psychosocial stress levels (Yamamoto et al., 2007). In the present study, we examined the relationship between IMPS-measured stress score and intraocular pressure among apparently healthy subjects in an attempt to elucidate the effects of psychosocial stress on intraocular pressure. We hypothesized that psychosocial stress was positively associated with intraocular pressure after controlling for the effects of likely confounding variables.

Methods Subjects and procedure Every year, about 5,000 workers chosen from among approximately 136,000 teaching and non-teaching workers employed at public elementary, junior high, and senior high schools in Kyushu and Okinawa receive a general health check-up at Kyushu Central Hospital in Fukuoka, Japan, based on their desire to undergo medical examination for the purpose of detecting any early-stage illnesses. The subjects included in the present study were selected from a smaller pool of 1,941 workers examined at the hospital between November 2004 and March 2005. The subjects were invited to participate after they had been provided with a full explanation of the study, and written informed consent was obtained from all participants. A total of 1,499 workers responded to the invitations, yielding a response rate of 77.2%. Thirty-eight of those subjects screened for participation who were taking topical medicine for either glaucoma or elevated intraocular pressure were excluded, and the remaining 1,461 subjects were analyzed. Forty-two (2.9%) of the 1,461 subjects were taking medicine for hyperuricemia, 69 (4.7%) for hyperlipidemia, 16 (1.1%) for diabetes, and 126 (8.6%) for hypertension. It is unknown whether hyperuricemia and hyperlipidemia affect intraocular pressure, and HbA1c and blood pressure have been controlled for in the analysis. The

mean ages of the 883 men and 578 women were 48.18.0 and 48.17.0 years, respectively, and 92–94% of the subjects were employed as teachers. The participants were asked to answer a demographic questionnaire that recorded age, gender, and occupation. We also collected each subject’s medical and family history, as well as information about cigarette-smoking habits, alcohol consumption, physical activity, and subjective somatic symptoms. All participants underwent blood sampling after an overnight fast. Anthropometric measurements were conducted under the same conditions. Blood pressure was measured with the subject in a sitting position by applying a sphygmomanometer to his or her right arm. Body mass index was calculated as the subject’s weight in kilograms divided by the square of his or her height in meters (kg/m2). Intraocular pressure was measured by one examiner for each eye using a non-contact tonometer (Topcon CT-90) generally in the early afternoon, but in the morning for 528 (36%) of the subjects. If a reading was high, several consecutive measurements were obtained, and the lowest measurement was recorded. Psychosocial stress was measured using the IMPS as described previously (Yamamoto et al., 2007). We refer to the score measured using the IMPS as a “stress score” in this study.

Statistical analysis Throughout the study, separate analyses were conducted for men and women. Unpaired t-tests were used to test for differences between men and women in terms of the means of subjective stress, stress score, BMI, glycosylated hemoglobin, systolic blood pressure, diastolic blood pressure, and intraocular pressure. For the parametric two-group comparisons, p values were based on Welch’s test for groups with unequal variances, if the hypothesis of equal variance was rejected at the 0.05 level of significance. Pearson’s correlation coefficients were used to explore the correlation between stress score and intraocular pressure. Partial correlations were used to assess the correlation between stress score and intraocular pressure, with variables controlling for age, biomedical parameters (BMI, glycosylated hemoglobin, and systolic blood pressure), and lifestyle factors (alcohol consumption, smoking, and exercise). Alcohol consumption was assigned numeric values ranging from 0–3 as follows: no drinking0; occasional drinker1; frequent drinker, 360 ml of sake at one sitting 2; and frequent drinker, 360 ml of sake at one sitting3 (360 ml of sake, 32 proof, contains about 45 g of absolute alcohol). A “frequent drinker” was defined as a person who drinks alcohol almost daily. Smoking status was assigned numeric values ranging from 0–3 as follows: never smoked0; former smoker1; current smoker of 1–19 cigarettes per day 2; and current smoker, 20 cigarettes per day3. Habitual exercise was assigned numeric values ranging from 1–4 as follows: no day per week of physical activity engaged in for more than 30 minutes in addition to routine daily activities1; 1 day of physical activity per week2; 2–3 days of physical activity per week3; and 4–7 days of physical activity per

Yamamoto, K et al. J Physiol Anthropol, 27: 43–50, 2008

week4. To test the hypothesis of this study that psychosocial stress is associated with intraocular pressure, regardless of confounding variables, hierarchical multiple regression analyses were performed. Age was entered as a first step, biomedical parameters (BMI, glycosylated hemoglobin, and systolic blood pressure) were entered as a second step, and lifestyle factors (alcohol consumption, smoking, and exercise) were entered as a third step in order to determine whether age, biomedical parameters or lifestyle factors affected the association between stress score and intraocular pressure. P values of less than 0.05 were considered significant.

Results Sample characteristics Demographic and lifestyle data for a total of 1,461 subjects are summarized in Table 1. Regarding alcohol consumption, 15% of the men and 39% of the women consumed no alcohol, while more than half of the men and 22% of the women were frequent drinkers. In addition, 73% of the men and 94% of the women did not smoke. Moreover, 47% of the men and 68% of the women participated in no exercise beyond their routine daily physical activities, while 15% of the men and 6% of the women exercised 4 days or more per week.

Stress score, biomedical parameters, and intraocular pressure Table 2 shows that women reported more subjective stress than men, and the women’s mean stress score was higher than that of the men. Men had higher values than women for BMI, glycosylated hemoglobin, systolic blood pressure, and diastolic blood pressure (Table 2). The mean intraocular pressures of the right and left eyes for men and women were 14.98 and 14.53 mm Hg, respectively. There was no difference in intraocular pressure between the right and left eyes in either men or women. Intraocular pressures in the right and left eyes, and the mean intraocular pressure of the right and left eyes were both higher in men than in women, although the differences were small (Table 2). The intraocular pressure of 528 subjects (36%) was measured in the morning, while the intraocular pressure of the remaining subjects was measured in the early afternoon. The mean intraocular pressures of the right and left eyes for the subjects measured in the morning and for the subjects measured in the early afternoon were 14.91 mm Hg and 14.74 mm Hg, respectively. There was no difference in intraocular pressure between the subjects measured in the morning and the subjects measured in the early afternoon (t(1459)1.23, p0.218).

Correlation between stress score and intraocular pressure IMPS-measured stress score was significantly correlated with intraocular pressure in women, as shown in Table 3. These correlations remained significant among women after

Table 1

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Sample characteristics* Characteristics

Age 30–39 years, % 40–49 years, % 50–59 years, % 60–69 years, % Mean, y (SD) Occupation Teacher, % Non-teacher, % Alcohol consumption None, % Occasional drinker, % Frequent drinker 360 ml of sake¶/time, % 360 ml of sake/time, % Smoking status Never smoked, % Former smoker, % Current smoker 1–19 cigarettes/day, % 20 cigarettes/day, % Exercise§ 0 days/week, % 1 day/week, % 2–3 days/week, % 4–7 days/week, %

Men (N883)

Women (N578)

14.9 39.3 37.9 7.8 48.1 (8.0)

12.1 42.6 40.3 5.0 48.1 (7.0)

91.7 8.3

93.8 6.2

14.9 32.3

39.1 39.4

43.1 9.6

20.8 0.7

39.2 33.6

90.6 3.8

9.1 18.1

5.2 0.3

46.6 18.3 20.1 15.1

67.6 15.9 10.8 5.7

* In some instances, the percentage total is either greater or less than 100% due to rounding. ¶ Sake is a brewed alcoholic beverage, which is approximately 32-proof, made from fermented rice. § Exercise is physical activity beyond routine daily activities that is carried out for more than 30 minutes on any given day.

Table 2 Means and standard deviations of psychosocial and biomedical variables by sex among public school workers Men (N883)

Women (N578)

p value*

Subjective stress (SD) 2.8 (0.9) 3.1 (0.9) Stress score (SD) 12.7 (11.1) 17.3 (12.9) BMI, k/m2 (SD) 25.2 (3.3) 23.1 (3.4) Glycosylated hemoglobin % (SD) 5.10 (0.80) 4.90 (0.40) Systolic BP, mm Hg (SD) 131.4 (17.6) 119.5 (17.7) Diastolic BP, mm Hg (SD) 81.3 (11.3) 73.6 (11.1) IOP, right eye, mm Hg (SD) 14.95 (2.64) 14.49 (2.67) IOP, left eye, mm Hg (SD) 15.02 (2.61) 14.56 (2.75) IOP, mean, mm Hg (SD) 14.98 (2.47) 14.53 (2.58)

.001 .001 .001 .001 .001 .001 .001 .002 .001

BMI indicates body mass index; BP, blood pressure; IOP, intraocular pressure. *Unpaired t-test.

controlling for age, BMI, glycosylated hemoglobin, and systolic blood pressure, although slight attenuation was observed after controlling for these variables. When lifestyle factors such as alcohol consumption, smoking, and exercise were incorporated into the analysis, the correlation remained significant (Table 3).

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In contrast, stress score was not significantly correlated with intraocular pressure in men (Table 3). After controlling for age and biomedical parameters, a significant correlation between stress score and intraocular pressure was observed in men (Table 3). However, controlling for lifestyle factors affected the Table 3 Partial correlations between stress score and IOP, controlling for the effects of age, biomedical parameters, and lifestyle factors among public school workers Control Variables Added Sequentially Stress score Stress score Age Stress score Age BMI, HbA1c, and SBP Stress score Age, BMI, HbA1c, SBP Alcohol consumption, Smoking, and Exercise a

Men (N883)

Women (N578)

IOP (mean)

IOP (mean)

0.066 a (p0.050)

0.116 a (p0.005)

0.061 (p0.070)

0.112 (p0.007)

0.068 (p0.045)

0.103 (p0.014)

0.066 (p0.054)

0.104 (p0.014)

Pearson’s correlation coefficients. HbA1c hemoglobin; SBP, systolic blood pressure. Table 4

indicates

glycosylated

correlation and attenuated the results to a level of nonsignificance.

The effects of stress score, biomedical parameters, and lifestyle factors on intraocular pressure The results of hierarchical multiple regression analyses are presented in Table 4. In women, stress score was significantly associated with intraocular pressure after controlling for age and biomedical parameters. The association remained significant after controlling for lifestyle factors, indicating that stress level affects intraocular pressure independent of age, biomedical parameters, and lifestyle factors. Additionally, a significant negative association between age and intraocular pressure was observed in women, along with a significant positive association between systolic blood pressure and intraocular pressure (Table 4). However, only 2.1% of the variance in intraocular pressure was accounted for by stress score and age. Model 3 accounted for 11% of the variance in women. In contrast to the results for women, stress score was not found to be significantly associated with intraocular pressure in men after controlling for age, whereas stress score was associated with intraocular pressure when biomedical parameters were incorporated into the model (Table 4). However, the significant association between stress score and intraocular

Effects of age, biomedical parameters, and lifestyle factors on the association between stress score and IOP among public school workers Multiple R

R2

F

Model 1 Stress score, age* Model 2 Stress score*, age** BMI, HbA1c*, SBP** Model 3 Stress score Age** BMI HbA1c SBP** Alcohol consumption Smoking** Exercise

.099

.010

4.247

.270

.073

13.511

.296

.088

10.288

Model 1 Stress score**, age* Model 2 Stress score*, age** BMI, HbA1c, SBP** Model 3 Stress score* Age** BMI HbA1c SBP** Alcohol consumption Smoking Exercise

.144

.021

5.878

.318

.101

12.435

.336

.113

8.739

Intraocular pressure (mean)

Men (N883)

Women (N578)

B (SE) indicates unstandardized coefficients (standard error); b , standardized coefficients. * p0.05; ** p0.01.

B (SE)

b

.014 (.007) .034 (.011) .042 (.027) .191 (.104) .031 (.005) .031 (.097) .280 (.076) .010 (.073)

.065 .108 .056 .062 .220 .011 .124 .004

.020 (.008) .065 (.016) .038 (.034) .129 (.275) .038 (.007) .240 (.138) .356 (.211) .113 (.116)

.100 .179 .049 .020 .259 .072 .070 .039


pressure was nullified when lifestyle factors were incorporated into the analysis along with the biomedical parameters. In addition, age was found to have a significant negative association with intraocular pressure, and systolic blood pressure and smoking both had a significant positive association (Table 4). Model 3 accounted for 9% of the variance in men.

Discussion The mean intraocular pressures among men and women were 14.98 and 14.53 mm Hg, respectively, paralleling the results obtained in previous studies of general samples (Shiose and Kawase, 1986; David et al., 1987). While some population-based studies have demonstrated higher intraocular pressure in women than in men (Bengtsson, 1972; Shiose and Kawase, 1986; Klein et al., 1992), the present results indicate that men have higher intraocular pressure than women. Although it was not possible to account for the discrepancy between the results of the current study and those of previous studies, it should be noted that some reports have shown no difference in intraocular pressure between men and women (Carel et al., 1984; David et al., 1987). The morning measurement of intraocular pressure in 36% of the subjects in the current study could have affected our results, as intraocular pressure is known to exhibit diurnal variations (Bengtsson, 1972; Klein et al., 1992; Wilensky et al., 1993). However, any effect of diurnal variation on the present intraocular pressure results is likely negligible, since we found no difference in intraocular pressure between the subjects measured in the morning and those measured in the early afternoon. Our results support previous studies which suggest that intraocular pressure tends to be high during the daytime, with only a small range of pressure variation (Bengtsson, 1972; Weitzman et al., 1975). The present results showing a significant negative association between intraocular pressure and increasing age in both men and women are consistent with previous observations of decreasing intraocular pressure with age in the Japanese population (Shiose and Kawase, 1986; Shiose, 1990); these findings are in contrast to those showing that intraocular pressure tends to increase with age in Western populations (Carel et al., 1984; David et al., 1987; Klein et al., 1992). Intraocular pressure has been shown to be associated with various factors, including biomedical parameters such as blood pressure and serum glucose, and behavioral factors such as coffee intake, alcohol intake, and exercise (Leske and Podgor, 1983; Carel et al., 1984; Poinoosawmy and Winder, 1984; Buckingham and Young, 1986). Although there is substantial evidence suggesting that acute physical or psychological stress affects intraocular pressure (Shily, 1987; Sauerborn et al., 1992; Kaluza et al., 1996; Brody et al., 1999; Leung and Yap, 1999), few studies have examined the association between psychosocial stress and intraocular pressure. We observed 1,461 apparently healthy subjects, and found that stress score measured using the IMPS was significantly and positively associated with intraocular pressure, independent of likely

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confounding variables such as age, BMI, glycosylated hemoglobin, systolic blood pressure, alcohol consumption, smoking, and exercise. To the best of our knowledge, this study is the first to explicitly demonstrate an association between psychosocial stress and intraocular pressure. It has also been observed that glucocorticoids increase intraocular pressure when administered orally or topically (Kass and Sears, 1977), and that patients with Cushing’s syndrome caused by adrenal adenoma or hyperplasia had high intraocular pressure levels, which decreased after appropriate treatments (Haas and Nootens, 1974; Kass and Sears, 1977). Furthermore, an increase in intraocular pressure has been found to have a high degree of temporal correlation with cortisol, with a phase difference of 3 hours, suggesting that diurnal variations in plasma cortisol levels are related to diurnal variations in intraocular pressure (Weitzman et al., 1975). Our results showing that IMPS-measured stress score was significantly associated with intraocular pressure may reflect the stress-associated changes in internal milieu relating to cortisol levels. It is well-recognized that psychosocial stress evokes central and peripheral stress responses such as perturbations of the hypothalamic-pituitary-adrenal (HPA) axis and activation of the sympathetic nervous system, causing the release of excessive cortisol into the bloodstream (Chrousos, 2000). Our findings appear to support the idea that excessive and sustained cortisol secretion associated with psychosocial stress is in part responsible for increases in intraocular pressure among people suffering from psychosocial stress. We found that stress score was significantly and positively associated with intraocular pressure in women, independent of confounding variables; however, this association was not observed in men. There are a number of plausible explanations for gender differences in the effects of psychosocial stress on intraocular pressure. Although the findings to date have been heterogeneous and contradictory, numerous studies have reported that HPA axis response to psychological stress tests differs between men and women (Kirschbaum et al., 1999; Seeman et al., 2001; Traustadóttir et al., 2003). Additionally, the HPA axis has been shown to exhibit hyper-responses to psychosocial stress tests in healthy young men treated with estradiol (Kirschbaum et al., 1996) and in elderly men treated with dehydroepiandrosterone (Kudielka et al., 1998). These findings suggest that gonadal steroids may exert a substantial influence on the reactivity of the HPA axis in humans, which could be a plausible explanation for the gender difference in the effects of psychosocial stress on intraocular pressure observed in the current study. Other possible explanations would be related to recognized differences between men and women in the nature of psycho-behavioral responses to stress, as well as in their respective capacities to tolerate stress (Frankenhaeuser et al., 1978; Kessler and McLeod, 1984). If men and women exhibit psychologically different responses to a similar stressful situation, these differences would be expected to be reflected as differences in brain function, and might also lead to different HPA-axis responses to stress. The

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present findings emphasize how important it is to keep gender differences in mind when designing and interpreting research on psychosocial stress. It remains unclear whether or not an increase in intraocular pressure associated with psychosocial stress eventually leads to the onset of ocular hypertension and open-angle glaucoma. Earlier studies have suggested that the risk of developing glaucoma is related to intraocular pressure (David et al., 1977; Armaly et al., 1980; Davanger et al., 1991; Leske et al., 1995). However, other factors are considered to play important roles in the development of open-angle glaucoma, since the overall incidence of glaucoma in patients with ocular hypertension who are followed for years has remained low, and the vast majority of patients with ocular hypertension have not exhibited pathological changes related to glaucoma (David et al., 1977; Shiose, 1990). Furthermore, a considerable portion of open-angle glaucoma patients studied had normal intraocular pressure (Shiose et al., 1991; Bonomi et al., 1998; Iwase et al., 2004). Our results indicating that if there is indeed an association between psychosocial stress and intraocular pressure, this association is at most a weak one, taken together with these findings, suggest that the relationship between psychosocial stress and open-angle glaucoma remains equivocal. The current study has several limitations. First, stress score measurements were self-reported, and were therefore subject to bias. Here, the women reported more subjective stress than did the men, and the women’s average stress score was higher than that of the men; these results parallel those of previous studies indicating that women perceive stress more intensely than men (Koh et al., 2001), and that the incidence of depressive disorders is higher in women than in men (Piccinelli and Wilkinson, 2000). Thus, the bias associated with selfreport in the current study may be negligible. Second, there was no evidence of an association between IMPS-measured stress score and physiological parameters of stress in the current study’s subjects. However, we demonstrated in our previous study that IMPS-measured stress score was positively associated with obesity and unfavorable glycemic changes, which is in agreement with a model suggesting that psychosocial stress exerts a detrimental physical effect by inducing obesity and insulin resistance, which in turn indicates that the IMPS is a valid means for the evaluation of psychosocial stress levels in a healthy population (Yamamoto et al., 2007). Third, these data are cross-sectional, and therefore no causal relationship between psychosocial stress and intraocular pressure can be identified. However, the possibility of reverse causality, i.e. that an increase in intraocular pressure would cause psychosocial stress, is small, since both intraocular hypertension and openangle glaucoma are often asymptomatic disorders, and those affected in the general population are often unaware of their condition (Quigley, 1996; Bonomi et al., 1998). Further longitudinal studies are needed in order to clarify any causal relationship between psychosocial stress and open-angle glaucoma.

In summary, we demonstrated that psychosocial stress measured using the IMPS was positively associated with intraocular pressure, independent of likely confounding variables such as age, BMI, glycosylated hemoglobin, systolic blood pressure, and lifestyle factors. This relationship was stronger in women than in men, and perturbations of the HPA axis associated with psychosocial stress were considered to be partly responsible for increased intraocular pressure in people suffering from stress. Further research is needed to elucidate the relationship between stress-related increases in intraocular pressure and open-angle glaucoma. Acknowledgements This study was supported by a Grantin-Aid for Scientific Research, No. 16207018, from the Japan Society for the Promotion of Science.

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Received: July 4, 2007 Accepted: November 21, 2007 Correspondence to: Kazuhiko Yamamoto, Institute of Health Science, Kyushu University, Shiobaru, Minami-ku, Fukuoka 815–8540, Japan Phone: 81–80–3963–7881 Fax: 81–92–553–4424 e-mail: [email protected]