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Department of Psychiatry, Nagoya City University Medical School, Nagoya and Psycho-Oncology Division, National Cancer Centre Research Institute East, Chiba
Epidemiology and Prevention Division, Research Centre for Cancer Prevention and Screening, National Cancer Centre, Tokyo
Psycho-Oncology Division, National Cancer Centre Research Institute East, Chiba
Epidemiology and Prevention Division, Research Centre for Cancer Prevention and Screening, National Cancer Centre, Tokyo, Japan
Correspondence: Dr Shoichiro Tsugane, Epidemiology and Prevention Division, Research Centre for Cancer Prevention and Screening, National Cancer Centre, 5 -1-1Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.Tel: +81 3 3542 2511 extension 3385; Fax: +81 3 3547 8578; e-mail: stsugane{at}ncc.go.jp
Declaration of interest None. Funding detailed in Acknowledgements.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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Aims To investigate the possible association between alcohol intake and suicide.
Method We used nationwide population-based cohortdata from the Japan Public Health Centre-Based Prospective Study cohort. Atotal of 43 383 men aged 40–69 years participated. Death from suicide was defined according to ICD–10 as codes X60–X84.
Results During the 367817 person-years of follow-up, there were168 suicides. Compared with occasional drinkers, the pooled multivariate relative risk (RR; with 95% CI) of suicide for non-drinkers and regular heavy drinkers was 2.3 (1.2–4.6) and 2.3 (1.2–4.7) respectively. The RR increased with the amount of alcohol consumed (P for trend=0.004).
Conclusions There is a U-shaped association between alcohol consumption and subsequent suicide.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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METHOD |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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Baseline questionnaire survey
A self-administered questionnaire was distributed to all cohort members in
1990 (Cohort I) and 1993–4 (Cohort II), mostly between February and
March, to determine socio-demographic characteristics, personal medical
history, smoking status, alcohol intake, alcohol-related flushing, physical
activity, and other lifestyle-related factors (e.g. food intake). The
questionnaire used for Cohort II was modified to include questions on social
support.
Alcohol consumption
In Cohort I, we defined non-drinkers (<1 day/month), occasional drinkers
(1–3 days/month) and regular drinkers (1–2 days/week or more)
based on the frequency of alcohol consumption. Subjects in Cohort II were
asked about their alcohol consumption habits, i.e. whether they were never,
ex-, or current drinkers. To match the variables of alcohol intake in the two
cohorts, the ‘non-drinker’ category was defined as never drinkers
and ex-drinkers combined in Cohort II. Current drinkers were divided into
occasional drinkers (1–3 days/month) and regular drinkers (1–2
days/week or more), based on the frequency of consumption. Among regular
drinkers, weekly ethanol intake was calculated by multiplying frequency per
week by the amount of alcohol consumed daily. The amount of ethanol in each
alcoholic drink was calculated as follows: 180 ml sake (rice wine) as 23 g
ethanol, 180 ml shochu or awamori (white spirits) as 36 g, 633 ml beer as 23
g, 30 ml whisky or brandy as 10 g and 60 ml wine as 6 g. The method for
calculating ethanol intake has been reported in detail elsewhere
(Tsugane et al, 1999;
Sobue et al, 2001).
Participants were classified into six groups: non-drinkers, occasional
drinkers, and four groups of regular drinkers according to the quartile of
weekly ethanol intake (<138 g/week, 138–251 g/week, 252–413
g/week and 
414 g/week).
To evaluate the validity of the estimation of alcohol intake from the baseline questionnaires, we collected four 7-day dietary records (a total of 28 days) from volunteers in each cohort. Spearman’s rank correlations for estimated alcohol intake between the baseline questionnaires and dietary records were 0.79 in 94 men in Cohort I (Tsubono et al, 2003) and 0.59 in 176 men in Cohort II (unpublished data). This indicates that our questionnaire had moderate validity for ranking participants according to their alcohol consumption.
Facial flushing
Previous studies have indicated that approximately half of those from East
Asia have very low aldehyde dehydrogenase 2 (ALDH2) activity. This enzyme
limits alcohol intake by means of the unpleasant symptoms that occur after
alcohol consumption owing to the low capacity to metabolise aldehyde
(Ferguson & Goldberg,
1997). Facial flushing after alcohol consumption is an excellent
indicator of the presence of inactive ALDH2
(Takeshita et al,
1993; Yokoyama et al,
1997). Moreover, facial flushing is well known to be associated
with reduction in both drinking and progression to alcoholism
(Higuchi et al, 1992).
Thus since the mechanism underlying the association of alcohol consumption and
suicide is not clear (Hufford,
2001) we also investigated the relationship between alcohol
consumption and suicide in individuals with and without facial flushing. A
facial flushing questionnaire was used, which Yokoyama et al
(1997) reported had good
reliability (high sensitivity and specificity) for inactive ALDH2.
Follow-up and identification of suicide
We followed all participants from baseline until 31 December 1999 for
Cohort I and 31 December 2000 for Cohort II. Data on migration were obtained
from the residential registry annually. Of the initial participants, 1966
(4.3%) moved out of the study area and 36 (0.08%) were lost to follow-up. Data
on deaths of participants who remained in their original area were based on
death certificates from the local public health centre. For those who died
after moving from their original area, the cause of death was extracted from
death certificates kept by the Ministry of Health, Labour and Welfare, Japan.
Death by suicide was defined according to ICD–10
(World Health Organization,
1992) as codes X60–X84. All death certificates in Japan are
submitted to a local government office and forwarded to the public health
centre in the area of residence. Mortality data are then sent to the Ministry
of Health, Labour and Welfare and coded for National Vital Statistics.
Registration of deaths is mandatory in Japan under the Family Registration Law
and death certificates must be completed by a licensed physician. The verdict
of suicide is based on the results of the medico-legal examination by a
licensed physician and the police investigation as required by Japanese law.
Thus, the data are believed to be sufficient in terms of quality and
completeness.
Statistical analysis
Person-years of follow-up were calculated from baseline until the date of
suicide, the most recent date when survival status was confirmed in censored
cases, and at the end of the study periods (31 December 1999 for Cohort I and
31 December 2000 for Cohort II) for survivors, whichever occurred first. The
crude suicide rate was calculated by dividing the number of suicide cases by
the number of person-years. For each cohort, the Cox proportional hazards
model was used to estimate relative risk (RR) and 95% confidence intervals
(CIs) of suicide related to alcohol consumption at baseline using the SAS
program version 8.2 for Windows (PROC PHREG; SAS Institute, Cary, North
Carolina, USA). The RRs were adjusted for age, area, living alone and
unemployment. Linear trends were tested in the Cox proportional hazards models
by treating the categories as ordinal variables. The interaction test was
performed for facial flushing status. All P values reported are
two-sided and the significance level was set at P<0.05.
We used the fixed-effects model to combine the loge RRs; the cohort-specific RRs were weighted by the inverse of their variance after testing for heterogeneity among cohorts (Petitti, 1994). The pooled P value for the interaction test was calculated by the sum of logs method (Becker, 1994).
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RESULTS |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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The association between alcohol consumption at baseline and subsequent death by suicide is shown in Table 2. Compared with occasional drinkers, the pooled multivariate RRs for non-drinkers and regular drinkers who consumed more than 414 g of ethanol per week were 2.3 (95% CI 1.2–4.6) and 2.3 (95% CI 1.2–4.7) respectively. Among non-drinkers in Cohort II, ex-drinkers had a significantly increased risk of suicide compared with occasional drinkers, but never drinkers did not, even after adjusting for potential confounders. Among drinkers the risk of suicide increased with the amount of ethanol consumed, and the trend test revealed statistical significance (P for trend=0.004). There is a U-shaped association between alcohol consumption and subsequent death by suicide (Fig. 1).
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To maintain statistical power, we recategorised drinkers into three groups. Because groups of occasional drinkers and regular drinkers who consumed 138–251 g ethanol showed almost the same risk as groups of regular drinkers who consumed less than 138 g and 252–413 g ethanol respectively, we combined these categories. Thereafter, we analysed the association between alcohol consumption and subsequent death by suicide among drinkers further adjusting for flushing status. Regular heavy drinkers who consumed more than 414 g of ethanol per week had a significantly higher risk of suicide than those who drank occasionally or consumed less than 138 g of ethanol per week (pooled multivariate RR=2.3, 95% CI 1.4–3.8).
Among men for whom data on alcohol-related flushing status were available (n=39 241), 43.2% reported being non-flushers and 56.8% being flushers. Flushers did not have a significantly increased risk of suicide compared with non-flushers (pooled multivariate RR=1.3, 95% CI 0.9–1.8). To determine whether alcohol consumption differed in terms of subsequent death by suicide between non-flushers and flushers, we analysed the data in separate facial flushing strata. Among non-flushers, a non-significant elevated risk was observed for regular drinkers who consumed more than 414 g of ethanol per week (pooled multivariate RR=2.1, 95% CI 0.9–4.7) compared with those who drank occasionally or consumed less than 138 g of ethanol per week; a borderline significant positive trend was also found (P for trend=0.07; Fig. 2). Among flushers, regular drinkers who consumed more than 414 g of ethanol per week had a significantly increased risk (pooled multivariate RR=2.5, 95% CI, 1.3–4.8) compared with those who drank occasionally or consumed less than 138 g of ethanol per week, and a positive trend was observed (P for trend=0.007). The interaction test for facial flushing status did not show statistical significance (P=0.96).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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To the best of our knowledge, only five cohort studies have investigated the association between alcohol consumption and subsequent suicide (Paffenbarger et al, 1969; Ross et al, 1990; Andreasson et al, 1991; Klatsky & Armstrong, 1993; Turvey et al, 2002) but their findings were inconsistent. Three of these reports indicated that individuals consuming large amounts of alcohol were more likely to die by suicide than those who never drank or consumed moderate amounts (Ross et al, 1990; Andreasson et al, 1991; Klatsky & Armstrong, 1993). The other two studies found no significant association (Paffenbarger et al, 1969; Turvey et al, 2002). Our present findings indicate that heavy drinkers among middle-aged Japanese men, who constitute the majority of Japanese suicide victims, are not the only group vulnerable to subsequent death by suicide. Non-drinkers are also at risk. The increased risk for death by suicide among non-drinkers was an unexpected finding, and there are several possible explanations.
First, because the findings were somewhat attenuated after excluding the first 2 years of follow-up, non-drinkers might have several underlying physical diseases, which could be risk factors for later suicide. Second, one epidemiological study investigating drinking habits and depression among middle-aged and elderly Japanese males revealed a significantly higher degree of depression among non-drinkers than among moderate and even problem drinkers (Sato et al, 1990). Underlying depression in non-drinkers may contribute to the higher risk for suicide. Third, non-drinkers in Cohort II perceived less social support, for example, in the form of close friends and confidants, and this might contribute to the increased risk of subsequent suicide (Heikkinen et al, 1993). There might also be other factors associated with a non-drinking lifestyle, such as specific personality traits, coping strategies, religious beliefs and a past history of alcohol dependence, although we do not have clear empirical data supporting the association. Finally, the difference between never drinkers and ex-drinkers which are both classed as non-drinkers in the present study, should be considered more carefully because each showed different RR compared with occasional drinkers in Cohort II. An increased risk of suicide might be observed only in exdrinkers but not in never drinkers. Our findings, like those of other health outcomes (de Lorimier, 2000), suggest a U-shaped association between alcohol consumption and suicide. However, further research is needed to determine why non-drinkers are more likely to die by suicide than moderate drinkers.
Alcohol-related flushing and suicide
The dose–response effect of alcohol consumption on death by suicide
was significant in regular drinkers with alcohol-related flushing, although a
borderline significance was also observed among non-flushers and the
interaction test for facial flushing did not yield statistically significant
results. Several recent studies have demonstrated potential roles for genetic
factors, including polymorphisms, in psychiatric disorders that are associated
with suicide behaviours (Hasegawa et
al, 2002; Huang et
al, 2003) but the current findings do not suggest any clearly
different effect of alcohol consumption on suicide among non-flushers (active
ALDH2) and flushers (inactive ALDH2).
Methodological advantages of this study
Our study had several methodological advantages. First, the prospective
design made it possible to avoid recall bias. Most epidemiological studies of
alcohol consumption and suicide have used a retrospective design with proxy
respondents. Second, this study included a large population-based sample with
a high response rate (approximately 80%) and a very low rate of loss to
follow-up. Third, we measured alcohol consumption using a validated
questionnaire, whereas most previous cohort studies did not use a validated
measurement for alcohol consumption
(Paffenbarger et al,
1969; Ross et al,
1990; Andreasson et
al, 1991; Turvey et
al, 2002). Fourth, the similar findings in the two cohorts
strengthens the results.
Limitations
Our study had some limitations. First, several important items of data were
not available because the primary aims of the cohort (JPHC Study) did not
include provision of evidence for suicide. In particular, the lack of any data
on psychiatric disorders such as depression and alcohol misuse/dependence is
the most important limitation. Second, because the numbers of suicides are
small in each alcohol consumption group, the results might be overinterpreted.
Third, ICD–10 suicide statistics might not be reliable because
under-reporting and misclassification of suicide can occur (such as accidental
drowning and poisonings) and any event in the undetermined intent category can
be misclassified as suicide (Rockett &
Smith, 1993). However, this type of misclassification would be
unlikely to have influenced the results because we observed similar results
after taking deaths from undetermined causes into account. Fourth, there may
be measurement errors in the alcohol consumption and other lifestyle factors
resulting from the use of the questionnaire. In addition, the influence of
modification of drinking habits during the follow-up period cannot be ignored.
A reduction or increase of alcohol consumption might lead to attenuation of
the true association. Fifth, since two of the metropolitan areas were excluded
because of different definitions of the study population, our findings may not
be directly generalisable to the entire Japanese urban population. However,
our findings can at least be generalised to middle-aged and elderly Japanese
men in rural areas. Finally, because the participants were middle-aged
Japanese men, the findings may not be applicable to those from different
generations and/or to women.
Further research
Although there are several limitations, the observed association between
alcohol consumption and suicide is still important, and future studies,
particularly of the cooccurrence of alcohol dependence and mood disorders,
should yield interesting results.
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Clinical Implications and Limitations |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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LIMITATIONS
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ACKNOWLEDGMENTS |
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TOPABSTRACTINTRODUCTIONMETHODRESULTSDISCUSSIONClinical Implications and...ACKNOWLEDGMENTSREFERENCES |
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This study was supported by a Grant-in-Aid from the Cancer Research and Second-Term Comprehensive Ten-Year Strategy for Cancer Control from the Ministry of Labour, Health and Welfare of Japan.
Members of the JPHC Study Group (principal investigator S.Tsugane):M.Inoue, T.Hanaoka, S. Tsugane): M. Inoue, T. Hanaoka, S. Tsugane, S. Yamamoto and T. Sobue, Research Centre for Cancer Prevention and Screening, National Cancer Centre, Tokyo; J. Ogata, S. Baba, T. Mannami and A. Okayama, National Cardiovascular Centre, Suita; K. Miyakawa, F. Saito, A. Koizumi, Y. Sano and I. Hashimoto, Iwate Prefectural Ninohe Public Health Centre, Ninohe; Y. Miyajima, N. Suzuki, S. Nagasawa and Y. Furusugi, Akita Prefectural Yokote Public Health Centre, Yokote; H. Sanada, Y. Hatayama, F. Kobayashi, H. Uchino, Y. Shirai, T. Kondo, R. Sasaki and Y. Watanabe, Nagano Prefectural Saku Public Health Centre, Saku; Y. Kishimoto, E. Takara, T. Fukuyama, M. Kinjo and M. Irei, Okinawa Prefectural Ishikawa (Chubu) Public Health Centre, Ishikawa; K. Imoto, H. Yazawa, T. Seo, A. Seiko and F. Ito, Katsushika Public Health Centre, Tokyo; A. Murata, K. Minato, K. Motegi and T. Fujieda, Ibaraki Prefectural Kasama (Mito) Public Health Centre, Mito; K. Matsui, T. Abe and M. Katagiri, Niigata Prefectural Kashiwazaki Public Health Centre, Kashiwazaki; M. Doi, A. Terao and Y. Ishikawa; Kochi Prefectural Tosayamada (Chuo-higashi) Public Health Centre, Tosayamada; H. Sueta, H. Doi, M. Urata, N. Okamoto and F. Ide, Nagasaki Prefectural Arikawa (Kamigoto) Public Health Centre, Arikawa; H. Sakiyama, N. Onga and H. Takaesu, Okinawa Prefectural Miyako Public Health Centre, Hirara; F. Horii, I. Asano, H.Yamaguchi, K. Aoki, S. Maruyama and M. Ichii, Osaka Prefectural Suita Public Health Centre, Suita; S. Matsushima and S. Natsukawa, Saku General Hospital, Usuda; S. Watanabe and M. Akabane, Tokyo University of Agriculture, Tokyo; M. Konishi and K. Okada, Ehime University, Matsuyama; H. Iso and Y. Honda, Tsukuba University, Tsukuba; H. Sugimura, Hamamatsu University, Hamamatsu; Y. Tsubono, Tohoku University, Sendai; M. Kabuto, National Institute for Environmental Studies, Tsukuba; S. Tominaga, Aichi Cancer Centre Research Institute, Nagoya; M. Iida and W. Ajiki, Osaka Medical Centre for Cancer and Cardiovascular Disease, Osaka; S. Sato, Osaka Medical Centre for Health Science and Promotion, Osaka; N. Yasuda, Kochi University, Kochi; S. Kono, Kyushu University, Fukuoka; K. Suzuki, Research Institute for Brain and Blood Vessels, Akita; Y. Takashima, Kyorin University, Mitaka; E. Maruyama, Kobe University, Kobe; the late M. Yamaguchi, Y. Matsumura and S. Sasaki, National Institute of Health and Nutrition, Tokyo; T. Kadowaki, Tokyo University, Tokyo, Japan.
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Received for publication October 12, 2004. Revision received May 26, 2005. Accepted for publication June 8, 2005.
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