Diurnal variations in suicide by age and gender in Italy

Journal of Affective Disorders 65 (2001) 253–261 www.elsevier.com / locate / jad

Research report

Diurnal variations in suicide by age and gender in Italy a, b Antonio Preti *, Paola Miotto a

Psychiatry Branch, Genneruxi Medical Center, Via Costantinopoli 42, I-09129 Cagliari, Italy b Alcohol and Drug Dependence Unit, Conegliano TV, Italy Received 10 July 1999; received in revised form 6 April 2000; accepted 20 April 2000

Abstract Background: Recent Italian statistics on suicide distribution by time of day also report data on gender and age of victims, factors which have been shown to influence the seasonal distribution of suicide and which could also affect the influence of biological circadian rhythms on suicidal behaviour. This study aims to identify and evaluate any diurnal variations that may be present in suicide occurrence by age and gender in Italy, considering data from 1994 to 1997. Methods: The null hypothesis that there are no variations in the distribution of suicides by time of day (or over the three major periods of the day: morning, afternoon, evening / night) was tested with the x 2 goodness-of-fit test and with ANOVA. Results: A clear diurnal variation in the distribution of suicides over time can be observed for both genders, with a peak in the late morning (08:00–11:00 h), and a subsequent decrease to a trough in the night hours. This trend varies with age for both genders: in particular, the age groups 45–64 and 65 1 show a clear suicide peak in the morning (08:00–11:00 h), whereas younger people have a peak number of suicides in the late afternoon (16:00–19:00 h). Adults (25–44 years old) show an intermediate trend, with a less pronounced peak between the morning and early afternoon hours. The observed trend is more marked among males; however, the distribution of suicides by time of day is clearly congruent by age between both genders. Conclusions: Diurnal variation in suicide occurrence by age group may be affected by factors distributed unevenly across age groups. In particular, age distribution of disorders leading to suicidal ideation, and the sensitivity of biological systems of different age groups to environmental cues may affect each group’s risk of suicide. Socio-relational factors are also likely to contribute to diurnal variation in suicide risk by age and gender. Children and adolescents can generally be presumed to be at school during the morning, therefore their opportunity for self-harm is restricted to afternoon hours. The elderly, on the other hand, may find themselves alone in the morning, when family and friends spend more time away from home due to daily work activities. Limitations: Data are based on time of death and not on presumed time of the suicidal act. For suicides committed by certain methods (e.g., poisoning) there may be a considerable difference between time of act and time of death. Clinical relevance: The existence of a temporal window in suicide risk implies an improvement in the surveillance of people at risk of suicide and greater attention to chronobiological factors affecting those suffering from mental disorders leading to suicide ideation.  2001 Elsevier Science B.V. All rights reserved. Keywords: Suicide; Mood disorders; Circadian rhythm; Serotonin; Social factors; Age; Adolescence

*Corresponding author. Tel.: 1 39-70-480-922; fax: 1 39-70-499-149. E-mail address: [email protected] (A. Preti). 0165-0327 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved. PII: S0165-0327( 00 )00232-9

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1. Introduction Mortality by suicide shows clear rhythms according to seasonal change (Kevan, 1980; Chew and McCleary, 1995). These circannual rhythms appear to be influenced by climatic factors such as tempera` ture and sunlight exposure (Souetre et al., 1987; Maes et al., 1994; Preti, 1997). Photoperiod, the naturally occurring alternation of light and dark, seems to particularly influence suicidal behaviour, leading to significant diurnal variation in deaths by suicide by time of day (Williams and Tansella, 1987; Maldonado and Kraus, 1991; Gallerani et al., 1996). Studies based on official statistics show a peak of suicides between the morning and the early afternoon (Williams and Tansella, 1987). Studies carried out on limited samples more often yield negative results (Barraclough, 1976). When observed, this peak is present for both genders, though in some studies, females have a peak later in the day than males (Maldonado and Kraus, 1991; Gallerani et al., 1996). The well documented link between suicide and mood disorders, and the frequently reported findings of abnormalities in biological rhythms in these mental disorders, suggest that some as yet little understood factor contributes to diurnal variation of suicides (Goodwin and Jamison, 1990; Duncan, 1996). The study of such a near circadian variation in suicidal behaviour may offer useful information to the study of factors principally affecting the lethal outcome of a self-destructive act. Not all suicide attempts have a lethal outcome. In many cases the key factor is the method used: violent means more often lead to death than gentler methods (such as drug intoxication or gas poisoning). The impulsivity underlying the act can also influence the chances of survival for the attempter, since an impulsive attempt suggests unpredictability, which reduces the opportunity for surveillance and rescue. All these factors (mood change, availability of means, surveillance, intensity of the impulsive drive to suicide) may be subject to variations through the course of the day. Italian suicide statistics have long reported data on the distribution of suicides according to time of day. Initially data were divided into five periods, leading to an inaccurate division of the events according to the different phases of the day. More recently, the subdivision of suicides has included six intervals

(early morning, late morning, early afternoon, late afternoon, evening, night), allowing a better evaluation of diurnal variations. Recent statistics also report data according to gender and age, factors which have been shown to influence the distribution of suicides according to seasonal changes and which could also affect the influence of biological circadian rhythms on suicidal behaviour (McCleary et al., 1991; Hakko et al., 1998; Preti and Miotto, 1998). This study sets out to evaluate any variations that might exist in the occurrence of suicides in Italy according to time of the day, taking age and gender into account. The study sample includes all suicides reported in Italy from 1994 to 1997.

2. Methods Data on suicides were drawn from official judicial statistics collected by the Italian National Institute for Statistics (ISTAT). Data were collected from the police and carabinieri (military police), who compile detailed case reports based on the preliminary death certificate completed by the examining doctor, and on extensive questioning of key informants and relevant witnesses. Classification of suicides was made according to the Ninth (IX) revision of the International Classification of the Diseases (ICD). ISTAT data report sex, age, and time distribution of suicides. Analyses refer to these different groups of data. Since data are based on the time of death, but not on the presumed time of the act, the proportion of deaths brought about by quick lethal means gives a measure of the degree of reliability of the diurnal variations of suicides observed, therefore these quick suicides have been grouped separately. The following have been considered quick suicides: hanging (ICD 9 code: 953); firearms (ICD 9 code: 955); jumping from a high place (ICD 9 code: 957); crashing accident (ICD 9 code: 958.0 and 958.5). For suicides by these methods it is likely that the time of the act and the time of death coincide or are separated only by a brief interval. For suicides by other means (poisoning by drugs or gas, or drowning) the time of death is likely not to coincide with the time of the act. In some cases, for example in suicides by drowning, it can be difficult to establish

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the time of death with precision, while in other cases, for example in suicides by drug intoxication, death may come many hours after the act. The proportion of suicides by quick means has been calculated to give a measure of the bias inherent in using the time of death as a proxy for the time of the suicidal action, but the main results of the study deal with the sample as a whole (i.e., irrespective of the method used for suicide). Suicides are reported according to six time intervals: early morning (04:00–07:00 h); late morning (08:00–11:00 h); early afternoon (12:00–15:00 h); late afternoon (16:00–19:00 h); evening (20:00– 23:00 h); night (24:00–03:00 h). In 1997, the time of death was not indicated for 198 cases (147 males, 51 females, respectively, 5.6 and 6% of total suicides). Data were analysed to verify if there was evidence of significant variation in the distribution of suicides according to the time of day or to the three major periods of the day (morning, 04:00–11:00 h; afternoon, 12:00–19:00 h; evening–night, 20:00–03:00 h). The null hypothesis was that there would be no such variations in the distribution of suicides. The x 2 goodness-of-fit test was used to test the null hypothesis for time of day; ANOVA was used to test the null hypothesis for major periods of the day. Amplitude of the diurnal variations in suicides is given as the peak’s percentage above the mean.

3. Results

3.1. Demographic data A total of 11 043 male suicides and 3700 female suicides were identified in Italy during the 4-year study period, considering the age range of 14–65 years old and over. This corresponds to a yearly mean of 2760 male suicides (mean yearly rate, 11.6 per 100 000) and a yearly mean of 925 female suicides (mean yearly rate, 3.5 per 100 000). A total of 7585 suicides by quick means were reported among males (67% of the total number of suicides). Among females the proportion of suicides by quick means was clearly lower (2169, corresponding to 57% of total suicides). In all age groups more men committed suicide than women: 14–24 years old, ratio m:f, 925:242;

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25–44 years old, ratio m:f, 3128:888; 45–64 years old, ratio m:f, 3308:1166; 65 years old and over, ratio m:f, 3655:1394. Standardised suicide rates (mean yearly rate per 100 000) increase with age: among males, 14–24 5 3.5; 25–44 5 6.0; 45–64 5 7.9; 65 and over 5 15.4; among females, 14–24 5 0.9; 25–44 5 1.7; 45–64 5 2.4; 65 and over 5 4.2.

3.2. Distribution of suicides according to the time of the day. There is no time subdivision of suicides according to the method used for the act. Therefore, the following results concern the entire sample, subdivided by age and gender but irrespective of the method used for the act. A clear diurnal variation in the distribution of suicides by time is observed in both genders, with a peak in late morning (08:00–11:00 h), and a subsequent decreasing trend to a trough in the night hours (Fig. 1). This trend is more evident among males ( x 2 5 952.3, df 5 5, P 5 0.0001; amplitude 5 1 59%), than among females ( x 2 5 397.8, df 5 5, P 5 0.0001; amplitude 5 1 62%). For both genders, and all age groups, the null hypothesis of a substantial homogeneity in the distribution of suicides during the day has to be rejected. The uneven trend at all ages is more marked among males than among females (Table 1). Nevertheless, the distribution of suicides according to time of day is clearly congruent between both genders (Spearman rank order test, males versus females: 14–24 years old, r 5 0.98, P 5 0.02; 25–44 years old, r 5 0.98, P 5 0.02; 45–

Fig. 1. Distribution of suicides by hour, Italy (1994–1997).

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Table 1 Distribution of suicides by hour, Italy, 1994–1997

Males: Total 14–24 25–44 45–64 65– → Females: Total 14–24 25–44 45–64 65– →

04:00– 07:00 h

08:00– 11:00 h

12:00– 15:00 h

16:00– 19:00 h

20:00– 23:00 h

24:00– 03:00 h

Amplitude (%)

All df 5 5

1519 121 450 402 544

2931 131 658 973 1166

2365 195 641 736 790

2102 216 604 633 640

1455 163 518 418 349

671 99 257 146 166

59 40 26 76 91

x 2 5 952.30 x 2 5 33.23 x 2 5 129.20 x 2 5 426.00 x 2 5 526.40

P 5 0.0001 P 5 0.0001 P 5 0.0001 P 5 0.0001 P 5 0.0001

461 21 89 135 215

1004 47 212 322 420

836 53 212 272 297

740 62 190 249 236

462 47 122 144 148

197 12 63 44 78

62 55 43 65 81

x 2 5 397.80 x 2 5 28.68 x 2 5 79.41 x 2 5 164.10 x 2 5 157.90

P 5 0.0001 P 5 0.0001 P 5 0.0001 P 5 0.0001 P 5 0.0001

64 years old, r 5 1.00, P 5 0.02; 65 years old and over, r 5 1.00, P 5 0.02). In both genders, youths (14–24 years old) show a trend that clearly differs from the other age groups. The 45–64 age group and 65 1 years olds have a clear peak of suicides in the morning (08:00–11:00

h), whereas the young have a suicide peak in the late afternoon (16:00–19:00 h). Adults (25–44 years old) show an intermediate trend, with a less pronounced peak between the morning and the early afternoon (Fig. 2). However, though the suicide peak occurs in the

Fig. 2. Distribution of suicides by time, Italy (1994–1997).

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Table 2 Distribution of suicides by time, Italy, 1994–1997 Morning

Afternoon

Evening–Night

ANOVA (df 5 2 / 21)

Males and females: Total 14–24 25–44 45–64 65– →

739 (267) 40 (8) 176 (47) 229 (104) 293 (113)

755 (68) 65 (16) 205 (16) 236 (24) 245 (40)

348 (148) 40 (16) 120 (45) 94 (50) 92 (38)

F 5 12.96 F 5 8.85 F 5 9.94 F 5 10.89 F 5 16.39

P 5 0.0002 P 5 0.001 P 5 0.0009 P 5 0.0006 P 5 0.0001

Males: Total 14–24 25–44 45–64 65– →

556 (193) 31 (6) 138 (31) 171 (79) 213 (85)

558 (53) 51 (9) 155 (19) 171 (21) 178 (28)

265 (111) 32 (12) 96 (37) 70 (36) 64 (27)

F 5 12.89 F 5 10.17 F 5 7.79 F 5 10.09 F 5 16.34

P 5 0.0002 P 5 0.0008 P 5 0.002 P 5 0.0008 P 5 0.0001

Females: Total 14–24 25–44 45–64 65– →

183 (75) 8 (4) 37 (18) 57 (28) 79 (27)

197 (18) 14 (6) 50 (9) 65 (9) 66 (13)

82 (37) 7 (5) 23 (8) 23 (14) 28 (11)

F 5 12.66 F 5 3.72 F 5 8.96 F 5 10.71 F 5 15.42

P 5 0.0002 P 5 0.04 P 5 0.001 P 5 0.0006 P 5 0.0001

morning hours when the day is divided into six periods, dividing the day into three major periods puts the highest number of suicides for both genders in the afternoon (Table 2), indicating this period as a particularly high risk time of the day.

4. Discussion Though the results of this study are compelling, caution should be exercised in considering possible bias and faults inherent in its methodology. The use of time of death as a proxy for the presumed time of the suicidal act is a problem acknowledged in previous studies. In some cases (for example in suicides by drowning) it can be difficult to establish the time of death with precision, while in others (for example in suicides by drug intoxication), death may come many hours after the time of the act. The proportion of deaths by a quick lethal means has here been used as a test for the reliability of our data. It is felt that the use of the time of death as a proxy for the time of suicidal act is acceptable since the majority of suicides in our sample (62% on average) occurred by quick lethal means. It is likely, therefore, that most deaths occurred a short time after the

suicidal act. In an Italian study carried out on a limited sample (152 cases) in the town of Ferrara and considering the presumed time of the act (and not the time of the death), Gallerani et al. (1996) found that the peak of suicides fell in the late morning (about 12:00–13:00 h). Unfortunately, no comparison was reported in their study between time of death and presumed time of the suicidal act: therefore, it was not possible to establish if there was a difference between the two moments, and, if so, how great that difference might be. The limitations of sample did not allow the Authors to evaluate the influence of age. In the present study, the peak of suicides by time is in the morning, but as a whole the higher number of suicides in both genders occurs during the afternoon. Such a trend, however, varies with age: among 65 1 year olds, the highest number of suicides is in the morning (04:00–11:00 h), whereas among the young, (14–24 years old) the highest number of suicides is clearly in the afternoon (12:00–19:00 h). Bias in ascertaining the cause of death is a possible source of generalisation of our results: underestimation of suicide is a world-wide phenomenon (O’Carroll, 1989), particularly for some social groups (children, those employed in certain profes-

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sions, people belonging to religious groups condemning suicide). Suicides such as poisoning, overdose or car fatalities can be masked as accidental deaths, or recorded as deaths from undetermined causes. Furthermore, it cannot be excluded that the opportunity to hide or conceal the real cause of death in a suicide may vary by time of day, as a function of the surveillance and pressure exerted by the social network of the deceased over the procedures of ascertainment. However, studies carried out in Western countries, and not just in Italy, show that official statistics on suicide are likely to underestimate suicide occurrence but not to conceal or to change the sign of social and environmental influences (Pescolido and Mendelsohn, 1986; Williams et al., 1987). Recent empirical evidence also suggests that undercounts have consistently been in far more modest proportions than previously supposed (Moscicki, 1997). It seems, therefore, that officially reported mortality data may be considered reasonably sound, enough to be used to study risk factors and correlates of completed suicide (Sainsbury and Jenkins, 1982; O’Carroll, 1989). Trends in suicide distribution by time of day are also likely to be real and subject to scant bias due to underestimation. What underestimation does exist should be expressed in an unvarying random fashion throughout the day. The data analysed in this study were collected from a wide territory, rather than a single area; this should compensate for local variations in the habits and attitudes of those who carry out the inquiry or the ascertainment of cause of death. Beyond its limitations, this study confirms that there is a period during the day when suicide risk is higher. This high risk period varies according to age but not gender. Among the young (14–24 years old) suicides peak in the late afternoon (16:00–19:00 h), whereas among the elderly the peak is in the morning (08:00–11:00 h). In both genders, and at all ages, the lowest number of suicides are in the night hours (24:00–03:00 h). Causal and concurrent factors contributing to this diurnal suicide trend should therefore be sought by considering events or circumstances which vary according to age but not gender. Only one previous study has explored the role of age in the diurnal variation of suicidal behaviour. Maldonado and Kraus (1991) found differences in suicide occurrence in Sacramento county by time of

the day according to age group: in their study, the age group 10–34 had a peak of suicides in the evening (16:01–20:00 h); suicides in the age group 35–64 peaked between 12:01 and 16:00 h; and age group 65–94 had a suicide peak between 08:01 and 12:00 h. Maldonado and Kraus did not subdivide between genders, and three age groups were considered, as opposed to four in the present study. Their results based on data collected over a very broad time span (from 1945 to 1983—a period during which significant changes in the recognition and ascertainment of suicide deaths are likely to have occurred), whereas this study reports data from a broad archive (a total of 14 743 suicides) collected, however, over a limited range of years (1994–1997). It is not yet possible to establish the precise causes of this diurnal variation in deaths by suicide. The observation of a temporal window for higher suicide risk does not automatically imply the existence of a circadian rhythm underlying uneven diurnal suicide risk, though the results are suggestive. Photoperiod is influenced by latitude: in fact, latitude variations of suicide rates have been reported in Italy as elsewhere (Ellner, 1977; Preti, 1998). Daylight duration, which is also likely to contribute to seasonal fluctuations in suicide occurrence, may affect suicide risk by acting on the timing of biological processes subject to circadian variations (Maes et al., 1994; Hakko et al., 1998). Near 24-h oscillations in biological processes are timed by an endogenous clock located in the hypothalamus suprachiasmatic nucleus (Ikonomov and Stoynev, 1994; Florez and Takahashi, 1995). This clock is specifically sensitive to activity of serotonergic neurons (Meyer-Bernstein and Morin, 1996; Pickard and Rea, 1997). Abnormalities in serotonergic functions have been described in suicides, and a link has been established between suicide risk and lower brain serotonergic function (Asberg et al., 1987; Mann, 1995, 1998). Serotonergic functions show a clear circadian and seasonal pattern, and this pattern has been linked to the seasonal occurrence of suicides (Tagliamonte et al., 1974; Brewerton, 1989; Maes et al., 1995). Genetic alterations of serotonergic functions have been described and linked to a higher risk of both mental disorders and suicide (Nielsen et al., 1994; Roy et al., 1997). Older people, who bear the higher risk of suicide in the population,

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may be at higher risk from disruption of serotonergic functions, since the efficiency of aminergic neurons subject to circadian fluctuations tends to vary with age (Timiras et al., 1983; Pietraszek et al., 1990). However, fluctuations in serotonergic functions are not the only causes of chronobiological suicide risk. Many other biological systems show temporal fluctuations in their functions, and these chronobiological rhythms may contribute to suicide risk in particular seasons or time of the day (Maes et al., 1996). Socio-relational factors are also likely to contribute to diurnal variation in suicide risk by age and gender. One key factor in suicide, apart from the availability of lethal means, is the opportunity for self-harm, which varies as a function of surveillance (Chew and McCleary, 1994). Children and adolescents are generally confined at school during the morning, therefore their opportunity for self-harm is restricted to afternoon hours. The elderly, on the other hand, may find themselves alone in the morning, when family and friends spend more time outof-doors due to daily working activities. Therefore, the elderly may have an increased opportunity for self-harm in the morning since surveillance decreases in this period. The different age distribution of mental disorders involved in suicide risk may also be relevant in explaining diurnal variations in suicide behaviour. Disorders which show little evidence of diurnal fluctuations (such as personality disorders, anorexia nervosa and addiction) are more often observed among young suicides (Tolstrup et al., 1985; Blumenthal, 1988; Henriksson et al., 1993). Mood disorders tend to prevail among older people, who are thus exposed to more intense diurnal variations in mood and biological rhythms (Goodwin and Jamison, 1990). Depressive, melancholic patients typically report a worsening of symptoms in the morning, and this may contribute to enhance their risk of suicide in this period of the day. However, a smaller part of depressive patients with atypical features show a worsening of mood in the evening: this trend may have minimised the main tendency, particularly among the young. The majority of atypical depressives are bipolar II (Benazzi, 1999). This disorder often goes unrecognised, yet has important characteristics which are significantly likely to influence its course and outcome, such as

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younger average age of onset, high rate of comorbidity with other psychiatric disorders, and a higher frequency of suicidal thoughts (Hantouche et al., 1998; Manning et al., 1999; Perugi et al., 1999). The impulsive risk-taking traits associated with cyclothymic and hyperthymic temperaments which often precede the onset of a bipolar II disorder have been thought to play an important role in unsafe behaviour leading ultimately to HIV infection (Perretta et al., 1998), and are also likely precipitating factors in suicidal behaviour, particularly among the young (Rihmer and Pestality, 1999). In summary, suicidal behaviour in Italy shows clear diurnal variations, which vary as a function of age. Such temporal risk factors should imply improvements in the surveillance of people at risk of suicide and greater attention to chronobiological factors affecting those suffering from mental disorders leading to suicide ideation.

Acknowledgements The Authors would like to thank the ISTAT staff in Caliari for their help and kindness, and Mr. Thomas Eagle for help in the revision of the English translation.

References Asberg, M., Schalling, D., Traskman-Bendz, L., Wagner, A., 1987. Psychobiology of suicide, impulsivity, and related phenomena. In: Meltzer, H.Y. (Ed.), Psychopharmacology: The Third Generation of Progress. Raven Press, New York, pp. 655–668, Ch. 65. Barraclough, B.M., 1976. Time of day chosen for suicide. Psychol. Med. 6, 303–305. Benazzi, F., 1999. Prevalence of bipolar II disorder in atypical depression. Eur. Arch. Psychiatry Clini. Neurosci. 249, 62–65. Blumenthal, S.J., 1988. Suicide: a guide to risk factors, assessment, and treatment of suicidal patients. Med. Clin. North Am. 72, 937–967. Brewerton, T.D., 1989. Seasonal variation of serotonin function in humans: research and clinical implications. Ann. Clin. Psychiatry 1, 153–164. Chew, K.S.Y., McCleary, R., 1994. A life course theory of suicide risk. Suicide Life-Threatening Behav. 24, 234–244. Chew, K.S.Y., McCleary, R., 1995. The spring peak in suicides: a cross-national analysis. Soc. Sci. Med. 40, 223–230.

260

A. Preti, P. Miotto / Journal of Affective Disorders 65 (2001) 253 – 261

Duncan, Jr. W.C., 1996. Circadian rhythms and the pharmacology of affective illness. Pharmacol. Ther. 71, 253–312. Ellner, M., 1977. Research of international suicide. Int. J. Soc. Psychiatry 23, 187–194. Florez, J.C., Takahashi, J.S., 1995. The circadian clock: from molecules to behaviour. Ann. Med. 27, 481–490. Gallerani, M., Avato, F.M., Dal Monte, D., Caracciolo, S., Fersini, C., Manfredini, R., 1996. The time for suicide. Psychol. Med. 26, 867–870. Goodwin, F.K., Jamison, K.R., 1990. In: Manic-Depressive Illness. Oxford University Press, New York. Hakko, H., Rasanen, P., Tiihonen, J., 1998. Seasonal variation in suicide occurrence in Finland. Acta Psychiatr. Scand. 98, 92– 97. Hantouche, E.G., Akiskal, H.S., Lancrenon, S., Allilaire, J.F., Sechter, D., Azorin, J.M., Bourgeois, M., Fraud, J.P., ChatenetDuchene, L., 1998. Systematic clinical methodology for validating bipolar-II disorder: data in mid-stream from a French national multi-site study (EPIDEP). J. Affect. Disord. 50, 163–173. Henriksson, M.M., Aro, H.M., Marttunen, M.J., Heikkinen, M.E., Isometsa, E.T., Kuoppasalmi, K.I., Lonnqvist, J.K., 1993. Mental disorders and comorbidity in suicide. Am. J. Psychiatry 150, 935–940. Ikonomov, O.C., Stoynev, A.G., 1994. Gene expression in suprachiasmatic nucleus and circadian rhythms. Neurosci. Biobehav. Rev. 18, 305–312. Kevan, S., 1980. Perspective on season of suicide: a review. Soc. Sci. Med. 14, 369–387. McCleary, R., Chew, K.S.Y., Hellsten, J.J., Flynn-Bransford, M., 1991. Age- and Sex-specific cycles in United States suicides, 1973 to 1985. Am. J. Public Health 81, 1494–1497. Maes, M., De Meyer, F., Thompson, P., Peeters, D., Cosyns, P., 1994. Synchronized annual rhythms in violent suicide rate, ambient temperature and the light–dark span. Acta Psychiatr. Scand. 90, 391–396. Maes, M., Scharp, S., Verkerk, R., D’Hondt, P., Peeters, D., Cosyns, P., Thompson, P., De Meyer, F., Wauters, A., Neels, H., 1995. Seasonal variation in plasma L-tryptophan availability in healthy volunteers. Relationships to violent suicide occurrence. Arch. Gen. Psychiatry 52, 937–946. ´ S., D’Hondt, P., Peeters, D., Wauters, A., Maes, M., Scharpe, Neels, H., Verkerk, R., 1996. Biochemical, metabolic and immune correlates of seasonal variation in violent suicide: a chronoepidemiologic study. Eur. Psychiatry 11, 21–23. Maldonado, G., Kraus, J.F., 1991. Variation in suicide occurrence by time of day, day of the week, month, and lunar phase. Suicide Life-Threatening Behav. 21, 174–187. Mann, J.J., 1995. Violence and aggression. In: Bloom, F.E., Kupfer, D.J. (Eds.), Psychopharmacology: The Fourth Generation of Progress. Raven Press, New York, pp. 1919–1928, Ch. 163. Mann, J.J., 1998. The neurobiology of suicide. Nat. Med. 4, 25–30. Manning, J.S., Haykal, R.F., Akiskal, H.S., 1999. The role of bipolarity in depression in the family practice setting. Psychiatr. Clin. North Am. 22, 689–703.

Meyer-Bernstein, E.L., Morin, L.P., 1996. Differential serotonergic innervation of the suprachiasmatic nucleus and the intergeniculate leaflet and its role in circadian rhythm modulation. J. Neurosci. 16, 2097–2111. Moscicki, E.K., 1997. Identification of suicide risk factors using epidemiologic studies. Psychiatr. Clin. North Am. 20, 499– 517. Nielsen, D.A., Goldman, D., Virkkunen, M., Tokola, R., Rawlings, R., Linnoila, M., 1994. Suicidality and 5-hydroxindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. Arch. Gen. Psychiatry 51, 34–38. O’Carroll, P.W., 1989. A consideration of the validity and reliability of suicide mortality data. Suicide Life-Threatening Behav. 19, 1–16. Perretta, P., Akiskal, H.S., Nisita, C., Lorenzetti, C., Zaccagnini, E., Della Santa, M., Cassano, G.B., 1998. The high prevalence of bipolar II and associated cyclothymic and hyperthymic temperaments in HIV-patients. J. Affect. Disord. 50, 215–224. Perugi, G., Akiskal, H.S., Ramacciotti, S., Nassini, S., Toni, C., Milanfranchi, A., Musetti, L., 1999. Depressive comorbidity of panic, social phobic, and obsessive-compulsive disorders reexamined: is there a bipolar II connection? J. Psychiatr. Res. 33, 53–61. Pescolido, B.A., Mendelsohn, R., 1986. Social causation or social construction of suicide? An investigation into the social organization of official rates. Am. Sociol. Rev. 51, 80–101. Pickard, G.E., Rea, M.A., 1997. Serotonergic innervation of the hypothalamic suprachiasmatic nucleus and photic regulation of circadian rhythms. Biol. Cell 89, 513–523. Pietraszek, M.H., Urano, T., Serizawa, K., Takahashi, S., Sumiyoshi, K., Takada, Y., Takada, A., 1990. Circadian rhythm of serotonin: influence of age. Thromb. Res. 60, 253–257. Preti, A., 1997. The influence of seasonal change on suicidal behaviour in Italy. J. Affect. Disord. 44, 123–130. Preti, A., 1998. The influence of climate on suicidal behaviour in Italy. Psychiatry Res. 78, 9–19. Preti, A., Miotto, P., 1998. Seasonality in suicides: the influence of suicide method, gender and age on suicide distribution in Italy. Psychiatry Res. 81, 219–231. Rihmer, Z., Pestality, P., 1999. Bipolar II disorder and suicidal behavior. Psychiatr. Clin. North Am. 22, 667–673. Roy, A., Rylander, G., Sarchiapone, M., 1997. Genetics of suicide. family studies and molecular genetics. Ann. NY Acad. Sci. 836, 135–157. Sainsbury, P., Jenkins, J.S., 1982. The accuracy of officially reported suicide statistics for purpose of epidemiological research. J. Epidemiol. Community Health 36, 43–48. ` Souetre, E., Salvati, E., Belugou, J.L., Douillet, P., Braccini, T., Darcourt, G., 1987. Seasonality of suicides: environmental, sociological and biological covariations. J. Affect. Disord. 13, 215–225. Tagliamonte, A., Gessa, R., Biggio, G., Vargiu, L., Gessa, G.L., 1974. Daily changes of free serum tryptophan in humans. Life Sci. 14, 349–354. Timiras, P.S., Cole, G., Croteau, M., Hudson, D.B., Miller, C., Segall, P., 1983. Changes in brain serotonin with aging and modification through precursor availability. In: Agnoli, A.,

A. Preti, P. Miotto / Journal of Affective Disorders 65 (2001) 253 – 261 Crepaldi, G., Spano, G., Trabucchi, M. (Eds.), Aging. Raven Press, New York, pp. 23–35. Tolstrup, K., Brinch, M., Isager, T., Nielsen, S., Nystrup, J., Severin, B., Olesen, N.S., 1985. Long-term outcome of 151 cases of anorexia nervosa. The Copenhagen Anorexia Nervosa follow-up study. Acta Psychiatr. Scand. 71, 380–387.

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Williams, P., Tansella, M., 1987. The time for suicide. Acta Psychiatr. Scand. 75, 532–535. Williams, P., De Salvia, D., Tansella, M., 1987. Suicide and the Italian psychiatric reform: an appraisal of two data collection systems. Eur. Arch. Psychiatry Neurol. Sci. 236, 237–240.