Gender differences in the association of mixed anxiety and depression with suicide

The incidence of depression is higher in women than men butthe reverse pattern is seen with suicide. In a cohort of 50692 Norwegians we found that suicide risk associated with comorbidanxiety and depression was two-fold higher in men (OR=7.4,95% CI 3.1–17.5) than women (OR=2.9, 95% CI 0.8–10.6),although statistical evidence for a difference was weak (P=0.4).If real, these gender differences could reflect either a moresevere symptom profile in men with self-reported anxiety anddepression, perhaps because of gender differences with regardto the stigma associated with mental illness, or gender differencesin the way men respond to mental illness (e.g. self-medication/help-seeking).

INTRODUCTION

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INTRODUCTION

Depression is thought to be the most important antecedent ofsuicide; however, the epidemiology of suicide and depressiondiffer in a number of respects. Most strikingly, in high-incomecountries, rates of suicide are three to four times higherin men than women. In contrast, population surveys indicatethat the prevalence of depression,¹ suicidal thoughts andsuicide attempts² is higher in women than men. There are severalpossible explanations for these contrasting patterns.³ First, men use more lethal methods of suicide than women, so casefatality is higher in men. Second, women with depression aremore likely than men to seek help from friends, family andhealth services.⁴ Last, it is possible that depression ismore stigmatised in men than in women, so men may be less likelyto report symptoms. Evidence for this latter explanation is mixed.^5,6 In a cohort study examining the association of psychiatriccaseness (measured using the General Health Questionnaire (GHQ))with suicide, GHQ-positive men were more than four times morelikely to die by suicide than GHQ-positive women.⁶ This study was underpowered as only 16 suicides occurred over the follow-upperiod. It is noteworthy that in a Danish register-based study,women who were admitted to hospital for the treatment of psychiatricillness appeared to be at greater suicide risk than men.⁷

We have further investigated this issue in a large population-basedcohort of men and women from the Nord-Trøndelag regionof Norway who completed the Hospital Anxiety and DepressionScale (HADS)⁸ questionnaire in 1995–1997. A previousanalysis of this cohort⁹ found that mixed anxiety and depressionwas strongly associated (OR $>=$ 6.00) with suicide risk.

Method

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Method

The Nord-Trøndelag Health Study (HUNT 2) was carriedout in 1995–1997 (www.hunt.ntnu.no/index.php?side=english). Participants completed the 14-item HADS.⁸ Of the 92 936 eligibleindividuals aged 20 years and older, 66 140 (71.2%) enteredHUNT 2. Of these, 50 692 (76.6%) had valid responses on allbackground variables, including depression (HADS–D) andanxiety (HADS–A) scores. The death registry (StatisticsNorway; www.ssb.no/english) was used to identify all deathsup to 31 December 2004. Suicides were defined as deaths codedE950–E959 (suicide) and E980–E989 (excluding E988.8,undetermined intent) using ICD–9 or X60–84 (suicide)and Y10–34 (undetermined intent) using ICD–10.

We used Cox proportional hazards regression with calendar timeas the time axis in Stata Version 9.0 for Windows to examineassociations of mixed anxiety and depression with suicide.Mixed anxiety and depression was evaluated as a dichotomousvariable using a cut-off score of $>=$ 8 on both HADS–A and HADS–D for caseness,¹⁰ and as a continuous variableusing the total sum of HADS–A and HADS–D (HADS–Tscore). To study whether the associations differed in men comparedwith women, we fitted appropriate interaction terms.

Our initial models controlled for age (in 10-year bands) andgender. We then examined the effect on associations of controllingfor marital/cohabitation status, frequency of alcohol consumption( $<=$ monthly, 2–4 times per month, $>=$ 5 per month, $<=$ monthly butprevious alcohol problems), smoking (never, former, current),and educational level (<9 years, 9–12 years, >12years).

Results

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Results

Altogether 26 044 women (mean age 46.5 years) and 24 648 men(mean age 47.3) were included in the analysis. At baseline,1542 (5.9%) women and 1183 (4.8%) men reached caseness formixed anxiety and depression. More men than women reportedalcohol intake $>=$ 5 times a month (18.4% v. 8.1%, P<0.0001),but fewer men were daily smokers (28.5% v. 30.7%, P<0.0001).Gender differences in other baseline characteristics were minor:40.2% of women v. 38.8% of men lived alone and 69.8% of womenv. 71.5% of men had received $>=$ 9 years of education.

At the end of the follow-up period, 14 (0.05%) women and 27(0.11%) men had died by suicide. Only 11 (27%) suicides occurredamong people with mixed anxiety and depression at baseline.Among the 30 remaining suicides, 18 had a HADS–D scorebelow 4, whereas 12 scored 4–7. Of note there were no suicides among participants with `pure' depression, i.e. HADS–Dscore >8 and HADS–A score <8 (n=2178).

In analyses controlling for age and gender, mixed anxiety anddepression was strongly associated with suicide risk in ananalysis based on men and women combined (HR=7.07, 95% CI 3.51–4.25);this association was attenuated in the fully adjusted model(HR=4.82, 95% CI 2.43–9.55). In gender-stratified analysesthe fully adjusted HR for suicide in men with mixed anxietyand depression at baseline was 7.41 (95% CI 3.14–17.51)and in women it was 2.90 (95% CI 0.79–10.59). Althoughthe HR was over twofold higher in men than in women, therewas no statistical evidence of a difference in gender-specificassociations (Table 1).

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Table 1 Association of mixed anxiety and depression and suicide risk in women (n=26 044) and men (n=24 648)

Discussion

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Discussion

Caseness on a brief psychiatric rating scale was associatedwith a five-fold increased risk of suicide over an 8-year follow-up.In keeping with a previous study⁶ the effect estimates wereindicative of higher suicide risk in men than women with mixedanxiety and depression but there was no statistical evidenceto support such a difference. Both studies are relatively smalland sizeable gender differences cannot be ruled out. Disparitiesin the size of the gender difference between the two studiescould be attributed either to chance or to psychometric differencesbetween the instruments used to measure mental disorder. Alhoughthe correlation between HADS–T and the GHQ is as high as 0.75,¹⁰ they measure different symptom profiles. For example,anhedonia, the major depressive feature assessed by HADS, hasbeen proven to be the least gender-specific among depressive symptoms.¹¹

Surprisingly, most suicides occurred among HADS-negative participantsand half of all suicides had HAD–D scores <4 at baseline,indicating either underreporting or, more plausibly, the relativelytransient nature of common mental disorder.

There are several limitations to our study. First, all participant characteristics were measured only once and we had no informationon life-events or anxiety and depression symptom fluctuationin the follow-up period. Second, although HADS can indicatecaseness in a variety of settings¹⁰ it does not reflect theprevalence of more severe mental disorders known to increase suicide risk. Nevertheless, there is growing evidence thatself-reported symptoms of anxiety and depression have goodprognostic and predictive value.^11,12 Last, although depression/anxietydisorders account for over half of all suicides and are morecommon in women in the general population, other psychiatricconditions associated with suicide such as alcohol and drugmisuse occur more frequently in men and may contribute to thegender disparities in suicide rates.

In summary, these findings provide some support for the notionthat gender differences related to the risk of depressive disordersand suicide are attributable to gender-differences in the reportingof psychiatric symptoms.¹³ Other contributory factors mayinclude gender differences in help-seeking, acceptable suicidemethods, depressive symptom profile and the psychiatric conditionscontributing to population suicide rates.

REFERENCES

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