SS Anxiety Disorders and Risk for Suicidal Ideation and Suicide Attempts A Population-Based Longitudinal Study of Adults Jitender Sarcen, MD, FRCPC; Brian J. Cox, PhD; Tracie O. Afifi, MSc; Ron de Graaf, PRD; Gordon J. G. Asmundson, PhD; Margreet ten Have, PhD; Murray B. Stein, MD, MPH Context: Controversy exists whether anxiety disorders are independently associated (ie, alter adjusting for co- morbid mental disorders) with suicidal ideation and sui- cide attempts, Objective: To examine whether anxiety disorders are risk factors for suicidal ideation and suicide attempis in a large population-based longitudinal study Methods: Data come from the Netherlands Mental Health Survey and Incidence Study, a prospective population- based survey with a baseline and 2 follow-up assess- ments over a 3-year period. The Composite Interna- onal Diagnostic Interview was used to assess DSM- HIL-R mental disorders. Lifetime diagnoses of anxiety disorders (social phobia, simple phobia, generalized anx ety disorder, panic disorder, agoraphobia, obsessive compulsive disorder) were assessed at baseline. Mul- Liple logistic regression analyses were used to examine whether anxiety disorders were associated with suicidal ideation and attempts at baseline (n=7076) and whether anxiety disorders were risk factors for subsequent onset of suicidal ideation and attempts (n=4796) Results: Alier adjusting for sociodemographic factors andall other mental disorders assessed inthe survey, base- line presence of any anxiety disorder was significantly associated with suicidal ideation and suicide attempts in both the cross-sectional analysis (adjusted odds ratio for suicidal ideation, 2.29; 95% confidence interval, 1.85- 2.82; adjusted odds ratio for suicidal attempis, 248; 05% confidence interval, 1.70-3.62) and longitudinal analy- sis (adjusted odds ratio for suicidal ideation, 2.32; 05% confidence interval, 1.31-4.11; adjusted odds ratio for suicide attempts, 3.64; 95% confidence interval, 1.70- 7.83). Further analyses demonstrated that the presence of any anxiety disorder in combination with a mood dis- order was associated with a higher likelihood of suicide fltempts in comparison with a mood disorder alone. Conelusions: This isthe first study to demonstrate that 1 preexisting anxiety disorder is an independent risk fac- tor for subsequent onset of suicidal ideation and al- tempts. Moreover, the data clearly demonstrate that co- morbid anxiety disorders amplify the risk of suicide alemptsin persons with mood disorders. Clinictans ad policymakers need to be aware of these findings, and fur- ther research is required to delineate whether treatment of anxiety disorders reduces the risk of subsequent sui- cidal behavior. Arch Gen Psychiatry. 2005;62:1249-1257 UICIDAL IDEATION (SI) AND suicide attempts (SAs) are highly prevalent in the com- munity (119-149 and 2.8%. 4.6%, respectively)" and are strong risk factors for completed sui- cide.’ Psychological autopsy studies have demonstrated that the majority of sui- cides occur on the individual's first SA.°* Thus, it is highly important to under- stand risk factors for suicidal behavior and intervene prior to the individual making the first SA. A well-established risk factor for suicidal behavior is the presence of mental disorders, especially mood disor- substance use disorders,’ and Author Affiliations: Department of Psychistry, University of Manitoba, ‘Winnipeg (Drs Sarcen and Cox and Ms Alii) Trimbos | Institute, Netherlands Insteate of Mental Health and Addiction, UUnecht (Drs de Graaf and ten Have), Amxiey and Illness Behaviours Laboratory, University of Regina, Regina, saskatchewan (Dr Asmundson) and Departments of Psychiatry and Family and Preventive Medicine, University of California, San Diego (rstein), ders,!°" schizophrenia." Although there has been significant in- terestin whether anxiety disorders are risk factors for suicidal behavior, this re- mains a controversial area." Cross- sectional community'**"* and clintal tue es! have repeatedly demonstrated in univariate models that anxiety disorders are associated with SI, Ss, and com- pleted suicides. Among the anxiety disor- ders, panic disorder has received the great estaltention. In multivariate models, i has been questioned whether panic disorder fs associated with suicidal behavior after adjusting for other anxiety disorders and other mental disorders.""*"*"* Because anxiety disordersare highly comorbid with other anxiety disorders and tend to elus- (©2003 American Medical Association. AI rights reserved, ‘Downloaded From: https:/jamanetwork.com/ on 02/16/2023ter together.” we suggest that it is important to ad- dress whether anxiety disorders asa group of mental dis- orders have an impact on suicidal behavior after adjusting for other types of mental disorders (especially mood and substance use disorders). To date, none of the pub- lished studies using large community samples on anxi- ety disorders and suicidal behavior have examined whether anxiety disorders asa group, after adjusting for other mental disorders, are associated with suicidal behavior. ‘An even more important limitation of the literature on this topic is that most studies, with the exception of a few," have used cross-sectional, retrospective data. Such retrospective reports have been criticized for the lack of temporal information on whether anxiety disor- ders preceded the onset of sueidal behavior" among those with comorbidity, Prospective longitudinal evaluation of whether anxiety disorders are risk factors for new-onset suicidal behavior is required, The current study addresses whether anxiety disor- ders have a significant impact on suicidal behavior us- {ng data from the Netherlands Mental Health and Inci- dence Survey (NEMESIS),"** a large, Dutch, general population survey. We examined the impact of anxiety isorders on suicidal behavior in 2 stages. First, we es- lumated whether the presence of lifetime anxiety disor- der diagnoses hada cross-sectional association with life- time suicidal behavior at baseline assessment. Second, we examined whether anxiety disorders at baseline had a sig- nificant impact on first-ever incidence of SI and SAs at follow-uspassessments, To the best of our knowledge, this represents the list prospective examination of whether anxiety disorders predict subsequent onset of suicidal be- havior in a large population-based sample ss} BASELINE AND FOLLOW-UP SAMPLES ‘The NEMESIS is « population-based study with repeated measurements among the same respondents. A stratified, ran- dom sampling procedure was used. First, sample was drawn from 90 Dutch municipalities stratified by urbanicty and asul- ficient distribution over the 12 provinces of the Netherlands. Post oflce records were used to draw a sample of private house- holds (addresses). The numberof houscholds selected in each ‘municipality was in proportion ta its population. One respon- dentin each household was selected randomly, according to whose birthday was most recent, on the condition that he or she was between I8 and 64 years of age and sulicently fluent in Dutch. To maximize the response rate and to compensate forany seasonal influences, the initial data collection phase was spread over the entire period from February to December 1990, {At baseline, a total of 7076 people (response rate of 69.7%) were interviewed and ae refered toasthe baseline sample. Two follow-up assessments were conducted, once tl yearalter the baseline and once a 3 years alte the baseline. Of the 7076 par- Licipants at baseline, 3018 respondents were available for e- interview atthe fist follow-up assessment and 4848 respon- dents at the second follow-up assessment. A total of 4798 respondents had valid information ata 3 assessments. Previ- fous analysis” ofthe NEMESIS data has demonstrated that the presence of a DSM-IIL-R mental disorder was only a modest pre- tictor of attrition in this sample MEASURES, Mental Disorders ‘he DSW Axis mental disorders were diagnosed with tesson 1.1 ofthe Compose Ineratonal Dghostc Inter view (C1D1)."'A computerized version of the CHD] ws ed forall waves ofthe NEMESIS The CID isa structured inte sie developed by the Word Heath Organization, based on the Diagnostic Interview Schedule andthe Present Sate E thinatenandadmintscedby waned interviewers" The CDI ta doctented relay and vay foal mental dre de ezamined in the eure survey "> Lifetime DSMIPR dagnoses were assed at baseline, The individual anuetydsordelslncded in theanalysts were ses Siv-compulave disorder (OCD), generalized anni dsrder (GAD) spe phobia soci phobi agoraphobia, and panied trier. The ty dr dognosrs toca n issue were Highly relable ed on previous methodologic sts ofthe (HDL varable that measured te prsenceofany anit di ter vas locate. aswel having any hfe mood disor dr aor depression, pois disorder, and dysiys) mex Suredat baseline was ds included nthe analysts, Other mena Glsorderasesed inthe survey included lfchne alcool suse or dependence drgabie or dependence, eating orders (= itniatanores) ond scicophreniAlespondnt wh screen estve onthe pychoissulsezion ofthe CID Intl suvey ‘here reintervicwed by a tained clinician to diagnose the pres tne or absence of pcos, Based on this cinta appeal, the sme prevalence of schizophrenia inthe NEMESIS was tee Suieidality tems rom the C1D1 questionnaire were used to measure Stand Sav and were the same questions used in the Epidemiologt Glichment Arensurvey®and the Us National ComorbitySar- ‘ey (NCS). At baseline, SI was assessed by the fllowing ques- tion: "Have your ever so low you thought about comit- ting suicide?” Similarly, the presence ofa Teast 1 Metime SA twat measured using a question that asked, “Have you everat- tempted suicide?” Atthe follow-up acesment, the same ques tions were repeated with the tm trsme limited tothe tnter- ‘ening period between assessments. Prevalence of fete Stand SAs at baseline assessment (ne 7076) was 11.1% and 2.7%, respectively. The sever inc dence oft was defined whena person didnot report Stor SAs baccline bt endorsed SI tether follow-up peiod. Atheist. and second follow-up periods, there were 41 and + new cases oft respectively. This, the total number of nev cases of tat citer follow-up assessment vas 83 (20% ofthe sample a sk, 340) Similarly, the fist-ver incidence ofan SA was defined when a person didnot reportan SA at basline but endorsed making ‘m1 SA a either fellow-up period. We included individuals n= dbrsing sat baseline in the sample at risk for the SA analyst ‘the frst and second follow-up periods, there were 24 and 15 new eases of SAs respectively Thus, the total numberof new caves of SAsat ether ollow-p was 39 (0.8% the sample Mrik, n= 4070). SOCIODEMOGRAPHIC VARIABLES Age was measured in numberof years and was used as a con- tinuous variable inthe analyses, Education was measured by highest level of aainment as incicated by 3 categories: primary? lower vocational, secondary/middle vocational, higher vocs- (©2003 American Medical Association. AI rights reserved, ‘Downloaded From: https:/jamanetwork.com/ on 02/16/2023Table 1. Cross-sectional Analysis of Anxiety Disorders and Sulide Variables inthe Baseline Sample "Seis eaton ana Sele Alpe st aselne ‘aeaton lean ‘ents atts ‘Aunty ocrsr 0, (iets), OR AOR) na. (ncaed, (n= 20), OR kota wenwine hac She.) @mrecy_(ewenycarwene Vnase Sha.) mec (eee) (ec acl aia mao Bh Ba) ase bang stag crabzioy 7) ai) assay rte aAbi29) Simpl pots sa tara aad tat (22) Gt) (BABAg (ze2IRB (OsT-I5 — (OS) HA) (AOR TENG (LTDA (120268) Guersindaniey 2a ag aa gar soar 3) Gad) Sab BTog (Las2H (LAEZIOy (ds) aT) AIRSHH (ONEDOH) OsTHI7D) Obessiecompasive ZBL HOT ggg tO Zt “isoaee 8h 5) eritBong (btn obits) hd) PaBSng ose) adisany Ps carder tao a ag gt 2 2) (ian) GOTIO IHS (L9BSEg VaeSz§ BS) — DS) GANT AGH (LatOsy (128828) Joorpeti itt eee ee eee en a neg oa a pa 26) aabB20§ (LxZ2e1y HokzzmN (31) 138) (BIB OGG (LALIT (1.165854 ‘aay sores TB gato aA (83) G2) Thy rah Seag (82) thy eating 78g ‘Abravitons: ADA, dusted ds a, Cleon ara OR. eds at (aust): A, not appa ‘Alrumbers were unvighd, anal pcertages were worhiad 808-1 eats aghsenents for agg, Sx elucaion. mafia status ural status, major depression, Boa disor, siya, eating are, aleholuse ior rg use dors ad copa (ech Gogol ws ested sopra nthe sae aresson). "HOA.2 deste adhetants for al vara m AOS! and srstaneus austen ech fhe thr ant ard Spook path poos tional/academic. Marital status was divided into 4 categories: respondents witha lifetime mood disorder only with those with never married, married/common-law, widowed, orseparated/ lifetime mood and anxiety disorders on suicide variables. All divorced. Urbanicity was dichotomized into categories: mu-_ analyses were conducted unadjusted and then adjusted for so- ricipalities with fewer than 500 addresses per square kilome-_ciodemographic variables and other mental disorders at base- ter were considered rural, and larger municipalities were line (alcohol use disorders, drug use disorders, eating disor- considered urban, ders, schizophrenia). STATISTICAL ANALYSIS Po nsuts | Inall analyses, the appropriate statistical weight was used to en- sie the data Were epreschiativeofthenational population Stan- CROSS-SECTIONAL ANALYSIS dard errors were calculated by using the Taylor series incariz- ‘OF ANXIETY DISORDERS tion method in the SUDAAN progeat i Fist, we examined the relationship between anxiety disor- AND SUICIDE VARIABLES AT BASELINE ders and St and SAsiin the baseline sample (ic, cross-sectional snalysis). Second, among the subsamples at risk, we exam- IL is noteworthy that, among all respondents with SI at ined whether lifetime anxiety disorder diagnosis athaseline was baseline, 52.4% had a least 1 anxiety disorder (Rabble 1), associated with subsequent onset SL and SAs (at either fol Similarly, among all respondents reporting SAs at base- low-up time period), We conducted 3 ses of regressions: t- ine, 64.19 had atleast lanety disorder. After adjust- adjusted: adjusted for soctodemographicsand other mentaldis- ng for sociodemographies and mental disorders a5- frders and adjusted for secodemograpies, oe mene ee a ene ans aiey disorders and each ofthe otheranaeydordes It isimpor- ene he arses He reser of 4 feat anally tant to underscore that we used the more stringent approach “ gnosis sMiajeting os omettidhy inutghewes Gisioliceeand ted With lifetime St and SAs at baseline. Examination See eee PERS ilar Merman Gfspecific anxiety disorders (Table 1) demonstrated that neously entered the presence or aence ofeach thefollow- _eachlifetimeanxiety disorder was tronaly associated with inline DSACHER mental disorders inthe same tegres. ‘lifetime St (ds atio,3.74-10.37) and lifetime SAs (odds sion: major depression, bipolar disorder, dysthymia, ening ratio, 4.92-10.0)) For lifetime St, when adjusting for so- disorder lcokel abuse of dependence drug sbute or depen: clodcmographiefaciors and other mental disorders and dence, and schizophrenia ‘We also examined whether stratiication by mood disorder alfected the relationship between anxiety disorders and sti cide variables. We stratified the sample into groups based on lifetime diagnoses at baseline: (1) both anxiety disorder and mood disorder, (2) anxiety disorder only, (3) mood disorder simultaneously adjusting for each of the other anxiety disorders all ofthe anxiety disorders (except simple pho- biaand OCD) remained significantly associated with SL A slightly different pattern was found for lifetime SAs at baseline. In multivariate analyses, we found that panic only, and (4) neither mood disorder nor anxiety disorder. Us-_ disorder, agoraphobia without panic and simple phobia ing multiple logistic regression, we calculated the odds of SI (ROL OCD, GAD, or social phobia) were significantly as- and SAs foreach of the first 3 groups with reference tothe group sociated with lifetime SAs, even after adjusting for other with neither anxiety nor mood disorder. Next, we compared mental disorders and sociodemographic variables. (©2003 American Medical Association. AI rights reserved, ‘Downloaded From: https:/jamanetwork.com/ on 02/16/2023‘Amit osorer OR AOR AOR 39), OR AOR AOR atBaeaie ) faery (PCIE (ANCHE No.) No. (s) (SEH) (eNRC)_—_ (8D) Socal habia aa 2s eT 2o1-7ay§ (L4D53m) (120839) (65) 25) (158-982)) (061-515) (041-400) Simple phobia 20 tas oat (105-4009 (071-285) (058226) (90) GOB) ABANIOG (145-716) (LOT-BEATA Generale arty az 2th a7 82k ab 2a ‘deocer (1s6-916)§ (LoZSOKN (LONE 72)) (45) BOS) BADABIEI§ (078-710) (064-825) Dbsese-compulse a cdeorder ermacang (126-3286) (.113596)) (26) (G1) (1.82.95.16)| (014-2606) (015-1699) Pane deodee 1508) om gs katt ©3537) 16219) O79 G3) 103) (LMB-BARIL (026-465) (000-436) Aowrapttiawibout 112 tot 113 om ak gmt te nic 24 4a) (73812) SESS SZ Bs) FT) (LORI (OSES) (020520) Anyansioy Scorer 67831 Me BM] | gaat A (156) G69) (1955005 (131-411) (184 650), @aztnENs (170-783)) ‘bravo: ADA, dusted ods a, leone ara OR. eds at (aust: A, not applabie “Ad uber wre unvighd, an allpcerages were woh #A08-T incest adhsenent far age, Sx eluabon mara sus utanurl status, major ‘ior, rug use disorder ad chopra (ech gnosis ws entsed separa nthe a "OR 2 deste adhetants for al vara m ADS and srsaneus adjustments recht th nt rd. Secor poo pots IMPACT OF BASELINE ANXIETY DISORDER (ON FIRST-EVER INCIDENCE (OF SUICIDE VARIABLES ‘Table 2 demonstrates that, similar to the pattern found in the cross-sectional analysis, the presence of an anxi- ety disorder at baseline was significantly associated with first-ever incidence of SI and SAs in multivariate mod- cls. Among those respondents with first-ever incidence of SAs, 55.0% had at least 1 anxiety disorder at baseline. Similarly, among those respondents with first-ever inci- dence of SI, 37% had at least | anxiety disorder at base- line, The impact of specific anxiety disorders om first- ever incidence of SL and SAsis also illustrated in Table 2 Alter adjusting for other mental disorders and sociode- ‘mographie variables, social phobia, GAD, and OCD re- mained associated with firstever incidence of SI. In ad- dition, when adjusting for all the mental disorders and each of the other anxiety disorders, social phobia, GAD, and OCD remained significantly associated with first ever incidence of SI. In multivariate models, baseline simple phobia was the only anxiety disorder diagnosis that remained significantly associated with firstever in- idence of an SA. (CROSS-SECTIONAL ANALYSIS (OF ANXIETY DISORDERS AND SUICIDE VARIABLES STRATIFIED BY MOOD DISORDER ‘Table 3 demonstrates that stratification by presence of mood disorder affected the relationship between anxi- ely disorders and suicide variables. Importantly, the re- spondents with 1 or more lifetime anxiety disorders at baseline who had never met criteria fora mood disorder remained at significantly higher risk of lifetime SI (ad- justed odds ratio [AOR], 326) and SAs (AOR, 3.63), even alter adjusting for comorbid mental disorders (alcohol or drug use disorders, eating disorders, and schizophre- nia) and sociodemographic factors. Although individu- als with mood disorders without anxiety disorders had higher odds of SI and SAs than persons without mood disorders, respondents meeting criteria for both a mood and an anxiety disorder had substantially increased odds of SI (AOR, 17.60) and SAs (AOR, 16.96) compared with persons with neither. ‘We further analyzed whether the presence of an anxi- ety disorder in combination with a mood disorder el: tevated the risk of suicidal behavior in comparison with those with a mood disorder alone. Compared with the mood disorder without anxiety disorder group, we found, a significantly elevated risk of SI and SAs in those with both a mood and anxiety disorder. These findings re- ‘mained significant (SI AOR, 1.86; SA AOR, 2.17) after adjusting for sociodemographic factors and other men- tal disorders (schizophrenia, eating disorders, and sub- stance use disorders) IMPACT OF BASELINE ANXIETY DISORDER ON FIRST-EVER INCIDENCE OF SUICIDE VARIABLES STRATIFIED BY MOOD DISORDER Compared with individuals with neither mood nor anxi- ety disorders at baseline, the presence of an anxiety dis- order, with or without a mood disorder, was associated with substantially higher likelihood of first-ever SI (AOR, 3.34) and SA (AOR, 3.24) (Table 4). These findings re- (©2003 American Medical Association. AI rights reserved,Stalled by Mood Disorder inthe Baseline Sample Table 3. Cross-sectional Analysis Relationship Between Anxiety Disorders and Sulide Vat ‘mond date Sr) cise, eam, on ons on son Disorders at passing ‘ho. (sr ‘no-(s)" (st) cere “host rey eecy a 1 BESET TOD To nor asocerooy 646 (100) 85 (107) S46 260450) 325 2a2440}# TOE(TON) 22°08) Aad aBTeTE S63 zosae Mood dsorerosy —483(71) 201 241) TOOT BST ISamht O56 ras i2zHHt GAT (a7) 421106) oAD(SoeteOs 7aR E1200 Anes ané mood disorder 431(65) 344(817) 2001 1681-2501} 176013002220} 687101) TRIGA) 25a T6aKsasNH 1696 IDBt2ESH Age anémoaddsode; MR «MA TOL(LSDOSH TBB(LATOGGH NA MA 26U(L7OGA0}E217(LESZEE teen ou “a numbers unightd and allpcertages were woh Peat #A08-T eats adhsenns far agg, Sx eluabon ara satus utara sus, major ior rg ee diode and scope ech gna need xpath a ‘Abravitons: ADA, usted ods at, Cl, condenser OR. eds at (aust: A, not ppeabie Tew ont Se a Table 4. Incidence of Sulcide Variables in Relation to Baseline Ansely Disorder (Stratified by Mood Disorder) Among Those at Risk Sule Atamps al Follow-up Assessments (ctrence group, mood ‘beedrel). ‘Atompls Atoms on nont —n=a0st), (n= 38), ont Disorders at Basen Ho. (%)""_ No. (4) (ore) (]xrent __ne.() Wo.) (eee) (ear Nether amie Ssorer—_160(771) 38(664) 100 700) 3 (726) 14 (833) 1.00 100) nor mood dort Ansty sor cay 41808) 16(100) 328(1786054 a34(1 75840 4s9(100) 5(154) 424 (111-945) sa4ctooacog Mood isorér only 923(72) 16(167) 4002177304 Au6(t7EE 72} 447(01) 4(t03) 239(07e737) 2a4(O70755) Ansty andeod dsorer 250,58) 15(179) S03(2500774 464 275-943} 20/84) 16(410) 900(4552140y 1005 438-28204 Anwstandimecd disorder NAMA «1.25(060265) 1at(0e0287) © WAHAB (1.SBRGNNG AAS (LAL-AZO0§ ‘Airavitons: ADA, dusted ods a, lcs ara OR eds at (aust A, not ppiabie “a numbers unightd and allpcertages were woh #A08-T eats adhsenns far agg, Sx eluabon ara satus utara sus, major ior rg ee diode and scaophrana ech gna need apr nh a P08 Scan mained significant after adjusting for comorbidity with other mental disorders and sociodemographic charac- \eristics, Furthermore, respondents with mood and anxi- ety disorders had significantly higher likelihood of SAs (AOR, 4.15), but not SI, compared with respondents with a mood disorder without anxiety disorders, Eee} To the best of our knowledge, the current study is the first population-based, prospective, longitudinal exami- nation of the impact of anxiety disorders on Sl and SAs. The main finding from this study is that the presence of an anxiety disorder at baseline was a risk factor for sub- sequent onset of Sl and SA, even after adjusting for com- mon mental disorders, These findings contribute to re- solving the contentious issue of whether anxiety disorders are risk factors for suicidal behavior." Together with strong evidence that anxiety disorders are highly under- recognized and undertreated in the community" and primary care,* the current findings suggest that un- treated anxiety disorders might be missed opportunities {or preventing suicidal behavior. Puture randomized con- trolled tials are required to assess whether early inter vention and treatment of anxiety disorders reduces the likelihood of subsequent suicidal behavior. roma public health perspective, a very important find- ing of the current study is that mood disorders in combi- nation with anxiety disorders had the highest likelihood of SL and SAs compared with those with neither anxiet nor mood disorders in both cross-sectional and longit- dinal evaluation, Furthermore, the presence of a combi- nation of mood and anxiety disorder was associated with ‘higher risk for SAs compared with those with mood dis- orders alone. These findings are consistent with previous studies demonstrating that suicidal behavior is associ- (©2003 American Medical Association. AI rights reserved,ated with presence of multiple mental disorders'* and mood disorders in combination with ansiety disorders."*” Over- all, these findings imply that public health treatment strat- egies aimed at reducing suicidal behavior in the commnu- nity should target individuals with mood disorders alone, anxiety disorders alone, and especially those with both an anxiety and a mood disorder. ‘Among the specificanxiety disorders, the current study found that OCD, social phobia, and GAD were strongly linked with SI at baseline and follow-up. Adjusted mod- clsdid not find an association between these anxiety dis- orders and SAs, Previous work has also found that so- cial phobia was associated with SI but not SAs in the Epidemiologic Catchment Area study. However, SAs were found to be associated with uncomplicated OCD in the Epidemiologic Catchment Area study.” Its possible that the relationship between these anxiety disorders and sui- cidal behavior may differ. Suicidal ideation may be di- rectly related to GAD, social phobia, and OCD. How- ever, SAs may be indirectly mediated through comorbidity with other mental disorders. Among the anxiety disorders studied in the NEMESIS, simple phobia was found to be associated with Stand SAS, in unadjusted models, but only SAs in multivariate mod- cls adjusting for other mental disorders, These findings \were consistent in cross-sectional and longitudinal analy- ses and fit with previous analysis of the NCS data show- ing positive association between simple phobia and SI and Ss." There ate at least 4 possible explanations for these findings. First, simple phobia might have a direct association with suicidal behavior due to its association with significant distress. Previous work from the NCS” demonstrated that simple phobia often has an early age of onset and even in its noncomorbid form is associated with significant role impairment Second, simple phobia might be indirectly associated with suicidal behavior through an interaction with other comorbid disorders assessed here. In the NCS, simple pho- bia was shown to be highly comorbid with other mental disorders (83.4% have a least 1 other disorder, most com- monly another anxiety disorder or a mood disorder)” We found partial support for this hypothesis: simple pho- bia was not associated with increased risk for Sl, al- though it was associated with increased risk for SAs. The sample lacked the power totes! for interactions ina more definitive, disorder-by-disorder fashion, Third, siimple phobia might be indirectly associated with suicidal behavior through another diagnosis not as- sessed in the current survey. For example, posttrau- matic stress disorder (PTSD) has been positively associ- ated with suicidal behavior in a range of clinical and epidemiologic studies.*** Using the NCS data, multi- variate models adjusting for the effects ofall other anxi- ety disorders found that PTSD was the only anxiety dis- order that remained associated with suicidal behavior.” We suggest that the lack of assessment of PTSD in the NEMESIS may be an important explanation of why simple phobia remained associated with suicidal behavior in the current study; specifically, we hypothesize that some of the diagnoses of simple phobia in the NEMESIS are really cases of PTSD-related phobic avoidance that are not ad- equately categorized in this regard. Finally, tis possible thatthe diagnosis of simple pho- bia in community samples may be a marker for a sub- threshold anxiety disorder. Because the enteria for simple phobia (trong, unreasonable fear ofa situation) are rela- Lively easier to mect compared with other anxiety diag- noses, individuals diagnosed with simple phobia in com- ‘munity samples may have subthreshold presentations of other anxiety disorders (PTSD, panic disorder, agora- phobia). There isemerging evidence that individuals suf- fering with subthreshold (ie, DSMertera) anxiety symp toms have significant impairment and suicidal behavior.” Overall, we believe that the most likely reason forthe as sociation of simple phobias with suicidal behaviors is €o- morbidity with other unmeasured or subthreshold men- tal disorders. Further epidemiologic studies are required to replicate and better understand the current findings. Broader assessment of a wider range of mental disorders (especialy PTSD) in community samples would be im- portant in such inquires Unlike previous studies ofthe Epidemiologic Catch- rent Area” and NCS." we found a cross-sectional as- sociation of panic disorder with Stand SAs in mulivar~ fate models. A potential reason for the discrepancy between our findings and previous work is based on how agoraphobia was entered in the multivariate model. in previous studies/* all eases meeting erteia for agora- phobia (with or without panic disorder) were catego- rized as agoraphobia, rather than as panic disorder, thus potentially obfuscating the relationship between panic disorder and suicidality. We believe that panic disorder with agoraphobia isa severe form of panic disorder and therefore created 2 mutually exclusive categories (1) panic disorder with or without agoraphobia and (2) agorapho- bia without pante disorder. n doing so, we found strong cross-sectional relationships between panic disorder and Sland SAs, even when adjusting forall other covariates In the cross-sectional evaluation, agoraphobia without panic disorder was also associated with suicidal behav for. However, neither agoraphobia nor panic disorder was, associated with first-ever incidence of suicidal behavior (except in the unadjusted SA models). There are 2 pos- sible explanations for these findings: (1) an association between these anxiety disorders and follow-up suicidal behavior exists but was not found because of the small number of new eases of SI and SAS (ie, power Was too low to detect this association prospectively) oF 2) su cidal behavior may occur prio tothe onset of panic dis- order and agoraphobia. Future studies ae required in ado- lescent and young adult samples to determine the order of onset of panie disorder and suicidal behavior. ETIOLOGIC MECHANISMS There are a number of possible explanations for the re lationship between anxiety disorders and suicidal be: havior. Fist, direct effects may be present such that in- dividuals suffering with high levels of anxiety, worry and fear may seek escape from their suffering by consid ering or altempting suicide. Possible indirect mecha- nisms include comorbidity with other mental disorders, such as substance use disorders oF mood disorders, that ‘may mediate the relationship between anxiety disorders (©2003 American Medical Association. AI rights reserved,and suicide variables. Our current analysis does provide some support for this hypothesis because some associa- dons between anxiety disorders and suicidal behavior were effected when adjusting for comorbidity. Com- mon factors such as childhood trauma," genetic fac- tors,” and personality factors (neuroticism,? impulsiv- ity," and self-criticism”) may explain some of the risk of anxiety and suicidal behavior. Childhood maltreat- ment has been associated with mental disorders*”” and suicidal behavior.” Some of the biologie factors, stich as low levels of hydroxyindoleacetic acid in the cerebro- spinal fluid (CSF-HIAA, a metabolite of serotonin), may link both anxiety disorders and suicidal behav- tor." Finally, a whole host of factors, such as no reli- gious alliliation.**° poor social support,’ and experi- ences of traumatic events," may interact with the presence of a mental disorder to lead to suicidal behav for. In summary, suicidal behavior is a complex process because of numerous interrelated factors, and although the present study suggests that anxiety disorders play an important role, the mechanism of the increase in sui- tidal behavior associated with anxiety disorders re- mains to be determined. STUDY LIMITATIONS. First, although SI and SAs are linked with completed sui- cide, the current study cannot comment on whether anxi- ety disorders are associated with completed suicides. Fu- ture studies using psychological autopsy design’ are required to systematically assess fora broad range of anxi- ety disorders among those who have completed suicide. Second, this study did not assess for important variables known to be associated with suicidal behavior such as PTSD and Axis Il personality disorders (eg, borderline and antisocial). Some of the findings in the current study ‘may have been affected if these variables had been in- cluded in the models. Third, although the reliability of the CIDL-based diagnoses used in the current survey have been demonstrated to be high.” they are unlikely to match the accuracy of elinician-based diagnoses. Fourth, be- cause the baseline assessment of suicidal behavior was based on a longer time frame (lifetime) than the fol- low-up assessments (1-year and 2-year periods), itis pos- sible that recall errors of Sl and SAs may be more likely fm the baseline assessment than the follow-up assess- ‘ments. This issue could affect the number of incident cases of Sland SAs. Filth, the short period of follow-up led to a low total number of eases with incident SI and SAs. Therefore, in the longitudinal analysis, we may not have hhad enough power to detect some elects. For example, in the incidence analysis, the presence of a mood disor~ der without anxiety disorders (Table 4) was associated with SI but not SAs, The later finding is counterintal- tive and is likely a type Il error due to the small sample sizein these categories. There isample evidence that mood disorders are associated with SAs at follow-up." None- theless, itis important to underscore that even in the con- text of a small number of new cases of SI and SAs, we were able 1o demonstrate that anxiety disorders were risk factors for new onset SI and SAs, Future studi quired to replicate and extend our findings using longer follow-up periods, larger samples, and adolescent co- horts and elderly cohorts. Finally, although the pres- ence of an anxiety disorder elevated the risk of SI and ‘Asat follow-up assessments, it must be considered that, because SI and SAs are low base-rate phenomena, most individuals with anxiety disorder did not develop SI oF SAs at follow-up. Further work is required to delineate the clinical and sociodemographic features that diffe entiate between anxious subjects who go on to develop suicidal behavior vs those who do not develop suicidal behavior. Fess] The current study demonstrated that as a group of dis- orders, anxiety disorders were highly prevalent among, those with suicidal behavior in a large community sample with repeated assessments. We also found that anxiety disorders are independent risk factors for sui- cidal behavior, even after adjusting for comorbidity with common mental disorders, Furthermore, stratified analysis based on the presence of an anxiety or mood disorder demonstrated that the presence of at least 1 anxiety disorder without a mood disorder was assoc ated with an increased likelihood of suicidal behavior. Finally, the presence of an anxiety disorder in combina- Vion with # mood disorder was associated with in- creased likelihood of suicidal behavior compared with those with a mood disorder alone. These findings un- derscore the importance of early recognition and treat- ment of anxiety disorders, especially those with comor- bid mood disorders. Submitted for Publication: February 15, 2005; final re- vision received April 14, 2005: accepted April 28, 2005. Correspondence: Jitender Sareen, MD, PZ-430, 771 Ban- natyne Ave, Winnipeg, Manitoba, R3E 3N4 Canada (sa- reen@cc-umanitoba.ca) Funding/Support: The Netherlands Mental Health and Incidence Survey was conducted by the Netherlands In- stitute of Mental Health and Addiction (Trimbos Insti tute), Utrecht, The Netherlands Ministry of Health, Wel- fare, and Sports (the Hague) provided financial support to conduct the survey. Preparation ofthis article was sup- ported by New Emerging Team grant PTS-63186 from the Institute of Neurosciences, Mental Health and Ad- diction, Canadian Institutes of Health Research, O- ‘awa, Ontario; an operating grant from the Canadian In- stitutes of Health Research; and an establishment grant from the Manitoba Health Research Council, Winnipeg, (Dr Sareen) Acknowledgment: We thank lan Clara, MA, for his sta- tistical work and Shay-Lee Belik, BSe(Hons), for her as- sistance in manuscript preparation Se ee 1. 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