DEPRESSION AND ANXIETY 00:1–8 (2012)

Review
THE IMPORTANCE OF ANXIETY IN BOTH MAJOR
DEPRESSION AND BIPOLAR DISORDER
David Goldberg, D.M., FRCP, FRCPsych, FAcad Med Sci1 and Jan Fawcett, M.D.2

Background: Generalized anxiety disorder (GAD) is frequently co-morbid with

major depression (MDD), and this becomes more so when the duration re-
quirement is relaxed. Both anxiety diagnoses and anxious symptoms are more
common in both unipolar and bipolar depression. This paper explores the re-
lationship between anxious symptoms and GAD with both unipolar and bipo-
lar depression. Method: MDD and bipolar disorder (BPD) are compared in
three important respects: the extent of their co-morbidity with anxious symp-
toms and GAD, the effects that anxiety has on outcome of MDD and BPD,
and the effects that anxiety has on the probability of suicide in each disorder.
Results: Anxious diagnoses occur frequently in association with depressive dis-
orders, albeit to a different extent in the various subtypes of depression. In both
disorders, anxiety affects the outcome and makes suicidal thoughts, and com-
pleted suicide more likely. Conclusions: Anxious phenomena should be assessed
whenever a depressive disorder is diagnosed. It is likely that the raised ex-
pectancy of anxious phenomena is related to an individual’s premorbid level
of negative affect, and it is possible that suicidal phenomena are related to
subthreshold hypomanic symptoms. Depression and Anxiety 00:1–8, 2012.

C 2012 Wiley Periodicals, Inc.

Key words: major depression; bipolar disorder; anxious symptoms; co-morbid

anxiety disorders; suicide; outcome

INTRODUCTION pressive disorder are amended, or clinicians routinely

Mood disorders have traditionally been diagnosed sep-
arately from anxiety disorders and even though moder-
ate levels of anxiety at least have been observed in pa-
tients diagnosed with major depression with a frequency
of 62%,[1] the criteria for major depression do not in-
clude current anxiety symptoms. There are two possi-
ble solutions to this-–either the criteria for major de-
1 Institute
of Psychiatry, King’s College, London
2 University
of New Mexico School of Medicine;Chairman
Mood Disorders Group, American Psychiatric Association
Correspondence to: David Goldberg, Department of Health
Services and Population Research, Institute of Psychiatry, de
Crespigny Park, London SE5 8AF, UK.
E-mail: davidpgoldberg@yahoo.com
Received for publication 29 June 2011; Revised 12 December 2011;
Accepted 29 January 2012
DOI 10.1002/da.21939
Published online in Wiley Online Library (wileyonlinelibrary.com).

C 2012 Wiley Periodicals, Inc.
include a rating of anxiety when they diagnose MDD.
Since there is a reluctance both in the DSM-V and the
ICD-11 classifications to make changes in the defini-
tion of major depression, this article will consider the
second of these possibilities. The close relationship be-
tween MDD and generalized anxiety disorder (GAD)
is partly due to shared symptoms and partly to shared
genetic risk factors[2, 3] and temperament, in particu-
lar negative affect or neuroticism.[4] For this reason the
American Psychiatric Association held a special confer-
ence in 2010,[5] and this paper takes forward some of the
themes raised. The other reason for concentrating on
GAD is that it is classified as an “anxious misery” disor-
der with MDD, as opposed to a fear disorder like other
anxiety disorders.[6–8] Although all internalizing disor-
ders may be expected to show considerable co-morbidity
with MDD, GAD appears to be a special case. Fear disor-
ders such as phobias and panic disorder also share some
genetic variance with anxious misery disorders, but form
a separate group. Anxious symptoms and GAD also have
a high co-morbidity in bipolar disorders, and both dis-
orders will therefore be compared in what follows.
2 Goldberg and Fawcett

TABLE 1. Percentage of each depressive diagnosis that is co-morbid either with GAD or any anxious diagnosis,
showing odds ratios, from Zimmerman et al.[10]

Major depression, n = 286 Bipolar 1 disorder, n = 65 Bipolar 2 disorder, n = 33 Normal controls, n = 1,273

Generalised anxiety disorder 10.9% (OR 9.1) 17.6% (OR 19.5) 8.4% (OR 6.5) 1.18%
Any anxiety diagnosis 44.6% (OR 3.1) 55.4% (OR 19.5) 59% (OR 4.8) 19.6%

METHOD may be compared with the results from the prospective

Embase, Medline, Pubmed, and Psychinfo were exam-
ined in order to identify papers that were most relevant
to the problem of the effects that anxious symptoms and
diagnoses have on depressive illnesses. Preference was
given to studies with large representative samples of de-
pressive illnesses wherever possible.
RESULTS
THE HIGH CO-MORBIDITY BETWEEN ANXIETY
DISORDERS AND DIAGNOSES AND MAJOR
DEPRESSION AND BIPOLAR DEPRESSION
Major depression has high co-morbidities with the
whole range of anxiety disorders, the tetrachoric corre-
lations between them ranging from 0.62 for GAD, 0.52
for agoraphobia and social phobia, 0.48 for panic dis-
order, and 0.42 for obsessive compulsive disorder. The
comparable figures for bipolar illness are rather lower:
agoraphobia 0.52, panic 0.51, GAD 0.49, and OCD 0.40.
GAD is no longer the main anxiety diagnosis involved,
and its coefficient is substantially lower.[9] These figures
longitudinal study in Munich.[10]
It can be seen that the percentage of cases of each diag-
nosis that are co-morbid with GAD are comparable, and
that the co-morbidity between “any anxiety diagnosis”
is even greater for bipolar disorders than it is for MDD.
In the Step-BD study,[11] the co-morbidity of GAD with
BP1 was 12.9%, and for BP2 it was 19.1%; for “any anx-
iety” the figures are 34.2% and 19.1%. For both MDD
and bipolar disorder, it is clear that there is substantial
co-morbidity with all the anxiety disorders.
The co-morbidity between MDD and GAD has been
documented many times, in both community samples
and among consulting samples. All these report high lev-
els of co-morbidity between MDD and GAD.[6, 8, 12–14]
It is important to note that these surveys in fact un-
derestimate the co-morbidity between anxious symptoms
and MDD, since GAD has to have lasted 6 months,
whereas MDD need only to have lasted 2 weeks. Thus
the many cases where anxious symptoms develop con-
currently with the depressive symptoms are not included
in these estimates. If the duration requirement for GAD
is reduced, the prevalence of GAD greatly increases, and
the syndromes with shorter durations are no less severe

TABLE 2. Evidence for raised rates for anxiety disorders in bipolar patients and in patients with mixed manic/
depressive features

Investigators Details of study Main findings

Kessler R, Chiu WT, Demler O, Walters
EF (2005) and Simon NM, Otto, MW,
Wisniewski SR, et al. (2004)[9, 11]
Stein MB, Kirk P, Prablin V, et al.
(1995) [13] and Angst J, Cui L, Swendsen
J, et al. (2010)[52]
Schaffer A, Cairney J, Veldhuizen S, et al.
(2010)[53] and Kendler KS, Prescott CA,
Myers J, et al. (2003)[14]
Angst J, Gamma A, Bowdon CL, et al. (in
press)[54] and Kessler RC, Brandenburg
N, Lane M, et al. (2006)[15]
n = 500 patients with BPD STEP-BD study.
National Co-morbidity Survey Replication
Study, N = 5,692.
Canadian Community Health Survey:
Mental Health and Well-Being 36,984
respondents.
Bridge Study multinational, cross-sectional,
observational study in 18 countries; 925
MDD; “mixed states” had both manic and
depressive features.
L/T “any anxiety disorder” in 52.8% BPD1,
and 46.1% of BPD2; cases were more
severe, poorer role function and QOL.
L/T GAD in only 19.5% of BPD1, and
16.5% of BPD2 (Six anxiety disorders,
MINI plus percent interview, DSM-IV
criteria).
Life-time expectancies of “any anxiety
disorder” were: MDD + Mania = 87.1%
MDD only = 52.6% (CIDI using
DSM-IV criteria for anxiety disorders).
Compared subjects with BPD (N = 467)
and MDD (N = 4145). Lifetime anxiety
disorder: 61.2% in BPD, 29.3% in MDD
OR 2.55 (CIDI using DSM-IV as anxiety
criteria).
33.2% fulfilled Dx for mixed states; of these,
more common if past history of BPD,
co-morbid anxiety disorder (P < .001)
was most common in these patients
(DSM-IVTR criteria applied by
clinicians, Mini International
Neuropsychiatric Interview).

Depression and Anxiety

 Importance of Anxiety in MDD and GAD 3

TABLE 3. Evidence on the effect of anxious symptoms accompanying MDD, on the outcome of depression, when
compared with depression without anxious symptoms

Investigators Details of study Main findings

Clayton PJ, Grove WM,
Coryell W, et al. (1991)[19]
Coryell W, Endicott J,
Winokur G (1992)[20]
Reich J (1993)[21]
Tyrer P, Seivewright H,
Simmonds S, et al.
(2001)[22]
Fava M, Alpert JE, Carmin
CN, et al. (2004)[23] and
Fava M, Rush AJ, Alpert
JE (2008)[24]
Coryell (2010)[25]
NIMH Collaborative Program on the
Psychobiology of Depression 327 patients
with RDC unipolar depression
NIMH Collaborative Program on the
Psychobiology of Depression 359 pts with
5 years follow-up
VA study, family history method Compares
17 probands with MDD only, 14 with
MDD + anxiety and 29 controls
Systematic review
STAR*D Study
NIMH Collaborative Depression Study,
assessed annually >16.5 years. 476 MDD,
335 BPD patients
Depressed subjects with higher ratings for anxiety took
longer to recover. There was also a significant
relationship between anxiety in depressed probands and
depression among 832 blindly interviewed first-degree
relatives, but no increase in anxiety disorders. (Anxiety
measured by six items in the SADS-L interview).
Depressive symptoms at intake were more longstanding
and severe among patients with specific anxiety
symptoms, and these patients went on to experience
more depressive morbidity during the ensuing 5 years.
Those with panic, obsessional, or phobic symptoms had
poorer psychosocial outcome at follow-up. The study
concluded that anxiety syndromes in depressive illness
were prognostically significant epiphenomena, rather
than evidence of an additional disorder.
Anxious depressives were more likely to have alcohol
abuse, anxious personality and dramatic personality than
pure depressives or controls, and were also much more
likely to be diagnosed with alcohol abuse. (Anxiety
measured by SCID interview using DSM-IIIR criteria).
Anxiety and depression together have a worse prognosis
than either disorder on its own. Long-term follow-up
data in a 12-year outcome study of neurotic disorder
reinforce this finding both with regard to social
functioning and the clinical course of anxiety and
depressive disorders (Anxiety measured by SCID using
DSM-III criteria).
Anxious depressives were found to be (a) older, less well
educated, and more likely to endorse a range of other
associated symptoms. (b) Anxious depressives had
significantly poorer outcomes, with remission being less
likely and taking longer to occur. (Anxiety measured by
Hamilton Depression Rating Scale
Anxiety-Somatization factor score of 7+).
Among MDD, OCD symptoms predicted worse outcome,
but panic did not Anxiety symptoms during depressive
illnesses strongly predict persistent morbidity (anxiety
disorders at baseline by RDC criteria).

RDC = Research Diagnostic Criteria

than those that have lasted 6 months.[15] The authors
of this study concluded that “ . . . a large number of peo-
ple suffer from a GAD-like syndrome with episodes of
less than 6 months duration. Little basis for excluding
these people from a diagnosis is found in the associa-
tions examined here.” Similar findings are reported in
the World Health Organization’s study of psychologi-
cal disorders in general medical settings, if the duration
requirement for anxious symptoms is reduced from 6
months to 1 month, the prevalence of “co-morbid anx-
iety and depression” increases from 3.4 to 5.7% of at-
tenders to primary care physicians, whereas the preva-
lence of MDD on its own decreases from 4.7% to
2.3%.[16]
Two longitudinal studies—in the United Kingdom[17]
and New Zealand[18] —have addressed the differ-
ences between co-morbid major depression and GAD,
versus either disorder on its own. Although subjects with
GAD only and those with MDE only were similar to
each other, co-morbid cases are distinguished by having
more severe disadvantages in early life. They not only
have more symptoms-–they have more risk factors as
well.
THE EFFECTS OF ANXIOUS SYMPTOMS AND
DIAGNOSES ON OUTCOME
All of the studies shown in Table 2 show that ma-
jor depression accompanied by anxious symptoms has a
worse prognosis than depression on its own, and several
mention that it takes longer to recover. It can be seen in
Table 4 that all studies of bipolar disorder also show a
worse prognosis when anxiety is present.

Depression and Anxiety

4 Goldberg and Fawcett

TABLE 4. Evidence on the effect of anxious symptoms accompanying bipolar disorder, on the outcome of depression

Investigators Details of study Main findings

Feske U, Frank E, Mallinger Maintenance Therapies in Bipolar Disorder Study History of panic attacks proved to be a significant correlate
AG, et al. (2000)[26] examined the correlates of response to the acute of nonremission. Anxiety, as assessed with the composite
treatment of 124 consecutively treated patients variable, was associated with longer time to remission
with bipolar I disorder. (Anxiety disorders by N = 64 with SADS; n = 60 with
SCID).
Simon NM, Otto MW, NIMH Systematic Treatment Enhancement Lifetime co-morbid anxiety disorders >50%; associated
Wisniewski SR, et al. Program for Bipolar Disorder, STEP BD 500 with with younger age at onset, decreased likelihood of
(2004)[11] BPDI or BPD. recovery, poorer role functioning and quality of life (six
Anxiety disorders by Mini International
Neuropsychiatric Interview using DSM-IV criteria).
Dickstein DP, Rich BA, 31 children with Bipolar disorder type 1; 32 with High prevalence of anxiety (BPD 77.4%), anxiety predates
Binstock AB, et al. chronic, nonepisodic irritability. BPD onset, and those with co-morbid anxiety have
(2005)[27] earlier age of onset of BPD than those without. Children
with BPD plus anxiety have more hospitalizations than
those without anxiety (Anxiety by Kiddie-SADS-PL).
Gaudiano BA, Miller I 92 patients with BPD + anxiety were compared with Individuals with bipolar disorder and an anxiety disorder
(2005)[28] BPD patients without such co-morbidity. Patients possessed greater current symptom severity, even after
were assessed on a monthly basis by blind assessors controlling for depression severity. Co-morbid anxiety
over 28 months. was associated with poorer treatment response in the
sample regardless of treatment type, particularly in
subsequent depressive symptoms (SCID-I; Ham-D and
mania scales).
Levander E, Frye MA, Stanley Foundation Bipolar Network 350 subjects, Of 350 subjects, 163 (46.5%) met criteria for an anxiety
McElroy S (2007)[29] with and without alcohol problems. disorder, mainly panic or OCD. (GAD not included)
(Anxiety by Structured Clinical Interview for DSM-IV).
Coryell W, Solomon DA, NIMH Collaborative Depression Study, followed The presence of higher levels of anxiety during bipolar
Fiedorowicz JG, et al. prospectively for a mean of 17.4 years (SD = 8.4) mood episodes appears to mark an illness of substantially
(2009)[30] BPD1 and BPD2. greater long-term depressive morbidity (SADS for
somatic and psychic anxiety measures; also Longitudinal
Interval Follow-up Evaluation interview).
Coryell (2010)[25] NIMH Collaborative Depression Study, assessed Anxiety symptoms were also predictive when they occurred
annually >16.5 years. 335 BPD patients. in bipolar depression but their effects were much less
persistent than with MDD. Result was little changed by
the exclusion of subjects with preexisting anxiety
disorders (SADS for somatic and psychic anxiety
measures; also Longitudinal Interval Follow-up
Evaluation interview).

THE EFFECTS OF ANXIOUS SYMPTOMS AND
DIAGNOSES ON SUICIDE ATTEMPTS AND
COMPLETED SUICIDE
An early study of 954 psychiatric inpatients included
major depression and bipolar depression, and studied
32 patients who completed suicide: they showed six
symptoms, including two anxious symptoms, character-
ized patients who completed suicide within a year of
admission.[31]
When major depression is accompanied by anxious
symptoms, it can be seen from Table 5 that there is a sub-
stantially increased rate of suicide compared with depres-
sion alone. This appears to be true for suicidal ideas, at-
tempted suicide, and completed suicide. One study only
showed that major depressives without anxiety were no
more likely to commit suicide than those without a DSM
diagnosis.[32]
It can be seen from Table 6, whereas it is generally
true that anxious symptoms also increase the probability
of suicide attempts in unipolar disorder, one study shows
Depression and Anxiety
that the SMR for completed suicide is highest in unipolar
depression, next highest in BPD1, lower in BPD2.[39]
DISCUSSION
The studies reviewed have shown that anxious symp-
toms and diagnoses not only accompany all types of de-
pression with an increased expectancy, but they also have
a worse effect on the outcome of the depression and
are more likely to result on suicide. It is for this reason
that clinicians should routinely elicit anxious symptoms
whenever they diagnose depression.
It is worth noting that anxiety is affecting morbidity,
but not mortality. A Norwegian study using the Hospital
anxiety and depression scales in a Norwegian population
of more than 93,000 adults, showed that while depressive
symptoms have an effect on increasing mortality equiva-
lent to the harmful effects of smoking, anxious symptoms
do not. When all possible confounders are controlled for,
 Importance of Anxiety in MDD and GAD 5

TABLE 5. Evidence on the effect of anxious symptoms accompanying MDD, on the probability of suicide attempts,
when compared with depression without anxious symptoms

Investigators Details of study Main findings

Bronisch T, Wittchen H-U The Munich Follow-up Study, 1,366 population
(1994)[32] sample Diagnostic Interview Schedule.
Sareen J, Cox BJ, Afifi TO, Netherlands Mental Health Survey, prospective
et al. (2005)[33] population-based survey of 7,076, three
assessments over 3 years; CIDI used for
DSM-IIIR Dx’s.
Foley DL, Goldston DB, Great Smoky Mountains Study, 1,420 individual
Costello EJ, Angold A subjects with 6,676 records across eight waves
(2006)[34] of data collection. Child and Adolescent
Psychiatric Assessment (CAPA).
Boden JM, Fergusson DM, Christchurch Health and Development Study.
Horwood L (2007)[35] 25-year longitudinal study, >1,000 participants.
Pfeiffer PN, Ganoczy D, 887,859 patients with depression identified from
Ilgen M et al. (2009)[36] VA data-bases. National database of veterans in
depression treatment (NARDEP).
Coryell W (2010)[25] NIMH Collaborative Depression Study 335 with
bipolar I or II disorder.
Nock MK, Hwang I, National Co-morbidity Survey Replication,
Sampson NA, Kessler RC Representative survey of 9,282 US adults.
(2010)[37]
Cases of depression without anxiety were no more likely to
attempt suicide than the population with no DSM-IIIR
diagnosis; but cases with both a major depression and a
lifetime anxiety disorder diagnosis showed significantly
elevated odds ratios. Co-morbidity of anxiety and
depression, and not depression itself, seems to be a risk
factor for suicide attempts (“Anxiety” includes panic
attacks and phobias only).
Study showed that anxiety disorders constituted an
independent risk factor for suicide, with an OR of 2.29.
However, the presence of any anxiety disorder in
combination with a mood disorder was associated with a
higher likelihood of suicide attempts in comparison with
a mood disorder alone (six Anxiety disorders measured
by CIDI, DSM-IIIR criteria).
Suicidal risk was greatest in association with current
depression plus generalised anxiety (odds ratio, 468.53)
or depression plus a disruptive disorder (odds ratio,
222.94). Unless co-morbid, anxiety and substance use
disorders were not proximally associated with suicidality
(Lifetime DSM-IV Dx’s “created”).
Anxiety disorders were strongly associated with suicidal
ideation/attempts (ORs 7.96, 5.85). Control for
co-occurring mental disorders reduced this to 2.8, 1.9.
Two or more anxiety disorders increased risk 6× for
ideation, 4× for attempts. Estimates of the population
attributable risk suggested that anxiety disorders
accounted for 7–10% of the suicidality in the cohort.
Addition of an anxiety × depression interaction term
showed no significant effects (Lifetime DSM-IV Dx’s
from CIDI).
Odds of completed suicide were significantly increased for
patients with co-morbid anxiety disorders: panic disorder
(OR, 1.26), generalized anxiety disorder (OR, 1.27), and
anxiety disorder, not otherwise specified (OR, 1.25).
1,892 suicides occurred during the study period (No
research interview; all were depressed, and cases of BP1
were excluded).
Anxiety symptoms were predictive when they occurred in
bipolar depression but their effects were much less
persistent than in unipolar depression (SADS for somatic
and psychic anxiety measures; also Longitudinal Interval
Follow-up Evaluation interview).
Approximately 80% of suicide attempters in the United
States have a prior mental disorder. Depression predicts
suicide ideation, but not suicide plans or attempts among
those with ideation. Severe anxiety/agitation and poor
impulse control (to predict which people with suicidal
ideation go on to make a plan or attempt [full-range
anxiety disorders, CIDI using DSM-IV criteria, checked
against SCID]).

a low level of anxiety actually reduces mortality to some
extent.[44]
Cassano and his colleagues put forward the concept
of a spectrum of mood disorders,[45] having shown that
mild hypomanic symptoms are common both in bipo-
lar disorder and in major depression, and the number of
these symptoms is related to the likelihood of suicidal
thoughts. Indeed, the similarities are so great that some
have asked whether MDD and BPD are that different
from one another. When MDD cases were compared
with BPD-2 cases in the Zurich longitudinal study,[41]
identical symptom profiles were found for 27 of the 29

Depression and Anxiety

6 Goldberg and Fawcett
TABLE 6. Evidence on the effect of anxious symptoms accompanying bipolar disorder, on the probability of suicide
attempts
Investigators Details of study
MacKinnon DF, Zandi PP, NIMH Bipolar Disorder Genetics Initiative,
Gershon E (2003)[38] 603 individuals (44%) gave accurate
information about rapid switching-–76%
BP1, 17% BP2.
Simon NM, Otto MW, NIMH Systematic Treatment
Wisniewski SR, et al. Enhancement Program for Bipolar
(2004)[11] Disorder 500 patients with BP1 or BP2.
Angst J, Angst F, Zurich Study N = 406, 186 UPD, 130
Gerber-Werder R BPD1, 60 BPD2 followed up from 1963
(2005)[39] to 1985.
Simon GE, Hunkeler E, Two large prepaid health plans 32,360
Fireman B (2007)[40] individuals treated for BPD.
Angst J, Gamma A, The Zurich epidemiological study; seven
Ajdacic-Gross V, Rassler interviews over 22 years, BPD cases
W (2010)[41] compared with UPD cases.
Goldstein TR, Birmaher B, Course and Outcome of Bipolar Youth
Axelson DA, et al. (COBY) multi-site longitudinal study,
(2009)[42] 413 young people with BPD completed
1+ follow- up interview over 4 years,
longitudinal Interval Follow-Up
Examination (LIFE) assessed suicide.
Merikangas KR (2011)[43] National Co-morbidity Survey-Adolescent
Supplement (NCS-A) 10,123 adolescents
ages 13–18.
symptoms of depression, depression recurred in 79% of
cases in both groups, and in both between 15 and 18%
of cases pursued a chronic course. The differences were
that BPD tended to start earlier, to run a more severe
course and to have higher rates of co-morbidity with
anxiety and more suicide attempts.[41] It is evident that
there is overlap between unipolar and bipolar depres-
sion, so that among cases of major depression there are
cases with many characteristics of bipolar disorder. The
occurrence of subthreshold manic symptoms in MDD
has been noted in several recent papers.[10, 46, 47]
However, the association between depression and all
types of anxiety disorders may relate to the fact that mea-
sures of negative affect[48] and harm avoidance[10] are
raised in depression, and these temperamental styles are
related in turn to the experience of anxiety. Watson in his
revised structural model includes fear disorders, unipolar
and bipolar depression as examples of “emotional disor-
ders,” and points out that structural data indicate that
Depression and Anxiety
Main findings
Suicide attempts were more frequent with rapid switching
(n = 268) than among those without (n = 335), on
average 1.52 times (SD, 4.41) compared to 0.58 times
(SD, 1.44) without (n = 335); P < 0.001 (Diagnostic
Interview for Genetic Studies interview; anxiety
disorders do not include GAD).
Lifetime co-morbid anxiety disorders were common,
occurring in over one-half of the sample, and were
associated with younger age at onset, decreased
likelihood of recovery, and greater likelihood of suicide
(six Anxiety disorders by Mini International
Neuropsychiatric Interview using DSM-IV criteria).
Suicide rates were highest among UPD patients (SMR =
26.4), BPD1 (SMR = 13.6), BPD2 (SMR = 10.6), and
lowest among manic patients (SMR −4.7). Cases
diagnosed using DSM-IIIR criteria.
Co-morbid anxiety disorder was associated with
significantly higher risk of both suicide attempt (HR
1.40, 95% CI 1.14–1.72) and suicide death (HR 1.81,
95% CI 1.09–2.99). Men had a significantly lower rate of
suicide attempt [hazard ratio (HR) 0.68, 95% confidence
interval (CI) 0.56–0.83] but a higher rate of suicide death
(HR 2.70, 95% CI 1.69–4.31).
Between ages 20 and 50 BPD subjects had a more severe
course, a higher annual presence of symptoms and
treatment rates, higher suicide attempt rates and higher
co-morbidity with symptoms of, and treatment for
anxiety.
53 (12.8%) attempted suicide over 4 years, these were more
likely to have a family history of suicide attempt or
completion, and more often met criteria at intake for
generalized anxiety disorder. Higher baseline depression
and anxiety scores also characterized suicide attempters.
Youth with both mania and depression had similar rates of
role impairment, number of symptoms of depressions,
suicide attempts, and co-morbid anxiety and behavior
disorders to those with unipolar depression.
GAD actually is more strongly related to the unipo-
lar mood disorders than to other anxiety disorders.[49]
Barlow looks upon anxiety as a central concept in un-
derstanding the emotional disorders, and sees its devel-
opment in terms of a triple vulnerability: a genetically
determined basic vulnerability accounting for approxi-
mately half the variance, then a generalized psychologi-
cal vulnerability based on early experiences from a care-
giver leading to the development of a sense of control
over salient events, and finally a more specific psycho-
logical vulnerability in which one learns to focus anxiety
on specific objects or situations.[50]
Thus, there appear to be at least two different influ-
ences affecting the manifestations of depressive illness,
the variable admixture of hypomanic symptoms that are
related to the greater occurrence of suicidal ideas, and
the accompaniment of anxious symptoms that may be
related to a more complex set of genetic and early de-
velopmental processes. A person who is both anxious
 Importance of Anxiety in MDD and GAD
and depressed with symptoms of each that are just be-
low the threshold is more severely ill than a person who
only has the same number of depressive symptoms, but
they have no anxious symptoms. This is indeed the ratio-
nale for the diagnosis of “Mixed anxiety and depression
disorder,” currently being considered as a diagnosis for
DSM-V.[51]
A limitation of this study is that it relies on large studies
of general population samples, to the relative neglect of
small studies of samples of patients from specialized clin-
ics. Although this avoids bias due to skewed samples, it
inevitably neglects large numbers of papers. Some of the
possible factors considered are based upon single studies
that require replication.
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