Review

Anxiety and depression in psychosis: asystematic review of associations withpositive psychotic symptoms

Hartley S, Barrowclough C, Haddock G. Anxiety and depression inpsychosis: a systematic review of associations with positive psychoticsymptoms.

Objective: This review explores the inuence of anxiety and depressionon the experience of positive psychotic symptoms, and investigates thepossibility of a causal role for anxiety and depression in the emergenceand persistence of psychosis.Method: A systematic literature search was undertaken, producing anumber of papers which comment on the links between anxiety anddepression, and the experience of delusions and hallucinations. Inaddition, evidence which could contribute to our understanding of thecausal role of anxiety and depression was highlighted.Results: The ndings show that both anxiety and depression areassociated in meaningful ways with the severity of delusions andhallucinations, the distress they elicit and their content. However, thecross-sectional nature of the majority of studies and the focus on certainsymptom subtypes tempers the validity of the ndings. Data from non-clinical samples, studies which track the longitudinal course of psychosisand those which examine the impact of anxiety and depression on theprognosis for people experiencing psychosis, oer some support for thepossibility of an inuential role for anxiety and depression.Conclusion: We conclude that anxiety and depression are related topsychotic symptom severity, distress and content and are also linkedwith sub-clinical experiences, symptom development, prognosis andrelapse. These links may imply that anxiety and depression could betargets for therapeutic intervention. The article concludes withsuggestions for further research, highlighting avenues which maycircumvent the limitations of the body of work as it stands.

S. Hartley1,2, C. Barrowclough1,G. Haddock11School of Psychological Sciences, University ofManchester, Manchester, UK and 2Greater ManchesterWest Mental Health NHS Foundation Trust, Prestwich,UK

Key words: psychosis; delusion; hallucination; anxiety;depression

Samantha, Hartley, School of Psychological Sciences,University of Manchester, 2nd FloorZochonisBuilding,Brunswick Street, Manchester, M13 9PL, UK.E-mail: samantha.hartley@manchester.ac.uk

Accepted for publication December 18, 2012

Summations

Anxiety and depression are related to psychotic symptom severity, distress and content. They are also associated with sub-clinical psychotic experiences, symptom development, prognosisand relapse.

These links may imply that anxiety and depression could be targets for therapeutic intervention.

Considerations

The data are largely cross-sectional and/or correlational in nature and so conclusions of causalitymay be invalid.

Many studies have focussed on specic symptom subtypes, such as persecutory delusions.

327

Acta Psychiatr Scand 2013: 128: 327346 2013 John Wiley & Sons A/S. Published by John Wiley & Sons LtdAll rights reservedDOI: 10.1111/acps.12080

ACTA PSYCHIATRICA SCANDINAVICA

Introduction

People meeting criteria for a schizophrenia spec-trum diagnosis will frequently experience one ormore comorbid conditions, which may impact onthe prognosis and understanding of psychosis (1).The pertinence of investigating the links betweenconcurrent emotional conditions and psychosis hasbeen demonstrated (2), despite the diagnostic andaetiological barriers that are seen to separate thetwo. This review will seek to highlight the researchevidence available, providing a focus on anxietyand depression as two specic emotional condi-tions, which have been selected due to their preva-lence (3, 4), and hypothesized role in causal modelsof psychosis (5, 6). Given their considerable inter-relatedness (7), it seems valuable for the investiga-tion of the inuences of anxiety and depression onpsychosis to be carried out in conjunction, to eluci-date where there is overlap, and where divergence,in terms of their relationship with psychosis. First,an overview of the prevalence of anxiety anddepression in psychosis will be provided, followedby a summary of the theoretical frameworks thathave been put forward to account for the relation-ships. The results of the systematic review will thenbe presented, within which the authors will seekthe answers to two key questions: in what ways areanxiety and depression related to the experience ofdelusions and hallucinations; and is there evidencethat anxiety and depression could have a causalrole in the development and experience of psycho-sis? The ndings of the review will be synthesizedand interpreted and nally, avenues of researchthat require further investigation or claricationwill be highlighted.Part of the review will focus on the relationship

between key variables, and delusions or auditoryhallucinations, rather than psychosis as a syn-drome, or schizophrenia as a diagnostic entity.This single symptom approach has recentlyenjoyed a surge in usage owing to the key advanta-ges it aords, which were identied some time ago(8). Delusions and auditory hallucinations are thequintessential experiences of psychosis and oftenthe most distressing, therefore providing clarity inthis area will not only elucidate common experi-ences but also provide some insight into therapeu-tic opportunities.

Prevalence

A review of studies on the rates of depression inschizophrenia concluded that all those includedreported at least some considerable level ofdepression in the context of schizophrenia, with a

modal rate of 25% (4). As later highlighted by thesame author (9), dierences in denitions ofdepression in the context of psychosis impede ourunderstanding of its nature and impact. Using lib-eral criteria to dene the presence of depressivesymptoms, Koreen et al. (10) showed that 75% ofthose in their rst episode of schizophrenia wereexperiencing depression, and in general commu-nity samples, the odds of meeting criteria fordepression are substantially higher for those meet-ing criteria for schizophrenia (11). The conver-gence of depression and psychosis has beenacknowledged (12, 13), although the dichotomybetween aective concerns and psychosis origi-nally proposed by Kraepelin (14), still persists,and underlies the diagnostic systems that governmedical interventions.A recent comprehensive review of anxiety disor-

ders in the context of schizophrenia has shown thatanxiety (when taken to mean any experience ofclinically signicant anxious symptoms) is presentin 16%85% of samples, with the overall rate forclinical studies (as opposed to epidemiologicalones) averaging 50% (15). Similar ndings havebeen reported using a sample of out-patients, with41.5% reaching criteria for a concurrent anxietydisorder (16). Rates are also substantial in commu-nity samples who meet criteria for a diagnosis ofschizophrenia (17) and reports of lifetime rateseven higher at 67% (18), with earlier papers report-ing comparable gures (19, 20).The diagnostic trumping and associated lowered

awareness of the role for anxiety and depression inpsychosis is, in part, founded on and reinforced bythe exclusion rules inherent in the DSM-IV diag-nostic system (21). Foulds (22) described theschizophrenia spectrum diagnoses as supersedingemotional concerns; taking primacy over andassimilating them. In contrast, van Os et al. (23)suggest that schizophrenia is at the upper end of aspectrum spanning normality, aective disordersand psychosis; thus although the hierarchy per-sists, the presence of aective concerns is notsuperseded by the presence of psychosis, it ismerely a dierent expression of the same diathesis.When these hierarchies and constraints of diag-

nostic systems are disregarded, and the co-occur-rence is examined, it is clear that the two classes ofmental health problem frequently coexist. Withregard to anxiety disorders, Coso & Hafner (3)revealed that a large proportion of an Australiansample with schizophrenia spectrum diagnoses metcriteria for anxiety disorders, with 17% social pho-bia, 13% Obsessive-compulsive disorder (OCD)and 12% generalized anxiety disorder. Crucially,and most disturbingly, only three of those people

328

Hartley et al.

from the sample experiencing concurrent anxietywere being oered therapeutic or medical supportfor this, due to the diagnostic hierarchy. Similarly,when Bermanzohn et al. (24) disregarded thetrumping rules, they found that 49% of partici-pants with a diagnosis of schizophrenia or schizo-aective disorder also met criteria for one or moreassociated problem area, with 27% displayingmajor depression, 29% OCD and 11% panic dis-order. Bermanzohn et al. question whether theseconcurrent diagnoses represent parallel, but sepa-rate experiences that emerge along with psychosis,or whether the anxious and depressive symptomsare part of the intrinsic nature of schizophrenia. Ineither case, it would seem important to note thatbranding these concurrent concerns as secondaryexperiences on the basis of a rigid structure ofdiagnostic supremacy may have impacts on thera-peutic ecacy and aetiological understanding.Furthermore, the substantial rates of anxiety anddepression in the context of psychosis underlinethe importance of exploring the specic linksbetween the presence of high levels of these emo-tional conditions and the presence and experienceof delusions and hallucinations.

Theoretical frameworks

Although there is no universally accepted model,various theories have been espoused to explainin what ways and by what means anxiety anddepression may inuence the occurrence of psy-chotic experiences. Bentall et al. (25) suggestthat delusions, specically those of a persecutorynature, arise in defence against low self-esteemand depression that would otherwise have devel-oped as a result of the gulf between perceptionsof the actual and ideal self. Other authors pro-pose a more direct role for anxiety and depres-sion in the formation and maintenance ofdelusions and hallucinations. Garety et al. (5)suggest that triggers or intrusions give rise toemotional changes, which then feed back intothe processing and content of experiences, aug-menting their distressing nature and encouragingexploration of possible causes of the aectivechanges. The reasoning biases that guide thiscausal exploration are exacerbated by the pres-ence of anxiety and depression. Morrison (6)also highlighted negative mood as a criticalaspect of a cognitive model of psychosis, inwhich it is the misinterpretation of essentiallynormal experiences as threatening events thatleads to distress and the maintenance of symp-toms via a vicious cycle of negative mood, phys-iological changes and safety-seeking behaviours.

A more specic conceptualization of depressionin the context of psychosis as post-psychoticdepression (PPD) has also received considerableattention (2628). The lack of a denitive frame-work within which to consider the impact ofanxiety and depression reduces the cohesion ofthe research eld, which may limit the conclu-sions that can be drawn. The authors thereforefelt it important to conduct a review without thedrive of one specic theoretical model; theresearch evidence will be sought systematicallyand reviewed without bias to produce a sum-mary from which the research eld can moveforward.

Aims of the study

This review will synthesize and critique the currentunderstanding relating to the links between anxietyand depression, and psychosis. The systematicsearch will produce a pool of papers that commenton the associations between these emotional condi-tions and delusions and hallucinations, and alsopapers pertaining to convergence overtime, in non-clinical samples, and with the consequences ofpsychosis.

Material and methods

Systematic review: search methods

To gather information relevant to the two keyquestions in this article, a systematic literaturereview was undertaken.The search engine PSYCINFO was accessed via the

University of Manchester Library Ovid online sys-tem between March and April 2011. The searchterm combinations used can be seen in Table 1.Records with abstracts were obtained and reviewedfor all of the initial search results. This produced asubset of articles that complied with the inclusionand exclusion criteria laid out in Table 1. The crite-ria were selected to produce a pool of articles thatfocussed on psychological approaches to the studyof mental health problems. The exclusion criteriawere imposed sequentially, that is, those earlier inthe list were applied initially; records that reachedthe nal list of included articles would thereforehave avoided the endorsement of all 10 exclusioncriteria. Any papers that did not violate any of thespecic exclusion criteria but nevertheless, failed toprovide any direct analysis of, or purport any the-ory regarding the relationship between anxiety and/or depression and psychosis and or delusions/hallu-cinations (i.e. the second inclusion criterion) werealso excluded; an example of this would be an epi-

329

Anxiety, depression and psychotic symptoms

demiological paper that used the terms anxietyand psychosis in its abstract, but that upon inspec-tion, did not aim to investigate any links betweenthe two. Full texts of those articles that compliedwith all of the criteria were then accessed via theUniversity of Manchester electronic or paperlibrary systems, or via inter-library loan whererequired. A summary of the search process andresults can be seen in Table 2. The articles werereviewed with regard to content relevant to thebody of this article and also for any other relevantpapers not highlighted by the initial search; thesenew papers were then also sought. A total of 16papers were added as a result of the review ofreferences listed in papers produced by the initialsearch.

Anxiety and depression: interrelatedness and overlap

As briey noted above, one reason for conductinga simultaneous review into anxiety and depression,and their links with psychosis is that the formeroverlap somewhat. Comorbidity among anxietyand depression is high (29), although cognitivemodels have proposed that they have divergentcontent (30), and factor analysis has shown thatself-statements from each can be reliably distin-guished (31). One proposition is that there is moreoverlap at the more acute, symptom level than interms of diagnostic categories (32). Various modelshave been proposed to account for the dierentndings; there may be discrete but sometimes con-current syndromes that exist along a spectrum;anxious and depressive symptoms are expressionsof one underlying diathesis; one condition predis-poses to the other; or the overlap is spurious and aresult of convergence in measure items or deni-tions (33). Thus, the eld is somewhat divided andthe evidence ambiguous. Including both emotionalconditions in this review will oer the opportunityfor areas of convergence and divergence to behighlighted, although elucidating the overlapbetween anxiety and depression is not a core aimof this article.

Results

In what ways do anxiety and depression relate to delusions andhallucinations?

A summary of the empirical ndings relating tothe associations between anxiety, depression andthe dierent aspects of delusions and hallucina-tions can be seen in Table 3. For clarity, these havebeen grouped into those examining symptomseverity, distress and content.

Depression

Severity of psychotic symptoms. The literature dem-onstrates that depression is signicantly associatedwith symptom severity in both chronic and early

Table 1. Literature search details

Inclusion Criteria Paper published in English Specific quantitative analyses/other standardized

investigation of the linksbetween anxiety and/or depression and psychosis,delusions or hallucinations

Published between 1950 and 2011Exclusion criteria 1. Journal introductory piece or record of

conference discussion2. Pharmacological treatment review3. Mental health care service review/audit4. Animal study5. Genetic or biomarker investigation6. Case study7. Paper solely analysing the psychometric properties

of a measure/scale8. Focus on psychosis in the context of a primary Axis

1 diagnosis that is not a schizophrenia spectrumdiagnosis or is a primary physical or organic diagnosis

9. Focus on carers emotional dysfunction,rather than that of the person experiencingpsychosis

10. [for anxiety-related searchesonly] Focus exclusively on attachment anxiety

Search termscombinations

Anxiety psychosisAnxiety delusionAnxiety hallucinationDepression psychosisDepression delusionDepression hallucination

All search termcombinations wereentered using the ANDfunction within the abstractfield, with journal articleselected as the documenttype and 1950-presentdesignated as the time frame.

Table 2. Literature search results

Search term combinationsNumber of abstracts

produced by initial search

Exclusions (based on each numbered exclusion criterion listed in Table 1)

1 2 3 4 5 6 7 8 9 10Did not includespecific analyses

Finalinclusion

Anxiety + psychosis 865 9 75 16 11 28 46 31 220 6 7 391 25Anxiety + delusion 73 0 5 0 0 3 12 2 15 0 0 25 11Anxiety + hallucination 39 0 1 0 0 1 3 1 12 0 0 16 5Depression + psychosis 1926 20 322 62 15 179 90 69 491 10 N/A 608 60Depression + delusion 102 0 8 0 0 9 18 3 23 0 N/A 33 8Depression + hallucination 41 0 1 0 0 1 6 0 13 0 N/A 15 5

330

Hartley et al.

Table3.

Relatio

nships

betw

eenan

xietyan

dde

pression

,the

severityan

dconten

tofd

elusions

andha

llucina

tions

andthedistress

associated

with

theseexpe

riences

Anxiety

Depression

Stud

ySa

mple

Metho

dology

Mainfin

ding

sStud

ySa

mple

Metho

dology

Mainfin

ding

s

Severity

Hupp

ert&

Smith

(43)

32ou

t-patients;

diag

nosedwith

Schizoph

reniaor

Schizoaffective

disorder;n

otacuteep

isod

e.

Cross-sectiona

l;exam

ined

relatio

nships

betw

eenpa

nican

dsocial

anxie

tysymptom

swith

levels

ofpsycho

ticsymptom

s.Interview

andself-repo

rtqu

estio

nnaires.

Social

anxie

tysymptom

srelatedto

posit

ivesymptom

s.Pa

nican

dsocial

anxie

tywere

relatedto

parano

ia.

Smith

etal.(37

)10

0pa

rticipa

ntswith

adiag

nosisof

non-affective

psycho

sis,

recruitedwith

in3mon

thsof

arelapse

inpo

sitiv

esymptom

s.

Cross-sectiona

lassessm

ents

ofpo

sitiv

ean

dne

gativ

epsycho

ticsymptom

s,de

pression

,self-

esteem

,and

core

sche

ma.

Depression

linkedwith

persecutory

delusion

s,au

ditory

hallu

cina

tions

andgran

diosede

lusion

s(th

elatte

r,ne

gativ

ely).O

nlythelatte

rfinding

persistedin

aregression

.De

pressio

nassociated

with

convictio

nan

dpreo

ccup

ationin

delusion

albe

liefs.

Oosthu

izen

etal.(45

)80

particip

ants

diag

nosedwith

FirstE

pisode

Psycho

sis.

Long

itudina

lana

lysisat

3tim

e-po

ints:

6wee

ks,3

mon

thsan

d6mon

ths.

Assessed

thepresen

ceof

aDep

ressionFactor

includ

ing

depressio

n,gu

ilt,a

nxiety

and

somatic

concern.

Thede

pression

factor

didno

tcorre

late

with

levelo

fpositive

psycho

ticsymptom

sor

with

chan

gein

total

psycho

ticsymptom

scores

over

thefollo

w-uppe

riod.

Drakeet

al.(38

)25

7pa

rticipa

ntswith

aschizoph

reniaspectru

mdiag

nosis,

expe

riencing

theirfirs

tadm

ission

and

havin

gaminim

um4

wee

khistoryof

positiv

epsycho

ticsymptom

s.

Cross-sectiona

lassessm

ents

ofpa

rano

ia,insight,d

epression,

andself-esteem

.

Grea

terd

epressionassocia

tedwith

high

erlevels

ofpa

rano

ia.

Delespau

let

al.(53

)57

particip

ants

diag

nosed

with

schizoph

renia,

inremission

.

Expe

riencesamplingmetho

dology;

tenqu

estio

nsets

over

6da

ys.

Anxiety,visual

andau

ditory

hallu

cina

tions

mea

suredby

sing

le,

self-repo

rtite

ms.

Anxietylevels

pred

icted

hallu

cina

tory

expe

rience,

with

anxietylevels

increa

sed

atthetim

epo

intp

riortothe

emerge

nceof

theha

llucina

tion.

Sopp

ittan

dBirchw

ood(40)

21pa

rticipa

ntswith

chronic

schizoph

renia,

expe

riencing

auditory

hallu

cina

tions

for

atleast6

mon

ths.

Cross-sectiona

lassessm

ents

ofconten

tofa

ndbe

liefs

abou

tvoices,d

epression.

Sign

ificant

relatio

nships

betw

een

depressive

symptom

san

dpo

sitivepsycho

ticsymptom

sscores.

Raman

than

(55)

25pa

rticip

ants

with

adiag

nosis

ofschizoph

reniaan

dexpe

riencingau

ditory

hallu

cina

tions.

Clinical

interviewswith

participa

nts

assessingmoo

d,vario

usaspe

ctsof

belie

finthereality

ofthe

hallu

cina

tion

andothe

rpsycholog

ical

constru

cts.

Retro

spectiv

erepo

rtsof

anxie

tyoccurring

priortotheha

llucina

tion

wereassocia

tedwith

decrea

sed

convict

ionof

the

reality

of

the

hallu

cina

tion.

Saxet

al.(42

)42

in-patientswith

adiag

nosis

ofmajor

depression

with

psycho

ticfeatures

(n=

25)o

raschizoph

reniaspectru

mdisorder

(n=

17)w

ithno

previous

treatmen

tor

admissio

ns.

Cross-sectiona

lmea

suresof

positiv

ean

dne

gativ

epsycho

ticsymptom

san

dde

pression

Sign

ificant

diffe

rences

intotal

depression

butn

ottotal

psycho

sisbe

twee

ngrou

ps.

Sign

ificant

relatio

nshipbe

twee

nde

pression

andpo

sitiv

epsycho

ticsymptom

sin

theschizoph

renia

diag

nosisgrou

pbu

tnot

inde

pression

grou

p.Startup

etal.(58

)30

in-patientswith

schizoph

renia

spectru

mor

bipo

lard

iagn

oses,

expe

riencingpe

rsecutory

delusion

s.

Cross-sectiona

land

long

itudina

lwith

3mon

thfollo

w-uppe

riod.

Assessmen

tof

anxiety,worry,p

sychotic

symptom

san

dcatastroph

izing

.

Delusion

algrou

pha

dsimila

rscores

onan

xietymea

sure

tothosewith

GAD.

No

associa

tions

betw

eenan

xiety

andde

lusion

alconvictio

n.

Oosthu

izen

etal.(45

)As

above

Asab

ove

Thede

pression

factor

didno

tcorre

late

with

levelo

fpo

sitivepsycho

ticsymptom

sor

with

chan

gein

total

psycho

ticsymptom

scores

over

thefollo

w-uppe

riod.

Watson

etal.(57

)10

0pa

rticipa

ntswith

adiag

nosis

ofno

n-affectivepsycho

sis,

recruitedat

thetim

eof

relapse.

Cross-sectiona

llyassessed

anxiety,

depressio

n,an

dbe

liefs

abou

tilln

ess,

insigh

tand

self-esteem

.

Anxietywas

sign

ificantly

associa

tedwith

both

observer-

ratedan

dpe

rceivedsymptom

severity.

Watson

etal.(57

)As

above

Depression

was

sign

ificantly

associated

with

perceived

symptom

severitybu

tnot

observer-ra

tedseverity.

Moo

rey&

Soni

(17)

30pa

rticip

ants

with

adiag

nosis

ofSc

hizoph

reniaattend

ing

out-p

atient

clinics

.

Cross-sectiona

llyassessed

anxiety,

psycho

ticsymptom

s,de

mog

raph

ican

dge

neralilln

essrelatedvaria

bles.

Anxietywas

sign

ificantly

related

tode

lusion

alseverity

butn

otha

llucina

tory

severity.

Hupp

ert&

Smith

(43)

Asab

ove;

depression

mea

suredby

theBe

ckDe

pressio

nInventory(BDI)

andtheDe

pression

subscale

oftheDA

SS41

andthe

Depression

was

nots

ignific

antly

corre

latedwith

anyof

the

psycho

ticsymptom

mea

sures.

331

Anxiety, depression and psychotic symptoms

Table3.

(Con

tinue

d)

Anxiety

Depression

Stud

ySa

mple

Metho

dology

Mainfin

ding

sStud

ySa

mple

Metho

dology

Mainfin

ding

s

Free

man

&Ga

rety

(44)

15pa

rticipa

ntsdiag

nosedwith

parano

idschizoph

reniaor

delusion

aldisorder

and

expe

riencingcurre

ntpe

rsecutorybe

liefs

and14

participa

ntswith

GAD.

Cross-sectiona

l,self-repo

rtassessmen

tsof

worry,a

nxiety

andworry

processes.

Anxietyas

assessed

byall

mea

suresdidno

tcorrelate

sign

ificantly

with

delusion

alconvictio

nor

preo

ccup

ation.

Free

man

&Ga

rety

(44)

Asab

ove;

depression

mea

suredby

the(BDI)

Depressio

ndidno

tcorrelate

with

delusion

alconvictio

nor

preo

ccup

ation.

Distress

Startupet

al.

(58)

Asab

ove

Anxiou

sworry

andcatastroph

izing

relatedto

delusion

aldistress,a

lthou

ghan

xietyits

elfd

idno

t.

Smith

etal.(37

)As

above

Depressio

nwas

sign

ificantly

associa

tedwith

amou

ntan

dintensity

ofdistress

inrelatio

nto

delusion

albe

liefs

andau

ditory

hallu

cina

tions.

Free

man

&Ga

rety

(44)

Asab

ove

Theclinica

lgroup

sha

dsimila

rlevels

ofan

xietyan

dworry.Traitan

xiety

andworry

concerning

delusion

althou

ghts

strong

lycorre

latedwith

delusion

aldistress

althou

ghan

xietyas

assessed

bytheBA

Ididno

t.

Free

man

&Ga

rety

(44)

Asab

ove

Depressio

ndidno

tcorrelate

with

delusion

aldistress.

Conten

tBe

ntall

etal.(50

)He

teroge

neou

sgrou

pof

173

participa

ntswith

either

schizoph

reniaspectru

mdisordersor

major

depressio

n,or

late-onset

schizoph

renia-like

psycho

sis;

88of

which

were

curre

ntly

expe

riencingpe

rsecutory

delusion

s.

Assessed

thepresen

ceof

parano

idde

lusion

san

dman

ypsycho

logical

constru

cts,

includ

ingde

pression

,an

xiety,s

elf-e

stee

m,a

ttributions,

cogn

itive

perfo

rman

ce.

Inafactor

analytic

mod

el,a

factor

consistin

gof

depression

,anxiety,

low

self-esteem

andpe

ssim

istic

thinking

was

associated

with

thepresen

ceof

parano

idde

lusion

s.

Sopp

ittan

dBirchw

ood(40)

Asab

ove

Deroga

tory

voiceconten

tand

malevolen

ceof

voices

was

associa

tedwith

depressio

n,as

was

voiceintru

sivene

ssan

dloud

ness,a

lthou

ghclarity,

distractibility

andfre

quen

cywereno

t.

Free

man

etal.(39

)25

participa

ntswith

curre

ntpe

rsecutoryde

lusion

san

ddiag

noses

ofschizoph

renia,

schizoaffective

disorder

orde

lusion

aldisorder

Cross-sectiona

lassessm

ents

ofde

pression

,anxiety,s

elf-e

stee

m,

safety

beha

viou

rsan

dpsycho

ticsymptom

s.

Power

ofthepe

rsecutorydidno

tcorre

late

with

anxiety.Indicatio

nthat

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332

Hartley et al.

psychosis groups, with study sample sizes rangingfrom 15 to 257. Eight papers reported ndingsregarding links between depression and theseverity of delusional and hallucinatory experi-ences, with ve investigating positive symptomsgenerally and one focussing on persecutory beliefs.Examining the relationship cross-sectionally in a

sample of people with a diagnosis of non-aectivepsychosis, with measures including the Positive andNegative Syndrome Scale (PANSS) (34), Scale forthe Assessment of Positive Symptoms (SAPS) (35)and Beck Depression Inventory (BDI) (36), Smithet al. (37) found that the presence of greater depres-sion and reduced self-esteem were related to theseverity of auditory hallucinations and persecutorydelusions. Similarly, in a sample of people experi-encing their rst admission with a schizophreniaspectrum diagnosis, Drake et al. (38) demonstratedthat depression was related to the severity of para-noia. The subjectively perceived severity of symp-toms at the point of relapse has also shown to beassociated with levels of depression (39), althoughthe same study diverged from previous ndings toshow that observer-rated symptoms were not.Thus, depression is related to the severity of experi-ences in both chronic samples, those with at rstadmission and at the point of relapse.Soppitt & Birchwood (40) demonstrated that the

number of positive symptoms as assessed usingstructured SCAN (41) interviews and scores on theBDI were signicantly, positively related, in agroup of people with a chronic schizophrenia diag-nosis and a recent history of voice hearing. Morespecically, the ndings showed that voice intru-siveness and loudness (in other words, distinct,specic aspects of severity) were related to BDIscores, although voice frequency was not.The signicant associations across a range of

conceptualizations of severity are suggestive of alinear relationship between depression and positivesymptoms, that is as depression increases, so doesthe severity of delusions and hallucinations; theirnumber, intensity and perceived intrusiveness.However, the results of a mixed-population studytemper this conclusion. Sax et al. (42) utilized twogroups of individuals: one with a diagnosis ofmajor depressive disorder, with concurrent psy-chotic features and the other with schizophreniaspectrum diagnoses also experiencing depressivefeatures. The ndings revealed that the associationbetween depressive features and positive psychoticexperiences was evident only in the latter group.Thus, although both groups experienced both psy-chosis and depression, the two experiences wereonly statistically related in the group with a diag-nosis of schizophrenia. These ndings provide cau-Ta

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333

Anxiety, depression and psychotic symptoms

tion against conceptualizing psychosis as simplythe end product of a severe depressive episode. Itmay be that there is a distinct aspect of experience,appraisal, predisposition or processing in thosewho go on to develop psychosis that supports therelationship between depressive and positive psy-chotic symptoms, which also serves to augmenttheir psychosis to a level that attracts a primarydiagnosis of a schizophrenia spectrum disorder.Huppert & Smith (43) did not nd any links

between depression and a range of psychotic symp-tom measures, while Freeman & Garety (44)showed that depression did not correlate with delu-sional conviction or preoccupation, although thesmall sample size (n = 15) may have been an issuefor the latter study. In addition, a study by Oos-thuizen et al. (45) revealed that a depressive factor(which also included a measure of anxiety, guiltand somatic concern) did not correlate with theseverity of positive symptoms in a sample of peoplewith rst episode psychosis. However, the inclu-sion of other aspects of experience within the con-struct renders specic conclusions regarding thelinks with depression ambiguous.In conclusion, depression is associated with the

severity of both delusions and hallucinations andpositive symptoms more generally. Five of theeight papers revealed signicant links betweendepression and some aspects of positive symptoms(but not all those that were under investigation ineach study); including the severity of auditory hal-lucinations, persecutory delusions, grandiose delu-sions, levels of paranoia and specic aspects ofvoice hearing. Evidence to the contrary may belimited by small samples sizes and confoundingfactors. Findings pertaining to delusions havetended to focus on those of a persecutory nature,so generalizability is reduced.

Distress associated with psychotic symptoms. Interms of the psychological reaction to psychoticexperiences, only two studies investigated this rela-tionship, in samples of people with non-aectivepsychosis and those specically experiencingparanoia. Findings have shown that individualswith more depression are more distressed by theirexperiences and have more auditory hallucinationsof negative content and a higher degree of negativecontent (37). However, distress associated withparanoia has been shown to be unrelated todepression (44), although the small sample size ofthe latter study will have raised the possibility of atype II error.

Content of psychotic symptoms. Delusional andhallucinatory content often appears to be unu-

sual, although it has been postulated that thethemes can be related to underlying emotionality.Freeman & Garety (2) proposed that, in psycho-sis, all the major emotions have delusions thatcan be thematically linked with them, which isconsistent with a direct role for emotion in delu-sion formation (although the opposite causalpathway cannot be ruled out). There is someconsistency in terms of the studies reviewed, indemonstrating that depression seems to be associ-ated with specic aspects of delusional themes orappraisals of them. Seven papers reported onlinks between depression and the content ofbeliefs and voices. One study proposed a modelof a specic delusional experience, although didnot provide any empirical data and therefore isnot included in summary ndings. Four concen-trated on links within a specic delusional theme-paranoia, whereas three investigated links withinvoice-hearing experiences.For example, Soppitt & Birchwood (40)

reported that depression was signicantly linkedwith derogatory voice content in verbal hallucina-tions (as opposed to non-derogatory voice con-tent), although clarity, distractibility andfrequency were unrelated to the severity of depres-sion. Similarly, assessing people with a diagnosisof schizophrenia or schizoaective disorder, Lucas& Wade (46) showed that depression was higher inthose with subjectively appraised malevolent voicecontent, and beliefs that the voice is more power-ful, a nding which has since been replicated (47).However, as with the other ndings reported

here, a cross-sectional design fails to provide evi-dence as to the direction of the relationshipbetween depression and voice content; it is notclear whether the presence of depression contrib-utes to the derogatory nature of voice content, orthat the derogatory content develops indepen-dently from levels of depression, but once present,increases depression due to its impact on generalnegative aect. In addition, ndings that depres-sion and negative self-evaluation are related inpeople with schizophrenia (48) indicate that thelatter could be mediating the relationship betweendepression and derogatory comments.Some delusional themes are so intrinsic to the

experience that they become labelled as syn-dromes in their own right; Cotards syndromedescribes the pervasive feeling that one is dead ordoes not exist. Exploring this very specic delu-sional subtype, Gerrans (49), suggests various waysby ways depression could be linked with the emer-gence and persistence of feeling that oneself isunreal, although the lack of empirical evidenceprovided means that this paper should not be

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Hartley et al.

included in summary analysis of the ndings in thissection.Paranoid delusions have been shown to relate to

high levels of depression in a mixed sample study,Bentall et al. (50), although the lack of specicityin the predictor variable used (which conateddepression, anxiety, low self-esteem and pessimisticthinking) reduces the utility of the ndings in par-tialling out the unique inuence of depression.Furthermore, the diagnostically heterogenous nat-ure of the sample reduces the possibility of general-izing the ndings. In addition to the objectiveappraisal of the content of experiences, depressionhas also been found to relate to beliefs about thedelusion or hallucination, and the subjective expe-rience of these positive symptoms. Accordingly, inpersecutory delusions, there is a trend for higherlevels of depression to be associated with higherratings of the power of the persecutor, and, simi-larly, the control of the persecutory situation (39).Furthermore, there are indications that the perva-sive threat content of the delusional experience andlevels of depression are related in a rst episodesample (26).Focussing again on persecutory beliefs in a non-

aective psychosis sample, Green et al. (51) exam-ined the specic content of delusional ideas,mapped on to a categorical coding frame includingassessments of the agent and nature of the threat,the signicance, pervasiveness and imminence ofthe persecutor and the relative power of the indi-vidual and perceived persecutor. Pertinent to thecurrent review is the relationship between theseaspects of the delusional content and levels ofdepression, which the authors also examined. Thendings revealed that various aspects of the delu-sional experience correlated signicantly with lev-els of depression, including a negative relationshipwith ratings of power of the participant and, asexpected, the reverse relationship with power ofthe persecutor. Interestingly, the dierencebetween the rated power of the persecutor and par-ticipant correlated signicantly with levels ofdepression, suggesting that it is this gulf in per-ceived power that is most pertinent, rather thanthe absolute power of either party. In addition,participants who rated their persecution asdeserved exhibited higher levels of depression.In conclusion, all four studies into persecutory

beliefs revealed some signicant link betweendepression and the content or appraisal of theexperience, such as beliefs around power andthreat. Similarly, those investigating voice hearingrevealed relationships with heightened depressionand malevolent and powerful voice content.Despite these ndings, the concentration of evi-

dence around specic delusional themes (i.e. para-noia), although providing a homogenous sampleand thus rm conclusions, does not allow us toconclude that depression is related to delusionalthemes; the research evidence does not so farextend beyond this single type of experience.

Anxiety

Severity. Findings relevant to the severity of psy-chotic experiences have demonstrated that anxietyis related to levels of paranoia, delusions and cantrigger acute augmentation in auditory hallucina-tions. Eight papers investigated the links betweenanxiety and delusional and hallucinatory severity,with sample sizes ranging from 15 to 100. Four ofthese examined positive symptoms in general,whereas two studied auditory hallucinations inparticular and two concentrated on delusionalseverity.Huppert et al. (43) showed that social anxiety

symptoms were related to positive symptoms andbizarre behaviour, and that panic and social anxi-ety were related to levels of suspiciousness andparanoia, in a sample of people with a diagnosis ofschizophrenia or schizoaective disorder. How-ever, the specicity of the anxious experienceinvestigated (i.e. related to social interactions)reduces the generalizability of the ndings to con-clusions regarding the impact of generic anxiousfeatures.Moorey & Soni (17) revealed that anxious symp-

toms and delusions were related in a communitysample, although the same was not true for audi-tory hallucinations. The sample was relativelysmall, with only 30 people with a diagnosis ofschizophrenia, although the random selection ofparticipants reduces bias and thus may add gravityto the authors conclusion.Freeman et al. (52) highlight one route by which

the presence of anxiety could impact on the sever-ity or persistence of an archetypal positive psy-chotic symptom, paranoia. They uncovered asignicant association between anxiety and safetybehaviours, which are a strategy often adopted bythose experiencing ideas of persecution. Safetybehaviours are those carried out with the intentionof avoiding the harm predicted by the persecutorybelief. If anxiety makes safety behaviours morelikely then it also increases the likelihood that thebelief in the potential persecution is reinforced, asthe lack of harm subsequent to performing safetybehaviour is misattributed to the adoption of thesafety behaviour rather than the lack of potentialfor harm; the opportunity to gain disconrmatoryevidence is lost.

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Anxiety, depression and psychotic symptoms

A major limitation of the cross-sectional datahitherto reported is that the potential causal prox-imity of anxiety to the occurrence or severity ofdelusions and hallucinations cannot be reliablyelucidated. Delespaul et al. (53) used momentarysampling techniques to investigate the occurrenceof auditory hallucinations over a short time period,using repeated self-report assessments of emotionalintensity and voice hearing in the context of anexperience sampling study (54). Using analysesthat appropriately accounted for the nested-natureof the ESM data, Delespaul et al. established thatanxiety was signicantly increased immediatelyprior to an increase in the severity of voice hearing.The use of these momentary assessments providesa unique insight not aorded to the largely cross-sectional investigations in the area of depression.The authors of the aforementioned study suggestthat these ndings may support a model in whichhallucinations arise to buer against the cognitivedissonance caused by increased anxiety. Whetheror not that is the case, these data at least point tothe possibility of anxiety as a causal or catalyticfactor in the day-to-day occurrence of auditoryhallucinations. Ramanthan (55) provided an earlyprequel to this study, showing that increased anxi-ety prior to an incidence of voice hearing was asso-ciated with lower convictions in the reality of thehallucination; whether this measure relates directlyto severity or not is not clear.Drawing together these ndings, anxiety has

been shown to be associated with the severity ofdelusions and auditory hallucinations, and puta-tive mechanisms have been explored. The eld isnot conclusive, though; Startup et al. (58) showedthat anxiety was not related to delusional convic-tion in a sample of in-patients experiencing perse-cutory delusions, although it is not clear ifconviction can be viewed as synonymous withseverity. In addition, the sample included bothpeople meeting criteria for a schizophrenia spec-trum diagnosis and those with a bipolar disorderdiagnosis, somewhat undermining the generaliz-ability to more homogenous diagnostic groups.Freeman & Garety (44) also demonstrated thatanxiety (assessed by multiple measures) was notrelated to delusional conviction or preoccupation,although as previously reported, the small samplesize (n = 15) may have increased the possibility ofa type II error. As part of a depressive factor,including measures of guilt, depression, somaticconcern and anxiety, Oosthuizen et al. (45) showedthat anxiety was not signicantly associated withpositive psychotic symptom severity. However, theinclusive nature of the factor used may haveclouded any pertinent results for anxiety (or

depression) that may have been revealed with theuse of independent measures of these constructs,especially given the divergence in ndings for thetwo emotions thus far revealed by the studies out-lined above.In addition to clinically rated symptom severity,

there is evidence that perceived symptoms asassessed with the Illness Perception Questionnaire(56) are related to the severity of anxiety (57),although the use of a sample who were at the pointof relapse reduces the generalizability of these nd-ings. Regarding both depression and anxiety, thediscovery that subjectively perceived symptomseverity is related to the level of these emotionscould have multiple implications; perceived symp-tom severity may be akin to actual symptom sever-ity, and so the nding supplements those reportedabove. Alternatively, it may signify that it is thesubjective appraisal of ones own illness experiencethat leads to (or develops from) feelings of anxietyand depression, which would converge with nd-ings in the realm of PPD (27). Watson et al. notedthat the correlation between anxiety and depres-sion and symptomatology was stronger for per-ceived symptoms, rather than observer-rated,adding weight to the latter hypothesis.The ndings seem to suggest that anxiety is

related to the severity of delusions and hallucina-tions, although the evidence is not as extensive ormultifaceted as that related to depression. Somestudies also did not use the usual construct of anxi-ety, with one focussing specically on social anxi-ety and one conating anxiety with other aectivefeatures such as guilt and depression, so specicitywith regard to links with anxiety per se is reduced.

Distress. There is evidence that anxiety is relatedto the level of distress experienced as a result ofdelusional beliefs, although there is a relative pau-city of studies. Two studies have provided data rel-evant to this link.Focussing on mechanisms rather than syn-

dromes, Startup et al. (58) observed that processesusually associated with anxiety, such as generalworry and catastrophizing, are related to distressconcerning persecutory delusions, However, mea-sures of anxiety as a construct (rather than the spe-cic thought processes discussed above) did notproduce any signicant eects, and further, theauthors conceded that the possibility that worryand anxiety are consequences of delusional distresscannot be discounted. The ndings relating to anx-ious thought processes, although intriguing andpossibly indicative of future research avenues,cannot be included in any overarching conclusionsregarding anxiety as a general construct. As previ-

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Hartley et al.

ously reported, the inclusion of people meeting cri-teria for a bipolar rather than schizophrenia spec-trum diagnosis reduces the generalizability of thendings somewhat.Also in the context of persecutory delusions,

Freeman & Garety (44) demonstrated that traitanxiety was strongly correlated with delusional dis-tress. Thus, there is evidence that delusional distressis linked with anxiety, the lack of replication may bedue to issues with sample characteristics. There isno evidence for a link between anxiety and distressassociated with auditory hallucinations.

Content. Comparisons can be drawn between anx-ious experience and the content of delusions andhallucinations. Freeman and Garety discernedthat, like anxiety, persecutory delusions concernanticipation of danger and have a content ofphysical, social or psychological threat (59). Fourempirical papers reported ndings on linksbetween anxiety and the content or appraisal ofpositive psychotic experiences and these focussedlargely on paranoid beliefs.In a cross-sectional study utilizing structural

equation modelling, Bentall et al. (50) report thatparanoid delusions are associated with a pessimis-tic thinking style and high rates of anxiety,although comparisons to those with specic delu-sions of other types were not made.Furthermore, there are indications that the per-

vasive threat content of the delusional experienceand levels of anxiety are related (39), although thishas not been replicated (51) and similar analysesrelating to the power of the persecutor did notreveal signicant associations with anxiety (39).Justications for persecution that rest on blame(poor-me paranoia) seem to be associated withhigh levels of anxiety, possibly due to the anticipa-tion of danger (60) although lack of explicit com-parison with other groups renders the conclusionslimited.Anxiety seems to be related to threat and beliefs

around lack of self-blame, although ndingsaround threat content are ambivalent and a gen-eral lack of comparison groups limits the infer-ences that can be made.

Is there evidence to suggest that anxiety and depression play acausal role in the development and experience of psychosis?

Relevant research. Uncovering causal relationshipsin psychological research is fraught with diculty,not least because experimental manipulations,which would seek to test potential triggers orcontributory factors by inducing unpleasant men-tal states violate numerous ethical principles. Fur-

thermore, the multitude of factors potentiallyinvolved renders uncovering independent causalpathways dicult. The ndings discussed aboveprovide some clarity as to the precise relationshipbetween anxiety and depression and the experienceof psychotic symptoms, although the role of theseemotions in the development and maintenance ofdelusions and hallucinations is less well elucidated.Sources of information that could point towards(but, admittedly, not ultimately conrm) a causalrole for psychological factors in the developmentof mental health problems include prospective lon-gitudinal research; research that focuses on thestage of rst illness development and examineslinks that may be present prior to experiencesreaching diagnostic levels (where the chronicity ofthe illness and associated consequences are lessconfounding); and research that assesses theimpact of potential causal factors on the courseand consequences of the experience. In this sectionof the review, such relevant information resultingfrom the literature search will be considered, andpertinent conclusions oered that could contributeto the understanding of a potential role for anxietyand depression in the development or experienceof psychosis.

The emergence and persistence of emotional distur-bance and chronological relationship with psychoticexperiences. A total of 25 papers produced by theliterature search provided evidence pertaining tothe chronological relationship between emotionaldysfunction and psychotic experiences. Thesequential primacy of emotional disturbance overdelusional or hallucinatory experience, and thepersistence and stability of emotional disturbancemay help to clarify whether or not anxiety anddepression inuence or trigger the development ofpsychotic symptoms.Studies have indicated that emotional distur-

bance can predate the onset of psychosis (61).Retrospectively, Herz & Mellville (62) identieddysphoric symptoms as the most prevalent prior torelapse. Hamera et al. (63) replicated this nding,showing that self-evaluated signs of relapse wereoften coded as anxious (41%) or depressive (28%)in type. Interestingly, the authors also showed thatmany people took actions to divert relapse follow-ing their awareness of the indicator, and that thosewith anxious and depressive indicators had betterconcurrent functioning than those with psychoticindicators.A study of depression in the context of rst

episode psychosis has revealed that almost halfof the sample (49%) met the lifetime criteria forat least one major depressive episode, with 21%

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Anxiety, depression and psychotic symptoms

meeting criteria at the time of assessment (64),reecting earlier ndings (65). These co-occur-rences, early in the development of the psychosis,may point to depression having a fundamental for-mative role. Alternatively, it could be that bothsyndromes share a common cause, as Romm et al.(64) suggested. Furthermore, the retrospective nat-ure of the self-reported presence of depression tem-pers the validity of the ndings, especially asdepressive episodes often involve concurrent mem-ory biases (66).Additional ndings from an early psychosis

sample were presented by Sim et al. (67), whoexamined the comorbidity of depressive and anx-ious syndromes in people experiencing rst episodepsychosis. Disregarding the rules surroundingdiagnostic hierarchy, the authors found depressionto be present (historically or currently) in 16.5% ofcases; OCD in 5.1% and social phobia in 8.9%and other studies have shown that depression andanxiety constitute key aspects of the prodromalperiod (6870).Signicantly, Yung et al. (71) showed that the

presence of depression and anxiety in prodromal/high risk groups appears to increase the risk oftransition into psychosis. Similarly, Krabbendamet al. (72, 73) reported that, given the presence ofhallucinatory experiences, those with depressedmood at year 1 were at increased risk of psychosisat a 3-year follow-up assessment.Prospective assessments have shown that the

existence of panic at baseline can predict the pres-ence of psychotic symptoms after 24 months, inthose with a diagnosis of schizophrenia or schizo-aective disorder (74). The use of a rst admissionsample in this study serves to highlight the impor-tance of anxious features at this early stage of ill-ness development, although the specicity of theanxious event reduces the generalizability of thendings. Similarly, Iyer et al. (69) describe depres-sion and anxiety as being the most frequent earlysigns in a sample of people with rst episode psy-chosis, even with a large pool of 27 possible factorsincluding social withdrawal and sleep disturbance.Specically in terms of paranoid beliefs, there isevidence from correlational analyses that anxietycontributes to a detrimental change in the level ofpersecutory beliefs over a 3-month follow-upperiod (58).Birchwood et al. (75) completed an ongoing,

prospective assessment of various specic aspectsof psychopathology, monitored by both partici-pants themselves and observers at fortnightlyjunctures. Plotting of the data revealed that overhalf of the sample relapsed in the course of9 months and within this group, 50% showed

increases on the scales (including anxiety, depres-sion and disinhibition) between 2 and 4 weeksprior to relapse. A similar, more recent study ofrelapse predictors found correlations between delu-sion formation and aective events akin to stan-dardized constructs of anxiety and depression,including feeling anxious and feeling depressedor low (76). Koreen et al. (10) provide cautionagainst generalizing the results relating to depres-sion described above as a trigger of psychotic epi-sodes to other groups, as their ndings indicatedthat depression was prodromal to schizophrenia inonly 7% of a sample experiencing their rstepisode of psychosis.As part of a pharmacological trial, Tollefson

et al. (77) identied ve items from the PANSSthat appeared to predict relapse in psychotic symp-toms: depression, anxiety, guilt, somatic concernand preoccupation, (the PANSS Depression clus-ter). Extending this, the results showed that partic-ipants with reduced depression were subsequentlyat less risk of relapse during the following 4 weeks,compared to those whose depression had worsenedor remained stable. This dynamic relationshippoints to the aective features identied in the clus-ter being fundamentally related to relapse, whichwas dened as reduction in symptoms followed bya worsening of them. However, the addition ofpreoccupation, somatic concern and guilt in thepredictor variable render conclusions relevant tothe current review somewhat ambiguous.Birchwood (78) and others (79) have found evi-

dence to suggest that depression can follow thesame course as positive symptoms and can alsopresent during follow-up without a change in posi-tive symptoms i.e. post psychotic depression orPPD (80, 81). The picture is complicated by nd-ings that severity of depression in the acute phaseis not necessarily correlated with the appearance ofPPD (82), therefore divergent mechanisms mayunderlie these two phenomena, with earlier work(27, 83) suggesting that illness beliefs and apprais-als are key to the development of PPD, a ndingextended by Shahar et al. (84) to a mid-episode,substance using sample.Green et al. (85) followed participants with

recent-onset psychosis for 1 year, showing depres-sion was concurrent with psychosis more oftenthan would be likely by chance, and earlier ndingshave showed that in-patients with schizophreniaexperience depression at onset and during theacute phase (86). Tibbo et al. (87) have demon-strated similar ndings for anxiety, showing thatparticipants retrospectively report the onset ofanxious features to occur prior to the onset of psy-chosis, although a proportion also experienced

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Hartley et al.

them developing after or during the onset ofschizophrenia. There is also evidence that depres-sion and anxiety tend to remit with recovery fromacute psychosis (10).Findings indicate that anxiety and depression

predate the development of psychotic experiences,and often precede exacerbations in their severity,thus supporting the hypothesis that they havesome role in their development or resurgence.

Anxiety and depression in non-clinical samples.A total of 21 papers reported investigations intothe role of anxiety and depression in non-clinicalsamples. Evidence from this type of study may helpto clarify the causal proximity of emotion on psy-chotic experience; if the two constructs are linkedoutside of the clinically signicant range, then thepossibility that emotional dysfunction is only pres-ent as a reaction to the highly distressing nature ofa psychotic episode can be somewhat undermined.There is evidence that risk factors for non-clini-

cal psychotic features overlap with those for otherpsychological disturbances, including anxiety anddepression (88). Furthermore, that depressivefeatures co-vary with delusional and hallucinatoryexperiences in a similar way in both non-clinicaland clinical samples (89) and that anxious individ-uals in the general population have more halluci-natory experiences (90).More generally, investigations into the psycho-

metric dimension of schizotypy revealed that self-reported depressive and anxious symptoms arepositively associated with psychometric ratings ofschizotypy, especially positive symptoms (91) andthis nding has recently been replicated (92).Repeated diagnostic assessments made by generalpractitioners also show that psychosis proneness isassociated with higher incidences of depression(93). Similarly, Paulick et al. (94) demonstratedthat predisposition to hallucinations is associatedwith rates of anxiety in a group that were not cur-rently active hallucinators, thus undermining pro-posals that anxiety is merely a product ofdistressing hallucinatory experiences. In a laterstudy, Paulick et al. (95) extended this, replicatingtheir initial nding and also showing that anxietymay mediate the relationship between resistance tointrusions and the tendency to experience halluci-natory phenomena.The ndings are not conclusive in this area,

however; Cangas et al. (96) and Morrison et al.(97) showed that mood variables did not signi-cantly predict vulnerability to experience auditoryhallucinations in a sample of students and healthprofessionals, although the use of a compositedepression and anxiety predictor variable in the

latter study may have shrouded signicant inde-pendent relationships.With regard to delusional beliefs in non-clinical

samples, Lincoln et al. (98) have used experimentalmanipulation to show that anxiety may mediatethe relationship between stress and paranoia, indi-cating that those exposed to stress may experienceparanoia if it is in the context of high trait anxiety.In a similar model, Freeman et al. (99) revealedthat anxiety and depression may moderate therelationship between insomnia and paranoia innon-clinical samples. Furthermore, Bensi et al.(100) have shown that decits in data gathering,often linked to the experience of paranoia, areassociated with anxiety in the general population.A further clarication of the relationship betweenanxiety and paranoia has been made by Jones &Fernyhough (101), who showed that anxiety inter-acts with attempts to suppress thoughts to increasethe experience of persecutory ideation, withthought suppression having the greatest impactwhen anxiety levels are high. However, the cross-sectional natures of these analyses render conclu-sions about the causal primacy of anxious experi-ences on paranoia ambiguous. Furthermore, as theauthors of the latter study themselves note, the lowproportion of the variance in persecutory ideationaccounted for by this interaction eect (4.5%)highlights that there must be other more pertinentfactors, or indeed a multitude of factors that cometogether to produce persecutory thoughts.The associations between anxiety, depression

and hallucinatory and delusional tendencies innon-clinical samples have been neatly summa-rized in a study by Cella et al. (102), showingthat both emotions predicted scores on measuresof delusional ideation (as previously demon-strated) (103) and voice hearing, and highlightingthat depression was the better predictor ofdelusion proneness.Extending the role of trauma in psychosis (104)

to a non-clinical population, Freeman & Fowler(105) found that anxiety (but not depression) sig-nicantly predicted the presence of paranoidthoughts, while anxiety and trauma experiencesboth predicted the presence of auditory hallucina-tions, with both relationships independent ofsocio-demographic factors. This nding points tothe possibility of an interactive model of childhoodvulnerability and anxiety leading to the presence ofpositive symptoms in later life.A fundamental component of theories of psy-

chosis is the role of dysfunctional reasoning pro-cesses in the development and maintenance ofpsychotic experiences (5). The notion of negativeemotions and reasoning biases interacting to

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support the formation of psychotic experiences hasbeen given weight by a non-clinical study of para-noid ideation. Lincoln et al. (106) looked at theimpact of anxiety and jumping to conclusionsbiases (107) on self-reported paranoia in a studentsample. The authors used an experimental manipu-lation of anxiety to assess the interaction ofinduced mood states and pre-existing paranoid ide-ation. The ndings showed that anxiety was associ-ated with paranoid ideation, but only in those withpre-existing high levels of paranoia (as tested priorto the experimental manipulation). Furthermore,this relationship was mediated by jumping to con-clusions biases. Thus, increased anxiety may leadto more prominent paranoia as a result of itsimpact on jumping to conclusions, but this eectonly occurs in those individuals with high baselinelevels of paranoia. In opposition to this, So et al.(108) failed to support a similar model in a Chinesesample of rst episode participants, showing thejumping to conclusions was not more evident in agroup induced to feel anxious.A number of studies have demonstrated that the

links seen in those meeting diagnostic criteria arealso evident in sub-syndromal samples and mayincrease conversion to experiences meetingdiagnostic criteria, with ndings also relating thelevel of anxiety and depression to other, well-documented risk factors.

Anxiety and depression, and outcome in psychosis. Atotal of 29 papers provided ndings related to theinuence of anxiety and depression on clinical out-come in psychosis. Investigations into the impactof various psychological constructs on the progno-sis of psychosis-related diculties have tended togroup into distinct categories; those that seek toestablish whether high levels of anxiety and/ordepression lead to more occurrences of a discretenegative event (such as self-harm or suicide); thosethat attempt to quantify participants quality oflife (from either an observer-rated or self-reportperspective) and assess whether this is related tothe presence of anxiety and/or depression; andthose that examine generic illness concepts suchas admission, relapses and chronicity, with manylinking these outcomes to levels of anxiety anddepression.Roy (109) demonstrated that concurrent depres-

sion in schizophrenia is related to higher rates ofrelapse and suicide, and comparisons by Coso &Hafner (3) showed that those who meet criteria forconcurrent anxiety disorder have had a greaternumber of hospital admissions than those who donot, conrming the need to clarify the role of anxi-ety and depression in symptomatology and experi-

ence. Various others (110113), have replicatedthese ndings with regard to suicidality and arecent study has shown that formally assessed anx-ious and depressive features are higher in thosewith a history of suicide (114). Furthermore, Ranet al. (115) have extended the support of an associ-ation between depressive experiences and suicideattempts in psychosis to the Chinese community,while Harvey et al. (116) have shown that the sig-nicant proportion of self-harm in rst episodepsychosis can be predicted by the presence ofdepression. However, Harkavy-Friedman et al.(117) highlighted that although depression and sui-cide are frequently associated in psychosis,attempts do occur outside of depressive episodes.Not all aspects of outcome are related to emo-

tional features; Naeem et al. (118) found no associ-ation between anxiety symptoms at baseline andthe outcome of cognitive therapy in a group ofpatients with schizophrenia, a result which bringswith it some optimism for successful interventions.As part of a large scale longitudinal research

programme, Sands & Harrow (119) reported thatdepression in schizophrenia is associated with pooroverall outcome, and additional consequences suchas suicidal tendencies, work impairment and rehos-pitalizations, with some of the ndings later repli-cated (120). Similarly, Salkongas et al. (121) haverevealed associations between depression, poorfunctioning and health status in both primary careand out-patient settings. Furthermore, Blackburn,Berry and Cohen (122) have provided a possibleroute from depression to low therapeutic ecacy,in the form of low attachment to care services.However, Koreen et al. (10) showed that depres-sive symptoms do not predict time to remission orglobal outcome in those experiencing rst episodeschizophrenia.Huppert et al. (123) observed that both anxiety

and depression signicantly predicted assessmentsof quality of life in those people with schizophre-nia, with the latter nding subsequently replicated(124129). Uzeno (130) has demonstrated thatsubjective psychological well-being is negativelyrelated to levels of depression in an early psychosissample, even when controlling for negativepsychotic symptoms. One reason for these ndingscould be that comorbid anxious and depressivefeatures impact on peoples appraisals of psychosisas a life event; indeed, Karatzias et al. (131) haveshown that those with concurrent aectivedisorder diagnoses hold more negative appraisalsof entrapment surrounding their experience andhave lower self-esteem. Similarly, Mausbach et al.(132) demonstrated that the intensity of depressioncorrelated with satisfaction with the activities that

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people engage in, highlighting a potential route tolow quality of life reports.There are some studies which point to depres-

sion and anxiety leading to better outcomes insome respects; Cougnard et al. (133) showed thatthe presence of anxiety and depression was associ-ated with non-compulsory (rather than compul-sory) admissions. In rst admitted patients,Bottlender et al. (134) revealed the unexpectednding that greater depression was related to bet-ter outcome. However, the specic context of thelatter ndings (acute hospital stay) may impingeon the ability to extrapolate the results to formmore general conclusions. It may be, for example,that those individuals who were more depressed inthis context were more motivated to overcometheir positive psychotic symptoms.Peralta & Cuesta (13) investigated the impact of

anxious and depressive features on outcome in thecontext of non-aective psychosis. They examinedthe correlates of an anxiety factor (composed ofvarious features of anxiety including tension andrestlessness) and a depression factor (comprisingvarious aspects of depression including hopeless-ness and circadian disturbances). The ndingsshowed that anxiety dened in this way was associ-ated with a more chronic course of illness, poorerresponse to treatment but, conversely, better glo-bal functioning and shorter duration of the epi-sode, portraying a very mixed picture of theinuence of this emotional condition. The depres-sion factor was associated with suicidal behaviour(although the fact that suicidal ideation was a spec-ied component of the depression factor makesthis nding somewhat tautological) and more cog-nitive disorganization. Retaining the single symp-toms rather than consolidating them into factorsmay have made these results less ambiguous;although there is a clear indication that depressionand anxiety (as dened here) do have a signicantimpact on outcomes in psychosis, the precisemechanisms involved remain unclear.To summarize, anxiety and depression seem to

lead to greater likelihood of numerous negativeconsequences, such as relapse, admissions, self-harm, functioning and quality of life and suicide,with the evidence especially strong for the lattertwo outcomes. There is some ambivalence withregard to more global measures of outcome orprognosis, and anxiety does not seem to be detri-mental to therapeutic ecacy.

Discussion

This review has summarized ndings relevant tothe role of anxiety and depression in the experience

of psychosis. Clearly, there is an abundance of evi-dence to suggest that these two aective conditionshave signicant associations with the severity, dis-tress and content of psychotic experiences. How-ever, most of the investigations generated by thesearch are also limited by their cross-sectionaldesign; there is no opportunity to discern whetherincreases in anxiety and depression precede or leadto greater symptom severity, or distress, thus con-clusions of causality in any instance must beavoided. Similarly, it is not clear whether the con-tent of symptoms develops from the nature of theemotional milieu, or that some specic types ofexperiences lead to greater levels of anxiety anddepression, with the cause rooted elsewhere.Moreover, there has been a tendency for much

of the research output to focus on paranoia or per-secutory delusions and thus restrict the study sam-ple to people with these particular experiences.Although the high prevalence of this particulartype of experience might provide a rationale forthis strategy, another possible factor is that mostof the studies reported here have the primary aimof elucidating the mechanisms behind paranoia,with analyses of the role of anxiety and depressionas somewhat secondary. The ndings are not nec-essarily undermined because of this, but a moregeneral investigation, using a heterogeneous sam-ple, or multiple studies each focussing on discreteexperiences (such as grandiose or somatic delu-sions, visual hallucinations) with consistent designsto facilitate cross-comparison, may allow morerm conclusions to be made that can then be gen-eralized to psychotic experiences on the whole.Longitudinal investigations have reported that

anxiety and depression can predate the rst epi-sode of psychosis, or acute relapses, which mayindicate their causal inuence or role in triggeringdistressing experiences. Conclusions in this contextrest on the assumption that, if anxiety and depres-sion occur prior to the development of psychosis,persist throughout its course and occur prior toexacerbations in symptoms, then they are likely tobe involved as causal forces in its development,rather than as emotional consequences of its pres-ence. This assumption is not without its aws; anx-iety and depression could merely be more readilydiagnosed or acknowledged (formally or infor-mally) and therefore their occurring prior to psy-chosis is merely an artefact of the lower thresholdfor awareness of their presence. In addition, theassumption rests on commitment to the hypothesisthat temporal precedence is equivalent to causality;it may be that there is a common cause, which bothpsychosis and anxiety and depression are triggeredby, which leads to the development of both, but

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which does not rely on the two being linkedcausally.Evidence of the links between anxiety and

depression and psychotic experiences in the generalpopulation undermines the suggestion that thesenegative emotions are only relevant in the contextof clinical samples as emotional reactions to thedistressing experiences (and possibly reections onillness identities); instead, the ndings point tofundamental relationships between anxiety anddepression and the experience of delusional beliefsand hallucinatory experiences. Moreover, ndingsdemonstrating that anxiety and depression canincrease conversion to diagnostic levels of psy-chotic experience are suggestive of a possible cau-sal role of emotional dysfunction in thetransformation to distressing and unhelpful experi-ences; depression and anxiety may be the catalyststhat trigger distressing experiences of psychosis insome individuals with predisposition or dicultearly life experiences.Studies of outcome for people experiencing psy-

chosis have revealed that depression and anxietyare often associated with poorer consequences interms of more hospitalizations, admissions andsubjective appraisal of the negative impact ofpsychosis-related diculties. In addition, rates ofsuicide and self-harm are shown to be related tolevels of depression and anxiety, highlighting aneed to further elucidate the process by whichthese aective experiences increase the likelihoodof these events in the context of psychosis. Moresubjective measures, such as quality of life, entrap-ment and satisfaction with life are also related tolevels of anxiety and depression, although whetherthese appraisals feed into the prevalence of themore discrete events listed above is not clear.The ndings indicate that therapeutic eort

directed towards the reduction of anxiety anddepression may be benecial to those experiencingpsychosis. Given the noted links prior to clinicalcaseness, increases preceding elevations in symp-toms and impact on outcome, it is likely that theseinterventions could be relevant throughout thecourse of psychosis. Cognitive behavioural therapyis already well-evidenced and recommended forthose meeting criteria for a diagnosis of schizo-phrenia (135) and this review suggests that it maybe pertinent to routinely consider strategies toreduce anxiety and depression in the context ofpositive psychotic symptoms. Particular strategiesmight include acknowledging and reducing safetybehaviours, relaxation techniques, activity plan-ning, thought diaries and behavioural experiments.Two pertinent issues have emerged from this

study: one is the need to clarify the causal direction

of relationships between anxiety and depressionand positive psychotic symptom characteristics,and the other is the need to focus on specic pro-cesses or subtypes of experience, to enable theoreti-cal ndings to be translated in implementabletherapeutic methods. The understandable dearthof experimental studies in this area makes it di-cult to construct any conclusions about causality.Researchers should seek to employ innovativemethods, such as experience sampling methodol-ogy (54), which can circumvent the diculties withexperimental procedures while providing observa-tional data that captures a more detailed view ofthe relationships between anxiety and depressionand psychotic symptoms. Moreover, the variedway in which depression and anxiety are concep-tualized, whether as diagnoses, symptoms, emo-tions or self-assessed dysphoria, renders the natureof any conclusions drawn from the data describedhere ambiguous. A number of studies have utilizedsamples with specic experiences (such as socialanxiety) rather than more generic anxious features,which might be explored more rigorously in futurework, although it may also make conclusionsregarding anxiety in general more ambiguous. Inaddition, some investigations reported here (50)have confounded levels of anxiety and/or depres-sion with other factors such as self-esteem, guilt.Studies exploring the unique inuence of anxietyand/or depression may oer less ambiguous con-clusions, although such work might also controlfor levels of other pertinent factors as these clearlymay have a role to play. Alternatively, utilizationof more distinctly and specically dened processeswould enable more rm conclusions to be drawn,and for these to feed in the development of tar-geted therapeutic procedures. The transdiagnosticinuence of numerous thought processes, includingthose traditionally associated with anxiety anddepression, such as rumination and worry, hasbeen highlighted (136). If the relationship betweenthese processes and the experience of specic psy-chotic events can be duly unpacked then contribu-tions could be made to working psychologicalmodels of delusions and hallucinations and to thetherapeutic resources available.

Additional relevant papers

The authors have been made aware of several addi-tional papers, not produced by this review, whichmay be of interest to the reader. These are notincluded in summary statements so as not to intro-duce bias into the systematic search process. Alarge cross-sectional study (137) demonstrated thatso-called neurotic symptoms were associated with

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both paranoia and hallucinatory experiences in thegeneral population, although others (138) haveestablished that there is not only some overlap inearly signs but also distinctiveness in those wholater go on to develop depression vs. psychosis.Longitudinal work (139) has shown that anxietyand depression were associated with the persis-tence of voices over 3 years in a sample comprisedof 80 adolescents. This is in contrast to Wigmanet al. (140), who found that depression and psy-chosis were associated cross-sectionally at pointsalong a longitudinal follow-up, but not over time.Echoing previous ndings (53), Thewissen et al.(141) used experience sampling methodology todemonstrate that increased anxiety predicted theonset of paranoia within daily life, and that depres-sion was predictive of longer paranoid episodes.

Acknowledgements

This review was supported by Greater Manchester West Men-tal Health NHS Foundation Trust via the Recovery researchprogramme.

Declaration of interest

None.

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