Depression in Schizophrenia: Depression in Schizophrenia: Symptom, Syndrome Symptom, Syndrome

or Co-morbibidty?or Co-morbibidty?

E. Timuçin OralE. Timuçin OralAssoc Prof of PsychiatryAssoc Prof of Psychiatry

Bakırköy Prof Dr Mazhar Osman State Hospital Bakırköy Prof Dr Mazhar Osman State Hospital for Research & Training in Neuropsychiatry for Research & Training in Neuropsychiatry

Istanbul / TurkeyIstanbul / Turkey

Facts about SchizophreniaFacts about Schizophrenia

OutcomeOutcome ~~15% fully recover15% fully recovereded ~~ 85% continue to have residual and/or active 85% continue to have residual and/or active ssxx ~~ 50% end up in hospital of day treatment 50% end up in hospital of day treatment 90% or more receive disability/welfare benefits or are 90% or more receive disability/welfare benefits or are

economically dependenteconomically dependent 75% or more are unmarried75% or more are unmarried Approximately 10% die by suicideApproximately 10% die by suicide Twice as likely as normal controls to die from other Twice as likely as normal controls to die from other

causescauses

Facts about SchizophreniaFacts about Schizophrenia

Culture:Culture: Prevalence doesn’t vary much Prevalence doesn’t vary much ((biological rolebiological role?)?)

Content of delusions tends to vary cross culturallyContent of delusions tends to vary cross culturally

Prevalence Prevalence of sof schizophrenia seems to be higher in chizophrenia seems to be higher in lower SES communitieslower SES communities (cause or the result?) (cause or the result?)

MMay impair occupationalay impair occupational & & social social functioning functioning Increased stress Increased stress ++ poverty may contribute to the poverty may contribute to the

development development

SchizophreniaSchizophrenia: : CourseCourse

Group 330% have repeated episodes of illness with some impairment between episodes

Group 225% have repeated episodes of illness with no impairment between episodes

Group 115% have only a single episode of illness with no subsequent impairment

Group 430% have repeated episodes of illness with gradually declining impairment between episodes

Schizophrenia & Schizophrenia & Related Disorders, Related Disorders,

McKenna 2003 McKenna 2003 Oxford PressOxford Press

Schizophrenic ProcessSchizophrenic Process

1010 2020 3030 4040 5050 6060

100100%%

FunctioningFunctioning

AgeAge ( (yryr))

Premorbid

Prodromal

Progression

StabilizationRelapse

J. A. Lieberman.

DSM-IV DSM-IV -- Schizophrenia Schizophrenia

““The characteristics of Schizophrenia The characteristics of Schizophrenia involve a range of cognitive and involve a range of cognitive and emotional dysfunctionsemotional dysfunctions that include that include perception, inferential thinking, language perception, inferential thinking, language and communication, behavioral and communication, behavioral monitoring, monitoring, affectaffect, fluency, and , fluency, and productivity of thought and speech, productivity of thought and speech, hedonic capacityhedonic capacity, volition and drive, and , volition and drive, and attention” attention”

APA. DSM-IV-TR; 2000.

ComorbidityComorbidity

Obsessive-Compulsive disorderObsessive-Compulsive disorder 7.8% with schizophrenia had OCD7.8% with schizophrenia had OCD 26% out of 50 patients met criteria for OCD26% out of 50 patients met criteria for OCD

DepressionDepression 25% prevalence rate with Schizophrenia25% prevalence rate with Schizophrenia

SuicideSuicide 10% of patients commit suicide10% of patients commit suicide Suicide attempts are 5 times higher than suicide rateSuicide attempts are 5 times higher than suicide rate

CChildhood hildhood DDisorders isorders PPreceding receding SSchizophreniform chizophreniform DDisorder isorder (odds ratios)(odds ratios)

Childhood anxietyChildhood anxiety

DepressionDepression

Conduct disorderConduct disorder

2.5 2.5

7.47.4

2.52.5

SchizophreniformSchizophreniformDDisorderisorder

ManiaMania

2.12.1

3.33.3

2.52.5

Kim-Cohen et al 2003

Depressive symptoms in Depressive symptoms in SchizophreniaSchizophrenia

M=FM=F

Main indication for 40% of hospital admissions Main indication for 40% of hospital admissions

(Falloon et al, 1978)(Falloon et al, 1978)

Associated with poor outcome, personal and Associated with poor outcome, personal and social adjustment social adjustment

Treatment non-compliance & increased risk of Treatment non-compliance & increased risk of suicide suicide (Carpenter et al, 1988)(Carpenter et al, 1988)

Pathologic Dimensions of Pathologic Dimensions of SchizophreniaSchizophrenia

Negative SymptomsNegative SymptomsAffective flatteningAffective flatteningAlogiaAlogiaAvolitionAvolitionAnhedoniaAnhedoniaSocial withdrawalSocial withdrawal

Positive SymptomsPositive SymptomsDelusionsDelusionsHallucinationsHallucinationsDisorganized speechDisorganized speechCatatoniaCatatonia

Cognitive DeficitsCognitive DeficitsAttentionAttentionMemoryMemoryExecutive functionsExecutive functions(e.g., abstraction)(e.g., abstraction)

Mood SymptomsMood SymptomsDepressionDepressionAnxietyAnxietyHopelessnessHopelessnessDemoralizationDemoralizationStigmatizationStigmatizationSuicidalitySuicidality

Social/Occupational DysfunctionSocial/Occupational DysfunctionWorkWork

Interpersonal relationshipsInterpersonal relationshipsSelf-careSelf-care

Comorbid Substance AbuseComorbid Substance Abuse

http://www.schizophrenia.com/schizpictures.html

Suicide & SchizophreniaSuicide & Schizophrenia

Male genderMale gender

Younger than Younger than 3030

DDepresepresssiiveve symptomssymptoms

UnemployedUnemployed

Max 3 months after Max 3 months after discharge discharge

Unadequate treatmentUnadequate treatment

PParanoid aranoid subtypesubtype

CComorbid alomorbid alccoohoholl use use

Adjustment problemsAdjustment problems

AAkatkathhiissiiaa

Nearly 10% of patients commit suicide:Nearly 10% of patients commit suicide:

Relationship Between Relationship Between

Schizophrenia - Mood Disorders / Suicide Schizophrenia - Mood Disorders / Suicide

CINP: Mood symptoms in schizophrenia are actually CINP: Mood symptoms in schizophrenia are actually a manifestation of schizophrenia rather than a a manifestation of schizophrenia rather than a discrete mood disorder (Judd, 1998)discrete mood disorder (Judd, 1998)

NIMH: Lifetime prevalence 1.5% (34 out of 20,291). NIMH: Lifetime prevalence 1.5% (34 out of 20,291).

Judd: 91% accompanied by mental or substance Judd: 91% accompanied by mental or substance abuse disordersabuse disorders

NCS: 18.6% were schizophrenia without comorbid NCS: 18.6% were schizophrenia without comorbid mood disordersmood disorders ((59% comorbid UP; 22% comorbid BP)59% comorbid UP; 22% comorbid BP)

Lifetime Suicide RatesLifetime Suicide Rates (Judd, 1996)(Judd, 1996)

UP (alone)UP (alone) 10,4%10,4% Schizophrenia + UPSchizophrenia + UP 27,5% 27,5% BP (alone)BP (alone) 28,5%28,5% Schizophrenia + BPSchizophrenia + BP 70.6%70.6% 37% at least one suicide attempt 37% at least one suicide attempt

7.9% in nonschizophrenic population (7.9% in nonschizophrenic population (p<0.0001p<0.0001))

40% reported suicidal ideation40% reported suicidal ideation 23% reported suicide attempts23% reported suicide attempts 6.4% died6.4% died

Patients who died had lower negative Patients who died had lower negative symptom severity symptom severity

Suspiciousness and Delusions were more Suspiciousness and Delusions were more severe among suicidessevere among suicides

Paranoid subtype: elevated risk (12%)Paranoid subtype: elevated risk (12%) Deficit subtype: Deficit subtype: reduced risk (1.5%) reduced risk (1.5%)

Fenton, et al. Am J Psychiatry, 1997Fenton, et al. Am J Psychiatry, 1997

FinFinlandland National Project for National Project for Prevention of SuicidePrevention of Suicide

77% of all followed% of all followed-up diagnosed as -up diagnosed as schschizoizophphrenreniaia

7878% attempted in active, 4% attempted in active, 400% in acute phase % in acute phase

6464% had d% had depresepresssiive symptoms ve symptoms

4040% were “violent” % were “violent”

2121% had a% had allccoohohol l abuseabuse

Age distribution was equalAge distribution was equal

Heilä, 1997Heilä, 1997

I am totally cured doctor. I am not paranoid anymore!

He is trying to convince

me

Characteristic SymptomsCharacteristic Symptoms

Schneider: specific types of delusions Schneider: specific types of delusions and hallucinationsand hallucinations

Bleuler: fragmented thinking, inability Bleuler: fragmented thinking, inability to relate to external worldto relate to external world

Kraepelin: emotional dullness, Kraepelin: emotional dullness, avolition, loss of inner unityavolition, loss of inner unity

Kraepelin: Kraepelin: The Borders of SchizophreniaThe Borders of Schizophrenia

““……it is certainly possible that its borders it is certainly possible that its borders are drawn at present in many directions are drawn at present in many directions too narrow, in others perhaps too wide.too narrow, in others perhaps too wide.””

““Good Prognosis Schizophrenia”Good Prognosis Schizophrenia”

Prominent affective symptomsProminent affective symptoms Acute onsetAcute onset Family history of affective disorderFamily history of affective disorder Good premorbid function Good premorbid function Presence of insightPresence of insight

Symptom Clusters in SchzophreniaSymptom Clusters in Schzophrenia

AffectiveAffective

DepressionDepression

AnxietyAnxiety

AggressionAggression

DysphoriaDysphoria

PsychomotorPsychomotoractivationactivation

CognitiveCognitive

LearningLearning

MemoryMemory

AttentionAttention

Executive Executive functionfunction

Language skillsLanguage skills

NegativeNegative

Flattened affectFlattened affect

AnhedoniaAnhedonia

AvolitionAvolition

Social Social withdrawalwithdrawal

AlogiaAlogia

PositivePositive

HallucinationsHallucinations

DelusionsDelusions

Bizarre Bizarre behaviorbehavior

Thought Thought disorderdisorder

AgitationAgitation

Depression in SchizophreniaDepression in Schizophrenia

Often been associated with Often been associated with Worse outcome (5)Worse outcome (5) Impaired functioningImpaired functioning Personal suffering (6)Personal suffering (6) Higher rates of relapse, rehospitalization and Higher rates of relapse, rehospitalization and

even suicide (10% of patients) even suicide (10% of patients) (8,11,710 11, 13)(8,11,710 11, 13)

Literature on depression in schizophrenia is Literature on depression in schizophrenia is imprecise whether the affect, symptom, or imprecise whether the affect, symptom, or syndrome of depression is involved. syndrome of depression is involved.

Affect, Symptom, Syndrome?Affect, Symptom, Syndrome?

AffectAffect a mood state (happiness - sadness). Not a mood state (happiness - sadness). Not pathological as long as situationally appropriate pathological as long as situationally appropriate

SymptomSymptom a sad mood state causes a distress. An a sad mood state causes a distress. An unwanted painful feeling a source of complaint. unwanted painful feeling a source of complaint.

SyndromeSyndrome a complex of features includes a complex of features includes cognitive and vegetative features cognitive and vegetative features

pessimism, guilt, impaired concentration, lack of confidence, loss of pessimism, guilt, impaired concentration, lack of confidence, loss of interest / pleasure, disturbances in sleep, appetite and energy levelinterest / pleasure, disturbances in sleep, appetite and energy level

Siris SG, Am J Psychiatry 2000; 157:1379–1389)

Differential Diagnosis of Differential Diagnosis of DepressionDepression

in Schizophreniain Schizophrenia

1.1. Medical/Organic FactorsMedical/Organic Factors

2.2. Negative Symptoms of SchizophreniaNegative Symptoms of Schizophrenia

3.3. Neuroleptic-Induced DysphoriaNeuroleptic-Induced Dysphoria

4.4. Neuroleptic-Induced AkathisiaNeuroleptic-Induced Akathisia

5.5. Reactions to Disappointment or StressReactions to Disappointment or Stress

6.6. ““Postpsychotic Depression”Postpsychotic Depression”

7.7. Prodrome of Psychotic RelapseProdrome of Psychotic Relapse

Siris SG, Am J Psychiatry 2000; 157:1379–1389)

Antipsychotic Receptor PharmacologyAntipsychotic Receptor Pharmacology

D1D1D2D2D4D45HT2A5HT2A5HT2C5HT2CMuscMusca1a1a2a2H1H1

HaloperidolHaloperidolee KKlozapinlozapinee

RisperidonRisperidonee

QuetiapineQuetiapine

SertindoSertindolele ZiprasidonZiprasidonee ZotepinZotepinee

OlanzapinOlanzapinee

ObjectiveObjectiveTo differentiate whether depression manifested as To differentiate whether depression manifested as only a cluster of symptoms, a syndrome or a co-only a cluster of symptoms, a syndrome or a co-morbid disease in schizophreniamorbid disease in schizophrenia

97 97 out of out of 100 patients 100 patients interviewed was interviewed was participateparticipatedd

Inclusion CriteriaInclusion CriteriaReceiving same medication Receiving same medication >1 >1 yearyear

Exclusion CriteriaExclusion Criteria Other psychotic diagnoses, Other psychotic diagnoses, Co-morbidity Co-morbidity AADD, MS or ECT treatment, MS or ECT treatmentss in the last year in the last year

Scales Scales Structured Clinical Interview for Diagnosis (SCID)Structured Clinical Interview for Diagnosis (SCID) Hamilton Depression Rating Scale (HDRS) Hamilton Depression Rating Scale (HDRS) Calgary Depression Scale for Schizophrenia (CDSS)Calgary Depression Scale for Schizophrenia (CDSS) Positive and Negative Syndrome scale (PANSS)Positive and Negative Syndrome scale (PANSS)

DefinitionsDefinitions

Dx of MD Dx of MD ((SCIDSCID)) = ‘co-morbidity group’ = ‘co-morbidity group’ ScoreScoredd > > 8 8 ((HDRSHDRS)) ++ >>12 12 ((CDSSCDSS)) = ‘syndrome group’ = ‘syndrome group’ ScoreScoredd < < 8 8 ((HDRSHDRS)) // < <12 12 ((CDSSCDSS)) = ‘symptom group’ = ‘symptom group’ Zero from all scales = ‘non-depression group’Zero from all scales = ‘non-depression group’

Patient CharacteristicsPatient Characteristics

47 Male (48,5%) and 50 Female (51,5%) patients. 47 Male (48,5%) and 50 Female (51,5%) patients. Mean age = 38.24Mean age = 38.24 59.8% single59.8% single,, 21,6% married and 16,5% divorced. 21,6% married and 16,5% divorced. 53,6% 53,6% elementary school, elementary school, 46,4% high school 46,4% high school

82% unemployed82% unemployed, , 15,5% still working15,5% still working

86,6% 86,6% in in middlemiddle, 1, 11,3% 1,3% in in lowerlower, , 2,1% 2,1% in in higherhigher economic classeconomic class

10,3% living alone 10,3% living alone

IllnessIllness Characteristics Characteristics

71,1% paranoid71,1% paranoid 16,5% undifferentiated16,5% undifferentiated 8,2% residual8,2% residual 4,1% disorganized4,1% disorganized

AAge of onsetge of onset:: 22,3 22,3 AAge of treatmentge of treatment:: 24,524,5

Median Median of of hospitalizationhospitalizations:s: 3 3 MMean duration of remissionean duration of remission:: 22,5 months. 22,5 months.

Group CharacteristicsGroup Characteristics

6 patients in co-morbidity group (6.2%)6 patients in co-morbidity group (6.2%) 10 patients in syndrome group (10.3%) 10 patients in syndrome group (10.3%) 58 patients in syndrome group (59.8%)58 patients in syndrome group (59.8%) 23 patients in non-depression group (23.7%)23 patients in non-depression group (23.7%)

No gender, education, socio-economic and marital No gender, education, socio-economic and marital status differences in status differences in between between groupsgroups

GGroups roups are are identical in social support identical in social support && SS SS coveragecoverage

90% 90% of of patients in co-morbid patients in co-morbid and and syndrome groupsyndrome groups s are are unemployed unemployed

Suicide ratesSuicide rates

2 in co-morbid group (33.3%)2 in co-morbid group (33.3%) 2 in syndrome group (20%)2 in syndrome group (20%) 19 in symptom group (32.7%)19 in symptom group (32.7%) 4 in non-depressed group (17.3%)4 in non-depressed group (17.3%)

All patients were All patients were receivingreceiving SGA SGA 40% of symptom group40% of symptom group & & 30% of non-depressed 30% of non-depressed

patients were receiving clozapinepatients were receiving clozapine None of the patients were applied clozapine in co-None of the patients were applied clozapine in co-

morbid groupmorbid group

100% of comorbid group100% of comorbid group 90% of syndrome group 90% of syndrome group 69% of symptom group 69% of symptom group 71% of non-depressed group 71% of non-depressed group

were diagnosed as paranoid sub-were diagnosed as paranoid sub-groupgroup

Depression in 1Depression in 1°° andand 2 2°° relatives relatives 4-6% in two groups4-6% in two groups 16.7% in co-morbid group16.7% in co-morbid group None in non-depressed groupNone in non-depressed group

ResultsResults

Frequency of depressive symptoms in Frequency of depressive symptoms in schizophrenia is very common while it is less schizophrenia is very common while it is less likely occurs as a syndrome or as an additional likely occurs as a syndrome or as an additional diagnosis. diagnosis.

Defining depression and the severity of Defining depression and the severity of depressive symptomatology is important in depressive symptomatology is important in schizophrenia as they may play a devastating role schizophrenia as they may play a devastating role in the coursein the course