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How To Recognize and Respond to

Prodromal Psychosis

Rajiv Tandon

University of Florida

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OUTLINE OF PRESENTATION

♦ WHY CURRENT EMPHASIS ON TOPIC

♦ DEFINING PRODROMAL PSYCHOSIS

♦ DSM-5 APPROACH

♦ IMPLICATIONS FOR PRACTICE

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FIVE ARS QUESTIONS♦ 2 Introductory questions

♦ Outcome ARS

♦ Treatment ARS

♦ Cognition ARS

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The patient may never achieve restitutio ad integrum

IRREVERSIBLE DECLINE

DEMENCE

UNIFORMLY BAD OUTCOME

PROGRESSIVE DECLINE

Kraepelinian PESSIMISM of Dementia Praecox

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Called a disease of the mind, it afflicts more than one third of

patients in mental institutions. A severely disabling and chronic illness affecting diverse aspects of higher brain function, it causes impaired cognition, distorted

perceptions and hallucinations. Highly resistant to standard treatments, it can present abruptly in healthy individuals or develop insidiously.

Kraepelin E, Dementia Praecox and Paraphrenia, 1919

DementiaPraecox

Schizophrenia, Circa 1898

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Mood Symptoms

Functionallmpairment

PositiveSymptoms

Negative Symptoms

Cognitive

Deficits Motor symptoms

Disorganization

Psychopathological Domains

Tandon et al., Schizophrenia Research 2009; 110: 1-23.

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Course of

Schizophrenia

Age (Years)

GoodFunction

Psycho-pathology

15 20 30 40 50 60 70

Premorbid Progression StableRelapsing

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Cognitive and/or functional impairment, Subthreshold negative sx

Negative symptomsAnd functional decline

Subthreshold or brief intermittent positive sx And functional decline

Psychotic episodeSingle or recurrent with full inter-episode recovery

Psychotic episodeSingle or recurrent with persistent cognitive deficits and/or negative symptoms

Fnctional deterioration and treatment resistance symptoms

Stage 0 Premorbid X

Stage Ia Early prodrome

X/- X

StageIb Late prodrome

X/- X/- X

Stage II Psychosis with recovery

X/- X/- X/- X

Stage III Psychosis with inter-episode deficits

X/- X/- X/- X/- X

Stage IV Intractable psychosis and/or deterioration

X/- X/- X/- X/- X/- X

Mood Symptoms

Functionallmpairment

PositiveSymptoms Negative

Symptoms

Cognitive Deficits Motor

Symptoms

Disorganization

New Findings: Stages & Dimensions of IllnessTandon et al., Schizophrenia Research 2009; 110: 1-23

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Early developmental derailmentPeri-adolescent brain dysmaturation

Post-illness onset deterioration

Cognitive deficits

Perceptualdistortions

Functional decline

The epigeneticlandscape

Geneticsusceptibility

Environmentalfactors

Birth Adolescence Adulthood

Premorbiddeficits

Psychotic“break”

Relapses

An integrative model of schizophrenia.

Normal development

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PRODROMAL PSYCHOSIS♦ WHY

♦ Need to prevent illness or at least prevent progression

♦ AS EARLY AS POSSIBLE

♦ HOW♦ By early identification and effective treatment

♦ WHEN

♦ IN PRODROMAL PHASE

♦ Tools to identify those at risk for “conversion”

♦ Tools to intervene to reduce risk

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Course of

Schizophrenia

Age (Years)

GoodFunction

Psycho-pathology

15 20 30 40 50 60 70

Premorbid Progression StableRelapsing

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Recovery

PremorbidProdromal

PsychoticTransitional

Phases of the schizophrenic illness.

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Recovery

Prodromal

Psychotic

TransitionalPremorbid

ManifestationsCognitiveNeuromotorBehavioral

Premorbid

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Premorbid and Prodromal Schizophrenia:

How Do We Know?♦ Tracking Back

History of individuals who develop schizophrenia

Were there points of intervention?

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Premorbid and Prodromal Schizophrenia:

How Do We Know?♦ “Unaffected Family Members”

1st and 2nd Degree Relatives

Do they manifest particular psychopathology?

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Diagnoses Among HR relatives of Schizophrenia(n=76) Attention Deficit Disorder 20Oppositional Defiant Disorder 11Depression 10Conduct Disorder 7Anxiety Disorders 6Bipolar Disorder 4Adjustment Disorder 2Substance use disorder 2No diagnosis 26

Total adds up to >76 because of comorbid disorders in some subject5 patients developed a psychotic disorder ( not included above)

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RecoveryProdromal

Psychotic

TransitionalPremorbid

Window of opportunity forEarly recognition and Primary prevention?

Premorbid

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Recovery

Psychotic

Transitional

ManifestationsCognitive declineAffective dysregulationSocial withdrawalEducational declineSubthreshold positive & negative Symptoms

ProdromalPremorbid

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Cognitive and/or functional impairment, Subthreshold negative sx

Negative symptomsAnd functional decline

Subthreshold or brief intermittent positive sx And functional decline

Psychotic episodeSingle or recurrent with full inter-episode recovery

Psychotic episodeSingle or recurrent with persistent cognitive deficits and/or negative symptoms

Fnctional deterioration and treatment resistance symptoms

Stage 0 Premorbid X

Stage Ia Early prodrome

X/- X

StageIb Late prodrome

X/- X/- X

Stage II Psychosis with recovery

X/- X/- X/- X

Stage III Psychosis with inter-episode deficits

X/- X/- X/- X/- X

Stage IV Intractable psychosis and/or deterioration

X/- X/- X/- X/- X/- X

Mood Symptoms

Functionallmpairment

PositiveSymptoms Negative

Symptoms

Cognitive Deficits Motor

Symptoms

Disorganization

New Findings: Stages & Dimensions of IllnessTandon et al., Schizophrenia Research 2009; 110: 1-23

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Youngest child of a successful businessman. Not very attentive and somewhat shy in grade school, and according to parents, he was “too good” a kid compared to his sibs and peers- not drinking, taking drugs, running around with a rowdy crowd or sexually active.

J. HChildhood: Attention problems

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In high school, began withdrawing. He stopped making friends and kept to himself.  Losing all interest in athletic activities.  He did not date.  Spent hours in his room, strumming on his guitar and listening to music, especially the Beatles.   

High school-Social withdrawal

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College: Educational declineAge 19-20 Drifts aimlessly through two years of

college, playing his guitar, listening to music, and watching movies.

Age 21 Drops out of college and goes to hollywood but fails to launch a musical career, returns to sporadically attend class and spends most of his time alone ( same movie dozens of times). 

Parents are pleased however, now that he says he has a girlfriend, a budding actress who talks to him off and on and that he travels a lot

Age 22 Moves back to live with parents

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Age 19 “anxiety attack” led him to see a doctor whotested him for dizziness.  All tests negative, but the doctor notes a strange “ flatness of affect” A “depressive reaction is diagnosed and an antidepressant is prescribed. Not continued.

Age 20: Makes suicidal gesture and is further withdrawn. Taken to a psychiatrist for “depression” Psychiatrist says hospitalization unnecessary and does psychotherapy twice a week

Beginning symptoms: Mood

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Tells psychiatrist about his obsession With an actress dominating his mind but fails to reveal some “ really crazy thoughts”

Writes to psychiatrist: “My mind is on the breaking point the whole time.  A relationship I had dreamed about went absolutely nowhere.  My disillusionment was complete”.

Parents express increasing concern to their son about his absent occupational goals and frequent mysterious absences. Psychiatrist prescribes “Tough Love” regimen in which the parents were to get John out of the nest and leave him on his own no matter what.

Age 22: Given by father $200 and asked to be on his own. Some days later.. Writes to “girlfriend” he was thinking of kidnapping her, highjack a plane and ask to be installed in the whitehouse. This is not mailed

The Breaking point and Missed Opportunities

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March 30 1981

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Course of Schizophrenia

Age (Years)

Good

Function

Psycho-pathology

Poor15 20 30 40 50 60 70

Premorbid Progression StableRelapsing

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Early developmental derailmentPeri-adolescent brain dysmaturation

Post-illness onset neurodeteriorationh

Glutamatergic/GABAabnormality

Dopaminergicdysregulation

NeurochemicalSensitizationOxidative stress

The epigeneticlandscapeEnvironmental

FactorsFamily environmentDrugs of abuseStress

Birth Adolescence Adulthood

Premorbiddeficits Prodrome”

Psychosis

Normal development

functional decline

Geneticsusceptibility

Pathophysiology of schizophrenia may involve a cascade ofSequential, cumulative events

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Attenuated positive syndrome

Brief Intermittent psychosis

Family history+ decline

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Prediction of Psychosis in Youth at High Clinical Risk

l OUTCOMESn Risk of conversion 35%

during f/u periodn 5 clinical features

improved prediction: “genetic” risk for schizophrenia + deterioration, higher severity of unusual thought content, suspicion/paranoia, greater social impairment, history of substance abuse

Cannon TD, et al. Arch Gen Psychiatry. 2008;65:28-37.

Cumulative survival distribution function modeling time to conversion to psychosis in 291 clinical high-risk (prodromal) patients and 134 demographically comparable normal control subjects (dashed line).

1.00

0.75

0.50

0.25

0

Su

rviv

al D

istr

ibu

tion

Fu

nct

ion

0 200 400 600 800 1000Days Since Baseline Assessment

ControlsProdromal patients

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DSM-5 Revision Principles

Clinical Utility, Validity, Reliability

♦ The DSM is above all a manual to be used by clinicians, and changes made for DSM-5 must be implementable in routine specialty practices.

♦ Recommendations should be guided by research evidence.

♦ Continuity with previous editions should be maintained when possible

♦ REDUCE USE of NOS

♦ SIMPLIFY

♦ REDUCE ARTIFICIAL COMORIBIDITY

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ICD DSM

TANGO DANCE

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DSM-5 Current Timeline

♦ Sept. 2010-April 2011: Ongoing revisions to proposed DSM-5 diagnostic criteria, based on public comment and results from first phase of field trials

♦ July 2010-March 2011: DSM-5 Field Trials, Phase I

♦ June 2011-February 2012: DSM-5 Field Trials, Phase II

♦ July-August 2011: Revised draft diagnostic criteria posted on DSM5.org

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DSM-5 Current Timeline

♦ 2012: Prepare final draft text♦ 2012: Revised draft criteria released to APA

Assembly and Board of Trustees for final review♦ 2012: Final revisions to draft criteria♦ 2012: APA Assembly approval of DSM-5♦ 2012: APA Board of Trustees approval of DSM-5♦ 2013: Release of DSM-5 at the APA Annual

Meeting in San Francisco, Ca

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Select Proposals Schizophrenia & Related

Disorders

Replace current subtypes with dimensions

Include diagnosis of “ultra high-risk for psychosis”

Modify criteria for Schizoaffective Disorder

Delink catatonia from schizophrenia

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DSM-5♦ Risk Syndromes

Psychosis Risk Syndrome to identify individuals who may be in early stages of major psychotic disorder

Minor Neurocognitive Disorder to identify patients at risk for developing major neurocognitive disorder, such as dementia

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Should we introduce a “Psychosis Risk

Syndrome” in DSM-V and ICD-11

l PROSPROSn Will allow early targetting of illness to prevent deterioration Will allow early targetting of illness to prevent deterioration

and better outcomesand better outcomesn We have tools to better define such high-risk conditionsWe have tools to better define such high-risk conditions

l CONSCONSn What about the negative consequences of false positive What about the negative consequences of false positive

diagnosesdiagnoses

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Proposed APS CriteriaAll six of the following:

A.Characteristic symptoms: at least one of the following in attenuated form, with intact reality testing but of sufficient severity and/or frequency that it is not discounted or ignored;

i. Delusionsii. Hallucinationsiii. Disorganized speech

B.Frequency/Currency: symptoms meeting criterion A must be present in the past month and occur at an average frequency of at least once per week in the past month;

C.Progression: symptoms meeting criterion A must have begun in or significantly worsened in the past year;

D.Distress/Disability/Treatment Seeking: symptoms meeting criterion A are sufficiently distressing and disabling to the patient and/or parent/guardian to lead them to seek help;

E.Symptoms meeting criterion A are not better explained by any other DSM-5 diagnosis, including substance-related disorder;

F.Clinical criteria for any DSM-5 psychotic disorder have never been met.

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Ongoing Field TrialsUniversity of Toronto

Michael Bagby, MD. Comparisons: schizophrenia, schizoaffective,

schizotypal, avoidant, OCPD Academic diagnosticians Actively enrolling APS as of March 2011

University of Texas HSC at San Antonio Mauricio Tohen, MD. Comparisons: schizophrenia, bipolar, major

depression, other Academic diagnosticians No APS enrolled yet as of March 2011

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Should we introduce a “Psychosis Risk

Syndrome” in DSM-V and ICD-11

VIGOROUS DISCUSSION IS ONGOING

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The Example of Diabetes Mellitus

Impaired Fasting Glucose as a high-risk condition for development of Diabetes Mellitus

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Monitoring of Impaired Glucose: WHEN

Routine examinations

More Frequent Screening if”Family History of Diabetes Mellitus

Obesity

OTHER RISK CONDITIONS

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IF Impaired Fasting Glucose

What to Do

Education

More frequent monitoring

Treat comorbid conditions

Reduce risk factors (eg., obesity)

Increase protective factors(eg., exercise, diet)

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IF Impaired Fasting Glucose

What Not to Do

Start insulin

Start vigorous oral hypoglcemic treatment

Give dismal prognosis

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Parallels with Attenuated Psychosis

Syndrome

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Monitoring of Attenuated Psychosis

Syndrome: When

Routine examinations

More Frequent Screening if”Family History of Schizophrenia

Appearance of “soft psychotic symptoms”

WITH DECLINE IN FUNCTION

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Attenuated Psychosis Syndrome: What to DoEducation

More frequent monitoring

Treat comorbid conditions

Depression, Anxiety Disorders

Reduce risk factors

Substance abuse, Family stress

Increase protective factorsFamily environment, Structure, Social integration

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Attenuated Psychosis Syndrome: What Not to

Do

Start antipsychotic therapy

Give dismal prognosis

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Symptomatic

Functionally Impaired

Cognitively Impaired

Treatment Seeking

Reliable and Valid

No adequate DSM-IV alternative

Similar to MCI

Promotes treatment and prevention research

SUMMARY of PROs

Woods SW, et al. The case for including Attenuated Psychotic Symptoms Syndrome in DSM-5 as a psychosis risk syndrome. Schizophrenia Research 2010;123:199-207

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✖ Most patients don’t convert

✖ Some patients remit without treatment

✖ Promotes antipsychotic overprescription

✖ There’s no standard of care

✖ Stigma, insurance discrimination

✖ Just use comorbid diagnoses

✖ Stage I of psychosis is better

SUMMARY of CONs

Corcoran CM, et al. The psychosis risk syndrome and its proposed inclusion in DSM-V: A risk-benefit analysis. Schizophrenia Research 2010;120: 16-22

McGorry PM. Risk syndromes, clinical staging, and DSM V: New diagnostic infrastructure for early intervention in psychiatry. Schizophrenia Research 2010;120: 49-53

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DSM-IV or DSM-5? “Perfection is the enemy of good.”

-- Goethe

The abuse of a thing is no argument against the use of it. -- Jeremy Collier, 1698

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THANK YOU !

Questions?

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THREE ARS QUESTIONSRepeat

♦ Outcome ARS

♦ Treatment ARS

♦ Cognition ARS