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How To Recognize and Respond to Prodromal Psychosis. Rajiv Tandon University of Florida. OUTLINE OF PRESENTATION. WHY CURRENT EMPHASIS ON TOPIC DEFINING PRODROMAL PSYCHOSIS DSM-5 APPROACH IMPLICATIONS FOR PRACTICE. FIVE ARS QUESTIONS. 2 Introductory questions Outcome ARS Treatment ARS

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outline of presentation
OUTLINE OF PRESENTATION

WHY CURRENT EMPHASIS ON TOPIC

DEFINING PRODROMAL PSYCHOSIS

DSM-5 APPROACH

IMPLICATIONS FOR PRACTICE

five ars questions
FIVE ARS QUESTIONS

2 Introductory questions

Outcome ARS

Treatment ARS

Cognition ARS

slide4

Kraepelinian PESSIMISM of Dementia Praecox

The patient may never achieve restitutio ad integrum

IRREVERSIBLE DECLINE

DEMENCE

UNIFORMLY BAD OUTCOME

PROGRESSIVE DECLINE

slide5

Schizophrenia, Circa 1898

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

patients in mental institutions. A severely disabling and chronic illnessaffecting 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

Dementia

Praecox

slide7

Psychopathological Domains

Disorganization

Negative

Symptoms

Positive

Symptoms

Functional

lmpairment

Mood

Symptoms

Cognitive

Deficits

Motor symptoms

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

course of schizophrenia
Course of Schizophrenia

Good

Function

Stable

Relapsing

Psycho-

pathology

Premorbid

Progression

15

20

30

40

50

60

70

Age (Years)

slide9

New Findings: Stages & Dimensions of Illness

Disorganization

Positive

Symptoms

Negative

Symptoms

Functional

lmpairment

Mood

Symptoms

Cognitive

Deficits

Motor

Symptoms

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

slide10

An integrative model of schizophrenia.

Early developmental derailment

Peri-adolescent brain dysmaturation

Genetic

susceptibility

Post-illness onset deterioration

Normal development

Premorbid

deficits

The epigenetic

landscape

Environmental

factors

Psychotic

“break”

Relapses

Cognitive

deficits

Perceptual

distortions

Functional decline

Birth Adolescence Adulthood

prodromal psychosis
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

course of schizophrenia1
Course of Schizophrenia

Good

Function

Stable

Relapsing

Psycho-

pathology

Premorbid

Progression

15

20

30

40

50

60

70

Age (Years)

slide13

Phases of the schizophrenic illness.

Recovery

Premorbid

Prodromal

Transitional

Psychotic

slide14

Premorbid

Premorbid

Recovery

Prodromal

Transitional

Psychotic

Manifestations

Cognitive

Neuromotor

Behavioral

premorbid and prodromal schizophrenia how do we know
Premorbid and Prodromal Schizophrenia: How Do We Know?

Tracking Back

History of individuals who develop schizophrenia

Were there points of intervention?

premorbid and prodromal schizophrenia how do we know1
Premorbid and Prodromal Schizophrenia: How Do We Know?

“Unaffected Family Members”

1st and 2nd Degree Relatives

Do they manifest particular psychopathology?

slide17

Diagnoses Among HR relatives of Schizophrenia

(n=76)

Attention Deficit Disorder 20

Oppositional Defiant Disorder 11

Depression 10

Conduct Disorder 7

Anxiety Disorders 6

Bipolar Disorder 4

Adjustment Disorder 2

Substance use disorder 2

No diagnosis 26

Total adds up to >76 because of comorbid disorders in some subject

5 patients developed a psychotic disorder ( not included above)

slide18

Premorbid

Premorbid

Recovery

Prodromal

Transitional

Psychotic

Window of opportunity for

Early recognition and

Primary prevention?

slide19

Premorbid

Recovery

Transitional

Prodromal

Psychotic

Manifestations

Cognitive decline

Affective dysregulation

Social withdrawal

Educational decline

Subthreshold positive

& negative Symptoms

slide20

New Findings: Stages & Dimensions of Illness

Disorganization

Positive

Symptoms

Negative

Symptoms

Functional

lmpairment

Mood

Symptoms

Cognitive

Deficits

Motor

Symptoms

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

slide21

J. H

Childhood: Attention problems

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.

slide22

High school-Social withdrawal

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.   

slide23

College: Educational decline

Age 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

slide24

Beginning symptoms: Mood

Age 19 “anxiety attack” led him to see a doctor who

tested 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

slide25

The Breaking point and Missed Opportunities

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

course of schizophrenia2
Course of Schizophrenia

Good

Function

Psycho-

pathology

Stable

Relapsing

Premorbid

Progression

Poor

15

20

30

40

50

60

70

Age (Years)

slide28

Pathophysiology of schizophrenia may involve a cascade of

Sequential, cumulative events

Early developmental derailment

Genetic

susceptibility

Peri-adolescent brain dysmaturation

Post-illness onset neurodeteriorationh

Normal development

The epigenetic

landscape

Premorbid

deficits

Prodrome”

Environmental

Factors

Family environment

Drugs of abuse

Stress

Psychosis

functional decline

Dopaminergic

dysregulation

Glutamatergic/

GABA

abnormality

Neurochemical

Sensitization

Oxidative stress

Birth Adolescence Adulthood

slide29

Attenuated positive syndrome

Brief Intermittent psychosis

Family history+ decline

prediction of psychosis in youth at high clinical risk
Prediction of Psychosis in Youth at High Clinical Risk

OUTCOMES

Risk of conversion 35% during f/u period

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

Controls

Prodromal patients

1.00

0.75

0.50

0.25

0

Survival Distribution Function

0 200 400 600 800 1000

Days Since Baseline Assessment

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).

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

dsm 5 revision principles clinical utility validity reliability
DSM-5 Revision PrinciplesClinical 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

dsm 5 current timeline
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

dsm 5 current timeline1
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

select proposals schizophrenia related disorders
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

dsm 5
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

should we introduce a psychosis risk syndrome in dsm v and icd 11
Should we introduce a “Psychosis Risk Syndrome” in DSM-V and ICD-11
  • PROS
    • Will allow early targetting of illness to prevent deterioration and better outcomes
    • We have tools to better define such high-risk conditions
  • CONS
    • What about the negative consequences of false positive diagnoses
proposed aps criteria
Proposed APS Criteria
  • All six of the following:
  • 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;
    • Delusions
    • Hallucinations
    • Disorganized speech
  • 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;
  • Progression: symptoms meeting criterion A must have begun in or significantly worsened in the past year;
  • 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;
  • Symptoms meeting criterion A are not better explained by any other DSM-5 diagnosis, including substance-related disorder;
  • Clinical criteria for any DSM-5 psychotic disorder have never been met.
ongoing field trials
Ongoing Field Trials
  • University 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
should we introduce a psychosis risk syndrome in dsm v and icd 111
Should we introduce a “Psychosis Risk Syndrome” in DSM-V and ICD-11

VIGOROUS DISCUSSION IS ONGOING

the example of diabetes mellitus
The Example of Diabetes Mellitus

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

monitoring of impaired glucose when
Monitoring of Impaired Glucose: WHEN

Routine examinations

More Frequent Screening if”

Family History of Diabetes Mellitus

Obesity

OTHER RISK CONDITIONS

if impaired fasting glucose what to do
IF Impaired Fasting GlucoseWhat to Do

Education

More frequent monitoring

Treat comorbid conditions

Reduce risk factors (eg., obesity)

Increase protective factors

(eg., exercise, diet)

if impaired fasting glucose what not to do
IF Impaired Fasting GlucoseWhat Not to Do

Start insulin

Start vigorous oral hypoglcemic treatment

Give dismal prognosis

monitoring of attenuated psychosis syndrome when
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

attenuated psychosis syndrome what to do
Attenuated Psychosis Syndrome: What to Do

Education

More frequent monitoring

Treat comorbid conditions

Depression, Anxiety Disorders

Reduce risk factors

Substance abuse, Family stress

Increase protective factors

Family environment, Structure, Social integration

attenuated psychosis syndrome what not to do
Attenuated Psychosis Syndrome: What Not to Do

Start antipsychotic therapy

Give dismal prognosis

slide50

SUMMARY of PROs

Symptomatic

Functionally Impaired

Cognitively Impaired

Treatment Seeking

Reliable and Valid

No adequate DSM-IV alternative

Similar to MCI

Promotes treatment and prevention research

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

slide51

SUMMARY of CONs

✖ 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

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

dsm iv or dsm 5
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

slide53
THANK YOU !

Questions?

three ars questions repeat
THREE ARS QUESTIONSRepeat

Outcome ARS

Treatment ARS

Cognition ARS