Psychosis Diagnoses in DSM-5: Debates and Changes

Jonathan M. Meyer, M.D. Asst. Clinical Professor of Psychiatry - UCSD Assoc. Clinical Professor of Psychiatry - Loma Linda University

DSM-5 Copyright
DSM-5 is a registered trademark, and all content, whether in final or proposed form, is protected by copyright held by the APA. All rights are reserved, and written permission is required from the APA for use in any way, commercial or noncommercial. Permission is not granted for use of the DSM-5 trademark.

Objectives
To review the DSM-5 changes to schizophrenia and schizoaffective disorder diagnoses To review in detail issues related to the possible inclusion of an attenuated psychosis syndrome diagnosis and dimensional ratings of symptoms

Psychosis Work Group Members

William Carpenter Deanna Barch Juan Bustillo Wolfgang Gaebel Raquel Gur Stephan Heckers Liaisons J. Raymond DePaulo Larry Siever Judith Rapoport Dolores Malaspina Michael Owen Susan Schultz Rajiv Tandon Ming Tsuang Jim van Os

Background

What Have We Learned

Schizophrenia is a multidimensional illness that extends beyond the positive/negative symptom domains
Cognitive deficits are a core feature, with greatest impact on working memory, processing speed Neurophysiological abnormalities are a common element when measured in the laboratory, including dysfunction in:
Mismatch negativity paradigms Prepulse inhibition Antisaccadic eye movements

These findings have propelled the search for genetic and imaging biomarkers predictive of:
Risk for developing schizophrenia in prodromal individuals Treatment response and adverse effects

Why Do We Persist With Clinical Criteria

Thomas Insel, MD, Director of NIMH, laments in his April 29, 2013 blog:
The weakness [of DSM] is its lack of validity. Unlike our

definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure.

The reality: neither imaging, genetic or other biomarkers (e.g. proteomics, lipidomics, skin testing) have reliably demonstrated sufficient predictive ability to be useful in the diagnosis, classification, or treatment guidance for most disorders.

What Proposed Changes Were Not Included?

The Attenuated Psychosis Syndrome

Extensive research over the past 20 years has helped identify individuals at ultra high risk for conversion to schizophrenia. High risk groups include those with:
Attenuated Psychotic Symptoms (APS) subthreshold, attenuated forms of positive psychotic symptoms during the past year Brief Limited Intermittent Psychotic Symptoms (BLIPS) episodes of frank psychotic symptoms that have not lasted longer than a week and have spontaneously abated Trait and State Risk Factor (Trait) first-degree relative with a psychotic disorder or who have a schizotypal personality disorder in addition to a significant decrease in functioning during the previous year.

Nelson et al. Ultra high risk (UHR) for psychosis criteria: Are there different levels of risk for transition to psychosis? Schiz Res 2011; 125(1): 62-8.

Summary of APS Proposed Criteria

Attenuated psychotic symptoms severe enough to cause distress or functional impairment but relatively intact reality testing Symptoms present at least one time per week over the past month and either started or worsened in the past year. Not better explained by another mental disorder, and have never met criteria for any psychosis.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

The Attenuated Psychosis Syndrome: Arguments in Favor of Diagnosis

Patients with APS are symptomatic, with evidence of functional and neurocognitive impairment APS is reliably and validly diagnosable with instruments developed for this purpose
The North American Prodrome Longitudinal Study (NAPLS) published data indicating the APS subjects were robustly distinguished from normal controls, help-seeking comparison subjects and familial high risk subjects on most measures.

Individuals with APS are at risk for clinical worsening No DSM-IV diagnosis adequately captures this group

Woods SW, et al. Validity of the Prodromal Risk Syndrome for First Psychosis: Findings From the North American Prodrome Longitudinal Study. Schiz Bull 2009; 35(5): 894-908.

NAPLS Outcomes

Woods SW, et al. Validity of the Prodromal Risk Syndrome for First Psychosis: Findings From the North American Prodrome Longitudinal Study. Schiz Bull 2009; 35(5): 894-908.

APS - The Concerns

Definitions of symptoms are varied, complex, and not solidly validated for routine clinical use Risk will be treated as an illness
Use of term prodromal is inaccurate and implies an inevitability There are various levels of risk, some of which may be quite low

Low conversion rates to schizophrenia and poor application of high risk criteria may generate high false positive rates in clinical practice
Research rates of accuracy are 25-35% in enriched populations, probably much lower in more genl psychiatric populations Incidence of schizophrenia is 1/10,000, meaning that most clinicians will never see a patient who converts to schizophrenia (high false pos rate) False positives: possible stigma and unnecessary treatment

McGorry PD, et al. Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: twelve-month outcome. J Clin Psych 2013; 74(4): 349-56

APS - Treatment Uncertainty

Concern: The treatment of APS is unproven, including the actual form of best treatment and timing of possible treatment options based upon the developmental stage, actual level of risk and current symptoms

Latest Data: 12-month double-blind, randomized trial (n=115) of

CBT + placebo: 9.6% CBT + risp: STx + placebo: 10.7% 21.8%

CBT + low dose risperidone, CBT + placebo, supportive therapy + placebo. Estimated 12-month transition rates:

Nonrandomized comparison group: 8.7% Due to drop outs (40/115), no statistical separation in transition rates between the groups.
McGorry PD, et al. Randomized controlled trial of interventions for young people at ultra-high risk of psychosis: twelve-month outcome. J Clin Psych 2013 April; 74(4): 349-56

The Dimensional Debate-Concepts

1. The categorical diagnosis of schizophrenia is clinically useful and quite stable over time; however, categorical diagnosis has several limitations:
It fails to capture the heterogeneity of schizophrenia In particular, categorical diagnosis is inadequately informative regarding what is wrong with individual patients As seen from research with ultra high risk patients, psychotic symptoms lie on a continuum with normal, as opposed to a yes/no approach to chronic psychosis.

2.

Psychopathology domains can easily be rated as dimensions and capture information critical for individualized treatment decisions.
Dimensional ratings can describe patients with varying symptom levels without the burden of having to place a patient in a poorly defined categorical box.

David AS. Why we need more debate on whether psychotic symptoms lie on a continuum with normality. Psychol Med 2010; 40(12): 1935-42

The Dimensional Approach to Schizophrenia - Goals

1. 2. 3. 4. 5. 6. 7. 8. 9. Better understanding of schizophrenia Distinct dimensions of illness Distinct stages of illness Elucidation of neurobiology More precise delineation of etiology More refined treatment development Direction at specific dimension-endophenotype Stage-specific treatment Novel treatment targets

Tandon R. Getting ready for DSM-5: Psychotic disorders. Current Psychiatry 2012; 11(4): E1-4

The Dimensional Debate-Concerns

1. There are too many pathologically distinct pathways to psychosis to develop a workable concept about the continuum between normal and psychotic The categorical vs. dimensional approach may be a false dichotomy: the more useful approach is likely to be a dimensionally enhanced categorical diagnosis:
Example: A diagnosis of schizophrenia would include ratings for the following components: Thought disorganization, hallucinations/delusions Affective Sx Negative Sx and cognitive deficits Violence/aggression

2.

Conclusions: the validity of dimensional vs categorical approaches to psychiatric diagnosis is not ultimately solvable until we get a firmer grip on the nature of the disorders with which we are confronted. (John Strauss, Yale)
Lawrie SM, et al. The 'continuum of psychosis': scientifically unproven and clinically impractical. Br J Psychiatry 2010; 197:423-5.

DSM-5 Suggested Dimensional Assessment for Schizophrenia

Not used for diagnosis, but to track ongoing progress Eight dimensions assessed on a 0-4 scale cross-sectionally, with severity assessment based on the past 7 days:
0 = None 1 = Equivocal 2 = Mild 3 = Moderate 4 = Severe

Items included: hallucinations, delusions, disorganized speech, psychomotor behavior, negative symptoms, impaired cognition, depression and mania

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

The New Criteria: Schizophrenia

Simplification of A Criterion
DSM-IV: A. Characteristic symptoms: Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated): (1) delusions (2) hallucinations (3) disorganized speech (e.g., frequent derailment or incoherence) (4) grossly disorganized or catatonic behavior (5) negative symptoms, i.e., affective flattening, alogia, or avolition Note: Only one Criterion A symptom is required if delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the person's behavior or thoughts, or two or more voices conversing with each other.

Summary of New A Criterion

1. Requirement for having at least one of the symptoms numbered 1-3 below 1. Delusions 2. Hallucinations 3. Disorganized speech 4. Grossly disorganized or catatonic behavior 5. Negative symptoms (diminished emotional expression or avolition) 2. Removed language regarding bizarreness of delusions or the number voices and what they say to each other or to the individual

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

B Criterion - No Major Change

The language regarding the extent and definitions of social/occupational dysfunction remains nearly identical.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

Debate Over Duration: Benefits of Removing 6 Month Requirement for Diagnosis

1. Greater clarity in the diagnosis of schizophrenia, fewer confusing diagnostic categories in the DSM used for the diagnosis of schizophrenia-like symptoms before the six month durational requirement is met, such as Schizophreniform Disorder and Brief Psychosis. Potential improvements in the ability to diagnose schizophrenia rapidly and therefore commence treatment on a timely basis. Growing evidence that quick and early onset of treatment for schizophrenia impacts positively on the long term course of treatment and reduces disruptions in life and adverse consequences such as hospitalizations or criminal justice involvement. Behaviors associated with untreated schizophrenia may paradoxically reinforce broad based stigma towards anyone given this diagnosis. Timely treatment is the best way to achieve positive outcomes and thereby reduce stigma and prejudice.

2. 3.

4.

NAMI Comments on the APAs Draft Revision of the DSM-5 Schizophrenia

Debate Over Duration: Risks of Eliminating the 6 Month Requirement

1. Risk of false positives, i.e. diagnosing someone with schizophrenia who turns out not to have it. (Unlike with risk syndrome, we are not aware of any studies that have been done on this). Risks of stigma and discrimination associated with a diagnosis of schizophrenia. Unfortunately, a diagnosis of schizophrenia still carries with it the potential for adverse consequences, including discrimination in insurance, employment, housing and other aspects of life. A diagnosis of schizophrenia can impact extremely negatively on a persons self image at a crucial time in his or her development toward adulthood.

2.

3.

NAMI Comments on the APAs Draft Revision of the DSM-5 Schizophrenia

Summary of C Criterion - No Change

Duration: Continuous signs of the illness for at least 6 months with at least one month of active phase symptoms (or less if treated). You can count residual or prodromal symptoms as part of the 6 month total illness duration.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

D Criterion - Minor Change

1. No change in the absence of concurrent depressive of manic symptoms at the same time as the active psychotic symptoms OR 2. If mood symptoms have occurred they are a minority of the total illness duration

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

E Criterion - No Major Change

Not attributable to drugs or medications or to other medical conditions.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

F Criterion - No Major Change

Relationship to a Pervasive Developmental Disorder: Refined the language to state that there needs to be prominent hallucinations or delusions in those with autism spectrum diagnoses for at least one month, plus the other schizophrenia criteria.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

Debate Over Subtypes

1. Rarely useful in clinical practice to inform treatment
Often inaccurately applied Low temporal stability Only paranoid and undifferentiated types commonly used

2. Biomarker studies have failed to provide reliable distinguishing characteristics to separate the subtype entities 3. Subtypes are not predictive of course, treatment response or outcome
Tandon R. Getting ready for DSM-5: Psychotic disorders. Current Psychiatry 2012; 11(4): E1-4

Schizophrenia Subtypes in the Literature

Evidence-based treatment guidelines, such as the Schizophrenia Patient Outcomes Research Team (PORT) project, do not rely on subtype designations. Review of published articles over the last 20 years (1990, 2000, 2010) shows that the use of traditional subtypes has fallen from 27.7% to 9.8% to 6.5%.

Braff D, et al. Lack of Use in the Literature From the Last 20 Years supports Dropping Traditional Schizophrenia Subtypes From DSM-5 and ICD-11 Schiz Bull 2013, in press (doi:10.1093/schbul/sbt068)

Subtypes are Gone!

DSM-IV: 295.30 295.10 295.20 295.90 Paranoid Type Disorganized Type Catatonic Type Undifferentiated Type

295.60 Residual Type DSM-5: No subtypes! Specifier: Catatonia will be used as a specifier for various psychotic disorders, major mood disorders and when associated with a general medical condition.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

Course Specifiers: DSM-IV

These specifiers can be applied only after at least 1 year has elapsed since the initial onset of active-phase symptoms: Episodic With Interepisode Residual Symptoms: This specifier applies when the course is characterized by episodes in which Criterion A for Schizophrenia is met and there are clinically significant residual symptoms between the episodes. With Prominent Negative Symptoms can be added if prominent negative symptoms are present during these residual periods. Episodic With No Interepisode Residual Symptoms: This specifier applies when the course is characterized by episodes in which Criterion A for Schizophrenia is met and there are no clinically significant residual symptoms between the episodes Continuous: This specifier applies when characteristic symptoms of Criterion A are met throughout all (or most) of the course. With Prominent Negative Symptoms can be added if prominent negative symptoms are also present. Single Episode In Partial Remission: This specifier applies when there has been a single episode in which Criterion A for Schizophrenia is met and some clinically significant residual symptoms remain. With Prominent Negative Symptoms can be added if these residual symptoms include prominent negative symptoms. Single Episode In Full Remission: This specifier applies when there has been a single episode in which Criterion A for Schizophrenia has been met and no clinically significant residual symptoms remain. Other or Unspecified Pattern: This specifier is used if another or an unspecified course pattern has been present.

Course Specifiers: DSM-5

First Episode:
Currently in acute episode Currently in partial remission Currently in full remission

Multiple Episodes:
Currently in acute episode Currently in partial remission Currently in full remission

Continuous Unspecified

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

The New Criteria: Schizoaffective Disorder

Schizoaffective Disorder: The Issues

1. Poor reliability in diagnosis due to disagreement among evaluators on estimates of mood episode duration relative to the psychosis Low temporal stability of the SAD diagnosis in 6- and 24-month follow-up studies Questionable clinical utility when SAD diagnosis given at hospital discharge
SAD diagnosis rarely confirmed using subsequent structured interviews (0/59 in one study)

2. 3.

Heckers S. Is Schizoaffective Disorder a Useful Diagnosis? Curr Psych Reports 2009; 11: 332-37

The ABC Longitudinal Study

232 1st-episode schizophrenia patients in Germany enrolled 1987-89 and followed up to 12 years
107 had follow-up data after mean 136 months

an der Heiden W, et al. Eur Arch Psychiatry Clin Neurosci 2005; 255: 174-84

Schizoaffective Disorder: Suggested Changes

1. Wording changes proposed to improve clarity and reliability. Examples:
Terms such as prominent mood symptoms and substantial portion would be provided exact definitions

2. OR scrap the diagnosis completely in lieu of:

Schizophrenia + affective disorder Bipolar (or MDD) + psychotic symptoms Categorical and dimensional specifiers would be needed to distinguish these entities.

Heckers S. Is Schizoaffective Disorder a Useful Diagnosis? Curr Psych Reports 2009; 11: 332-37

Summary of Schizoaffective Disorder: A, B and C Criteria

A. As before one must have a major depressive or manic episode together with the A criteria of schizophrenia. B. Hallucinations or delusions must persist for at least 2 weeks in the absence of major mood symptoms at some point. C. The mood symptoms have to be present for the majority of the total illness. (Note majority is not defined.)

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

Schizoaffective Disorder: Subtypes and Specifiers

Subtypes Bipolar type Depressive type Specifier With catatonia Course Specifiers Same as schizophrenia

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

The New Criteria: Other Psychotic Disorders

Brief Psychotic Disorder and Schizophreniform Disorder

a. Brief Psychotic Disorder: Sx at least 1 day but < 1 month. No major changes. Added catatonia specifier. b. Schizophreniform Disorder: Sx at least 1 month (or less if successfully treated) but < 6 months. No major changes aside from those consistent with meeting the revised schizophrenia Criterion A. Added catatonia specifier.

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

Substance-Induced Psychoses
Clarified distinction between substanceinduced psychotic disorder and other psychotic disorders accompanied by comorbid substance use by rewording the C criterion to mandate that other possible cause for the psychosis do not exist. DSM-5 provides examples of scenarios to suggest an independent psychotic disorder including psychosis that persists for more than a month after substance exposure, and psychosis that was documented before using substances.
Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

Delusional Disorders
1. Deleted shared delusional disorder (folie deux) as a separate subtype
Unspecified type covers this and other delusional disorders that are not erotomanic, grandiose, persecutory, jealous or somatic

2. May have specifier of bizarre content 3. Course specifiers same as schizophrenia

Reprinted with permission from the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, (Copyright 2013). American Psychiatric Association. All rights reserved.

Criteria Performance
Kappa Ranges (statistical measure of agreement between 2 raters that adjusts for chance agreement): Very good (kappa 0.600.79): only 3 diagnoses in this group: PTSD, complex somatic symptom disorder and major neurocognitive disorder Good (kappa 0.400.59): 7 diagnoses in this group including schizophrenia and schizoaffective disorder Poor (kappa 0.20-0.39): 4 diagnoses in this group (MDD, GAD, ASPD and mild TBI)

Regier DA, et al. DSM-5 Field Trials in the United States and Canada, Part II: Test-Retest Reliability of Selected Categorical Diagnoses. Am J Psych 2013; 170:5970

Criteria Performance

Regier DA, et al. DSM-5 Field Trials in the United States and Canada, Part II: Test-Retest Reliability of Selected Categorical Diagnoses. Am J Psych 2013; 170:5970

Conclusions
Changes are modest and generally improve clarity and remove excessive verbiage or subtypes. The drive to use dimensional ratings of psychosis severity is reinforced, and DSM-5 provides an 8 item list in the appendix. High risk patients do not have their own diagnosis, and the rationale appears sound for the time being to not assigning a diagnosis for a group that may never meet criteria for a chronic mental illness. Some day we may have biomarkers as useful aspects of diagnosis, but not yet . . . .