IS THERE A SCHIZOPHRENIA /

BIPOLAR DISORDER BORDER?

Stability of Diagnosis in Affective and Non-

Affective PsychosesMauricio Tohen M.D., Dr.PH., M.B.A.

Professor and Chairman

Department of Psychiatry and Behavioral Sciences

University of New Mexico

Albuquerque New Mexico, USA

Dr. Tohen discloses that he has been a scienific consultant or has received funding from Abbott,

Lilly, AstraZeneca, BMS, GSK, Sunovion, Otsuka, Merck, J&J, Forest, Lundbeck, Roche, Teva,

Wyeth, Technopharma, Bakister Pharmaceuticals, Wiley Publishers, Elsevier, Atlas Foundation,

NIMH, and NARSAD.

He was a Lilly employee (1997-2008)

His spouse was a Lilly employee (1998-2013)

American Indian Reservation

NEW

Importance of establishing sound clinical diagnoses of major psychiatric disorders with both cross-sectional

coherence and stability over time has long been

recognized.()

Psychiatric diagnoses vulnerable to instability

over timeLack of biomarkers

Lack of sufficient informationUnreliability information

elicited only from patients

Symptom-modifying effects

Treatment or substance abuse, Comorbid medical disorders Effects of prolonged disability

or institutional care

Natural history that includes changes in clinical manifestations over time

Standard diagnostic schemes rely on arbitrary criteria

Is Diagnosis in psychosis/mania stable?

Stability of Diagnosis after First Episode Affective/Non-affective Psychosis & Mania

Is there a schizophrenia/bipolar disorder diagnostic border ?

McLean-Harvard First-Episode Project (n=500) P. Salvatore, R. J. Baldessarini, H-M. K. Khalsa, J. Perez Sanchez-Toledo, C.A. Zarate Jr., E. Vieta, C. Maggini, M. Tohen. J Clin Psych 2009

Why First-Episode Studies?

Avoid confoundingchronicitypsychotropic medication

McLean-Harvard First-Episode Project (n=500) P. Salvatore, R. J. Baldessarini, H-M. K. Khalsa, J. Perez Sanchez-Toledo, C.A. Zarate Jr., E. Vieta, C. Maggini, M. Tohen; . J Clin Psych 2009

Exclusion criteria: delirium, acute intoxication or withdrawal; prior hospitalization; current illness >6 months; prior antipsychotic (≥4 wks) or mood stabilizer (≥3 months)

Blinded-expert consensus SCID-P (intake+24 months)

DSM-IV +ICD-10 diagnoses

Completion rate: 500/517 (96.7%)

Characteristics of 500 first-episode DSM-IV psychotic disorder patients ———————————————————————————Characteristic Value———————————————————————————Subjects N (%) All cases 500 (100%) Men 275 (55.0%)Age at onset (yrs) 31.7 ± 13.7Comorbid Disorders

Substance use 256 (51.2%) Axis II personality 111 (22.2%) Anxiety 88 (17.6%)Initial DSM-IV Disorders (%)

Any Bipolar I 231 (46.2%) Bipolar I ( manic) 148 (29.6%) Bipolar I (mixed) 83 (16.6%) Major Depressive 77 (15.4%) Psychosis NOS 66 (13.2%) Schizophrenia 48 (9.6%) Brief Psychotic 36 (7.2%) Delusional 22 (4.4%) Schizophreniform 19 (3.8%) Schizoaffective 1 (0.2%)

0255075100% Diagnostic Stability (2 yrs) All Diagnoses (100%/100%) Schizoaffective (0.2%/9.6%)Schizophreniform (11.0%/1.4%)Psychosis NOS (13.2%/3.0%)Brief Psychosis (7.2%/9.6%)Major Depression (15.4%/10.8%)Delusional (4,4%/3.4%)Schizophrenia (9.6%/11.2%)Bipolar-I Mixed (16.6%/31.2%)Bipolar-I Manic (29.6%/19.8%)ICD-10DSM -IVInitial Diagnoses (prev.: DSM/ICD)All Diagnoses (100%/100%)Diagnostic Stability: 500 First-Episode Psychoses

0 25 50 75 100% Diagnostic Stability (2 yrs)

All Diagnoses (100%/100%)

Schizoaffective (0.2%/9.6%)

Schizophreniform (11.0%/1.4%)

Psychosis NOS (13.2%/3.0%)

Brief Psychosis (7.2%/9.6%)

Major Depression (15.4%/10.8%)

Delusional (4,4%/3.4%)

Schizophrenia (9.6%/11.2%)

Bipolar-I Mixed (16.6%/31.2%)

Bipolar-I Manic (29.6%/19.8%)

ICD-10

DSM -IV

Initial Diagnoses (prev.: DSM/ICD)

All Diagnoses (100%/100%)

Diagnostic Stability: 500 First-Episode Psychoses

[From Salvatore et al. 2008, 2009]

DSM-IV vs. ICD-10 diagnostic stability (%) —————————————————————————

DSM-IV ICD-10 Schizophrenia-like/Schizophreniform 10.5 26.8

Psychosis NOS 51.5 66.7

Acute or Brief 61.5 66.7

Major depression with psychosis 70.1 85.2

Delusional disorder 72.7 88.2

Schizophrenia 75.0 94.6

Bipolar disorder 96.5 96.5

Overall 77.6 90.4

Changed Initial Diagnoses (%) Schizophreniform 17/19 (89.5%) Psychosis NOS 32/66 (48.5%) Major Depressive 23/77 (42.9%) Brief Psychotic 14/36 (38.9%) Delusional 6/22 (27.3%) Schizophrenia 12/48 (25.0%) Bipolar I (mixed) 7/83 (8.4%) Bipolar I (manic) 1/148 (0.7%) Any Bipolar I 8/231 (3.5%) Schizoaffective 0/1 (0.0%)

Overall Diagnostic Stability 388/500 (77.6%)

Categorical outcomes of DSM-IV diagnoses during follow-up

————————————————————————New From From Categories Non-Affective Affective ————————————————————To affective 19.8% 51.6%

To non-affective 23.5% 3.2%

To schizoaffective 56.8% 45.2%

All changes 42.4% 10.1%

Stable diagnoses 57.6% 89.9%

Factors associated with Dx Instability ————————————————Factor OR (95% CI) P————————————————————————Non-affective disorder 5.59 [3.45–9.07] <0.0001Auditory hallucinations 2.05 [1.27–3.31] 0.003Younger at onset 1.03 [1.03–1.05] 0.022Male sex 1.64 [1.01–2.68] 0.045Gradual onset 1.80 [1.01–3.20] 0.046

Suffolk County shifts baseline to 10 years Bromet et al

•Schizophrenia 26% to 50%

•Bipolar 21% to 24%

•Major depression 17% to 11%

•Drug-induced psychosis 12% to 8

• Other psychoses group (psychosis NOS) 25% to 7%

•Many became SCZ, shifts occurred between all groups

•Baseline misclassified 43% (33% 6-mth 21% 24-month)

Suffolk County –Bromet et al.

Stability of diagnoses (kappa)Diagnostic group/Period SCZ BPD MDD

Drug Induced Other

Baseline to 10 Years 0.43 0.65 0.48 0.26 0.13

6 Months to 10 Years 0.57 0.66 0.53 0.46 0.20

24 Months to 10 Years 0.75 0.76 0.70 0.68 0.46

Suffolk County -Summary•BPD & Schizophrenia > stable Dx than delusional disorder or psychotic depression, and much more than brief, NOS or schizophreniform

•Diagnostic changes mainly involved new affective symptoms predicted by several premorbid factors.

Suffolk County -Summary

• ICD diagnoses consistently more stable than DSM, especially acute or brief psychotic, and schizophreniform syndromes.

•4 major levels of Dx stability: high (BPD); moderate (schizophrenia, psychotic depression, delusional); low (schizophreniform, NOS, brief); and schizoaffective

Suffolk County -Summary

•Findings need to be replicated

•Critical re-evaluation of DSM-IV schizophreniform, brief psychotic disorders and related concepts

Overall Conclusions

Dx Borders = Permeable at onset

Rx = Similar

Clinical Epidemiology = Scientific FoundationTextbook of Psychiatric Epidemiology 3rd Edition

EDITED BY MING T. TSUANG,

MAURICIO TOHEN AND PETER JONES

ISBN: 9780470694671

E-BOOK ISBN: 9780470976722

APRIL 2011

ORDER ONLINE AT WWW.WILEY.COM

Thanks Much For Your Attention!