Program Outline. DSM-5 Schizophrenia Spectrum and Psychotic Disorders: Knowing it Better and Improving Clinical Practice.

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DSM-5 Spectrum and Disorders: Knowing it Better and Improving Clinical Practice Rajiv Tandon, MD Professor of Psychiatry University of Florida College of Medicine Gainesville, Florida Program Outline Changes from DSM-IV made in DSM-5 section on Disorders Conceptual Criteria Relationship of DSM-5 to RDoC with specific reference to psychotic disorders Clinical implications of changes in definitions of psychotic disorders in DSM-5 Diagnosis Treatment RDoC = Research Domain Criteria. Tandon R, et al. Psychiatr Clin North Am. 2012;35(3):557-569. Tandon R, et al. Die Psychiatrie. 2013;10:5-9. Overall Changes Removal of Multi-axial System Changes in Overall Structure Addition of Section 3 Section 2: 20 sections organized to describe interrelationship Diagnosis is a 3-step process Diagnosis Specifiers Severity Removal of Multi-axial System Move to a non-axial documentation of diagnosis Combines Axes 1 3 Psychosocial and contextual factors (formerly Axis 4) captured via Z codes in ICD-10 or in narrative Disability (formerly Axis 5) now described separately via WHODAS 2.0 and/or in narrative Partly replaced by addition of severity measures to diagnostic categories WHODAS 2.0 = World Health Organization Disability Assessment Schedule 2.0. Section II Definition and Description of Disorders DIAGNOSIS INVOLVES 3 STEPS 1st Level: Diagnose Disorder using Criteria Conceptual Development of DSM DSM-I 1952 Psychodynamic Functional Organic DSM-II 1968 DSM-III, 1980 Emphasis on Reliability Operational Criteria Multi-axial system Axis 1 vs 2 vs 3 2nd Level: Describe specific nature of disorder using Specifiers 3rd Level: Describe current severity of disorder utilizing simple and clinically useful Scales DSM-5 2013 Dimensional Utility Living document Validity DSM-IV 1994 Requires clinically significant distress or impairment DSM-III-R 1987 Most hierarchies dropped

Concept Author Historical Influences Timeframe Evolution of Concept of *Focus on validity *Existing treatments Neurodegenerative *Psycho-biology *Divergence between *Focus on found to be less *Minor disease model Adolf Meyer ICD & DSM systems reliability diagnostically specific Changes *Psychoanalytic Schneider vs Bleuler *Side effects of *Genetic & other neurobiological data *DSM-ICD model *Advent of effective antipsychotics Convergence *Expanding antipsychotic agents *Advent of lithium suggest blurred neurodiagnostic * International Pilot *Response to Dx-ic boundaries methods Study of Cooper Study *How to explain Hecker, heterogeneity? Kahlbaum, Greisinger Kraepelin Bleuler Schneider DSM-I DSM-II DSM-III DSM-IIIR & DSM-IV DSM-5 & beyond Morel ICD-1 ICD-6 7 ICD-8 ICD-9 ICD-10 ICD-11 & beyond Many psychoses vs Unitary psychosis Dementia Praecox Manic Depressive Insanity Secondary s eg, Pellagra, Encephalitis Lethargica Schizophrenic Reaction Broad Concept (latent, Pseudoneurotic, etc.) Very Narrow concept Mildly broadened / Psychosis concept Toward Deconstructing OR Psychosis: Dimensions & Intermediate Phenotypes Tandon R, et al. Schizophr Res. 2009;110(1-3):1-23. Disorders in DSM-5 Eliminate current subtypes of schizophrenia Add dimensional measures to assessment Modify criteria for Schizoaffective Disorder Treat catatonia uniformly across the manual Attenuated Psychosis Syndrome as condition for further study Definition of Psychosis Core Features Delusions Hallucinations Disorganized speech (thought disorder) Accompanying Features Catatonia Disorganized behavior Negative Cognitive deficits Subtypes in DSM-5 ELIMINATE SUBTYPES No long-term stability No diagnostic utility No research utility Poor reliability and validity INTRODUCE DIMENSIONS (to be rated on 0 4 scale) Reality distortion (delusions, hallucinations) Negative Disorganization Impaired cognition Depression Mania Psychomotor, including catatonia Tandon R, et al. Schizophr Res. 2013;150(1):3-10. Dimensions of Diagnosis-Specific Severity Assessment: Symptom Domains Disorganization Cognitive deficits Negative Different underlying Pathophysiology and treatment response Positive Motor Hallucinations Delusions Disorganized Speech Abnormal Psychomotor Behavior (catatonia) Negative Symptoms Impaired Cognition Depression Mania 0 = Not Present 1 = Equivocal 2 = Present, but mild 3 = Present and moderate 4 = Present and severe Tandon R, et al. Schizophr Res. 2009;110(1-3):1-23. Barch DM, et al. Schizophr Res. 2013;150(1):15-20.

Clinical Application Dimensions of Disorders Precision in measurement-based care Specific targeting of distinct dimensions of schizophrenia and other psychotic disorders Individualizing treatment with more precise responsebased treatment adjustments Schizoaffective Disorder in DSM-IV-TR Poor reliability Poor validity Low diagnostic stability Low utility Tandon R, et al. Schizophr Res. 2013;150(1):3-10. Malaspina D, et al. Schizophr Res. 2013;150(1):21-25. Disorder with Features Psychosis with Superimposed Disorder Schizoaffective Disorder Tandon R, et al. Asian J Psychiatr. 2008;1(2):22-27. DSM-IV-TR Criteria Schizoaffective Disorder A. Uninterrupted period of illness during which there is a major mood episode [major depressive, manic, or mixed] concurrent with criterion A of schizophrenia B. Delusions and hallucinations for 2 weeks in absence of prominent mood C. Symptoms that meet criteria for a major mood episode are present for a substantial portion of the total duration of the active and residual portion of the illness D. Disturbance not due to direct physiological effects of a substance or a general medical condition DSM-5 Criteria Schizoaffective Disorder A. An uninterrupted period of illness during which there is a major mood disorder (major depressive or manic) concurrent with Criterion A of schizophrenia B. Delusions and/or hallucinations are present at least for 2 weeks in the absence of a major mood episode during the lifetime duration of the illness C. A major mood episode is present for the majority of the total duration of the illness. (Note periods of successfully treated mood count towards the cumulative duration of the major mood episode) D. No Change Malaspina D, et al. Schizophr Res. 2013;150(1):21-25. Clinical Implications of Diagnosing Schizoaffective Disorder in DSM-5 More homogeneous category Reduction in diagnosis of schizoaffective disorder with more precise implications Significant mood with associated features Likely need for mood stabilizers or antidepressants Intermediate course between schizophrenia and mood disorders in schizophrenia will be picked up by dimensional assessments Improved clinical utility and reliability Natural Course of Premorbid Prodromal Active Remission Residual stage phase phase phase phase AGE 10 15 17 20 25 Disease onset First treatment Undetected/Untreated Illness Malaspina D, et al. Schizophr Res. 2013;150(1):21-25. Hales RE, et al (Eds). The American Psychiatric Publishing Textbook of Psychiatry. Fifth Edition. Arlington, VA: American Psychiatric Publishing; 2008.

Deterioration at Several Stages of Illness Opportunities to Prevent or Arrest Decline Genetic Susceptibility Environmental Factors Viruses Drugs of abuse Stress Obstetric complications Glutamatergic/ GABA abnormality Early developmental derailment Peri-adolescent brain dysmaturation Post-illness onset neurodeterioration Premorbid Deficits Prodrome Dopaminergic Dysregulation Normal development The Epigenetic Landscape Neurochemical Sensitization Oxidative stress Birth Adolescence Adulthood Functional Decline Keshavan MS, et al. Schizophr Res. 2008;106(2-3):89-107. Attenuated Psychosis Syndrome Characteristic : at least 1 of the following in attenuated form with intact reality testing, but of sufficient severity and/or frequency to be beyond normal variation: Delusions Hallucinations Disorganized speech Present in past month Occur at least once per week Begun or worsened in past year Distressing or significantly impact function Not caused by another disorder (eg, PTSD) Never met criteria for a psychotic disorder PTSD = posttraumatic stress disorder. Tsuang MT, et al. Schizophr Res. 2013;150(1):31-35. Diagnosis at 1 Year Follow-Up for Patients with Attenuated Psychosis Syndrome 25% No axis 1 diagnosis 40% Major depression, social phobia, OCD, adjustment, substance abuse OCD = obsessive-compulsive disorder. Woods SW, et al. Schizophr Bull. 2009;35(5):894-908. 35% disorder What Clinicians Should Do? 300-fold greater likelihood of developing a psychotic disorder over the next year (30% vs 0.1%) Monitor closely Detect transition early Reduce period of untreated psychosis Aggressively treat comorbidities Depression Anxiety disorders Substance use disorders DO NOT ROUTINELY USE ANTIPSYCHOTICS Consider family therapy, Omega-3 fatty acids, CBT, etc. CBT = cognitive-behavioral therapy. Tsuang MT, et al. Schizophr Res. 2013;150(1):31-35. Reasons for Change from Descriptive to Etio-Pathophysiological Classification Few therapeutic advances in past 50 years Descriptive psychiatric diagnosis has challenges Etio-pathophysiologic understanding of psychiatric disorders remains limited Psychiatric disorders do not precisely map on to biology Remainder of medicine has moved towards an etiopathologic classification of disease Insel T, et al. Am J Psychiatry. 2010;167(7):748-751. NIMH RDoC Initiative Develop new ways of classifying mental disorders based on neurobiological measures and dimensions of observable behavior Identify fundamental components that span multiple disorders (affect regulation, executive function, etc.) Develop reliable and valid measures of these fundamental components for use in basic and clinical settings Integrate genetic, neurobiological, behavioral, environmental, and experiential components NIMH = National Institute of Mental Health. Insel T, et al. Am J Psychiatry. 2010;167(7):748-751.

RDoC: Candidate Domains/Constructs and Units of Analysis (v. 2.1) NIMH RDoC Initiative Challenges Still mainly conceptual and NOT practical implementable reality Fundamental components of mental behavior are not defined Reliable and valid measures of all these components have not been developed There are constructs and measures that kind of map on to the negative, mood, and cognitive dimensions of schizophrenic illness No good construct/measure that maps on to positive of schizophrenia Insel T, et al. Am J Psychiatry. 2010;167(7):748-751. Defining Psychiatric Disorders: The Complementary Nature of DSM-5 and RDoC ETIOLOGY Risk Factors Protective Factors Modifiers + Interactions Between CONCEPT DISORDER CRITERIA PATHOPHYSIOLOGY Structural, Functional, and Neurochemical Abnormalities Pathogenesis Pathoplastic and Treatment Effects DESCRIPTION What It Is What It Is Not How do we diagnose DEFINING A DISORDER AND KNOWING WHAT IT IS Rapidly Multiplying Information & Increasing Knowledge Descriptive Psychiatric Diagnosis DSM-5 Don t Throw the Baby with the Bathwater We have nothing to replace descriptive psychiatric diagnosis with currently But our practice of descriptive psychiatric diagnosis must improve Recognize diagnostic categories as syndromes (NOT diseases), and availability of clinical/research utility Tandon R, et al. Schizophr Res. 2008;100(1-3):4-19. Descriptive Psychiatric Diagnosis is Still Needed Basis of psychiatric practice around the world Clinical utility of most diagnoses moderate high Of value in treatment selection, prognostication of course/outcome Does partly map onto biology Emerging genetic and brain imaging finding Descriptive Psychiatric Diagnosis is Improving We are learning from our mistakes Over-emphasis on reliability (beginning with DSM-III and ICD-10) is recognized and validity is prioritized in DSM-5 and ICD-11 Recognizing dimensional aspects of psychopathology, dimensional measures incorporated in most DSM-5 diagnostic categories Better methods in DSM-5 to meaningfully address heterogeneity Biological markers now incorporated in 2 groups of psychiatric disorders (sleep and MNCD) MNCD = mild neurocognitive disorder.

Is Still a Useful Diagnosis? Why Do We Diagnose? To enable clinician to provide specific treatment whose effects are predictable and precise To enable researchers to better define the nature of disorders To enable patients and their families to efficiently obtain effective help and know what to expect MY RECOMMENDATION Understand DSM-5 Its structure [Some Important Changes!!!] Its content [Areas of major and minor change] Use it rigorously In context of your practice In cultural and situational context Document and report limitations in its application Changes in Definition of Disorders from DSM-IV to DSM-5 Concept Definition Relationship between different disorders Dimensions of psychosis and their measurement Addition and Deletion of Disorders Catatonia NOS subtypes, shared psychotic disorder Changes in Criteria, Schizoaffective Disorder, Delusional Disorder Take-Home Points No More Multi-axial diagnoses Addition of Dimensions Addition of Section 3 with a lot of clinically useful materials that are not yet part of the official DSM nomenclature Diagnosis now includes 3 levels: Category, Specifiers, and Severity Tandon R, et al. Schizophr Res. 2013;150(1):3-10. Key Take-Aways from Changes in Chapter on Disorders Illness dimensions better describe heterogeneity of schizophrenic illness across patients than subtyping Measuring illness dimensions during treatment significantly helps in optimal individualization of treatment of psychotic disorders Differentiating core defining features of psychotic disorders from accompanying features aids differential diagnosis of various psychotic disorders Explicit criteria enable identification of individuals at high risk of developing a psychotic disorder over next year