The Essence of Schizophrenia • Originally called “dementia praecox” • Produces severe incapacity – “dementia” • Typically begins in adolescence – “praecox” WPA The Tragedy of Schizophrenia • • • • A catastrophic illness Tends to persist chronically 10% suicide rate Very common -- 0.5-1% of population • The “cancer of mental illness” WPA The Complexity of Schizophrenia • No single defining feature • Multiple characteristic symptoms • Symptoms from multiple domains • • • • Emotion Personality Cognition Motor Activity • Probably a multisystem disorder, analogous to syphilis WPA Simplifying the Complexity of Schizophrenia • Division of symptoms into two broad groups • Positive: distortions or exaggerations of normal functions • Negative: diminution of normal functions WPA Hughlings-Jackson: Positive and Negative Symptoms • Disease that is said to “cause the symptoms of insanity.” I submit that disease only produces negative mental symptoms answering to the dissolution, and that all elaborate positive mental symptoms (illusions, hallucinations, delusions, and extravagant conduct) are the outcome of activity of nervous elements untouched by any pathological process; that they arise during activity on the lower end of evolution remaining. WPA Positive Symptoms Symptom Hallucinations Delusions Disorganized Speech Bizarre Behavior Function Distorted Perception Inferential thinking Thought/Language Behavioral monitoring WPA Negative Symptoms Symptom Alogia Affective blunting Avolition Anhedonia Function Diminished Fluency of speech/thought Emotional expression Volition and drive Hedonic capacity WPA The Importance of Negative Symptoms • Impair ability to function in daily life • Holding a job • Attending school • Forming friendships • Having intimate family relationships WPA Subdivision of Symptoms into Three Dimensions • Psychotic Delusions Hallucinations • Disorganized Disorganized speech Disorganized behavior Inappropriate affect • Negative Poverty of speech Avolition Affective Blunting Anhedonia WPA Types of Hallucinations • Auditory • Visual • Tactile • Olfactory WPA Types of Delusions • Persecutory • Grandiose • Religious • Jealous • Somatic WPA Historical Concepts • Emil Kraepelin • Eugen Bleuler • Kurt Schneider • Others (e.g., Leonhard, Kleist, Langfeldt) WPA Emil Kraepelin: Dementia Praecox “Dementia praecox consists of a series of states, the common characteristic of which is a peculiar destruction of internal connections of the psychic personality....the majority of the clinical pictures are the expression of a single morbid process, though outwardly they often diverge very far from one another.” WPA Kraepelin: Course and Outcome • Split “dementia praecox” from manic-depressive illness • Early onset • Marked deterioration • Chronic course • Diversity of signs and symptoms • Importance of volition and affect WPA Eugen Bleuler: Loosening of Associations “Of the thousands of associative threads that guide our thinking, this disease seems to interrupt, quite haphazardly, sometimes single threads, sometimes a whole group, and sometimes whole segments of them.” WPA Bleuler: Fundamental Symptoms • Renamed the disorder “schizophrenia” • Focused on the characteristic symptoms • Emphasized fragmenting of thinking • Partial recovery possible • No full “restitutio ad integrum” • A broader concept • Heterogeneity: the “group of schizophrenias” WPA Bleuler’s Fundamental Symptoms • • • • • • Associations Affective Blunting Avolition Autism Ambivalence Attention WPA Bleuler’s Description of Fundamental Symptoms • Certain symptoms of schizophrenia are present in every case and at every period of the illness even though, as with every other disease symptom, they must have attained a certain degree of intensity before they can be recognized with any certainty…for example, the peculiar association disturbance is always present, but not each and every aspect of it…besides these specific permanent or fundamental symptoms, we can find a host of other, more accessory manifestations such as delusions, hallucinations, or catatonic symptoms…as far as we know, the fundamental symptoms are characteristic of schizophrenia, while the accessory symptoms may also appear in other types of illnesses. WPA Kurt Schneider WPA Schneider: The Psychotic Experience • Interested in pathognomonic symptoms • “First Rank Symptoms” (FRS) E.g., voices commenting Voices arguing Thought insertion • Involve a loss of the sense of autonomy of self, or “ego boundaries” WPA Importance of Schneiderian Ideas • Discrete phenomena—clearly pathological or “bizarre” • Discontinuous from normality • Potentially for good reliability • Ideal for objective criterionbased systems WPA Schneiderian Influences on Diagnostic Systems • Incorporated into Present State Examination (PSE) • Used in International Pilot Study of Schizophrenia (IPSS) • Influenced the International Classification of Disease (ICD) • Influenced the US Diagnostic and Statistical Manual (DSM) WPA Fundamental Questions about Schizophrenia • What are the characteristic symptoms? • What are the boundaries of the concept? • Is the disorder a single illness or multiple disorders? • If multiple, what are the subtypes? WPA Characteristic Symptoms • Schneider: specific types of delusions and hallucinations • Bleuler: fragmented thinking, inability to relate to external world • Kraepelin: emotional dullness, avolition, loss of inner unity WPA Schizophrenia as a “Polythetic Construct” • No single characteristic symptom • Many symptoms, all present in some, not present in all • Manifestations in thinking, emotion, interpersonal relationships • A multisystem disease WPA What are the Characteristic Symptoms of Schizophrenia? • Depends upon whom you ask • Depends upon theoretical construct • Depends upon what you mean by characteristic Common? Specific? Core? WPA Kraepelin: The Borders of Schizophrenia …it is certainly possible that its borders are drawn at present in many directions too narrow, in others perhaps too wide. WPA Boundaries of the Concept • Schizoaffective Disorder • Psychotic Mood Disorders • Nonpsychotic disorders Schizotypal Personality Simple Schizophrenia WPA “Good Prognosis Schizophrenia” • • • • • Prominent affective symptoms Acute onset Family history of affective disorder Good premorbid function Presence of insight WPA Narrowing of Concept: Rationale • Risk of tardive dyskinesia • Risk of erroneously treating mood disorders with neuroleptics • Risk of self-fulfilling prophesies of poor outcome • Risk of political abuse WPA Single or Multiple Illnesses • Whether dementia praecox in the extent here delimited represents one uniform disease, cannot be decided at present with certainty. -- Emil Kraepelin WPA WPA Heterogeneity: Competing Models • Single disease entity: multiple sclerosis • Multiple disease entities: mental retardation • Multiple domains of psychopathology WPA Single Disease Entity • A single illness • A single cause that produces diverse manifestations • Possible mechanism: process producing multiple brain lesions WPA Multiple Disease Entities • “The group of schizophrenias” • Multiple causes Purely genetic forms, e.g. phenylketonuria Purely environmental forms, e.g. virally induced Multifactorial forms • Manifestations reflect site of injury and time of the maturational process WPA Multiple Domains • Multiple dimensions of psychopathology e.g., psychotic, disorganized, negative • Different mechanism for each dimension • Disease process A dimension A • Disease process B dimension B • Disease process C dimension C • Mixed clinical presentation due to multiple disease processes WPA Methods for Subtyping • Traditional subtypes based on clinical presentation • Phenomenotype vs. biotype • Positive vs. mixed vs. negative WPA Traditional Subtypes • • • • • Paranoid Disorganized Catatonic Undifferentiated Residual WPA Traditional Subtypes • Divide patients based on their prominent presenting symptoms • Useful for prediction Prognosis Social and occupational function Response to treatment WPA Phenomenotype • • • • • • • Types of symptoms Severity of symptoms Longitudinal course Mode of onset Cognitive function Psychosocial adaptation Response to treatment WPA Biotype • Genetic loading and linkage • Birth and pregnancy complications • Viral risk factors • Neurophysiological measures • Neuropsychological measures • Neuroimaging measures • Neurochemical measures WPA Positive vs. Negative Positive Negative Poor premorbid Acute onset Psychotic symptoms Intact cognition Poor treatment response Neurochemical mechanism Reversible Good premorbid Insidious onset Negative symptoms Impaired cognition Good treatment response Structural mechanism Irreversible WPA DSM-IV Criteria for Schizophrenia: The Basics • Characteristic symptoms for one month • Social/Occupational Dysfunction • Overall Duration > 6 months • Not attributable to mood disorder • Not attributable to substance use or general medical condition WPA Criterion A: Characteristic Symptoms • At least two of the following, each present for a significant portion of time during a one 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 WPA Criterion A: Parenthetical Note • [Note: Only one “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.] WPA Criterion B: Social/Occupational Dysfunction • For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations or selfcare is markedly below the level achieved prior to the onset • OR when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement WPA Criterion C: Overall Duration • Continuous signs of the disturbance persist for at least six months • This six-month period must include at least one month of symptoms that meet criterion A (i.e., active phase symptoms), and may include periods of prodromal or residual symptoms • During these prodromal or residual period, the signs of the disturbance may be manifested by only negative symptoms or two or more symptoms listed in criterion A present in an attenuated form (e.g. odd beliefs, unusual perceptual experiences) WPA Criterion D: Schizoaffective and Mood Disorder Exclusion • Schizoaffective Disorder and Mood Disorder with Psychotic Features have been ruled out because of either: (1) No major depressive or manic episodes have occurred concurrently with the active phase symptoms; or (2) If mood episodes have occurred during active phase symptoms, their total duration has been brief relative to the duration of the active and residual periods WPA Criterion E: Substance / General Medical Condition Exclusion The disturbance is not due to the direct effects of a substance (e.g., drugs of abuse, medication) or a general medical condition WPA ICD 10 Criteria for Schizophrenia: The Basics • Characteristic symptoms for one month • If mood disorder is present, one month of characteristic symptoms must antedate it • Not attributable to organic brain disease or substance abuse WPA ICD 10: Characteristic Symptoms •At least one of the following: Thought echo, insertion, withdrawal, or broadcasting Delusions of control, influence, or passivity; delusional percept Voices commenting or discussing; voices coming from some part of the body Persistent delusions that are culturally inappropriate and completely impossible, such as religious or political identity, superhuman powers WPA ICD 10: Characteristic Symptoms •Or at least two of the following: Persistent hallucinations in any modality when accompanied by delusions Neologisms, breaks or interpolations in the train of thought, resulting in incoherence or irrelevant speech Catatonic behavior “Negative” symptoms such as marked apathy, paucity of speech, and blunting or incongruity of emotional responses WPA Similarities Between ICD and DSM • Both require one month of active symptoms • Both include references to negative symptoms • Both require presence of delusions and hallucinations for a diagnosis of schizophrenia WPA Differences Between ICD and DSM • Characteristic symptoms (more emphasis on FRS in ICD) • Overall duration of symptoms (one month for ICD vs. six months for DSM) • More specific and complex symptom list in ICD • Inclusion of Schizotypal Disorder and Simple Schizophrenia in ICD WPA ICD 10: Types of Schizophrenia • • • • • • Paranoid Hebephrenic Catatonic Undifferentiated Post-schizophrenic depression Simple schizophrenia WPA ICD 10: Categories of Psychosis • • • • Schizophrenia Schizotypal Disorder Persistent Delusional Disorders Acute and Transient Psychotic Disorders • Induced Delusional Disorder • Schizoaffective Disorders • Other Nonorganic Psychotic Disorders WPA DSM IV: Subtypes • • • • • Paranoid Disorganized Catatonic Undifferentiated Residual WPA DSM IV: Categories of Psychosis • • • • • • • Schizophreniform Disorder Schizophrenia Brief Psychotic Disorder Schizoaffective Disorder Delusional Disorder Shared Psychotic Disorder Psychotic Disorder due to a General Medical Condition • Substance-Induced Psychotic Disorder • Psychotic Disorder Not Otherwise WPA Specified Differential Diagnosis • Mood Disorders • Nonpsychotic personality disorders • Substance-induced psychotic disorders • Psychotic disorders due to a general medical condition (i.e., “organic” disorders) WPA Drugs That May Induce Psychosis • • • • Amphetamines Marijuana Hallucinogens Cocaine WPA Medical Conditions That May Present with Psychosis • • • • • • • • Temporal lobe epilepsy Tumor Stroke Trauma Endocrine/metabolic abnormalities Infections Multiple Sclerosis Autoimmune diseases WPA Evaluating Psychosocial Function • Premorbid • Current WPA Aspects of Psychosocial Function • • • • • • • Relationship to parents Relationship to siblings Relationship to peers Sexual adjustment Educational history Work function Recreational activities and interests WPA Laboratory Workup • No standard set of laboratory tests • Test selected on basis of clinical presentation, mode of onset, and past history WPA Some Common Laboratory Tests • • • • • • • • • Complete blood count Urinalysis Endocrine tests Liver function tests Electroencephalogram Computerized Tomography Magnetic Resonance Imaging Neuropsychological tests Projective tests WPA Cross Cultural Issues: Similarities Across Cultures • Schizophrenia is found throughout the world • Some symptoms tend to be identical worldwide Negative symptoms Thought Disorder Cognitive Impairment WPA Differences Across Cultures • Content of psychotic symptoms • Outcome • Frequency of acute psychotic episodes WPA Reasons for Frequency of Acute Psychosis • Infections • Nutrition • Delays in provision of medical care WPA Social Outcome in First Episode Schizophrenia: Nagasaki Follow-up after 2 years 1981-1982 Follow-up after 5 years 19841985 Follow-up after 10 years 19891990 64 65 58 Good Outcome 34.4 44.6 36.2 Poor Outcome 24.4 35.4 35.5 Hospitalized 31.3 20.0 29.3 With good outcome 39.1 50.8 44.8 With poor outcome 60.9 49.2 55.2 Number of cases at follow-up DAS overall evaluation (includes cases in the hospital) WPA Poor Outcome: Predictors • • • • • • • Prominent negative symptoms Early age of onset Insidious onset Poor premorbid adjustment Low educational achievement Low parental social class Male gender WPA Comparison of Course in Developed and Developing Countries Pattern of Course * 1 2 3 4 5 6 7 8 9 Developed Countries (n-604) 15.7 17.4 6.2 5.3 14.7 12.1 17.1 2.3 -- Developing Countries (n-474) 37.1 11.6 6.5 2.3 19.0 10.6 11.2 1.1 0.6 * 1. Single psychotic episode, complete remission 2. Single psychotic episode, incomplete remission 3. Single psychotic episode, non-psychotic episodes complete remission 4. Single psychotic episode, non-psychotic episodes incomplete remission 5. 2+ psychotic episodes, complete remission 6. 2+ psychotic episodes, incomplete remission 7. Continuous psychotic illness, no remission 8. Continuous non-psychotic illness 9. Not known WPA Reasons for Better Outcome in Developing Countries • Better social support from extended families • Less social pressure to achieve occupationally • Lower stress in rural environments and small villages • Less stigma toward mental illness WPA