1. WPA The Essence of Schizophrenia Originally called “dementia praecox”Originally called “dementia praecox” Produces severe incapacity – “dementia”Produces severe incapacity – “dementia” Typically begins in adolescence – “praecox”Typically begins in adolescence – “praecox”

2. WPA The Tragedy of Schizophrenia A catastrophic illnessA catastrophic illness Tends to persist chronicallyTends to persist chronically 10% suicide rate10% suicide rate Very common -- 0.5-1% of populationVery common -- 0.5-1% of population The “cancer of mental illness”The “cancer of mental illness”

3. WPA The Complexity of Schizophrenia No single defining featureNo single defining feature Multiple characteristic symptomsMultiple characteristic symptoms Symptoms from multiple domainsSymptoms from multiple domains EmotionEmotion PersonalityPersonality CognitionCognition Motor ActivityMotor Activity Probably a multisystem disorder, analogous to syphilisProbably a multisystem disorder, analogous to syphilis

4. WPA Simplifying the Complexity of Schizophrenia Division of symptoms into two broad groupsDivision of symptoms into two broad groups Positive: distortions or exaggerations of normal functionsPositive: distortions or exaggerations of normal functions Negative: diminution of normal functionsNegative: diminution of normal functions

5. 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.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.

6. WPA Positive Symptoms SymptomHallucinationsDelusions Disorganized Speech Bizarre Behavior Function Distorted Perception Inferential thinking Thought/Language Behavioral monitoring

7. WPA Negative Symptoms SymptomAlogia Affective blunting AvolitionAnhedonia Function Diminished Fluency of speech/thought Emotional expression Volition and drive Hedonic capacity

8. WPA The Importance of Negative Symptoms Impair ability to function in daily lifeImpair ability to function in daily life Holding a jobHolding a job Attending schoolAttending school Forming friendshipsForming friendships Having intimate family relationshipsHaving intimate family relationships

9. WPA Subdivision of Symptoms into Three Dimensions PsychoticPsychotic Delusions Hallucinations DisorganizedDisorganized Disorganized speech Disorganized behavior Inappropriate affect NegativeNegative Poverty of speech Avolition Affective Blunting Anhedonia

10. WPA Types of Hallucinations AuditoryAuditory VisualVisual TactileTactile OlfactoryOlfactory

11. WPA Types of Delusions PersecutoryPersecutory GrandioseGrandiose ReligiousReligious JealousJealous SomaticSomatic

12. WPA Historical Concepts Emil KraepelinEmil Kraepelin Eugen BleulerEugen Bleuler Kurt SchneiderKurt Schneider Others (e.g., Leonhard, Kleist, Langfeldt)Others (e.g., Leonhard, Kleist, Langfeldt)

13. 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.”

14. WPA Kraepelin: Course and Outcome Split “dementia praecox” from manic-depressive illnessSplit “dementia praecox” from manic-depressive illness Early onsetEarly onset Marked deteriorationMarked deterioration Chronic courseChronic course Diversity of signs and symptomsDiversity of signs and symptoms Importance of volition and affectImportance of volition and affect

15. 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.”

16. WPA Bleuler: Fundamental Symptoms Renamed the disorder “schizophrenia”Renamed the disorder “schizophrenia” Focused on the characteristic symptomsFocused on the characteristic symptoms Emphasized fragmenting of thinkingEmphasized fragmenting of thinking Partial recovery possiblePartial recovery possible No full “restitutio ad integrum”No full “restitutio ad integrum” A broader conceptA broader concept Heterogeneity: the “group of schizophrenias”Heterogeneity: the “group of schizophrenias”

17. WPA Bleuler’s Fundamental Symptoms AssociationsAssociations Affective BluntingAffective Blunting AvolitionAvolition AutismAutism AmbivalenceAmbivalence AttentionAttention

18. 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.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.

19. WPA Kurt Schneider

20. WPA Schneider: The Psychotic Experience Interested in pathognomonic symptomsInterested in pathognomonic symptoms “First Rank Symptoms” (FRS)“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”Involve a loss of the sense of autonomy of self, or “ego boundaries”

21. WPA Importance of Schneiderian Ideas Discrete phenomena—clearly pathological or “bizarre”Discrete phenomena—clearly pathological or “bizarre” Discontinuous from normalityDiscontinuous from normality Potentially for good reliabilityPotentially for good reliability Ideal for objective criterion- based systemsIdeal for objective criterion- based systems

22. WPA Schneiderian Influences on Diagnostic Systems Incorporated into Present State Examination (PSE)Incorporated into Present State Examination (PSE) Used in International Pilot Study of Schizophrenia (IPSS)Used in International Pilot Study of Schizophrenia (IPSS) Influenced the International Classification of Disease (ICD)Influenced the International Classification of Disease (ICD) Influenced the US Diagnostic and Statistical Manual (DSM)Influenced the US Diagnostic and Statistical Manual (DSM)

23. 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?

24. WPA Characteristic Symptoms Schneider: specific types of delusions and hallucinationsSchneider: specific types of delusions and hallucinations Bleuler: fragmented thinking, inability to relate to external worldBleuler: fragmented thinking, inability to relate to external world Kraepelin: emotional dullness, avolition, loss of inner unityKraepelin: emotional dullness, avolition, loss of inner unity

25. WPA Schizophrenia as a “Polythetic Construct” No single characteristic symptomNo single characteristic symptom Many symptoms, all present in some, not present in allMany symptoms, all present in some, not present in all Manifestations in thinking, emotion, interpersonal relationshipsManifestations in thinking, emotion, interpersonal relationships A multisystem diseaseA multisystem disease

26. WPA What are the Characteristic Symptoms of Schizophrenia? Depends upon whom you askDepends upon whom you ask Depends upon theoretical constructDepends upon theoretical construct Depends upon what you mean by characteristicDepends upon what you mean by characteristicCommon?Specific? Core Core?

27. 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.

28. WPA Boundaries of the Concept Schizoaffective DisorderSchizoaffective Disorder Psychotic Mood DisordersPsychotic Mood Disorders Nonpsychotic disordersNonpsychotic disorders Schizotypal Personality Simple Schizophrenia

29. WPA “Good Prognosis Schizophrenia” Prominent affective symptomsProminent affective symptoms Acute onsetAcute onset Family history of affective disorderFamily history of affective disorder Good premorbid functionGood premorbid function Presence of insightPresence of insight

30. WPA Narrowing of Concept: Rationale Risk of tardive dyskinesiaRisk of tardive dyskinesia Risk of erroneously treating mood disorders with neurolepticsRisk of erroneously treating mood disorders with neuroleptics Risk of self-fulfilling prophesies of poor outcomeRisk of self-fulfilling prophesies of poor outcome Risk of political abuseRisk of political abuse

31. WPA Single or Multiple Illnesses Whether dementia praecox in the extent here delimited represents one uniform disease, cannot be decided at present with certainty.Whether dementia praecox in the extent here delimited represents one uniform disease, cannot be decided at present with certainty. -- Emil Kraepelin

32. WPA

33. WPA Heterogeneity: Competing Models Single disease entity: multiple sclerosisSingle disease entity: multiple sclerosis Multiple disease entities: mental retardationMultiple disease entities: mental retardation Multiple domains of psychopathologyMultiple domains of psychopathology

34. WPA Single Disease Entity A single illnessA single illness A single cause that produces diverse manifestationsA single cause that produces diverse manifestations Possible mechanism: process producing multiple brain lesionsPossible mechanism: process producing multiple brain lesions

35. WPA Multiple Disease Entities “The group of schizophrenias”“The group of schizophrenias” Multiple causesMultiple 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 processManifestations reflect site of injury and time of the maturational process

36. WPA Multiple Domains Multiple dimensions of psychopathology e.g., psychotic, disorganized, negativeMultiple dimensions of psychopathology e.g., psychotic, disorganized, negative Different mechanism for each dimensionDifferent mechanism for each dimension Disease process A  dimension ADisease process A  dimension A Disease process B  dimension BDisease process B  dimension B Disease process C  dimension CDisease process C  dimension C Mixed clinical presentation due to multiple disease processesMixed clinical presentation due to multiple disease processes

37. WPA Methods for Subtyping Traditional subtypes based on clinical presentationTraditional subtypes based on clinical presentation Phenomenotype vs. biotypePhenomenotype vs. biotype Positive vs. mixed vs. negativePositive vs. mixed vs. negative

38. WPA Traditional Subtypes ParanoidParanoid DisorganizedDisorganized CatatonicCatatonic UndifferentiatedUndifferentiated ResidualResidual

39. WPA Traditional Subtypes Divide patients based on their prominent presenting symptomsDivide patients based on their prominent presenting symptoms Useful for predictionUseful for predictionPrognosis Social and occupational function Response to treatment

40. WPA Phenomenotype Types of symptomsTypes of symptoms Severity of symptomsSeverity of symptoms Longitudinal courseLongitudinal course Mode of onsetMode of onset Cognitive functionCognitive function Psychosocial adaptationPsychosocial adaptation Response to treatmentResponse to treatment

41. WPA Biotype Genetic loading and linkageGenetic loading and linkage Birth and pregnancy complicationsBirth and pregnancy complications Viral risk factorsViral risk factors Neurophysiological measuresNeurophysiological measures Neuropsychological measuresNeuropsychological measures Neuroimaging measuresNeuroimaging measures Neurochemical measuresNeurochemical measures

42. WPA Positive vs. Negative PositiveNegative 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

43. WPA DSM-IV Criteria for Schizophrenia: The Basics Characteristic symptoms for one monthCharacteristic symptoms for one month Social/Occupational DysfunctionSocial/Occupational Dysfunction Overall Duration > 6 monthsOverall Duration > 6 months Not attributable to mood disorderNot attributable to mood disorder Not attributable to substance use or general medical conditionNot attributable to substance use or general medical condition

44. 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):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(1) delusions (2) hallucinations(2) hallucinations (3) disorganized speech (e.g., frequent derailment or incoherence)(3) disorganized speech (e.g., frequent derailment or incoherence) (4) grossly disorganized or catatonic behavior(4) grossly disorganized or catatonic behavior (5) negative symptoms, I.e., affective flattening, alogia, or avolition(5) negative symptoms, I.e., affective flattening, alogia, or avolition

45. 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.][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.]

46. 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 self- care is markedly below the level achieved prior to the onsetFor 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 self- care 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 achievementOR when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement

47. WPA Criterion C: Overall Duration Continuous signs of the disturbance persist for at least six monthsContinuous 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 symptomsThis 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)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)

48. WPA Criterion D: Schizoaffective and Mood Disorder Exclusion Schizoaffective Disorder and Mood Disorder with Psychotic Features have been ruled out because of either: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

49. 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

50. WPA ICD 10 Criteria for Schizophrenia: The Basics Characteristic symptoms for one monthCharacteristic symptoms for one month If mood disorder is present, one month of characteristic symptoms must antedate itIf mood disorder is present, one month of characteristic symptoms must antedate it Not attributable to organic brain disease or substance abuseNot attributable to organic brain disease or substance abuse

51. WPA ICD 10: Characteristic Symptoms At least one of the following: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

52. WPA ICD 10: Characteristic Symptoms Or at least two of the following: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

53. WPA Similarities Between ICD and DSM Both require one month of active symptomsBoth require one month of active symptoms Both include references to negative symptomsBoth include references to negative symptoms Both require presence of delusions and hallucinations for a diagnosis of schizophreniaBoth require presence of delusions and hallucinations for a diagnosis of schizophrenia

54. WPA Differences Between ICD and DSM Characteristic symptoms (more emphasis on FRS in ICD)Characteristic symptoms (more emphasis on FRS in ICD) Overall duration of symptoms (one month for ICD vs. six months for DSM)Overall duration of symptoms (one month for ICD vs. six months for DSM) More specific and complex symptom list in ICDMore specific and complex symptom list in ICD Inclusion of Schizotypal Disorder and Simple Schizophrenia in ICDInclusion of Schizotypal Disorder and Simple Schizophrenia in ICD

55. WPA ICD 10: Types of Schizophrenia ParanoidParanoid HebephrenicHebephrenic CatatonicCatatonic UndifferentiatedUndifferentiated Post-schizophrenic depressionPost-schizophrenic depression Simple schizophreniaSimple schizophrenia

56. WPA ICD 10: Categories of Psychosis SchizophreniaSchizophrenia Schizotypal DisorderSchizotypal Disorder Persistent Delusional DisordersPersistent Delusional Disorders Acute and Transient Psychotic DisordersAcute and Transient Psychotic Disorders Induced Delusional DisorderInduced Delusional Disorder Schizoaffective DisordersSchizoaffective Disorders Other Nonorganic Psychotic DisordersOther Nonorganic Psychotic Disorders

57. WPA DSM IV: Subtypes ParanoidParanoid DisorganizedDisorganized CatatonicCatatonic UndifferentiatedUndifferentiated ResidualResidual

58. WPA DSM IV: Categories of Psychosis Schizophreniform DisorderSchizophreniform Disorder SchizophreniaSchizophrenia Brief Psychotic DisorderBrief Psychotic Disorder Schizoaffective DisorderSchizoaffective Disorder Delusional DisorderDelusional Disorder Shared Psychotic DisorderShared Psychotic Disorder Psychotic Disorder due to a General Medical ConditionPsychotic Disorder due to a General Medical Condition Substance-Induced Psychotic DisorderSubstance-Induced Psychotic Disorder Psychotic Disorder Not Otherwise SpecifiedPsychotic Disorder Not Otherwise Specified

59. WPA Differential Diagnosis Mood DisordersMood Disorders Nonpsychotic personality disordersNonpsychotic personality disorders Substance-induced psychotic disordersSubstance-induced psychotic disorders Psychotic disorders due to a general medical condition (i.e., “organic” disorders)Psychotic disorders due to a general medical condition (i.e., “organic” disorders)

60. WPA Drugs That May Induce Psychosis AmphetaminesAmphetamines MarijuanaMarijuana HallucinogensHallucinogens CocaineCocaine

61. WPA Medical Conditions That May Present with Psychosis Temporal lobe epilepsyTemporal lobe epilepsy TumorTumor StrokeStroke TraumaTrauma Endocrine/metabolic abnormalitiesEndocrine/metabolic abnormalities InfectionsInfections Multiple SclerosisMultiple Sclerosis Autoimmune diseasesAutoimmune diseases

62. WPA Evaluating Psychosocial Function PremorbidPremorbid CurrentCurrent

63. WPA Aspects of Psychosocial Function Relationship to parentsRelationship to parents Relationship to siblingsRelationship to siblings Relationship to peersRelationship to peers Sexual adjustmentSexual adjustment Educational historyEducational history Work functionWork function Recreational activities and interestsRecreational activities and interests

64. WPA Laboratory Workup No standard set of laboratory testsNo standard set of laboratory tests Test selected on basis of clinical presentation, mode of onset, and past historyTest selected on basis of clinical presentation, mode of onset, and past history

65. WPA Some Common Laboratory Tests Complete blood countComplete blood count UrinalysisUrinalysis Endocrine testsEndocrine tests Liver function testsLiver function tests ElectroencephalogramElectroencephalogram Computerized TomographyComputerized Tomography Magnetic Resonance ImagingMagnetic Resonance Imaging Neuropsychological testsNeuropsychological tests Projective testsProjective tests

66. WPA Cross Cultural Issues: Similarities Across Cultures Schizophrenia is found throughout the worldSchizophrenia is found throughout the world Some symptoms tend to be identical worldwideSome symptoms tend to be identical worldwide Negative symptoms Thought Disorder Cognitive Impairment

67. WPA Differences Across Cultures Content of psychotic symptomsContent of psychotic symptoms OutcomeOutcome Frequency of acute psychotic episodesFrequency of acute psychotic episodes

68. WPA Reasons for Frequency of Acute Psychosis InfectionsInfections NutritionNutrition Delays in provision of medical careDelays in provision of medical care

69. WPA Social Outcome in First Episode Schizophrenia: Nagasaki Follow-up after 2 years 1981-1982 Follow-up after 5 years 1984- 1985 Follow-up after 10 years 1989- 1990 Number of cases at follow-up 646558 Good Outcome 34.444.636.2 Poor Outcome 24.435.435.5 Hospitalized31.320.029.3 DAS overall evaluation (includes cases in the hospital) With good outcome 39.150.844.8 With poor outcome 60.949.255.2

70. WPA Poor Outcome: Predictors Prominent negative symptomsProminent negative symptoms Early age of onsetEarly age of onset Insidious onsetInsidious onset Poor premorbid adjustmentPoor premorbid adjustment Low educational achievementLow educational achievement Low parental social classLow parental social class Male genderMale gender

71. WPA Comparison of Course in Developed and Developing Countries Pattern of Course * 123456789 Developed Countries (n-604) 15.717.46.25.314.712.117.12.3-- Developing Countries (n-474) 37.111.66.52.319.010.611.21.10.6 * 1. Single psychotic episode, complete remission 2. Single psychotic episode, incomplete remission 2. Single psychotic episode, incomplete remission 3. Single psychotic episode, non-psychotic episodes complete remission 3. Single psychotic episode, non-psychotic episodes complete remission 4. Single psychotic episode, non-psychotic episodes incomplete remission 4. Single psychotic episode, non-psychotic episodes incomplete remission 5. 2+ psychotic episodes, complete remission 5. 2+ psychotic episodes, complete remission 6. 2+ psychotic episodes, incomplete remission 6. 2+ psychotic episodes, incomplete remission 7. Continuous psychotic illness, no remission 7. Continuous psychotic illness, no remission 8. Continuous non-psychotic illness 8. Continuous non-psychotic illness 9. Not known 9. Not known

72. WPA Reasons for Better Outcome in Developing Countries Better social support from extended familiesBetter social support from extended families Less social pressure to achieve occupationallyLess social pressure to achieve occupationally Lower stress in rural environments and small villagesLower stress in rural environments and small villages Less stigma toward mental illnessLess stigma toward mental illness