Schizophrenia and Other Schizophrenia and Other Psychotic DisordersPsychotic Disorders

A.Jayalangkara Tanra MD,Ph.D.A.Jayalangkara Tanra MD,Ph.D.

Department of Psychiatry, Department of Psychiatry, Faculty of Medicine,Faculty of Medicine,

Hasanuddin University, Hasanuddin University, Makassar,INDONESIA.Makassar,INDONESIA.

What is Psychosis?What is Psychosis? Generic termGeneric term ““Break with Reality”Break with Reality” Symptom, not an illnessSymptom, not an illness Caused by a Caused by a varietyvariety of conditions of conditions

that that affect the functioning of the affect the functioning of the brain.brain.

Includes hallucinations, delusions Includes hallucinations, delusions and thought disorderand thought disorder

PSYCHOSIS

Mood disorders

Schizophrenia “spectrum” disorders

“organic” mental

disorders

Substance

induced

DeliriumDementia

Amnestic d/o

“Functional”disorders

Differential Diagnoses: (Cont)Differential Diagnoses: (Cont) Personality Personality

disordersdisordersSchizoidSchizoidSchizotypalSchizotypalParanoidParanoidBorderlineBorderlineAntisocialAntisocial

Miscellaneous Miscellaneous PTSDPTSDDissociative disordersDissociative disordersMalingeringMalingeringCulturally specific phenomena:Culturally specific phenomena:

Religious experiencesReligious experiencesMeditative statesMeditative statesBelief in UFO’s, etcBelief in UFO’s, etc

SchizophreniaSchizophrenia

DefinitionDefinition The schizophrenic disorders are characterized in The schizophrenic disorders are characterized in

general by fundamental and characteristic general by fundamental and characteristic distortions of thinking and perception, and affectsdistortions of thinking and perception, and affects that are inappropriate or blunted. Clear that are inappropriate or blunted. Clear consciousness and intellectual capacity are usually consciousness and intellectual capacity are usually maintained although certain cognitive deficits may maintained although certain cognitive deficits may evolve in the course of time. evolve in the course of time.

The most important psychopathological phenomena The most important psychopathological phenomena includeinclude• thought echothought echo• thought insertion or withdrawalthought insertion or withdrawal• thought broadcastingthought broadcasting• delusional perception and delusions of controldelusional perception and delusions of control• influence or passivityinfluence or passivity• hallucinatory voices commenting or discussing the patient in hallucinatory voices commenting or discussing the patient in

the third personthe third person• thought disorders and negative symptoms.thought disorders and negative symptoms.

SchizophreniaSchizophrenia Schizophrenia occurs with regular Schizophrenia occurs with regular

frequency nearly everywhere in the world frequency nearly everywhere in the world in 1 % of population and begins mainly in in 1 % of population and begins mainly in young age (mostly around 16 to 25 years).young age (mostly around 16 to 25 years).

Schizophrenia is defined by Schizophrenia is defined by • a group of characteristic positive and negative a group of characteristic positive and negative

symptomssymptoms• deterioration in social, occupational, or deterioration in social, occupational, or

interpersonal relationshipsinterpersonal relationships• continuous signs of the disturbance for at least continuous signs of the disturbance for at least

6 months6 months

HistoryHistory Emil KraepelinEmil Kraepelin: This illness develops relatively : This illness develops relatively

early in life, and its course is likely deteriorating early in life, and its course is likely deteriorating and chronic; deterioration reminded dementia and chronic; deterioration reminded dementia („Dementia praecox“(„Dementia praecox“), but was not followed by any ), but was not followed by any organic changes of the brain, detectable at that organic changes of the brain, detectable at that time.time.

Eugen BleulerEugen Bleuler: He renamed Kraepelin’s dementia : He renamed Kraepelin’s dementia praecox as praecox as schizophreniaschizophrenia (1911); he recognized (1911); he recognized the cognitive impairment in this illness, which he the cognitive impairment in this illness, which he named as a „splittingnamed as a „splitting““ of mind. of mind.

Kurt SchneiderKurt Schneider: He emphasized the role of : He emphasized the role of psychotic symptoms, as hallucinations, delusions psychotic symptoms, as hallucinations, delusions and gave them the privilege of and gave them the privilege of „the first rank „the first rank symptoms”symptoms” even in the concept of the diagnosis of even in the concept of the diagnosis of schizophrenia. schizophrenia.

4 A (Bleuler)4 A (Bleuler) Bleuler maintained, that for the diagnosis of Bleuler maintained, that for the diagnosis of

schizophrenia are most important the following four schizophrenia are most important the following four fundamental symptoms:fundamental symptoms:

• affective bluntingaffective blunting• disturbance of associationdisturbance of association (fragmented thinking) (fragmented thinking)• autismautism• ambivalenceambivalence (fragmented emotional response) (fragmented emotional response)

These groups of symptoms, are called „four A’ s” These groups of symptoms, are called „four A’ s” and Bleuler thought, that they are „primary” for and Bleuler thought, that they are „primary” for this diagnosis.this diagnosis.

The other known symptoms, hallucinations, The other known symptoms, hallucinations, delusions, which are appearing in schizophrenia delusions, which are appearing in schizophrenia very often also, he used to call as a “secondary very often also, he used to call as a “secondary symptoms”, because they could be seen in any symptoms”, because they could be seen in any other psychotic disease, which are caused by quite other psychotic disease, which are caused by quite different factors — from intoxication to infection or different factors — from intoxication to infection or other disease entities.other disease entities.

Course of IllnessCourse of Illness

Course of schizophrenia:Course of schizophrenia:• continuous without temporary improvementcontinuous without temporary improvement• episodic with progressive or stable deficitepisodic with progressive or stable deficit• episodic with complete or incomplete episodic with complete or incomplete

remission remission

Typical stages of schizophrenia:Typical stages of schizophrenia:• prodromal phaseprodromal phase• active phaseactive phase• residual phaseresidual phase

Clinical PictureClinical Picture Diagnostic manuals: Diagnostic manuals:

• lCD-10lCD-10 („International Classification of Disease“, WHO) („International Classification of Disease“, WHO)• DSM-IVDSM-IV („Diagnostic and Statistical Manual“, APA) („Diagnostic and Statistical Manual“, APA)

Clinical picture of schizophrenia is according to lCD-Clinical picture of schizophrenia is according to lCD-10, defined from the point of view of the presence 10, defined from the point of view of the presence and expression of primary and/or secondary and expression of primary and/or secondary symptoms (at present covered by the terms symptoms (at present covered by the terms negative and positive symptoms)negative and positive symptoms)::• tthe he negative symptomsnegative symptoms are represented by cognitive are represented by cognitive

disorders, having its origin probably in the disorders of disorders, having its origin probably in the disorders of associations of thoughts, combined with emotional blunting associations of thoughts, combined with emotional blunting and small or missing production of hallucinations and and small or missing production of hallucinations and delusionsdelusions

• tthe he positive positive symptomsymptom are characterized by the presence of are characterized by the presence of hallucinations and delusionshallucinations and delusions

• tthe division is not quite strict and lesser or greater mixture he division is not quite strict and lesser or greater mixture of symptoms from these two groups are possibleof symptoms from these two groups are possible

Positive and Negative SymptomsPositive and Negative Symptoms

NegativeNegative PositivePositiveAlogiaAlogia HallucinationsHallucinationsAffective flatteningAffective flattening DelusionsDelusionsAvolition-apathyAvolition-apathy Bizarre behaviourBizarre behaviourAnhedonia-asocialityAnhedonia-asociality Positive formal thought Positive formal thought

disorderdisorderAttentional impairmentAttentional impairment

Andreasen N.C., Roy M.-A., Flaum M.: Positive and negative symptoms. In: Schizophrenia, Hirsch S.R. and Weinberger D.R., eds., Blackwell Science, pp. 28-45, 1995

The Criteria of DiagnosisThe Criteria of DiagnosisFor the For the diagnosis of schizophreniadiagnosis of schizophrenia is necessary is necessary presence of one very clear symptom presence of one very clear symptom - - from point a) to d)from point a) to d) or the presence of the symptoms from at least two groups or the presence of the symptoms from at least two groups - -

from point e) to h)from point e) to h)for one month or more:for one month or more:

a)a) the hearing of own thoughts, the feelings of thought the hearing of own thoughts, the feelings of thought withdrawal, thought insertion, or thought broadcastingwithdrawal, thought insertion, or thought broadcasting

b)b) the delusions of control, outside manipulation and influence, the delusions of control, outside manipulation and influence, or the feelings of passivity, which are connected with the or the feelings of passivity, which are connected with the movements of the body or extremities, specific thoughts, movements of the body or extremities, specific thoughts, acting or feelings, delusional perceptionacting or feelings, delusional perception

c)c) hallucinated voices, which are commenting permanently the hallucinated voices, which are commenting permanently the behavior of the patient or they talk about him between behavior of the patient or they talk about him between themselves, or the other types of hallucinatory voices, themselves, or the other types of hallucinatory voices, coming from different parts of bodycoming from different parts of body

d)d) permanent delusions of different kind, which are permanent delusions of different kind, which are inappropriate and unacceptable in given cultureinappropriate and unacceptable in given culture

The Criteria of DiagnosisThe Criteria of Diagnosise)e) the lasting hallucination of every formthe lasting hallucination of every formf)f) blocks or intrusion of thoughts into the flow of thinking and blocks or intrusion of thoughts into the flow of thinking and

resulting incoherence and irrelevance of speach, or resulting incoherence and irrelevance of speach, or neologismsneologisms

g)g) catatonic behaviorcatatonic behaviorh)h) „„the negative symptoms”, for instance the expressed apathy, the negative symptoms”, for instance the expressed apathy,

poor speech, blunting and inappropriatness of emotional poor speech, blunting and inappropriatness of emotional reactionsreactions

i)i) expressed and conspicuous qualitative changes in patient’s expressed and conspicuous qualitative changes in patient’s behavior, the loss of interests, hobbies, aimlesness, behavior, the loss of interests, hobbies, aimlesness, inactivity, the loss of relations to others and social inactivity, the loss of relations to others and social withdrawalwithdrawal

Diagnosis of Diagnosis of acute schizophorm disorderacute schizophorm disorder (F23.2) – if the (F23.2) – if the conditions for diagnosis of schizophrenia are fulfilled, but conditions for diagnosis of schizophrenia are fulfilled, but lasting less than one monthlasting less than one month

Diagnosis of Diagnosis of schizoaffective disorderschizoaffective disorder (F25) - if the (F25) - if the schizophrenic and affective symptoms are developing schizophrenic and affective symptoms are developing together at the same timetogether at the same time

F20-F29 F20-F29 Schizophrenia, Schizotypal Schizophrenia, Schizotypal and Delusional Disorders and Delusional Disorders

F20 F20 SchizophreniaSchizophrenia F20.0 F20.0 Paranoid schizophrenia Paranoid schizophrenia F20.1 Hebephrenic schizophrenia F20.1 Hebephrenic schizophrenia F20.2 Catatonic schizophrenia F20.2 Catatonic schizophrenia F20.3 Undifferentiated schizophrenia F20.3 Undifferentiated schizophrenia F20.4 Post-schizophrenic depression F20.4 Post-schizophrenic depression F20.5 Residual schizophrenia F20.5 Residual schizophrenia F20.6 Simple schizophrenia F20.6 Simple schizophrenia F20.8 Other schizophrenia F20.8 Other schizophrenia F20.9 Schizophrenia, unspecified F20.9 Schizophrenia, unspecified

F20-F29 F20-F29 Schizophrenia, Schizotypal Schizophrenia, Schizotypal and Delusional Disordersand Delusional Disorders

F21 F21 Schizotypal disorderSchizotypal disorder F22 F22 Persistent delusional disordersPersistent delusional disorders F22.0 F22.0 Delusional disorder Delusional disorder F22.8 F22.8 Other persistent delusional disorders Other persistent delusional disorders F22.9 F22.9 Persistent delusional disorder, unspecified Persistent delusional disorder, unspecified F23 F23 Acute and transient psychotic disordersAcute and transient psychotic disorders F23.1 F23.1 Acute polymorphic psychotic disorder with Acute polymorphic psychotic disorder with

symptoms of schizophrenia symptoms of schizophrenia F23.2 F23.2 Acute schizophrenia-like psychotic disorder Acute schizophrenia-like psychotic disorder F23.3 F23.3 Other acute predominantly delusional Other acute predominantly delusional

psychotic disorders psychotic disorders F23.8 F23.8 Other acute and transient psychotic disorders Other acute and transient psychotic disorders F23.9 F23.9 Acute and transient psychotic disorder, Acute and transient psychotic disorder,

unspecified unspecified

F20-F29 F20-F29 Schizophrenia, Schizotypal Schizophrenia, Schizotypal and Delusional Disordersand Delusional Disorders

F24 F24 Induced delusional disorderInduced delusional disorder F25 F25 Schizoaffective disordersSchizoaffective disorders F25.0 F25.0 Schizoaffective disorder, manic type Schizoaffective disorder, manic type F25.1 F25.1 Schizoaffective disorder, depressive type Schizoaffective disorder, depressive type F25.2 F25.2 Schizoaffective disorder, mixed type Schizoaffective disorder, mixed type F25.8 F25.8 Other schizoaffective disorders Other schizoaffective disorders F25.9 F25.9 Schizoaffective disorder, unspecified Schizoaffective disorder, unspecified F28 F28 Other nonorganic psychotic disorders Other nonorganic psychotic disorders F29 F29 Unspecified nonorganic psychosisUnspecified nonorganic psychosis

F20.0 Paranoid Schizophrenia F20.0 Paranoid Schizophrenia

Paranoid schizophreniaParanoid schizophrenia is characterized is characterized mainly by delusions of persecution, mainly by delusions of persecution, feelings of passive or active control, feelings of passive or active control, feelings of intrusion, and often by feelings of intrusion, and often by megalomanic tendencies also. The megalomanic tendencies also. The delusions are not usually systemized too delusions are not usually systemized too much, without tight logical connections much, without tight logical connections and are often combined with and are often combined with hallucinations of different senses, mostly hallucinations of different senses, mostly with hearing voices. with hearing voices.

Disturbances of affect, volition and Disturbances of affect, volition and speech, and catatonic symptoms, are speech, and catatonic symptoms, are either absent or relatively inconspicuous. either absent or relatively inconspicuous.

F20.1 Hebephrenic SchizophreniaF20.1 Hebephrenic Schizophrenia Hebephrenic schizophreniaHebephrenic schizophrenia is characterized by is characterized by

disorganized thinking with blunted and disorganized thinking with blunted and inappropriate emotions. It begins mostly in inappropriate emotions. It begins mostly in adolescent age, the behavior is often bizarre. There adolescent age, the behavior is often bizarre. There could appear mannerisms, grimacing, inappropriate could appear mannerisms, grimacing, inappropriate laugh and joking, pseudophilosophical brooding and laugh and joking, pseudophilosophical brooding and sudden impulsive reactions without external sudden impulsive reactions without external stimulation. There is a tendency to social isolation.stimulation. There is a tendency to social isolation.

Usually the prognosis is poor because of the rapid Usually the prognosis is poor because of the rapid development of "negative" symptoms, particularly development of "negative" symptoms, particularly flattening of affect and loss of volition. Hebephrenia flattening of affect and loss of volition. Hebephrenia should normally be diagnosed only in adolescents should normally be diagnosed only in adolescents or young adultsor young adults..

Denoted also as Denoted also as disorganized schizophreniadisorganized schizophrenia

F20.2 Catatonic SchizophreniaF20.2 Catatonic Schizophrenia Catatonic schizophreniaCatatonic schizophrenia is characterized is characterized

mainly by motoric activity, which might be mainly by motoric activity, which might be strongly increased (hypekinesis) or strongly increased (hypekinesis) or decreased (stupor), or automatic obedience decreased (stupor), or automatic obedience and negativism. and negativism.

We recognize two forms:We recognize two forms:• productive formproductive form — which shows catatonic — which shows catatonic

excitement, extreme and often aggressive excitement, extreme and often aggressive activity. activity. TreatmentTreatment by neuroleptics or by by neuroleptics or by electroconvulsive therapy.electroconvulsive therapy.

• stuporose formstuporose form — characterized by general — characterized by general inhibition of patient’s behavior or at least by inhibition of patient’s behavior or at least by retardation and slowness, followed often by retardation and slowness, followed often by mutism, negativism, fexibilitas cerea or by mutism, negativism, fexibilitas cerea or by stupor. The consciousness is not absent. stupor. The consciousness is not absent.

F20.3 Undifferentiated F20.3 Undifferentiated SchizophreniaSchizophrenia

Psychotic conditions meeting the general Psychotic conditions meeting the general diagnostic criteria for schizophrenia but diagnostic criteria for schizophrenia but not conforming to any of the subtypes in not conforming to any of the subtypes in F20.0-F20.2, or exhibiting the features of F20.0-F20.2, or exhibiting the features of more than one of them without a clear more than one of them without a clear predominance of a particular set of predominance of a particular set of diagnostic characteristics.diagnostic characteristics.

This subgroup represents also the former This subgroup represents also the former diagnosis of diagnosis of atypical schizophreniaatypical schizophrenia..

F20.4 Postschizophrenic F20.4 Postschizophrenic DepressionDepression

A depressive episode, which may be A depressive episode, which may be prolonged, arising in the aftermath of a prolonged, arising in the aftermath of a schizophrenic illness. Some schizophrenic schizophrenic illness. Some schizophrenic symptoms, either symptoms, either „„positivepositive““ or or „„negativenegative““, , must still be present but they no longer must still be present but they no longer dominate the clinical picture. dominate the clinical picture.

These depressive states are associated These depressive states are associated with an increased risk of suicide. with an increased risk of suicide.

F20.5 Residual SchizophreniaF20.5 Residual Schizophrenia AA chronic stage in the development of chronic stage in the development of

schizophrenia with clear succession from schizophrenia with clear succession from the initial stage with one or more episodes the initial stage with one or more episodes characterized by general criteria of characterized by general criteria of schizophrenia to the late stage with long-schizophrenia to the late stage with long-lasting negative symptoms and lasting negative symptoms and deterioration (not necessarily irreversible).deterioration (not necessarily irreversible).

F20.6 Simple SchizophreniaF20.6 Simple Schizophrenia

Simple schizophrenia is characterized by Simple schizophrenia is characterized by early and slowly developing initial stage early and slowly developing initial stage with growing social isolation, withdrawal, with growing social isolation, withdrawal, small activity, passivity, avolition and small activity, passivity, avolition and dependence on the others.dependence on the others.

The patients are indifferent, without any The patients are indifferent, without any initiative and volition. There is not initiative and volition. There is not expressed the presence of hallucinations expressed the presence of hallucinations and delusions.and delusions.

F21 F21 Schizotypal disorderSchizotypal disorder According to lCD-10 this disorder is According to lCD-10 this disorder is

characterized by eccentric behavior and characterized by eccentric behavior and by deviations of thinking and affectivity, by deviations of thinking and affectivity, which are similar to that occurring in which are similar to that occurring in schizophrenia, but without psychotic schizophrenia, but without psychotic features and expressed symptoms of features and expressed symptoms of schizophrenia of any type.schizophrenia of any type.

F22 Persistent Delusional F22 Persistent Delusional DisordersDisorders

Includes a variety of disorders in which Includes a variety of disorders in which long-standing delusions constitute the long-standing delusions constitute the only, or the most conspicuous, clinical only, or the most conspicuous, clinical characteristic and which cannot be characteristic and which cannot be classified as organic, schizophrenic or classified as organic, schizophrenic or affective. affective.

Their origin is probably heterogeneous, Their origin is probably heterogeneous, but it seems, that there is some relation to but it seems, that there is some relation to schizophrenia.schizophrenia.

F22.0 F22.0 Delusional DisorderDelusional Disorder A disorder characterized by the A disorder characterized by the

development of one delusion or of the development of one delusion or of the group of similar related delusions, which group of similar related delusions, which are persisting unusually long, very often are persisting unusually long, very often for the whole life. for the whole life.

Other psychopathological symptoms — Other psychopathological symptoms — hallucinations, intrusion of thoughts etc. hallucinations, intrusion of thoughts etc. are not present and are excluding this are not present and are excluding this diagnosis. diagnosis.

It begins usually in the middle age.It begins usually in the middle age.

F23 F23 Acute and Transient Acute and Transient Psychotic DisordersPsychotic Disorders

The criteria should be the following The criteria should be the following features:features:• acute beginning (to two weeks)acute beginning (to two weeks)• presence of typical symptoms (quickly presence of typical symptoms (quickly

changing “polymorphic symptoms”)changing “polymorphic symptoms”)• presence of typical schizophrenic symptoms.presence of typical schizophrenic symptoms.

Complete recovery usually occurs within a Complete recovery usually occurs within a few months, often within a few weeks or few months, often within a few weeks or even days.even days.

The disorder may or may not be The disorder may or may not be associated with acute stress, defined as associated with acute stress, defined as usually stressful events preceding the usually stressful events preceding the onset by one to two weeks. onset by one to two weeks.

F24 Induced Delusional Disorder F24 Induced Delusional Disorder A delusional disorder shared by two or A delusional disorder shared by two or

more people with close emotional links. more people with close emotional links. Only one of the people suffers from a Only one of the people suffers from a genuine psychotic disorder; the delusions genuine psychotic disorder; the delusions are induced in the other(s) and usually are induced in the other(s) and usually disappear when the people are separated.disappear when the people are separated.

The psychotic disorder of the dominant The psychotic disorder of the dominant member of this dyad is mainly, but not member of this dyad is mainly, but not necessarily, of schizophrenic type. The necessarily, of schizophrenic type. The original delusions of dominant member original delusions of dominant member and his partner are usually chronic, either and his partner are usually chronic, either persecutory or megalomanic.persecutory or megalomanic.

F25 Schizoaffective Disorders F25 Schizoaffective Disorders Episodic disorders in which both affective and Episodic disorders in which both affective and

schizophrenic symptoms are prominent schizophrenic symptoms are prominent ((during the during the same episode of the illness or at least during few same episode of the illness or at least during few daysdays)) but which do not justify a diagnosis of either but which do not justify a diagnosis of either schizophrenia or depressive or manic episodes. schizophrenia or depressive or manic episodes.

Patients suffering from periodic schizoaffective Patients suffering from periodic schizoaffective disorders, especially with manic symptoms, have disorders, especially with manic symptoms, have usually good prognosis with full remissions without usually good prognosis with full remissions without any remaining defects.any remaining defects.

They are divided in different subgroups:They are divided in different subgroups:• F25.0 Schizoaffective disorder, manic type F25.0 Schizoaffective disorder, manic type • F25.1 Schizoaffective disorder, depressive type F25.1 Schizoaffective disorder, depressive type • F25.2 Schizoaffective disorder, mixed type F25.2 Schizoaffective disorder, mixed type • F25.8 Other schizoaffective disorders F25.8 Other schizoaffective disorders • F25.9 Schizoaffective disorder, unspecifiedF25.9 Schizoaffective disorder, unspecified

Genetics of SchizophreniaGenetics of Schizophrenia

Many psychiatric disorders are Many psychiatric disorders are multifactorial (caused by the interaction of multifactorial (caused by the interaction of external and genetic factors) and from the external and genetic factors) and from the genetic point of view very often genetic point of view very often polygenically determined.polygenically determined.

Relative risk for schizophrenia is around:Relative risk for schizophrenia is around:• 1% for normal population1% for normal population• 5.6% for parents5.6% for parents• 10.1% for siblings10.1% for siblings• 12.8% for children12.8% for children

Etiology of SchizophreniaEtiology of Schizophrenia

The etiology and pathogenesis of The etiology and pathogenesis of schizophrenia is not knownschizophrenia is not known

It is accepted, that schizophrenia is It is accepted, that schizophrenia is „the group of schizophrenias“ which „the group of schizophrenias“ which origin is multifactorial:origin is multifactorial:• internal factors – genetic, inborn, internal factors – genetic, inborn,

biochemicalbiochemical• external factors – trauma, infection of external factors – trauma, infection of

CNS, stressCNS, stress

Etiology of Schizophrenia - Etiology of Schizophrenia - Dopamine HypothesisDopamine Hypothesis

The most influential and plausible are the The most influential and plausible are the hypotheses, based on the supposed disorder of hypotheses, based on the supposed disorder of neurotransmission in the brain, derived mainly fromneurotransmission in the brain, derived mainly from1.1. the effects of antipsychotic drugs that have in common the the effects of antipsychotic drugs that have in common the

ability to inhibit the dopaminergic system by blocking ability to inhibit the dopaminergic system by blocking action of dopamine in the brainaction of dopamine in the brain

2.2. dopamine-releasing drugs (amphetamine, mescaline, dopamine-releasing drugs (amphetamine, mescaline, diethyl amide of lysergic acid - LSD) that can induce state diethyl amide of lysergic acid - LSD) that can induce state closely resembling paranoid schizophreniaclosely resembling paranoid schizophrenia

Classical dopamine hypothesis of schizophreniaClassical dopamine hypothesis of schizophrenia: : Psychotic symptoms are related to dopaminergic Psychotic symptoms are related to dopaminergic hyperactivity in the brain. Hyperactivity of hyperactivity in the brain. Hyperactivity of dopaminergic systems during schizophrenia is result dopaminergic systems during schizophrenia is result of increased sensitivity and density of dopamine D2 of increased sensitivity and density of dopamine D2 receptors in the different parts of the brain.receptors in the different parts of the brain.

Etiology of Schizophrenia - Etiology of Schizophrenia - Contemporary ModelsContemporary Models

Dopamine hypothesis revisitedDopamine hypothesis revisited: various : various neurotransmitter systems probably takes place in neurotransmitter systems probably takes place in the etiology of schizophrenia (norepinephric, the etiology of schizophrenia (norepinephric, serotonergic, glutamatergic, some peptidergic serotonergic, glutamatergic, some peptidergic systems); based on effects of atypical systems); based on effects of atypical antipsychotics especially.antipsychotics especially.

Contemporary models of schizophreniaContemporary models of schizophrenia conceptualize it as a neurocognitive disorder, conceptualize it as a neurocognitive disorder, with the various signs and symptoms reflecting with the various signs and symptoms reflecting the downstream effects of a more fundamental the downstream effects of a more fundamental cognitive deficit:cognitive deficit:• the symptoms of schizophrenia arise from “cognitive the symptoms of schizophrenia arise from “cognitive

dysmetria” (Nancy C. Andreasen)dysmetria” (Nancy C. Andreasen)• concept of schizophrenia as a neurodevelopmental concept of schizophrenia as a neurodevelopmental

disorder (Daniel R. Weinberger)disorder (Daniel R. Weinberger)

Etiology of Schizophrenia - Etiology of Schizophrenia - Neurodevelopmental ModelNeurodevelopmental Model

Neurodevelopmental modelNeurodevelopmental model supposes in supposes in schizophrenia the presence of “silent lesion” in schizophrenia the presence of “silent lesion” in the brain, mostly in the parts, important for the the brain, mostly in the parts, important for the development of integration (frontal, parietal and development of integration (frontal, parietal and temporal), which is caused by different factors temporal), which is caused by different factors (genetic, inborn, infection, trauma...) during very (genetic, inborn, infection, trauma...) during very early development of the brain in prenatal or early early development of the brain in prenatal or early postnatal period of life. postnatal period of life.

It does not interfere too much with the basic brain It does not interfere too much with the basic brain functioning in early years, but expresses itself in functioning in early years, but expresses itself in the time, when the subject is stressed by the time, when the subject is stressed by demands of growing needs for integration, during demands of growing needs for integration, during formative years in adolescence and young formative years in adolescence and young adulthood.adulthood.

Treatment of SchizophreniaTreatment of Schizophrenia The acute psychotic schizophrenic patients will The acute psychotic schizophrenic patients will

respond usually to antipsychotic medication.respond usually to antipsychotic medication. According to current consensus we use in the first According to current consensus we use in the first

line therapy the newer atypical antipsychotics, line therapy the newer atypical antipsychotics, because their use is not complicated by appearance because their use is not complicated by appearance of extrapyramidal side-effects, or these are much of extrapyramidal side-effects, or these are much lower than with classical antipsychotics.lower than with classical antipsychotics.

conventional antipsychotics(classical neuroleptics)

chlorpromazine, chlorprotixene, clopenthixole, levopromazine, periciazine, thioridazinedroperidole, flupentixol, fluphenazine, fluspirilene, haloperidol, melperone, oxyprothepine, penfluridol, perphenazine, pimozide, prochlorperazine, trifluoperazine

atypical antipsychotics

amisulpiride, clozapine, olanzapine, quetiapine, risperidone, sertindole, sulpiride

Positive vs. negative symptomsPositive vs. negative symptomsPositive symptomsPositive symptoms

DelusionsDelusionsHallucinationsHallucinationsBehavioral dyscontrolBehavioral dyscontrolThought disorderThought disorder

Negative symptomsNegative symptoms(Remember (Remember

Andreasen’s “A”s)Andreasen’s “A”s)

Affective Affective flatteningflatteningAlogiaAlogiaAvolitionAvolitionAnhedoniaAnhedoniaAttentional Attentional impairmentimpairment

Psychotic DisordersPsychotic Disorders

Schizo-Schizo-phreniaphrenia

Usually Usually insidiousinsidious

ManyMany ChronicChronic >6 months>6 months

Delusional Delusional disorderdisorder

Varies Varies (usually (usually insidious)insidious)

Delusions Delusions onlyonly

ChronicChronic >1 mo.>1 mo.

Brief Brief psychotic psychotic disorderdisorder

SuddenSudden VariesVaries LimitedLimited <1 mo.<1 mo.

Onset Symptoms Course Duration

Psychosocial FactorsPsychosocial Factors Expressed emotionExpressed emotion Stressful life eventsStressful life events Low socioeconomic classLow socioeconomic class Limited social networkLimited social network

Some factors rejected as causalSome factors rejected as causal

““Schizophrenogenic Mother”Schizophrenogenic Mother”

““Skewed” family structureSkewed” family structure

Genetic factors:Genetic factors:(The evidence mounts…)(The evidence mounts…)

Monozygotic twins (31%-78%) vs Monozygotic twins (31%-78%) vs dizygotic twinsdizygotic twins

4-9% risk in first degree relatives of 4-9% risk in first degree relatives of schizophrenicsschizophrenics

Adoption studiesAdoption studies Linkage, molecular studiesLinkage, molecular studies

Genetics of Schizophrenia:Genetics of Schizophrenia:The take-home messageThe take-home message

Vulnerability Vulnerability to schizophrenia is to schizophrenia is likely inheritedlikely inherited

““Heritability” is probably 60-90%Heritability” is probably 60-90% Schizophrenia probably involves Schizophrenia probably involves

dysfunction of many genesdysfunction of many genes

Anatomical abnormalitiesAnatomical abnormalities Enlargement of lateral ventriclesEnlargement of lateral ventricles Smaller than normal total brain Smaller than normal total brain

volumevolume Cortical atrophyCortical atrophy Widening of third ventricleWidening of third ventricle Smaller hippocampusSmaller hippocampus

Physiologic studies:Physiologic studies:PET and SPECTPET and SPECT

Generally normal global cerebral flowGenerally normal global cerebral flow HypofrontalityHypofrontality Failure to activate dorsolateral Failure to activate dorsolateral

prefrontal cortex (problem-solving, prefrontal cortex (problem-solving, adaptation, coping with changes)adaptation, coping with changes)

Biochemical factors:Biochemical factors:The dopamine hypothesisThe dopamine hypothesis

All typical antipsychotics block DAll typical antipsychotics block D2 2

with varying affinitieswith varying affinities Dopamine agonists can precipitate a Dopamine agonists can precipitate a

psychosispsychosis• AmphetaminesAmphetamines• CocaineCocaine• L-dopaL-dopa

Dopamine systemsDopamine systems

Nigro-Nigro-striatalstriatal

SubstantiaSubstantiaNigraNigra

Caudate Caudate and and putamenputamen

Move-Move-mentment

Extrapyramidal Extrapyramidal symptoms, dystonias, symptoms, dystonias, Tardive dyskinesiaTardive dyskinesia

Meso-Meso-limbiclimbic

Ventral Ventral tegmental tegmental area, subst. area, subst. nigranigra

Accumbens Accumbens amygdalaamygdalaOlfactory Olfactory tubercletubercle

Emotions,Emotions,affect, affect, memorymemory

Positive symptomsPositive symptoms

Meso-Meso-corticalcortical

Ventral Ventral tegmental tegmental areaarea

PrefrontalPrefrontalCortexCortex

Thought, Thought, volition, volition, memorymemory

Blockade here can Blockade here can worsen negative worsen negative symptoms.symptoms.

Cell bodies Projections FunctionsClinical

implications

Typical NeurolepticsTypical Neuroleptics Low potency:Low potency:

• ChlorpromazineChlorpromazine• ThioridazineThioridazine• MesoridazineMesoridazine

High potency:High potency:• HaloperidolHaloperidol• FluphenazineFluphenazine• ThiothixeneThiothixene• Loxapine (mid)Loxapine (mid)

Neuroleptic (typicals):Neuroleptic (typicals):side effectsside effects

Acute dystoniaAcute dystonia Parkinsonian side effects (EPS)Parkinsonian side effects (EPS) AkathisiaAkathisia Tardive dyskinesiaTardive dyskinesia Sedation, orthostasis, QTC Sedation, orthostasis, QTC

prolongation, anticholinergic, lower prolongation, anticholinergic, lower seizure threshold, increased prolactinseizure threshold, increased prolactin

Atypical Antipsychotics:Atypical Antipsychotics: RisperidoneRisperidone OlanzapineOlanzapine QuetiapineQuetiapine ClozapineClozapine ZiprasidoneZiprasidone Aripiprazole (new-partial DA agonist)Aripiprazole (new-partial DA agonist)

Atypical antipsychotics:Atypical antipsychotics: Broader spectrum of receptor activity Broader spectrum of receptor activity

(Serotonin, dopamine, GABA)(Serotonin, dopamine, GABA) May be better at alleviating negative May be better at alleviating negative

symptoms and cognitive dysfunctionsymptoms and cognitive dysfunction Clozaril (clozapine) associated with Clozaril (clozapine) associated with

agranulocytosis, seizuresagranulocytosis, seizures

Atypical Antipsychotics: Side Atypical Antipsychotics: Side EffectsEffects

SedationSedation Hyperglycemia, new-onset diabetesHyperglycemia, new-onset diabetes Anticholinergic effectsAnticholinergic effects Less prolactin elevationLess prolactin elevation QTC prolongationQTC prolongation Some EPSSome EPS Increased lipidsIncreased lipids

Psychosocial TreatmentPsychosocial Treatment Education, compliance #1Education, compliance #1 Hospitalize for acute loss of Hospitalize for acute loss of

functioningfunctioning Outpatient treatment is rehabilitativeOutpatient treatment is rehabilitative Psychoanalysis, exploratory Psychoanalysis, exploratory

therapies have limited valuetherapies have limited value Families should be involvedFamilies should be involved

GeneticsGenetics Greatest risk factor is having a Greatest risk factor is having a

relative with SCZrelative with SCZ 70% of the heritability of 70% of the heritability of

schizophrenia is geneticschizophrenia is genetic MZ twin – 48% risk; DZ twin 17%MZ twin – 48% risk; DZ twin 17% Child of one parent with SCZ – 13%Child of one parent with SCZ – 13% Child of two parents with SCZ – 46%Child of two parents with SCZ – 46%

GeneticsGenetics Adoption studies indicate that Adoption studies indicate that

heritability rates are similar even if heritability rates are similar even if adopted awayadopted away

Probably polygenic/multifactorial Probably polygenic/multifactorial modelmodel

No clear gene responsible although No clear gene responsible although interest in various genesinterest in various genes

Neurodevelopmental TheoriesNeurodevelopmental Theories Hypothesis states that impaired Hypothesis states that impaired

foetal or neonatal brain development foetal or neonatal brain development many sow the seeds of the onset of many sow the seeds of the onset of psychotic symptoms in later lifepsychotic symptoms in later life

Patients with SCZ have lower than Patients with SCZ have lower than average IQ, often subtle average IQ, often subtle psychomotor, behaviourla, and social psychomotor, behaviourla, and social abnormalitiesabnormalities

Neurodevelopmental TheoriesNeurodevelopmental Theories Patients with SCZ have more Patients with SCZ have more

developmental structural brain developmental structural brain abnormalitiesabnormalities

Soft neurological signsSoft neurological signs Increase in craniofacial and Increase in craniofacial and

dermatoglyphic abnormalitiesdermatoglyphic abnormalities More obstetric complications More obstetric complications

recordedrecorded Exposure to influenza virus?Exposure to influenza virus?

Psychological TheoriesPsychological Theories Freud – delusions as a way of making Freud – delusions as a way of making

sense of the external worldsense of the external world Klein – failure to resolve the Klein – failure to resolve the

paranoid/schizoid positionparanoid/schizoid position Cameron – loss of conceptual Cameron – loss of conceptual

boundariesboundaries Goldstein – concrete thinkingGoldstein – concrete thinking Difficulties in filtering senory input?Difficulties in filtering senory input?

Familial/Social TheoriesFamilial/Social Theories Probably important in precipitating Probably important in precipitating

schizophrenia than causing itschizophrenia than causing it Lidz – marital schism/marital skewLidz – marital schism/marital skew Bateson – double bindBateson – double bind High expressed emotion High expressed emotion It has been hypothesised that life evetns It has been hypothesised that life evetns

could precipitate SCZ – more life events in could precipitate SCZ – more life events in the 3 weeks prior to episode than with the 3 weeks prior to episode than with healthy controlshealthy controls

PrognosisPrognosis 22% have one episode and no 22% have one episode and no

residual impairmentresidual impairment 35% have recurrent episodes and no 35% have recurrent episodes and no

residual impairmentresidual impairment 8% have recurrent epsiodes and 8% have recurrent epsiodes and

develop significant non-progressive develop significant non-progressive impairmentimpairment

35% have recurrent episodes and 35% have recurrent episodes and develop significant progressive develop significant progressive impairmentimpairment

TreatmentTreatment May require admission if acutely May require admission if acutely

disturbed or present a risk to self or disturbed or present a risk to self or othersothers

Admission may be useful in Admission may be useful in assessmentassessment

Essential to assess suicide risk as Essential to assess suicide risk as there is a mortality of about 10% there is a mortality of about 10% from suicide in SCZfrom suicide in SCZ

May require involuntary detention in May require involuntary detention in some casessome cases

Treatment contd.Treatment contd. Antipsychotic drugs are mainstay of Antipsychotic drugs are mainstay of

treatmenttreatment Generally atypicals are first-line Generally atypicals are first-line

treatment eg olanzapine, treatment eg olanzapine, respiridone, amisulpiriderespiridone, amisulpiride

May require depot injectionMay require depot injection Side effects of typicals can be Side effects of typicals can be

stigmatisingstigmatising Side effects of atypicals – screen for Side effects of atypicals – screen for

DMDM

Treatment contd.Treatment contd. Atypicals have fewer extra-pyramidal Atypicals have fewer extra-pyramidal

side effects and tend to be better for side effects and tend to be better for negative symptoms that typicalsnegative symptoms that typicals

Initial management may include use Initial management may include use of sedative medication such as of sedative medication such as lorazepamlorazepam

IM medication may be required in a IM medication may be required in a very disturbed, involuntary patientvery disturbed, involuntary patient

Treatment contd.Treatment contd. Maintenance treatment – generally Maintenance treatment – generally

maintenance on one medicationmaintenance on one medication Compliance may be a significant Compliance may be a significant

problem because of long-term nature problem because of long-term nature of treatment and lack of insightof treatment and lack of insight

Treatment contd.Treatment contd. Psychosocial treatment Psychosocial treatment

Education of patient and carersEducation of patient and carers Reduction of high expressed emotion – shown Reduction of high expressed emotion – shown

to affect relapse ratesto affect relapse rates Cognitive behavioural therapy – controversialCognitive behavioural therapy – controversial RehabilitationRehabilitation Self –help – Schizophrenia IrelandSelf –help – Schizophrenia Ireland

PrognosisPrognosis 22% have one episode and no 22% have one episode and no

residual impairmentresidual impairment 35% have recurrent episodes and no 35% have recurrent episodes and no

residual impairmentresidual impairment 8% have recurrent epsiodes and 8% have recurrent epsiodes and

develop significant non-progressive develop significant non-progressive impairmentimpairment

35% have recurrent episodes and 35% have recurrent episodes and develop significant progressive develop significant progressive impairmentimpairment

Prognosis contd.Prognosis contd. The majority therefore do not The majority therefore do not

recover fullyrecover fully Suicide rate is up to 13%Suicide rate is up to 13% Little evidence that anitpsychotic Little evidence that anitpsychotic

have altered the course of illness for have altered the course of illness for most patientsmost patients

However, evidence that prolonged However, evidence that prolonged psychosis which is untreated has a psychosis which is untreated has a bad prognosisbad prognosis

Prognosis contd.Prognosis contd. Good outcome is associated with:Good outcome is associated with:

• FemaleFemale• Older age of onsetOlder age of onset• MarriedMarried• Higher SEGHigher SEG• Living in a developing (as opposed to developed) Living in a developing (as opposed to developed)

countrycountry• Good premorbid personalityGood premorbid personality• No previous psych historyNo previous psych history• Good education and employment recordGood education and employment record• Acute onset, affective symptoms, good Acute onset, affective symptoms, good

compliance with medscompliance with meds

Prognosis contd.Prognosis contd. Some of the predictors of outcome Some of the predictors of outcome

are the consequence of a less severe are the consequence of a less severe illnessillness

Predicting risk of suicidePredicting risk of suicide Acute exacerbation of psychosisAcute exacerbation of psychosis Depressive symptomsDepressive symptoms History of attempted suicideHistory of attempted suicide