Chief Dr H.T.O. LADAPO, MD (Ukraine) FMC Psych.., FWACP, FHAN, MPH ( Unilag )

Mental Health CareMental Health CareChallenges in Challenges in Management of Management of Schizophrenia and Schizophrenia and other non affective other non affective psychosispsychosis

presented by presented by

Chief Dr H.T.O. LADAPO, MD (Ukraine) FMC Chief Dr H.T.O. LADAPO, MD (Ukraine) FMC Psych.., FWACP, FHAN, MPH (Unilag)Psych.., FWACP, FHAN, MPH (Unilag)

Introduction (1) Introduction (1)

Early Greek physicians described Early Greek physicians described delusions of grandeur, paranoia, delusions of grandeur, paranoia, and deterioration in cognitive and deterioration in cognitive functions and personality. functions and personality.

Schizophrenia did not emerge as Schizophrenia did not emerge as a medical condition worthy of a medical condition worthy of study and treatment until the study and treatment until the eighteenth century. eighteenth century.

Intoduction (2)Intoduction (2)

Emil Kraepelin delineated Emil Kraepelin delineated insanity: manic-depressive insanity: manic-depressive psychosis and dementia praecox psychosis and dementia praecox (or dementia of the young) (or dementia of the young)

In 1911 Eugen Bleuler suggested In 1911 Eugen Bleuler suggested the term schizophrenia (splitting the term schizophrenia (splitting of the mind) for the disorder.of the mind) for the disorder.

Intoduction (3)Intoduction (3)

He also described four primary He also described four primary symptoms (the four As): abnormal symptoms (the four As): abnormal associations, autistic behavior associations, autistic behavior and thinking, abnormal affect, and thinking, abnormal affect, and ambivalence.and ambivalence.

Intoduction (4)Intoduction (4) Nondisease models: Nondisease models:

-The societal reaction theory ("a -The societal reaction theory ("a sane reaction to an insane world")sane reaction to an insane world")

-Thomas Szasz's theory which states -Thomas Szasz's theory which states that schizophrenia is a myth that schizophrenia is a myth enabling society to manage enabling society to manage deviant behaviordeviant behavior

Epidemiology (1)Epidemiology (1)

Schizophrenia is a leading public Schizophrenia is a leading public health problem that exacts health problem that exacts enormous personal and economic enormous personal and economic costs worldwide. costs worldwide.

Schizophrenia affects just under 1 Schizophrenia affects just under 1 percent of the world's population percent of the world's population (approximately 0.85 percent).(approximately 0.85 percent).


NIMH’s Epidemiologic Catchment NIMH’s Epidemiologic Catchment Area (ECA) study – lifetime Area (ECA) study – lifetime prevalence 1.5%prevalence 1.5%

International Pilot Study of International Pilot Study of schizophrenia (IPSS)schizophrenia (IPSS)

Determinant of Outcome studies Determinant of Outcome studies by WHO (12 countries)by WHO (12 countries)


A 1987 review of over 70 A 1987 review of over 70 prevalence studies of prevalence studies of schizophrenia published since schizophrenia published since 1948 identified point prevalence 1948 identified point prevalence in various population groups in various population groups ranging from 0.06 percent to 1.7 ranging from 0.06 percent to 1.7 percent, with lower rates in percent, with lower rates in developing countries.developing countries.


Life time risk ranges from 0.7% to Life time risk ranges from 0.7% to 1.3%1.3%

The prevalence rate is similar in The prevalence rate is similar in different cultures when assessed using different cultures when assessed using similar instrument ( Jablensky et al similar instrument ( Jablensky et al 1992)1992)

Exceptions include Slovenia, Western Exceptions include Slovenia, Western Ireland, Catholics in Canada and Ireland, Catholics in Canada and Tamils of Southern IndiaTamils of Southern India


Low rates have been reported in Low rates have been reported in the Hutterrites and the the Hutterrites and the Anabaptist sects in the USAAnabaptist sects in the USA

Onset usually between the ages Onset usually between the ages of 15 and 45of 15 and 45

Peak age in men 15 - 25yearsPeak age in men 15 - 25years Peak age in women 25 – 35 yearsPeak age in women 25 – 35 years

Risk factorsRisk factors

Genetic FactorsGenetic Factors Ethnicity and Racial FactorsEthnicity and Racial Factors AgeAge Sex Sex Season and Birth OrderSeason and Birth Order Birth and Fetal ComplicationsBirth and Fetal Complications Social Class: ”downward drift” Social Class: ”downward drift”

and “social causation” theoriesand “social causation” theories

Risk factorsRisk factors

Marital StatusMarital Status ImmigrationImmigration Urbanization and IndustrializationUrbanization and Industrialization Life StressorsLife Stressors InfectionsInfections Suicide RiskSuicide Risk

Aetilogy (1)Aetilogy (1)

Cause is unknownCause is unknown

Results from a complex interplay Results from a complex interplay of genetic, environmental and of genetic, environmental and social factorssocial factors

Aetiology (2)Aetiology (2)

Neurobiological modelNeurobiological model

Structural abnormalities include:Structural abnormalities include: enlarged lateral ventricles enlarged lateral ventricles enlarged third ventricle, and enlarged third ventricle, and reduced volume of a number of reduced volume of a number of

structures, including hippocampus, structures, including hippocampus, amygdala, and frontal and amygdala, and frontal and temporal cortices. temporal cortices.

Aetiology (3) Aetiology (3)

Genetic factorsGenetic factors

Family studiesFamily studies Twin studiesTwin studies Adoption studiesAdoption studies

Population Prevalence (%)

Gen pop. 1.0

Non twin sibling 8.0

Child with one parent with schizophrenia 12.0

Dizygotic twin of schizophrenia patient 12.0

Child of two parents with schizophrenia 40.0

Monozygotic twin of a schizophrenia patient 47


Genetic factorsGenetic factors

Putative schizophrenia Putative schizophrenia susceptibility loci yielding some susceptibility loci yielding some evidence of confirmation include evidence of confirmation include loci on chromosomes 6, 8, and loci on chromosomes 6, 8, and 22.22.


Neurobiology Neurobiology blood flow to several brain blood flow to several brain

regions, including prefrontal and regions, including prefrontal and temporal areas, is altered in temporal areas, is altered in schizophrenia. These changes schizophrenia. These changes may be related to or may underlie may be related to or may underlie positive and negative symptoms positive and negative symptoms as well as some cognitive deficits.as well as some cognitive deficits.


Neurobiology Neurobiology

Biochemical basis of schizophreniaBiochemical basis of schizophrenia DopamineDopamine SerotoninSerotonin glutamateglutamate


Dopamine hypothesis:Dopamine hypothesis: It postulates a hyperactivity of It postulates a hyperactivity of

dopamine transmission at the D2 dopamine transmission at the D2 receptors in the mensecephalic receptors in the mensecephalic projection to the limbic striatum projection to the limbic striatum (Synder et al. 1974)(Synder et al. 1974)

Aetiology (8)Aetiology (8)Evidence in support of dopamine hyp.Evidence in support of dopamine hyp. There is a tight correlation between There is a tight correlation between

the therapeutic doses of the therapeutic doses of conventional antipsychotic drugs and conventional antipsychotic drugs and their affinities for D2 receptors their affinities for D2 receptors (Seeman, 1987)(Seeman, 1987)

Indirect dopamine agonists can Indirect dopamine agonists can induced psychosis in healthy subjects induced psychosis in healthy subjects and at very low doses provoke and at very low doses provoke psychotic symptoms in schizophrenia psychotic symptoms in schizophrenia (Carlsson 1988)(Carlsson 1988)

Postmortem and PET studies have Postmortem and PET studies have shown increased dopamine D2 shown increased dopamine D2 receptor level in the brain of receptor level in the brain of schizophrenic patients (Wing et al, schizophrenic patients (Wing et al, 1986)1986)

There is also emerging evidence for a There is also emerging evidence for a presynaptic dopaminergic abnormality presynaptic dopaminergic abnormality in schizophrenia (Laruelle et al 1999).in schizophrenia (Laruelle et al 1999).

Existing literature suggested heritable Existing literature suggested heritable abnormalities of prefrontal dopamine abnormalities of prefrontal dopamine function are prominent features of function are prominent features of schizophrenia (Egan et al, 2001) schizophrenia (Egan et al, 2001)

Serotonin Serotonin Serotonin receptors are involved in Serotonin receptors are involved in

the psychotomimetic and the psychotomimetic and psychotogenic properties of psychotogenic properties of hallucinogens [e.g (LSD)]; hallucinogens [e.g (LSD)];

the number of cortical 5-HT 2A and 5-the number of cortical 5-HT 2A and 5-HT 1A receptors is altered in HT 1A receptors is altered in schizophrenic brains; schizophrenic brains;

5-HT 2A and 5-HT 1A receptors play 5-HT 2A and 5-HT 1A receptors play a role in the therapeutic and/or side a role in the therapeutic and/or side effect profiles of atypical effect profiles of atypical antipsychotics (e.g., Clozapine); antipsychotics (e.g., Clozapine);

certain polymorphisms of the 5-HT certain polymorphisms of the 5-HT 2A receptor gene are associated 2A receptor gene are associated with schizophrenia;with schizophrenia;

the trophic role of serotonin in the trophic role of serotonin in neurodevelopment may be usurped neurodevelopment may be usurped in schizophrenia;in schizophrenia;

5-HT 2A receptor-mediated 5-HT 2A receptor-mediated activation of the prefrontal cortex activation of the prefrontal cortex may be impaired in some may be impaired in some schizophrenics;schizophrenics;

serotoninergic and dopaminergic serotoninergic and dopaminergic systems are interdependent and systems are interdependent and may be simultaneously affected may be simultaneously affected in schizophrenia (Liebermann et in schizophrenia (Liebermann et al. 1998, Harrison 1999).al. 1998, Harrison 1999).

Glutamate Glutamate Potent non-competitive antagonist of Potent non-competitive antagonist of

the NMDA subtype of glutamate the NMDA subtype of glutamate receptor (NMDA-R), induce receptor (NMDA-R), induce schizophrenia-like symptoms in healthy schizophrenia-like symptoms in healthy individuals and worsen some individuals and worsen some symptoms in Schizophrenia (Hirayasu symptoms in Schizophrenia (Hirayasu et al. 2001; Andreasen 1997). et al. 2001; Andreasen 1997).

Postmortem studies of schizophrenic Postmortem studies of schizophrenic brains additionally indicate brains additionally indicate abnormalities in pre and postsynaptic abnormalities in pre and postsynaptic glutamatergic indices.glutamatergic indices.

NMDA-R hypofunction in the cortical NMDA-R hypofunction in the cortical association pathways could be association pathways could be responsible for a variety of cognitive responsible for a variety of cognitive and other negative symptoms and other negative symptoms (Carlsson et al 2000).(Carlsson et al 2000).

It has been proposed that NMDA-R It has been proposed that NMDA-R antagonist can cause excess antagonist can cause excess compensatory release of glutamate compensatory release of glutamate that can over activate unoccupied that can over activate unoccupied non-NMDA glutamate receptors. This non-NMDA glutamate receptors. This might in part be responsible for their might in part be responsible for their behavioural effects. behavioural effects.

The effects of inhibiting NMDA-R The effects of inhibiting NMDA-R may manifest through dopamine may manifest through dopamine neurotransmission as dopamine neurotransmission as dopamine and glutamate systems in the and glutamate systems in the central nervous system have both central nervous system have both anatomical and functional inter anatomical and functional inter relationship.relationship.

Finally, NMDA-R hypo function may Finally, NMDA-R hypo function may also produce abnormalities in the also produce abnormalities in the neuroplasticity of neurons by neuroplasticity of neurons by altering synaptic connectivity.altering synaptic connectivity.


Neurodevelopmental hypothesis: Neurodevelopmental hypothesis: posits that insults occuring in-posits that insults occuring in-utero or shortly after birth are utero or shortly after birth are responsible for the structural responsible for the structural abnormalities which manifest in abnormalities which manifest in symptoms later in symptoms later in adolescence/adulthoodadolescence/adulthood

Evidence in support includesEvidence in support includes Absence of gliosis despite Absence of gliosis despite

evidence of neuronal lossevidence of neuronal loss Evidence of impaired maturation, Evidence of impaired maturation,

migration and pruning of neurons migration and pruning of neurons in schizophrenic brainsin schizophrenic brains

Cytoarchitectural abnormalities in Cytoarchitectural abnormalities in medial temporal lobemedial temporal lobe


Environmental factors:Environmental factors: maternal bonding maternal bonding early rearing early rearing PovertyPoverty immigration statusimmigration status StressStress viruses. viruses.


Social factorsSocial factors CultureCulture MigrationMigration Residence Residence Social isolationSocial isolation Occupation and social classOccupation and social class


Psychosocial stresses: Psychosocial stresses: experiencing life event in the experiencing life event in the

preceding six months doubles the preceding six months doubles the risk of developing schizophrenia risk of developing schizophrenia (Paykel 1978)(Paykel 1978)

There is however, no evidence that There is however, no evidence that schizophrenics experience more life schizophrenics experience more life events than the general populationevents than the general population


FamilyFamily Deviant role relationship: Deviant role relationship:

“schizophrenogenic mother”“schizophrenogenic mother” Lidzs & Lidzs (1948) described Lidzs & Lidzs (1948) described

marital schism and marital skewmarital schism and marital skew Bateston et al, 1956 described Bateston et al, 1956 described

Disorder family communications Disorder family communications (Double bind theory)(Double bind theory)


Psychodynamic factorsPsychodynamic factors

Mainly of historical interestMainly of historical interest

Freud's theory of schizophreniaFreud's theory of schizophrenia

Melanie Klein’s theoryMelanie Klein’s theory

CLINCAL FEATURESCLINCAL FEATURESDIAGNOSTIC CRITERIADIAGNOSTIC CRITERIA SchneiderSchneider LangfeltLangfelt New Haven Schizophrenia IndexNew Haven Schizophrenia Index St. Louis CriteriaSt. Louis Criteria Research diagnostic CriteriaResearch diagnostic Criteria Present State Examination (PSE)Present State Examination (PSE) ICD-10ICD-10 DSMDSM Positive vs. Negative symptomsPositive vs. Negative symptoms

SCHNEIDERIAN FIRST RANK SYMPTOMSSCHNEIDERIAN FIRST RANK SYMPTOMS

a)a) Audible thoughtsAudible thoughts

b)b) Voices arguing or discussing or bothVoices arguing or discussing or both

c)c) Voices commentingVoices commenting

d)d) Somatic passivity experiencesSomatic passivity experiences

e)e) Thought withdrawal and other Thought withdrawal and other experiences of influenced thoughtexperiences of influenced thought

f)f) Thought broadcastingThought broadcasting

g)g) Delusional perceptionsDelusional perceptions

h)h) All other experiences involving All other experiences involving volition, made affects, and made volition, made affects, and made impulsesimpulses

Second rank symptomsSecond rank symptoms

a)a) Other disorders of perceptionOther disorders of perception

b)b) Sudden delusional ideasSudden delusional ideas

c)c) PerplexityPerplexity

d)d) Depressive and euphoric mood Depressive and euphoric mood changeschanges

e)e) Feelings of emotional impoverishmentFeelings of emotional impoverishment

f)f) ““And several others as well”And several others as well”

DSM IV and ICD 10DSM IV and ICD 10

Types Types

Type I schizophrenia was Type I schizophrenia was characterized by predominantly characterized by predominantly positive symptoms, good positive symptoms, good premorbid functioning, sudden premorbid functioning, sudden onset, normal brain structures by onset, normal brain structures by computed tomography (CT), good computed tomography (CT), good response to treatment, and a response to treatment, and a better long-term course. better long-term course.

Type II schizophrenia was Type II schizophrenia was characterized mainly by negative characterized mainly by negative symptoms, an insidious onset, poor symptoms, an insidious onset, poor premorbid functioning, abnormalities premorbid functioning, abnormalities on CT scans, a tendency to drug on CT scans, a tendency to drug resistance, and a poorer long-term resistance, and a poorer long-term course and outcome, often resulting course and outcome, often resulting in behavioral deterioration. (Tim in behavioral deterioration. (Tim Crow)Crow)

Other typesOther types

ParanoidParanoid Hebephrenic/disorganisedHebephrenic/disorganised CatatonicCatatonic SimpleSimple ResidualResidual undifferentiatedundifferentiated

TREATMENT TREATMENT

PharmacotherapyPharmacotherapy

Psychosocial interventionPsychosocial intervention

Factors Influencing Factors Influencing Antipsychotic Drug SelectionAntipsychotic Drug Selection

Factors Considerations

Subjective response A dyphoric subjective response to a particular drug predicts poor compliance with that drug

Sensitivity to extrapyrimidal A serotonin-dopamine antagonist (SDA) adverse effects

Tardive dyskinesia Clozapine or (possibly another SDA)

Poor medication compliance Injectable form of a long-acting antagonist or high risk of relapse Haloperidol or fluphenazine)

Pregnancy Probably haloperidol (most data supporting its safety)

Cognitive symptoms Possibly an SDA

Negative symptoms Possibly an SDA

Psychosocial interventionPsychosocial intervention Individual psychotherapyIndividual psychotherapy Group therapyGroup therapy Family TherapyFamily Therapy Psychiatric RehabilitationPsychiatric Rehabilitation Social Skills TrainingSocial Skills Training Vocational RehabilitationVocational Rehabilitation Residential Treatment And Residential Treatment And

Housing ProgramsHousing Programs

Features Weighing Toward Good to Poor Prognosis in Schizophrenia

Good Prognosis Poor PrognosisLate onset Young onsetObvious precipitating factors No precipitating factorsAcute onset Insidious onsetGood premorbid social, sexual, Poor premorbid social, sexual, and work histories and work historiesMood disorder symptoms Withdrawn, autistic behavior (especially depressive disorders)Married Single, divorced, or widowedFamily history of mood disorders Family history of schizophreniaGood support systems Poor support systemsPositive symptoms Negative symptoms

Other features of poor Other features of poor prognosisprognosis Neurological signs and symptomsNeurological signs and symptoms History of perinatal traumaHistory of perinatal trauma No remissions in 3 yearsNo remissions in 3 years Many relapsesMany relapses History of assaultivenessHistory of assaultiveness

Other psychotic Other psychotic DisordersDisorders Delusional DisordersDelusional Disorders Schizophreniform PsychosisSchizophreniform Psychosis Reactive PsychosisReactive Psychosis Schizo-AffectiveSchizo-Affective Atypical-Folie a Deaux, culture bound Atypical-Folie a Deaux, culture bound

syndrome, Capgras,Cotard,Fregolisyndrome, Capgras,Cotard,Fregoli Schizotypal personality disorderSchizotypal personality disorder Postpartum psychosis Postpartum psychosis

Recent advancesRecent advances

Team working in LMUTeam working in LMU Found rare genetic variations that Found rare genetic variations that

have a major influence, but also have a major influence, but also found frequent genetic variations found frequent genetic variations that have only a minor effect on that have only a minor effect on the disease risk.“the disease risk.“

identify three so-called identify three so-called microdeletions.”microdeletions.”

Challenges Of Challenges Of Management Of Management Of Psychiatric DisordersPsychiatric Disorders Available service not centralized but Available service not centralized but

concentrated only in the cities within concentrated only in the cities within the country.the country.

Non inclusion of services in National Non inclusion of services in National health Insurance Scheme.health Insurance Scheme.

Problem of stigma and negative Problem of stigma and negative perception of mentally ill patientsperception of mentally ill patients

Challenges of religious doctrines Challenges of religious doctrines leading to mis management and leading to mis management and chronicity.chronicity.

Atypical drugs though available has given Atypical drugs though available has given hope for treatment of resistant and chronic hope for treatment of resistant and chronic condition thereby reducing chronicity.condition thereby reducing chronicity.

- cost of drugs is on the high side, many - cost of drugs is on the high side, many could not afford to purchase.could not afford to purchase.

- Infiltration of fake and genuine drugs in - Infiltration of fake and genuine drugs in drug market.drug market.

- Need for government subsidy of drugs to - Need for government subsidy of drugs to reduced burden of family and community.reduced burden of family and community.

IloperidoneIloperidone, also known as , also known as FanaptaFanapta, and previously known as , and previously known as ZomarilZomaril, is an , is an investigational atypical antipsychotic. It is being . It is being investigated mainly for the investigated mainly for the treatment of treatment of schizophrenia symptoms.symptoms.

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Chief Dr H.T.O. LADAPO, MD (Ukraine) FMC Psych.., FWACP, FHAN, MPH ( Unilag )