Early Onset Psychotic Disorders

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Presented by Dr Pavan Kumar

Chaired by Dr V K Bhat

Early Onset Psychotic Disorders


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Definition Early onset psychosis (EOP)

Any of a number of disorders in which positive psychotic

symptoms are a prominent feature.

Early onset schizophrenia (EOS)

Schizophrenia with onset prior to age 18.

Very early onset(VEOS)/Childhood onset(COS)

schizophrenia

Schizophrenia with onset prior to age 13, almost always

after 5. Onset prior to age 3 should raise strong suspicion of

autism spectrum disorder.


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Schizoaffective Disorder (SA) & Schizophreniform disorderand other disorders

Diagnosed using the same criteria as in adults.

Early onset schizophrenia spectrum disorders (EOSS)

Includes EOS, schizoaffective disorder andschizophreniform disorder with onset prior to age 18 and

VEOS or COS.

Multidimensionally impaired disorder (MDI)

A developmental disorder beginning during childhoodcharacterized by transient hallucinations, daily affective

lability, poor social skills, and extreme emotional reactivity.


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History Schizophrenia has been reported to occur in children since

the diagnosis was introduced by Emil Kraepelin.

From the early 1900s to 1980s, the term childhood

schizophrenia or prepubertal schizophrenia was used to

refer to a range of severe psychiatric disorders presentingin youth including autism.

In DSM II & ICD 8 all childhood onset psychosis including

autism grouped under a separate category of childhood

schizophrenia.

In the 1970s, Israel Kolvin and colleagues conductedseminal work to distinguish between primary psychotic

disorders and autistic disorder.

Beginning with ICD-9 and DSM-III, autism has been

recognized as a distinct disorder and schizophrenia hasbeen diagnosed using identical criteria as adults.


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Epidemiology In children, affective psychoses are considerably more

likely than schizophrenia spectrum disorders.

It appears that early onset schizophrenia and affective

psychoses are more common in individuals with family

histories of the respective disorders. Early onset schizophrenia appears slightly more common

in boys than girls.


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At age 13 years, the prevalence for all psychoses was0.9 in 10,000, showing a steady increase during

adolescence, reaching a prevalence of 17.6 in 10,000

at age 18 years.

Early onset schizophrenia appears slightly morecommon in boys than girls


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age had a strong effect on the manifestation of positive and

negative symptoms.

Positive symptoms increased linearly with age

negative symptoms were most frequent on early childhood

and late adolescence.

Bettes and Walker (1987)


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Etiology


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GENETICS individuals with early onset schizophrenia are significantly

more likely than those with adult onset schizophrenia to

have chromosomal abnormalities or mutations involving

genes in neurodevelopmental pathways.


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Family History Increased incidence of schizophrenia and spectrum

disorders

Increased incidence of affective disorders

Youth with early onset schizophrenia are at least twice aslikely as individuals with adult onset schizophrenia to have

a parent with the disorder and morbid risk of schizophrenia

for parents of individuals with early onset schizophrenia

ranges from 14 to 25 percent.


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Early Neuropathological

Manifestations

The following have been correlated with increasedincidence of schizophrenia

Perinatal complications

Alterations in brain structure and size

Minor physical anomalies Disruption of fetal neural development

(Akbarian et al., 1993; McClellan and McCurry, 1998)

it seems likely these are consequences rather than causes

of abnormal neurodevelopment


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cannabis use is associated with earlier age of onset of schizophrenia in

adults

It is possible that subtle social and developmentalimpairments that precede schizophrenia are also riskfactors for cannabis use

Perhaps a more plausible explanation is a gene environment interaction effect whereby cannabis exposurecauses schizophrenia only in those with a pre-existingsusceptibility

The COMT val158met polymorphism moderated the linkbetween psychosis and adolescent-onset cannabis use,

but not adult-onset cannabis use. The COMT val allele is associated with greater COMT

activity (relative to the COMT met allele) and reduceddopamine transmission in the prefrontal cortex.

cannabis may enhance the risk of schizophrenia invulnerable individuals during a critical period of adolescentbrain development


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Early Neuropathological

Manifestations

Neurointegrative defect in infants

PANDYSMATURATION

Fish postulated that a special form of early abnormal

neurodevelopment, "pandysmaturation", defined a priori as

constituting retarded cranial development in the first year oflife, combined with delay in early motor milestone attainment,

was related to genetic risk for schizophrenia, and was

associated with schizophrenia-spectrum disorders in young

adulthood.

Pandysmaturation has efficacy as an early life risk-indicator of

schizophrenia-spectrum disorder in young adulthood at least

in subjects at genetic risk, strengthening the evidence for a

generally genetic-based neurodevelopmental model of

schizophrenia-spectrum (as contrasted with affective)disorders.


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neurodevelopmental disruptions subtle differences in neuronal connectivity, especially in the

parietal, temporal, and frontal cortices and hippocampus.

lead to less efficient cortical processing

seem to involve disruption of normal neurodevelopmental

processes, particularly those that involve maturation of thefrontal cortex and its connections during the second and

third decades of life

These differences suggest aberrations in the normal

developmental processes of synaptic refinement and

pruning


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multiple disruptions or hits to these normalneurodevelopmental processes are required for

schizophrenia to develop.

Such disruptions might result from genetic vulnerabilities,

adversities in the intrauterine environment as a result offamine, infection, or inflammation, or various

environmental exposures later in life including severe

psychological stress and exposure to drugs of abuse,

particularly cannabis.

Early onset schizophrenia appears to have more profoundneurodevelopmental disruptions than adult onset

schizophrenia.


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Psychological and social factors Not causative

Bio-psycho-social model applicable

Mediates time of onset, course and severity

No social class particularly implicated

Expressed emotion has most influence


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Neurobiology

Decreased total cerebral volume

decreased grey matter volume

increased ventricular volume

decreased midsagittal thalamic area.

(Jacobsen and Rapoport, 1998; Badura etal., 2001)

patients with EOS have a more marked differential enlargementof the lateral ventricles and change in cortical gray matter

However none of these are diagnostic


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Neuroimaging Structural imaging studies have repeatedly demonstrated

an exaggeration of the normal pattern of cortical volume

loss that occurs throughout adolescence, with excessive

and progressive reductions being especially prominent in

the cingulate, temporal, and frontal cortices.

In addition, studies of prodromal individuals, many of

whom are adolescents, have shown regional gray matter

volume reductions are present before overt positive

symptoms and progress during the first few years of the

illness particularly in cingulate, temporal, and frontalcortices.


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NEUROCHEMICAL

Decreases in the brain chemistry ratio of N acetylaspartate

(NAA) to creatine (CRE)a putative marker of neuronal

integrity exclusively in the pre frontal cortex and

hippocampus


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Neuropsychologicalfindings Cognitive impairments

Attention

executive functioning

verbal recall

visuospatial abilities

fine motor skills


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Diagnosis and Clinical Features All types of early onset psychosis other than MDI are

diagnosed using the same criteria as the adult forms of the

disorder.

the characteristics of specific symptoms often show

important developmental characteristics


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Hallucinations Hallucinations are frequently multimodal, with the affected

youth seeing, hearing, or feeling the hallucinated being.

Children will frequently name the hallucinated being, often

using stereotypes such as an angel, the devil, or a

monster or will refer to it on the basis of a physical

characteristic such as the red sweater guy or the manwith no skin.

Youth very seldom complain about their hallucinations if

not asked directly.

It is also often helpful to ask family members if the childasks about being called when no one has said anything.

It is important to ascertain whether the child is in control of

the phenomena, which is not seen with true hallucinations,

or whether he or she can only moderate his or her own

response to the phenomena


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DELUSIONS

Delusions are seldom highly complex or systematic prior toage 16.

Inability to utilise logical reasoning and a tendency to blur

distinction between fantasy and reality makes it difficult to

reliably demonstrate delusions less than 5yrs age

In this age, related to fantasy figures, animals

Less elaborate

In older kids, related to identity disturbances, hypochondriacal,

persecutory

Only 50% cases have delusions


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Instead youth often report vague symptoms of everyone isout to get me or people are laughing at me.

Often reports from collateral sources are needed to

determine whether such reports are delusional or reality

based.

Frequently, youth with early onset schizophrenia present

with nonspecific symptoms such as poor attention or

increased aggression.


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THOUGHT DISORDER

Degree of communication dysfunction related to severity of

FTD

Problems in processing verbal information

Common symptoms are

Formal thought disorder

Loose associations Illogical thinking

Impaired discourse skills

Incoherence and poverty of speech


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Onset of early onset schizophrenia is often insidious,occurring over a few years.

In addition, premorbid symptoms such as being odd and

socially isolated or having multiple (but generally mild)

developmental delays in cognitive, motor, sensory, and

social functioning are common and appear more severe

than in adults with adult onset schizophrenia.

it is important to ask about changes in functioning and

behavior that have occurred over the past 3 to 4 years, to

specifically inquire about hallucinations and delusionsusing language that the child understands, and to

encourage the child to describe his or her experiences in

detail using his or her own words.


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Assessment Detailed exhaustive interviews of the child and family ICD-10/ DSM-IV criteria can be applied

Laboratory evaluations and neuro-imaging techniquesused to rule out organic psychosis

Baseline rating on psychopathology scales such as the

BPRS-C,

Schedule for Affective Disorders and Schizophrenia forSchool-Age Children (K-SADS; Ambrosini, 2000), the Childand Adolescent Psychiatric Assessment (CAPA; Angold &

Costello, 2000) and the Diagnostic Interview for Children and Adolescents

(DICA; Reich, 2000).

Baseline neuropsychological testing to evaluate cognitivedeficits


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Diagnostic Dilemmas Misdiagnosis Bipolar disorder vs schizophrenia

Causes for misdiagnosis

-Rarity of the disorder Overlap of presenting symptoms with other disorders

Some children with hallucinations do not haveschizophrenia (PTSD, dissociative and anxietydisorders)

Developmental disorders (PDD, language disorders)


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Differential Diagnosis Misdiagnosis of early onset schizophrenia is a major

concern.

Factors that may lead to misdiagnosis include children's

inherent difficulties in describing psychotic symptoms that

are outside their normal experience, overinterpretation of

transient psychotic symptoms, and the high prevalence of

positive psychotic symptoms in child psychiatric disorders

other than early onset schizophrenia.

However, failure to recognize early onset schizophrenia

when present may slow implementation of appropriatetreatments and worsen the youth's long-term prognosis.


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Differential Diagnosis Mood disorders

Historically approximately half of juveniles with bipolar

disorder were misdiagnosed as schizophrenia

Mania could present with florid psychosis

Depression could be mistaken for negative symptomsand vice versa

(McClellan and McCurry, 1999; Carlson, 1990)


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General medical conditions Delirium

Seizure disorders

CNS lesions (tumors, malformations, trauma)

Neurodegenerative disorders(Huntingtons chorea,lipid storage disorders)

Metabolic disorders(Wilsons, endocrinopathies)

Developmental disorders (velocardiofacial syndrome)

Toxic encephalopathies (amphetamines, cocaine,hallucinogens, phencyclidine, alcohol, marihuana,solvents, steroids, anticholinergics and heavy metals)

Infectious diseases (meningoencephalitis, HIV-AIDS)


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Non-psychotic behavioral and emotional disorders Severe emotional disorders

PTSD

Child maltreatment and abuse

Dissociative and anxiety disorders

Personality disorders


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Schizo-affective disorders Not well defined

Upto a quarter of children with schizophrenia maylongitudinally develop significant affective symptoms(eggers, 1989)

PDD including autism, CDD and Aspergers Obsessive compulsive disorder

Developmental and language disorders


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At 11 year follow-up, 38% (12 of 32) of patients met criteriafor bipolar 1 disorder, 12% (4 of 32) for major depressive

disorder (MDD), and 3% (1 of 32) for schizoaffective

disorder.

The remaining 47% of patients (15 of 32) were divided into

two groups on the basis of whether they were in remission

and neuroleptic-free (good outcome, n = 5) or still

severely impaired and/or psychotic regardless of

pharmacotherapy (poor outcome, n = 10)


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Course and Prognosis onset of overt psychotic symptoms is frequently insidious,

particularly in individuals younger than 15 years.

Afterward, approximately equal proportions of youth have

insidious and subacute onset, with rapid onset over the

course of several days being rare.

Rapid recovery from the initial episode appears rarer than

in adult onset schizophrenia.

In contrast, many youth with early onset schizophrenia

show improvement but continue to experience significant

positive symptoms despite medication adherence for 2 to 5years. The course tends to be chronic rather than more

episodic as is reported in adult onset schizophrenia.


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there appears to be significant decline in cognitivefunctioning during the 4-year period surrounding onset of

illness.

This cognitive decline appears to reflect both biologic brain

processes and interruption of normal development and

learning.

Suicidality was associated with more depressive

symptoms and fewer negative symptoms at first episode.

A recent study found that 30 percent of individuals with

early onset schizophrenia attempted suicide over the first10 years of illness with one of six of those who attempted

succeeding.


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Long-term prognosis in early onset schizophrenia alsoappears worse than in adult onset schizophrenia.

A meta-analysis of 320 studies of outcome in adult onset

schizophrenia found that about 40 percent of individuals

had good outcomes, whereas about 60 percent had a

chronic disabling course.

In contrast, a number of studies have found that very few

individuals with early onset schizophrenia (5 to 25 percent)

experience good outcomes and that 75 to 80 percent have

poor outcomes with about half of those having extremelypoor outcome.

Treatment resistance may also be more common, although

this has not been adequately studied.


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STAGES: Prodrome

Prodrome last from days to months Functional deterioration prior to onset of psychotic

symptoms is common

Social withdrawal and isolation

Idiosyncratic or bizarre preoccupations

Academic failure

Deteriorating self care skills

Dysphoria and anxiety symptoms

Aggressive behaviors


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Acute Phase

Predominance of positive symptoms Significant deterioration in functioning

Lasts from 1-6 months or longer

Symptoms shift from positive to negative over time

Duration depends on the timing of treatment and severityof illness


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Recuperative/ Recovery Phase

Lasts for several months Predominantly negative symptoms

Some may develop post-schizophrenic depression

In a few children, symptoms may totally resolve and the

illness may have an episodic course


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Residual Phase

May last for several months or years Some negative symptoms continue to persist

Overall level of functioning would be impaired


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Treatment

multimodal and should include pharmacotherapy, family andpatient psychoeducation and support, and interventions in thecommunity to support ongoing education and transition toemployment when appropriate.

little empiric support for specific treatments

The evidence is strongest for pharmacotherapy

studies have compared various atypical antipsychotics toplacebo

Olanzapine, Risperidone, aripiprazole

various antipsychotics differ in their side-effect profiles but havefew differences in efficacy

treatment-resistant early onset schizophrenia respondsignificantly better to clozapine than to haloperidol (Haldol) orolanzapine

Currently only two pilot studies of psychosocial interventionshave been conducted. They show promise but clearly suchinterventions need to be further developed and evaluated


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Prevention and Early Detection In theory at least, the onset of schizophrenia could be

prevented if an intervention reduced the premorbid riskstatus or exposure to causative risk factors.

The difficulty with the premorbid phenotype as currentlyconceived (i.e., subtle social and developmentalimpairments) is its extremely low specificity and positivepredictive value for schizophrenia in the generalpopulation.

The premorbid psychopathology in childhood-onsetschizophrenia is equally non-specific with a range of

diagnoses. An alternative approach is to target putative environmental

risk factors such as cannabis exposure.

A key argument used to support early intervention inpsychosis has been the finding that a long duration ofuntreated psychosis is associated with poor long-term

outcome in schizophrenia


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Psychosocial Interventions Psychoeducation and Family Interventions

CognitiveBehavioral Therapy

Cognitive Remediation


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COS AOS

poor premorbidfunctioning (impairedsociability) and earlydevelopmental delaysmore common & severe

Just over 20% of cases of

adolescent schizophreniahad significant earlydelays in either languageor motor development.

Premorbid IQ mid to low80s, some 1015 pointslower than in the adultform of the disorder

Similar developmentaland social impairments inchildhood

language and motordevelopmental delayshave been reported inonly about 10% ofindividuals who developschizophrenia in adult life

adult schizophreniformdisorder assoc withchildhood pan-developmentalimpairments involvingmotor development,

receptive language andIQ.


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0.9 in 10,000, showing asteady increase duringadolescence, reaching aprevalence of 17.6 in 10,000at age 18 years.

Prodrome-gradual butmarked decline in social andacademic functioning thatprecedes the onset of activepsychotic symptoms

Child- and adolescent-onsetcases are characterized by amore insidious onset, greater

disorganization, negativesymptoms, hallucinations indifferent modalities andfewer systematized orpersecutory delusions

1% prevalence

later-onset cases- higherfrequency of systematizedand paranoid delusions


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schizophrenia presenting inchildhood and adolescencelies at the extreme end of acontinuum of phenotypicseverity.

Premorbid functioning,prolonged first psychoticepisode and negativesymptoms at onset predictlong-term outcome thancategorical diagnosis

The risk of premature deathis increased in child- and

adolescent-onset psychoses. Males overrepresented

lower levels of criticism andhostility than parents ofadult-onset patients


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Conclusions

The last decade has seen a dramatic growth in ourunderstanding of the clinical course and neurobiologicalunderpinnings of schizophrenia presenting in childhood andadolescence.

It is now clear that adult-based diagnostic criteria have validity inthis age group and the disorder has clinical and neurobiologicalcontinuity with schizophrenia in adults.

Childhood-onset schizophrenia is a severe variant of the adultdisorder associated with greater premorbid impairment, a higherfamilial risk, more severe clinical course and poorer outcome.

The poor outcome of children and adolescents withschizophrenia has highlighted the need to target early andeffective treatments and develop specialist services for this high-risk group.

Unraveling neurocognitive and clinical heterogeneity should leadto improvements in our ability to deliver individually targetedtreatments, as well as the ability to identify those at risk in orderto prevent the onset of psychosis


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Early Onset Psychotic Disorders