Transcript
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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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THANK U
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