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Childhood Onset Schizophrenia

And Other Psychotic Disorders


Anne Cristine D. Guevarra, MD
Child Psychiatry Rotator

Children and adolescents

experience
the same range and types of psychotic
symptoms as do adults. They can lose the
connections between their thoughts (formal
thought disorder) and have perceptions without
external stimuli (hallucinations).

Psychosis
Mental life has been disrupted in its capacities
or forms, as a result of a process that generates
new forms of psychological experience.

McHugh PR, Slavney PR. The perspectives of psychiatry. Baltimore:


Johns Hopkins University Press, 1998.

What does it mean when a child reports


experiencing hallucinations or delusions?

The appearance of psychotic symptoms


in childhood, albeit rare, is an important
clinical entity.
This importance extends beyond their
clinical prevalence and has begun to
influence our understanding of the
principal psychotic conditions.

When one examines a 5-year old child who claims that he is


superman and can fly, the challenge is to determine whether the
child has a delusion. Similarly, in a child who complains about
hearing a voice telling her to do bad things, one must determine
whether she is talking about her conscience or is experiencing
auditory hallucinations.

From a cognitive and developmental standpoint,


certain clinical features in children create
diagnostic challenges. One problem is
distinguishing true psychotic phenomena in
children from nonpsychotic idiosyncratic
thinking, perceptions caused by

developmental delays, exposure to


disturbing and traumatic events, and
overactive and vivid imaginations.

Organic Psychoses
Neurologic Conditions
Seizure Disorder
Deteriorative Neurologic Disorders
Central Nervous System Lesions
Metabolic and Hormonal

Disturbances
Toxic Psychoses

Functional Psychoses
Childhood Onset

Schizophrenia
Mood Disorders
Brief Reactive Psychosis
Anxiety Disorders

Clinician-Rated Dimensions of
Psychosis Symptom Severity

Clinician-Rated Dimensions of
Psychosis Symptom Severity

Factors to Consider
Misdiagnosis remain due to symptom overlap
Anxiety and stress are probably the most common

causes of hallucinations in preschool children with


benign prognosis
Psychotic phenomena in school age children
generally tend to be more persistent, and are more
likely to be associated with drug toxicity or
significant mental illness

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Cognitive impairments, particularly impaired

concentration and ability to focus, usually


accompany psychosis in children.
When the psychosis is secondary to an organic
origin, there is often accompanying impairment in
the sensorium presenting as confusion and
disorientation, as is typical of delirium.
shyness, and disturbances in adaptive social
behavior seem to be the first signs of dysfunctional
premorbid development
Early language deficits and motor impairments

Diagnostic Challenges
Distinguishing true psychotic phenomena in

children from nonpsychotic:


idiosyncratic thinking, perceptions caused by

developmental delays,
exposure to disturbing and traumatic events, and
overactive and vivid imaginations

Differentiating between the premorbid state and

the active psychotic state

Childhood Psychosis
Adult Schizophrenia (?)
Childhood Onset Schizophrenia
Adult Schizophrenia
Childhood Onset Schizophrenia
= Adult Schizophrenia

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

COS vs Adult Schizophrenia


Similar to that of poor outcome adult cases
Psychosis of COS can usually be distinguished by

its severe and pervasive nature and its


nonepisodic, unremitting course
Children show poorer premorbid functioning in
social, motor, and language domains, learning
disabilities, and disruptive behavior disorders
Transient autistic symptoms such as hand flapping
and echolalia in toddler years are common,
probably reflecting more compromised early
brain development.
Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

History
Maudsley first wrote a description of the

insanity of early life in his textbook,


Physiology and Pathology of Mind
developmental approach
the mental faculty of children was not organized,

and hence the insanity in children must be of the


simplest kind, influenced more by reason of bad
descent or of baneful influences during uterine
life.

1874

1919

1920-1970

1971

1980s

History
De Sanctis may be credited first with setting out

childhood schizophrenia as different from mental


deficiency and from certain neurologic disorders,
such as epilepsy or postinfectious encephalopathy

1874

1919

1920-1970

1971

1980s

History
Kraeplin introduced the concept of

dementia praecox and noted its onset in


late childhood and adolescence
Suggested that 3.5% of patients with

schizophrenia had the onset of their illness


before the age of 10 years.
This led to an increased interest in
understanding the developmental aspects of
psychosis.

1874

1919

1920-1970

1971

1980s

History
The term psychosis was used so broadly in

children that a spectrum of behavioral


disorders and autism were grouped
together under the category of childhood
schizophrenia.

1874

1919

1920-1970

1971

1980s

History
The landmark studies of Kolvin first

established the clinical distinction between


autism and other psychotic disorders of
childhood

1874

1919

1920-1970

1971

1980s

History
Schizophrenia with childhood onset was

formally separated from autistic disorder

1874

1919

1920-1970

1971

1980s

Controversy & Confusion after


Separation
Research documented a small group of children

with autism spectrum disorder who developed


schizophrenia in later childhood or adolescence
Many children with childhood-onset schizophrenia
exhibit neurodevelopmental abnormalities, some
of which are also evident in children with autism
spectrum disorder
According to the DSM-5, schizophrenia can be
diagnosed in the presence of autism spectrum
disorder, provided that the diagnosis of
schizophrenia is specifically differentiated from
autism spectrum disorder.

Early-Onset Schizophrenia
onset of disease before the age of 18 years,

including childhood-onset as well as


adolescent-onset schizophrenia
associated with severe clinical course, poor
psychosocial functioning, and increased
severity of brain abnormality
current evidence supports the efficacy of
both psychosocial and pharmacological
interventions

Childhood-Onset Schizophrenia
a very rare and virulent form of schizophrenia now

recognized as a progressive neurodevelopmental disorder


more chronic course, with severe social and cognitive
consequences and increased negative symptoms
compared to adult-onset schizophrenia.
onset of psychotic symptoms before the age of 13 years,
increased heritable etiology, and evidence of widespread
abnormalities in the development of brain structures
including the cerebral cortex, white matter, hippocampus
and cerebellum.
Have higher than normal rates of premorbid
developmental abnormalities nonspecific markers of
abnormal brain development.

Childhood-Onset Schizophrenia
more significant deficits in measures of intelligence quotient

(IQ), memory, and tests of perceptuomotor skills compared


with adolescent-onset schizophrenia
increased impairment of cognitive measures such as IQ,
working memory, and perceptuomotor skills
premorbid markers of illness rather than sequelae, of the
disorder. Although cognitive impairments are greater in
younger patients with schizophrenia, clinical
presentation of schizophrenia remains remarkably similar
across the ages
the diagnosis of childhood-onset schizophrenia is continuous
with that in adolescents and adults, with one exception:
In childhood-onset schizophrenia a failure to achieve
expected social and academic functioning may
replace a deterioration in functioning.

Diagnosis of Schizophrenia
Active Phase
At least one of the following: delusions, hallucinations,
disorganized speech
At least one additional symptom present most of the time
for a month: delusions, hallucinations, disorganized
speech, grossly disorganized or catatonic behavior, or
negative symptoms (i.e. diminished emotional expression
or avolition)
Symptoms are present for a significant amount of time
during a single month AND cause impairment (social,
academic, occupational)
To meet full criteria for schizophrenia, continuous

signs of disturbance must persist for at least 6


months.

Epidemiology
Frequency of COS is less than one case in about

40,000 children, whereas among adolescents


between the ages of 13 and 18 years, the
frequency of schizophrenia is increased by a factor
of at least 50
resembles the more severe, chronic, and
treatment-refractory adult-onset schizophrenic
subgroups, in that the same core
phenomenological features are present
Co-morbid disorders: ADHD, depressive disorders,
anxiety disorders, speech & language disorders,
motor disturbances

Epidemiology
In adolescents, the prevalence of schizophrenia is

estimated to be 50 times that in younger children,


with probable rates of 1 tom2 per 1,000.
Male 1.67: 1 Female
Schizophrenia rarely is diagnosed in children
younger than 5 years of age.
The prevalence of schizophrenia among the
parents of children with schizophrenia is about 8%,
which is about twice the prevalence in the parents
of patients with adult-onset schizophrenia.

Etiology
a neurodevelopmental disorder

GENES + ENVIRONMENT Abnormal Early Brain


Development

white matter abnormalities and disturbances lead

to abnormal connectivity

Genetic Factors
Heritability estimates at 80%
8x more prevalent among first degree relatives

with schizophrenia
Higher concordance rates among monozygotic
twins than in dizygotic twins
Higher rates among relatives of childhood-onset
schizophrenia than in adult-onset schizophrenia
No reliable method can identify persons at the
highest risk for schizophrenia in a given family.

MRI Studies
progressive loss of gray matter
delayed and disrupted white matter growth
decline in cerebellar volume
Gray matter abnormalities were normalized over

time in the siblings, indicating a protective


mechanism in siblings that was not present in
those children with childhood-onset schizophrenia.
hippocampal volume loss across the age span
appears to be static among children with
childhood-onset schizophrenia

MRI NIMH Study


Progressive gray matter loss
Loss from parietal frontal dorsolateral
prefrontal temporal
Ventricular increases

Phenomenology and Neurobiology


of COS
Premorbid Development

higher rates of early language, social, and motor

developmental abnormalities, possibly reflecting


greater impairment in early brain development

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Phenomenology and Neurobiology


of COS
Risk Factors

Parental Age and Obstetric Complications


no correlation with maternal or paternal age
incidence of obstetric complications in COS patients did not

differ from that for the healthy sibling control group

Eye Tracking
genetic factors underlying eyetracking dysfunction (Smooth
pursuit eye movement) may be more salient for COS than AOS
Familial Schizophrenia Spectrum Disorders
rate of familial schizophrenia spectrum disorders was higher for

COS than AOS, and both were higher than community controls

Familial Neurocognitive Functioning


COS siblings had significantly poorer performance than
community controls, although the rates of neuropsychological
abnormalities for COS were not significantly higher than for AOS
Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Pervasive Developmental Disorder and


COS
PDD in COS may be a nonspecific marker of more

severe early abnormal neurodevelopment

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Neurocognitive Functioning in
COS Probands
perform poorly on tasks involving fine motor

coordination, attention, short-term and working


memory
Evoked-potential studies show diminished
amplitude of brain electrical activity during these
tasks, suggesting that allocation of necessary
attentional resources is deficient, which is also
shared by adults with schizophrenia
there was no evidence for a longer term
degenerative cognitive process in COS, at least
through early adulthood

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Comorbid Disorders
depression (54%)
obsessive-compulsive disorder (OCD;21%)
generalized anxiety disorder (GAD; 15%)
attention deficit hyperactivity disorder

(ADHD; 15%)

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Brain Development in COS


increasing ventricular volume and decreasing total

cortical, frontal, medial temporal, and parietal gray


matter volumes at 2, 4, and 6 years after initial
scan

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

What is the Pattern of GM Loss in


COS and its Relationship with
Normal Development?

back to front tissue loss, with early parietal gray

matter loss followed by frontal and temporal gray


matter loss later in adolescence
top-down fashion on the medial surface
GM loss in COS may reflect an exaggeration of
normal maturational process of synaptic/dendritic
pruning during adolescence

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Does the Cortical GM Loss in COS


Eventually
Resemble the Adult Onset Pattern
when Subjects Mature?
Cortical thickness analyses in adult onset

schizophrenia document GM loss mostly in


prefrontal and temporal cortices
as COS subjects mature, the robust and global GM
loss during the adolescent years becomes limited
to prefrontal and superior temporal cortices by age
24, thus mimicking a pattern seen in adult patients

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Is the GM Loss in COS a Medication


Effect?
The GM findings in COS appeared to be due to

schizophrenia and not due to medications

Is the GM Loss in COS Diagnostically


Specific?
The GM findings in COS appeared to be due to

schizophrenia and not due to medications

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

NATURE VS. NURTURE


NATURE & NURTURE
Deficits in measures of IQ, memory, and tests of
perceptuomotor skills
Children > Adolescents > Adults
Suggests that these deficits are NOT sequelae of the
disorder, but are MARKERS of brain dysfunction even
before the onset of illness

Vulnerability Factors
shyness, and disturbances in adaptive social

behavior
early language deficits and motor impairments
Intellectual delays

a socially odd child is


not usually
schizophrenic

Diagnosis & Clinical Features


premorbid history of social rejection, poor peer

relationships, clingy withdrawn behavior, and


academic trouble, delayed motor milestones and
language acquisition
Onset is insidious, starting with inappropriate
affect or unusual behavior
Auditory hallucinations
Visual hallucinations associated with lower IQ and
earlier age at onset
Visual, tactile, and olfactory hallucinations may be
a marker of more severe psychosis

Diagnosis & Clinical Features


Delusions increase in frequency with increased age
Blunted or inappropriate affect
Inappropriate giggling and crying
Formal thought disorders, including loosening of

associations and thought blocking


Illogical thinking and poverty of thought
do not have poverty of speech content, but they
speak less than other children and ambiguous in
the way they refer to persons, objects, and events

Diagnosis & Clinical Features


Communication deficits: unpredictably changing

the topic of conversation without introducing the


new topic to the listener (loose associations)
illogical thinking and speaking and tend to
underuse self-initiated repair strategies to aid in
their communication
fail to aid communication with revision, fillers, or
starting over NEGATIVE SYMPTOMS

Diagnosis & Clinical Features


The clinical presentation of schizophrenia remains

remarkably similar across the age


Schizophrenia in prepubertal children includes the presence
of at least two of the following:
hallucinations
delusions
grossly disorganized speech or behavior
severe withdrawal for at least 1 month
social or academic dysfunction must be present
continuous signs of the disturbance must persist for at least 6 months

The diagnostic criteria for schizophrenia in children are

identical to the criteria for the adult form, except that


instead of showing deteriorating functioning, children may
fail to achieve their expected levels of social and academic
functioning.

Differentials
Affective
disorders

Medical
conditions

Mood
congruent
psychotic
symptoms

Medical
illnesses

Stable clinical
outcome

Substance
use

Pervasive
development
al disorders
Severe
impairment in
reciprocal
communication,
social
interactions,
and odd
stereotyped
behaviors

Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Differentials
Conduct disorder and
various other
behavioral
disturbances

Atypical psychosis

associated
with
hallucinations

Multi
Dimensionally
Impaired
(MDI) by the
NIMH group
Lewiss Child & Adolescent Psychiatry: A Comprehensive Textbook 4th Edition

Course and Prognosis


Important predictors of course and outcome:
childs premorbid level of functioning
the age of onset
IQ
response to psychosocial and pharmacological interventions
degree of remission after the first psychotic episode
degree of family support

Less treatment responsive:


Early age at onset
with comorbid developmental delays
learning disorders
lower IQ
premorbid behavioral disorders, such as ADHD and conduct

disorder

Course and Prognosis


Predictors of a poorer course:
family history of schizophrenia
young age and insidious onset
developmental delays
lower level of premorbid function
chronic or length of first psychotic episode

An important factor in outcome is the accuracy

and stability of the diagnosis of schizophrenia.

Management & Treatment


Stage 1 (prodromal phase): The child
may experience some period of deteriorating function,
which may include social isolation, idiosyncratic
preoccupations and behaviors, and academic
difficulties.

Stage 2(acute phase): This is usually the


time when the child comes to the attention of a
mental health professional, when the clinical picture is
dominated by frank delusions and hallucinations and
other positive symptoms such as a formal thought
disorder or strange and idiosyncratic behaviors.

Management & Treatment


Stage 3 (recovery phase): The
symptoms usually begin to remit and dissipate.
However, often there may still be the presence of
some psychotic symptoms, although they are less
disturbing to the child. In this phase, the child may
continue to experience some levels of confusion,
disorganization, or lability in mood.

Stage 4 (residual phase): The positive


symptoms continue to subside, but the child
continues to experience apathy, lack of motivation,
withdrawal, and restricted or flat affect.

Pathology & Laboratory Examinations


No specific laboratory tests are diagnostically

specific for childhood-onset schizophrenia


Although data exist to suggest that
hypoprolinemia is associated with the risk of
schizoaffective disorder due to an alteration on
chromosome 22q11, no association of
hyperprolinemia with childhood-onset
schizophrenia has been identified.

Management & Treatment


Integrated Psychological Interventions:
Cognitive behavioral therapy
group skills training
cognitive remediation therapy
multifamily psychoeducation
supportive counseling on the prevention of psychosis

More effective than standard treatments in

delaying the onset of psychosis over a 2-year


follow-up period
Children may have less robust responses to
antipsychotic medications than adolescents and
adult

Management & Treatment


Pharmacotherapy is instituted in an attempt to

treat the underlying cause of the psychosis, or for


symptom control, in those children who have
psychotic symptoms secondary to a known origin.
Informed consent from the parents or guardian

should be obtained before treatment with


psychopharmacologic agents is instituted.

Pharmacotherapy
some efficacy:
Risperidone up to 3 mg per day
Olanzapine
randomized 6-week controlled trial of olanzapine in adolescents

with schizophrenia found that it was more efficacious than


placebo.

Aripiprazole
At two fixed doses, superior to placebo in the treatment of

positive symptoms of adolescent schizophrenia; however, more


than 40 percent of subjects in the active medication group did
not achieve remission.

Clozapine
more effective than haloperidol in improving both positive and

negative symptoms in treatment resistant schizophrenia in youth

Pharmacotherapy
Clozapine vs high dose Olanzapine
response rates were about twice as great for clozapine as

olanzapine (66% vs. 33%)


clozapine was found to be associated with a significant
reduction in all outcome measures, whereas olanzapine
showed improvement on some measures but not on all
clozapine was superior to olanzapine in alleviating negative
symptoms
Clozapine was associated with more adverse events, such as
lipid abnormalities and a seizure in one patient.

Management & Treatment


Psychosocial interventions should include working

with both the parents and the child.


Improving family functioning, problem solving,
communication skills, and relapse prevention have
been shown to decrease relapse rates in adults
Social skills training and may require specialized
educational programs, academic adjustments, and
support at school
Ongoing illness teaching and medication
education, are important to promote compliance
with treatment and to help in coping with the daily
and sometimes long-term implications of the
childs illness.

Psychosicial Interventions
Psychotherapists who work with children with

schizophrenia must take into account a childs


developmental level in order to support the childs
reality testing and be sensitive to the childs sense
of self.
Long-term supportive family interventions and
cognitive behavioral and remediation interventions
combined with pharmacotherapy are likely to be
the most effective approach to early-onset
schizophrenia.

Management & Treatment


Treatment strategies need to focus on the clinical

symptoms and morbidity of the underlying


disorder, while also addressing any comorbid
disorders or biopsychosocial stressors.
The assessment of the child with psychotic
symptoms should include a careful,
comprehensive, and thoughtful evaluation

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