Psychosis in Children and Youth: Focus on Early-Onset Schizophrenia

Sabina Abidi
Pediatrics in Review 2013;34;296
DOI: 10.1542/pir.34-7-296

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Article behavioral and mental health issues

Psychosis in Children and Youth: Focus on

Early-Onset Schizophrenia
Sabina Abidi, MD, FRCPC*
Practice Gap
Psychosis is the third most disabling condition worldwide in youth. Evaluation of children
Author Disclosure who present with a psychotic episode requires the clinician to understand the broad range
Dr Abidi has disclosed of causes and the criteria used to differentiate primary psychotic disorders, other psy-
no financial chiatric and nonpsychiatric illnesses, and drug effects.
relationships relevant
to this commentary. Objectives After completing this article, readers should be able to:
This commentary
1. Define psychosis and be aware of the conditions that can present with psychotic
contains a discussion
symptoms in children and youth.
of an unapproved/
2. Identify the qualifiers of psychotic symptoms and behaviors that are suggestive of
investigative use of
early-onset schizophrenia (EOS).
a commercial product/
3. Know the epidemiology, pathogenesis, and clinical correlates of EOS.
device.
4. Understand the pharmacologic and nonpharmacologic treatment modalities
recommended for management of EOS.
5. Be aware of ongoing efforts to identify those in the earliest stage of onset of
schizophrenia in children and youth (at risk or prodromal youth).

Matt is a 16-year-old in grade 10. Matt has always been a good student. He had 3 close
male friends who have known him for years. Matt plays basketball and recently took up
acoustic guitar. He has a good relationship with his parents, who describe him as always
having been a quiet kid, “a thinker.” Recently, however, Matt seems different. His grades
are going down at school from Bs to Cs; he failed English. He sits quietly in class wearing
his headphones and rarely talks to anyone, which is new for him. Teachers find him to be
distracted and distant, as if he is not paying attention or is “zoned out.” He started hang-
ing out with a new crowd of friends, who all seem to use cannabis regularly; he seems to
be avoiding his old friends and stopped playing his guitar. A few weeks ago Matt’s parents
became really concerned as he stopped going to school and started spending all of his
time in his room on the Internet. He is researching odd things, new interests that are
unfamiliar to his parents. Sometimes he refuses to come out, refusing even to eat. Yes-
terday he threw out his cell phone and all of his electronic
devices. Sometimes Matt seems frightened; he is not sleep-
Abbreviations ing well and paces at night. Recently, his mother has seen
him talking to himself. Matt’s parents are very worried and
CIP: cannabis-induced psychotic disorder
DUP: duration of untreated psychosis wonder what has happened to their son.
EOS: early-onset schizophrenia
FGA: first-generation antipsychotic Definition
OCD: obsessive-compulsive disorder In 2001, the World Health Organization ranked psychosis
PDD: pervasive developmental disorder as the third most disabling condition worldwide in youth.
PLE: psychotic-like experience The social and emotional impact of a psychotic disorder
SGA: second-generation antipsychotic can interfere seriously with neurodevelopmental processes
VEOS: very early-onset schizophrenia in a young person, which in turn has the potential to irre-
versibly alter the trajectory of his or her life. Interestingly,

*Assistant Professor Dalhousie University Faculty of Medicine, Child/Adolescent Psychiatrist, IWK Youth Psychosis Program, IWK
Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada.

296 Pediatrics in Review Vol.34 No.7 July 2013

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the true definition of psychosis eludes many. The word
itself is often perceived incorrectly, with many associa-
tions drawn from dramatic images in the media or incor-
rect historical references. In the history of psychiatry, the
words mad and psychosis have often been used inter-
changeably, negatively contributing to the stigma associ-
ated with the term and the illness itself.
In truth, psychosis is simply a word that refers to the
experience of being unable to distinguish what is real
from what is unreal. Psychotic is the adjective that de-
scribes the experience. A psychotic disorder is a brain dis-
ease marked by subjective symptoms that reflect the
disturbance in reality testing and objective signs of asso-
ciated impairment. The disorder is identified when these
symptoms and impairment are prolonged and cannot be
attributed to a cause other than a psychiatric disorder.
Schizophrenia is one psychotic disorder that, like many
psychiatric disorders, can begin in childhood. Schizophre-
nia occurring before age 13 years is termed very early-onset
schizophrenia (VEOS); when the condition begins later
but before age 17 years, it is termed early onset schizophre-
nia (EOS). VEOS is extremely rare (see below); thus, this
review refers primarily to EOS. Schizophrenia is a chronic
and persistent serious mental illness that requires ongoing
treatment. Schizophrenia historically has been thought of
as an illness with a very poor outcome in terms of morbid-
ity and mortality. However, recent advances in the field of
early intervention for psychotic disorders has allowed for
a shift in this pessimistic association, evidenced by better
outcomes and prognosis for those youth whose illness is
identified and treated early.
A psychotic experience describes a perception that oc-
curs in the absence of a stimulus. A hallucination, for ex-
ample, is the experience of hearing, seeing, tasting,
smelling, or feeling something without the occurrence
of an actual stimulating event. A common example is hear-
ing voices that are not actually there, which is an auditory
hallucination. Similarly, visual perceptual disturbances can
occur, such as seeing shadows, animals, or people that are
not there. A delusion is a disturbance of thought content
in which the person holds true a fixed, false belief, despite
the absence of proof or when the idea is not shared by
others. Common delusions include the belief that one is
being followed or in danger of harm (paranoid delusion).
Another example is the belief in having super powers or
omnipotent strength (grandiose delusion).
Clinical Aspects
A psychotic experience can occur for many different rea-
sons. When evaluating youth presenting with psychotic
experiences, clinicians must consider a list of potential
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behavioral and mental health issues psychosis
causes. (1) For example, substance abuse (hallucinogens
or psychedelics), specific medical conditions (hyperthy-
roidism, epilepsy, brain tumors, or Wilson disease), and
individual reactions to certain medications (psychostimu-
lants) all can cause psychotic experiences. In these instan-
ces, the experience can be related directly to the cause
temporally or causally (ie, when the cause is removed
or treated, the psychosis disappears).
Psychosis also can be a symptom of other psychiatric
illnesses, such as mood disorders (bipolar disorder or ma-
jor depression), dementia, delirium, or postpartum states.
In these illnesses, psychosis is a component of the presen-
tation but not the primary issue.
The psychiatric illnesses called primary psychotic dis-
orders are those that cause psychosis. Schizophrenia is
the most common of the primary psychotic disorders.
These disorders are similar to some degree in presenta-
tion and differ only slightly in terms of duration and level
of impairment. Schizophrenia, the most chronic of the
primary psychotic disorders, is marked not only by the
psychotic symptoms but also by a constellation of other
neuropsychiatric symptoms.
The symptoms of schizophrenia that have their onset in
adolescence or early adulthood (age older than 13 years)
(EOS) often are clustered into 4 distinct symptom domains:
1. The psychotic or positive symptom domain includes
hallucinations, delusions, disorganized thoughts, and
behaviors. Thoughts appear disorganized, interrupted,
tangential, and slow or even absent. Unusual behavior
often is a result of the psychotic experiences, a reflection
of the beliefs themselves (eg, hiding due to paranoid
fears). Sometimes the behaviors do not make sense
to the outside observer and can appear nonsensical.
2. The negative symptom domain is marked by apathy,
anhedonia, reduced or absent affect, lack of motiva-
tion, social withdrawal, and slowness of movement.
These symptoms often are mistaken as markers of de-
pression or even laziness. However, youth suffering
from depression tend to be more aware of and to seek
help for their symptoms, whereas youth with schizo-
phrenia often do not notice negative symptoms or
their effect on daily activities.
3. The altered cognition domain is marked by new dif-
ficulties in working memory, attention, processing
speed, and executive function.
4. The mood domain includes alterations in emotion or
affect regulation, often secondary to the psychotic
symptoms themselves.
It seems that the psychotic symptoms follow an inde-
pendent course over time compared with the negative or
Pediatrics in Review Vol.34 No.7 July 2013 297
behavioral and mental health issues psychosis
cognitive symptoms. The psychotic symptoms respond
better and more quickly to antipsychotic medication.
The negative and cognitive symptoms are poorly respon-
sive to medication. Unfortunately, the latter symptoms
can cause more impairment in social and occupational
functioning. Youth can present with (sometimes overlap-
ping) aspects of all 4 symptom domains in varying de-
grees of severity at the onset of illness, sometimes
making determination of a reliable diagnosis difficult.
Criteria outlined in the Diagnostic and Statistical Man-
ual of Mental Disorders (Fourth Edition, Text Revision)
(2) are used to help determine whether a youth is pre-
senting with schizophrenia:
A. Characteristic symptoms: The youth must present
with 2 or more of the following, each present for a sig-
nificant portion of time for a 1-month period: (1) de-
lusions, (2) hallucinations, (3) disorganized speech,
(4) grossly disorganized or catatonic behavior,
and/or (5) negative symptoms (only one criterion
A symptom is required if delusions are bizarre or if
hallucinations consist of a voice keeping a running
commentary on the youth’s behavior or thoughts
or 2 or more voices are conversing with each other).
B. Social or occupational dysfunction: Since the onset of
the disturbance and for a significant portion of time,
there is failure to reach expected level of interper-
sonal, academic, or occupational achievement (when
onset is in childhood or adolescence) or one or major
areas of functioning (work or self-care) are below that
achieved before onset.
C. Duration: Continuous signs of the disturbance per-
sist for 6 months. This 6 months includes 1 month
of symptoms (or less if successfully treated) meeting
criterion A and may include periods of prodromal or
residual symptoms (may be manifested by either only
negative symptoms or 2 or more criterion A symp-
toms present in attenuated form).
D. Schizoaffective and mood disorder exclusion: Schizoaf-
fective disorder and mood disorder with psychotic
features are mutually exclusive to symptoms of schizo-
phrenia; they have been ruled out.
E. Substance or general medical condition exclusion: The
disturbance is not due to the direct physiologic effects
of a substance or general medical condition.
F. Relationship to a pervasive developmental disorder
(PDD): If there is a history of autistic disorder or an-
other PDD, the additional diagnosis of schizophrenia
is made only if prominent delusions and hallucina-
tions are also present for at least 1 month (less if
treated).
298 Pediatrics in Review Vol.34 No.7 July 2013
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Very Early-Onset Schizophrenia
Schizophrenia typically has its onset after the age of 13
years. The rare form of the illness (VEOS; estimated prev-
alence 1 per 10,000 population) affects children younger
than 13 years. (3) VEOS is associated with greater familial
vulnerability and a worse prognosis. The disorder has a
clinical presentation, course, and outcomes that are mark-
edly different from those of EOS; however, currently the
same diagnostic criteria as for EOS are used to make the
definitive diagnosis.
Most children afflicted with VEOS seem to have had
more severe and an earlier onset of premorbid difficulties.
Some patients have developmental impairments that were
notable in the first few months of life. Similar to the
course of illness in EOS, there is a prodromal stage in
VEOS, but it is heterogeneous and may begin years be-
fore diagnosis is made. The prodrome to VEOS may be
marked by new-onset motor delay (50% of cases), speech
delay (50% of cases), language abnormalities, and social
abnormalities (87% of cases) of otherwise unknown cause.
(3) These children may have a lower IQs premorbidly,
sometimes in the intellectual disability (mental retarda-
tion) range. Many of these children are mistakenly identi-
fied as having a PDD, such as autism or Asperger
syndrome, because of similarities in presentation, such as
echolalia, arm flapping, and social isolation.
It is clear that VEOS is an illness of atypical features
compared with EOS, marked by earlier and more severe
disruption of brain development. The onset of the illness
appears to be more insidious than EOS, making early
identification difficult. The mean age of onset of the ill-
ness identified retrospectively is 6.9 years of age; how-
ever, diagnosis is made on average at 9.5 years. (3)
VEOS is more common in boys. The prodromal phase
in early childhood includes deterioration in school perfor-
mance, social withdrawal, disorganized or unusual behav-
ior, decreased ability to perform regular activities, poor
attention to self-care and hygiene, and sometimes a
change in behavior marked by aggression or hostility.
In VEOS, the psychotic symptoms manifest primarily
as auditory hallucinations (80%-100% of cases), whereas
other perceptual abnormalities are less common. Delu-
sions are less complex and tend to be of childhood
themes, such as monsters or “bad people,” although re-
ligious, somatic, and grandiose delusions can occur.
Thought disorganization tends to worsen over time.
Negative symptoms of flat or odd affect are common.
Treatment of VEOS is multimodal, with the mainstay
being antipsychotic medication. Education, support,
behavioral and social skills treatment, and cognitive

rehabilitation with inclusion of all family members and
school partners are all essential. The use of antipsychotic
medication is controversial in young children, with the
risk for adverse events being higher. Current recommen-
dations are to use the atypical antipsychotics (see the
Treatment section) with close monitoring of adverse
effects.
Most children with VEOS experience continuation of
the illness into adolescence and adulthood. Those who
have a more insidious onset of illness, severe premorbid
abnormalities, and negative symptoms fair worse than
other patients, with 70% living a dependent life into
adulthood. More than half have impaired social out-
comes. Approximately 15% to 30% may experience remis-
sion with treatment, but the illness tends to relapse with
worsening prognosis over time. (3)
Psychotic Experiences in Children Younger
Than 13 Years
In terms of identifying children who may have VEOS, it is
important to note that psychotic experiences in children
younger than 13 years are common and usually not path-
ologic. Features of psychotic experiences that are less
likely to be representative of risk for VEOS include the
following:
• Absence of premorbid difficulties
• Auditory hallucinations that are nonbizarre and related
to stressors in the child’s life
• Less notable interaction with the perceptual disturban-
ces (eg, children can experience them without disrup-
tion in daily activities)
• Absence of delusions
• Persistence of social and academic functioning despite
the experiences
Psychotic experiences also can present as symptoms of
other psychiatric illnesses in children. Children who have
severe depression or anxiety (posttraumatic stress disor-
der or social anxiety disorder) can present with perceptual
disturbances that are congruent with the primary illness
or mood. In these cases, the experiences usually present
only in the face of triggers related to the primary disorder.
Obsessive-compulsive disorder (OCD) is an illness
marked by intrusive thoughts and compulsive behaviors
about which the patient has insight. In OCD in child-
hood, however, there often is a lack of insight by virtue
of immature cognitive development or severity of OCD
symptoms. Sometimes the thoughts are described as
“voices” by these children, who may comprehend the
experience as being external to the self. These children
are not at a higher risk of developing schizophrenia.
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behavioral and mental health issues psychosis
Certainly children with PDD can present with psychotic
experiences that are inherent to the PDD itself and not
predictive of an increased risk for VEOS. These children
more commonly have auditory hallucinations as opposed
to delusions and do not present with negative symptoms.
It is extremely important to distinguish psychotic experi-
ences secondary to illnesses other than VEOS in child-
hood because the implications and approach to treatment
are vastly different.
Psychotic-Like Experiences in Adolescents
Older Than 13 Years
An experience that does not reach the psychotic symptom
threshold in adolescents in that there is maintained in-
sight that the phenomenon is not real is a psychotic-like
experience (PLE). PLEs are relatively common in healthy
adult populations. Large-scale catchment area studies re-
port a lifetime prevalence of PLEs, ranging from 10% to
20% in persons who do not develop a primary psychotic
disorder. Adolescents often present with subclinical PLEs
that may not signify risk for a psychotic disorder. Com-
prehensive clinical assessments of these youth reveal a
high incidence of other psychiatric disorders, such as
mood (depressive) or anxiety disorders. Furthermore,
youth who have suffered a recent death of someone close
to them or a traumatic event may manifest the associated
loss, grief, or depressed mood as PLEs. In many instances
of PLEs, once the identified (nonpsychotic) disorder is
treated, the PLEs dissipate or disappear. In other words,
the PLEs are a manifestation of illness other than a psy-
chotic disorder.
Treatment modalities used for these illnesses (eg, cog-
nitive behavioral therapy for anxiety or depression) can
target PLEs as a cognitive distortion and enable the youth
to understand and reframe the experience in the context
of the illness. Of particular importance is that without
comprehensive assessment, the other clinical correlates
of PLEs might be missed and the youth misidentified
or, worse, treated inappropriately as having a primary psy-
chotic disorder.
Identification of Adolescents at Risk for EOS
Although PLEs may not represent the onset of a psychotic
disorder, the paradox exists that in some patients, PLEs
may well be a marker of increased risk for schizophrenia.
Approximately 8% of children and youth will have a psy-
chotic symptom in attenuated form at some point that is
not pathologic. Some 3% of these youth may have PLEs
associated with other psychiatric conditions (anxiety or
mood) and roughly 1% will develop schizophrenia. (4)
Pediatrics in Review Vol.34 No.7 July 2013 299
behavioral and mental health issues psychosis
As this illness carries such potential for morbidity in
youth, the earliest possible identification of those who
might make a transition to a psychotic disorder is crucial.
The difficulty lies in distinguishing a true symptom of
risk from normal aberrations in behavior common in
adolescence. Qualifiers of PLEs as markers of risk in-
clude those associated with bizarre ideas or beliefs, gran-
diose ideation, behavior changes, sleep disturbance,
unusual suspiciousness, themes of persecution, and dis-
organized communication. These qualifiers must be
considered along with other key components of the
presentation:
• Identification of a change: Adolescents at higher risk
for EOS experience the onset of PLEs that reflect
a change (worsening frequency or severity) in the past
year. PLEs that are nondistressing and have been con-
stant in quality for years are less concerning.
• Perpetuation: PLEs that continue to present at least
once per week on average in the previous month
and continue to be distressing are of concern. Symp-
toms that were present but had dissipated before pre-
sentation are less concerning.
• Impairment: Concerning PLEs are those that are suf-
ficiently distressing to cause impairment in daily activ-
ities by way of distraction, disturbance in cognition, or
behavior change. Often, this impairment is marked by
deterioration academically or at work or by disturban-
ces in social functioning. PLEs that are mildly distress-
ing but do not affect function are less concerning.
• Causal factors: It is significant if there is no other
identifiable cause for the PLEs (eg, medication, a
medical condition, substance abuse, or other psychi-
atric condition).
• Psychotic threshold: Symptoms should be evaluated
with regard to whether they exceed the psychotic
threshold (judged by the degree of conviction with
which the experience is held).
If these characteristics are met and the PLEs consis-
tently cross the psychotic threshold in quality and also
cause impairment, the youth may have a psychotic disor-
der. In these cases, to exclude other possible causes of the
psychosis, an evaluation should be initiated that com-
prises the following:
• A detailed assessment that includes collateral informa-
tion from primary caregivers
• Evaluation for medical disorders
• Physical examination, including neurologic screen
• Comprehensive blood chemical analyses
• Toxicology screening for substances of abuse
300 Pediatrics in Review Vol.34 No.7 July 2013
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• If neurologic examination warrants or the presentation
is sufficiently severe, magnetic resonance imaging of
the head is recommended.
If results of these measures are unremarkable and the
severity of the psychosis persists, a referral for psychiatric
evaluation is warranted. If the youth presents with symp-
toms severe enough to compromise his or her safety, or
that of others, or to put the youth at risk for further men-
tal deterioration, an involuntary admission to the hospital
may be required for acute symptom stabilization and clar-
ification of diagnosis. Overall, however, treatment of
EOS in the outpatient setting in conjunction with family,
community, and support systems is always preferred.
Epidemiology
Although there seems to be a modest decrease in the in-
cidence of schizophrenia over time, the prevalence re-
mains stable. The lifetime morbid risk of developing
schizophrenia is 7.2 per 1000 population, with an esti-
mated median lifetime prevalence of about 4 per 1000
population. (5)
The median incidence of EOS and adult-onset schizo-
phrenia in males vs females is 1.4:1, with an earlier onset
of illness in males (age range, 15–25 years) compared
with females (age range, 19–35 years). (5) Males tend
to have a more severe illness course and worse outcome.
In males, schizophrenia is an illness of adolescence, hit-
ting youth in their prime.
The incidence of schizophrenia seems to show geo-
graphic variation. Urban settings show a higher incidence
of the disorder. (5) Areas of increased immigrant popu-
lations show both higher incidences and prevalence,
which is independent of migration effects. (5) It has been
postulated that the higher numbers in these areas may be
associated with race, ethnicity, the concept of social iso-
lation and depression, nutritional aspects, or increased
rate of infection; however, none of these associations
has been confirmed.
Although the prevalence of schizophrenia is modest
compared with other psychiatric disorders of children
and youth, the associated morbidity and mortality are
cause for attention. Persons afflicted with schizophrenia
have 2 to 3 times the risk of death compared with the gen-
eral population, usually by suicide or comorbid metabolic
conditions. There is a higher risk of cardiovascular disease
and its associated mortality inherent in having schizophre-
nia and also because of medications used as treatment.
Schizophrenia also is associated with an increased risk
for comorbid conditions, such as substance use and abuse
disorders (cannabis and alcohol in particular) and

depression and associated suicide. Youth with EOS often
struggle with navigating their adolescence and transition
to adulthood after symptom stabilization. Youth with
EOS require help grieving the loss of the adolescent ex-
periences missed because of the illness and the alteration
of life potential that may have occurred as a result.
Etiology and Pathogenesis
The acute psychotic state is associated with increased
levels of dopamine in the brain via increased synthesis,
release, and concentration in the synapse. (6) The alter-
ations in dopamine levels in the brain are associated with
the other manifestations of schizophrenia, including neg-
ative symptoms and cognitive deficits. In terms of brain
structure, the illness has been associated reliably with
universal decreases in gray matter, enlargement of the
(lateral and third) ventricles with reduction in brain vol-
ume, and focal changes in white matter tracts. (6)(7) The
abnormal brain structure and faulty circuitry (6)(7) leads
to hyperactivity in the mesolimbic areas of the brain,
linked to psychotic symptoms.
Also noted is hypoactivity in the frontal and prefrontal
cortex, which is associated with executive function defi-
cits and deficits in social cognition (the inability to accu-
rately perceive social cues from others or the tendency to
misinterpret cues), respectively. (6) These brain changes
and deficits seem to be independent of disease duration
or severity in that they can be seen in the earliest identifi-
able stages of the illness and remain stable over time. The
explanation, however, for the delayed onset of recogniz-
able symptoms of EOS in adolescence or young adult-
hood is unclear.
The exact cause of the brain changes seen in schizo-
phrenia has yet to be determined. The cause is heteroge-
neous and multifactorial. Undoubtedly, the illness is
heritable, as evidenced by higher rates of schizophrenia
in relatives of patients than in the general population.
There is a 10-fold increase in risk in a first-degree relative.
This risk increases to almost 50% when both parents are
affected and up to almost 80% between monozygotic
twins. Current theory suggests that those who develop
the illness all have the predetermined genetic vulnerability.
This vulnerability coupled with exposure to specific
triggers at particular stages of neuronal development
(eg, childhood and adolescence), when critical synaptic
changes are occurring, may confer increased risk of ab-
normal brain development. In some patients, the ongoing
interplay of these factors may lead to permanent brain
changes and the consequent crossing of a threshold, caus-
ing one’s symptoms to manifest irreversibly as illness. Five
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behavioral and mental health issues psychosis
environmental risk factors have been studied extensively
and found to contribute to increased risk for schizophrenia
in those born with genetic risk (4):
1. Prenatal and perinatal events, which may include ma-
ternal infection, smoking during pregnancy, obstetric
complications leading to fetal hypoxia, and maternal
malnutrition
2. Sociodemographic factors, such as growing up in
a more urban area
3. Living in areas of lower socioeconomic status or areas
of relative social isolation from those of similar ethnic
or migrant group
4. Early childhood trauma, such as exposure to traumatic
events, particularly abuse, in childhood
5. Exposure to cannabis
Cannabis and Psychosis
Although cannabis is not biochemically a psychedelic
drug, cannabis exposure has been found to produce tran-
sient psychotic states in 10% to 15% of users. (8) It seems
that many individuals with schizophrenia and indeed
those who have increased vulnerability for developing
schizophrenia are particularly sensitive to the psychoto-
mimetic properties of cannabis. Cannabis use (compared
with other drugs or alcohol) can increase morbidity in
and confer a poorer prognosis on those who have schizo-
phrenia by virtue of contributing to earlier and more
frequent relapses and hospitalizations, cognitive impair-
ment, poor response to medication, poor compliance
with medication use, and altered psychosocial function-
ing. (8)
It generally is accepted that cannabis exposure has the
potential to exacerbate psychosis even if compliance with
treatment is reasonable. However, the role of cannabis as
a potential causal factor in the development of schizo-
phrenia (potentially in a dose-response manner) has been
suggested only recently. (9) Exposure to cannabis at an
early age (early adolescence) carries an increased risk of
psychotic outcomes. (8)(9) Research in this area is occur-
ring at an exponential rate, and several theories have been
suggested as to the relationship between cannabis and
psychosis; however, no theory has yet been confirmed.
The association however is strong and exists.
The relationship between cannabis use and psychosis
is bidirectional. Those who have an increased risk of psy-
chosis are more likely to use cannabis, and those who use
cannabis are at increased risk for psychosis. An immediate
positive effect of cannabis has been reported in the earli-
est stages of use (minutes) that settles anxiety, depression,
and cognitive impairments associated with schizophrenia.
Pediatrics in Review Vol.34 No.7 July 2013 301
behavioral and mental health issues psychosis
(10) Most youth with psychosis do not get “high” on
cannabis but rather use it to treat these symptoms (anx-
iety, depression, insomnia) There is no evidence, how-
ever, that cannabis has any benefit on actual psychotic
experiences; indeed, there is general consensus that these
experiences worsen. (10)
Certainly, not every young person who uses cannabis
has a psychotic experience, nor do they all develop psy-
chosis. Thus, cannabis itself is not a sufficient cause for
developing illness. An increased risk has been confirmed
for psychotic outcomes in relatives of those with schizo-
phrenia who are exposed to cannabis. One study reports
the risk of schizophrenia is 10 times higher in relatives
who used cannabis compared with those who did not. (8)
Cannabis use is increasing worldwide, and the age of
initiation is decreasing. This fact, combined with the risk
of an illness that carries such morbidity and mortality,
makes cannabis use a significant public health concern.
For those youth who present with a family history of
schizophrenia or other psychotic outcomes, counseling
against cannabis use should be provided that refers to
their specific risk, not just to the reduction of harm in
general.
Clinicians often hesitate to diagnose a primary psy-
chotic disorder in the presence of substance use, particu-
larly that of cannabis. Many patients are identified instead
as having a drug-induced psychotic disorder as opposed
to a primary illness. Research reveals, however, that of those
who have been identified as having a cannabis-induced
psychotic disorder (CIP), many are identified as having
converted to schizophrenia 1–2 years later. The implica-
tion of this finding is that the cannabis-related psychotic
state may have been an unidentified prodromal risk
marker for schizophrenia.
Youth identified as having CIP who are at higher risk
for later development of schizophrenia usually are males
presenting with CIP at a young age and having a family
history of psychotic disorder.
Most youth identified as having a drug-induced psy-
chotic disorder are discharged from inpatient units
quickly and lost to follow-up. Given the noted risk, psy-
chosis should be attributed solely to drug misuse with
caution when cannabis is the presumed causal agent.
Moreover, in those who present with prolonged CIP re-
quiring hospital admission, ongoing monitoring of risk
for conversion to a primary psychotic disorder should en-
sue on discharge.
Course of Illness
Schizophrenia is an illness thought to develop in stages
or phases (Figure). The period between the onset of
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identifiable symptoms and the initiation of treatment is
called the duration of untreated psychosis (DUP). Before
the early psychosis movement of the 1990s that empha-
sized the growing awareness of and need for the earliest
identification of illness and initiation of treatment, the
DUP in North America was 2 to 5 years. The implication
of this time lag is significant in terms of its association
with poor outcomes and increased morbidity and mortal-
ity related to the illness. Recent efforts to identify the ill-
ness earlier have been rewarded with DUPs decreasing to
1 to 2 years and improved outcomes, particularly for youn-
ger patients.
The prodromal stage of the illness often occurs in
early adolescence, 1 to 2 years before the onset of iden-
tifiable psychotic symptoms (first episode of psychosis).
The prodromal stage historically was identified retro-
spectively. Current research efforts, however, have de-
veloped prospective screening and assessment tools
intended to identify those in the prodromal stage ac-
cording to the quality of their help-seeking psychotic
symptoms. These tools currently are used only in the
context of research; however, prospective intervention
studies are being conducted now in the attempt to iden-
tify treatment modalities (pharmacologic and nonphar-
macologic) that might delay, if not prevent, the onset of
the first episode of psychosis.
Schizophrenia is an illness that tends to relapse in the
face of poor compliance with treatment or exposure to
significant triggers. For some, a relapse can be severe
and present as another full psychotic episode. With each
successive relapse, the odds of regaining baseline func-
tioning decrease. Certainly, patients who have had mul-
tiple relapses are less responsive to pharmacotherapy and
may require higher doses of medications to effect
Figure. Course of schizophrenia.

treatment. For these patients, the chance of returning to
baseline potential in terms of social and occupational
function decreases.
Treatment
Treatment of the child or youth afflicted with schizo-
phrenia requires a multipronged approach, with careful
attention paid to (1) how the illness has intruded on the
youth’s ability to navigate adolescence, (2) other health
issues that may arise during treatment (ie, potentially se-
rious metabolic adverse effects [see below]), and (3)
ongoing barriers to recovery from illness (Table). Re-
gardless of age at onset, the cornerstone of treatment
for schizophrenia is the use of antipsychotic medication.
With the identification of the first episode of illness, the ini-
tial focus is on treating the psychotic symptoms. Once this
therapy occurs, patients are better able to participate in the
other treatment modalities that will foster their recovery.
All antipsychotic medications used to treat schizo-
phrenia share the common effect of decreasing dopamine
levels in the brain. The typical or first-generation antipsy-
chotics (FGAs), such as haloperidol, perphenazine, and
chlorpromazine, are effective in treating psychotic symp-
toms (11) by specifically targeting dopamine receptors in
all areas of the brain. This global blockade, however, can
lead to adverse extrapyramidal adverse effects among
other side effects. Extrapyramidal adverse effects are
marked by increased muscle tone in the upper and lower
Barriers to Recovery and
Table.
Predictors of Nonadherence
Denial of illness
Symptoms of illness
• Delusions
• Depression
• Cognitive impairment
Belief medication is no longer needed
Negative attitudes of family and friends
Stigma
Lack of insight
Substance abuse (cannabis in particular)
Adverse effects of medication
• Drug-induced dysphoria
• Akathisia
Cost of medication and inconvenience of treatment
Lack of a support network and specialized service for care
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behavioral and mental health issues psychosis
extremities, slowed movements, tremors, an inner sense
of restlessness (akathisia), and involuntary dystonic or
dyskinetic movements. Children and youth are more vul-
nerable to these effects, with evidence of irreversibility ap-
pearing in some patients. (12)
The atypical or second-generation antipsychotics
(SGAs) were designed to effect treatment but with less
risk of extrapyramidal adverse effects by targeting dopa-
mine indirectly. The SGAs antagonize dopamine recep-
tors in varying degrees but also target other receptors
(histaminergic and cholinergic).
This multiple receptor blockade can lead to a myriad
of metabolic abnormalities. Weight gain, hypercholester-
olemia, dyslipidemia, glucose intolerance, and cardiac
abnormalities are among the risks associated with SGAs
in youth and adults. (11)(12) Sedation, endocrine abnor-
malities, and anticholinergic adverse effects can be prob-
lematic. Furthermore, although there is a lower incidence
of extrapyramidal adverse effects with the SGAs, (11)
akathisia is reported commonly and is one of the leading
causes, along with weight gain, of noncompliance with
treatment. (11)
Both FGAs and SGAs are superior to placebo for treat-
ment of psychotic symptoms in schizophrenia. (11) Efficacy
is the same for both classes in treating positive symptoms,
with little evidence for superiority of any medication in ei-
ther class. (11) No significant difference in patient adher-
ence patterns between the classes has been found. (11)(12)
The SGAs are significantly more expensive than the
FGAs; however, some case reports and smaller studies re-
port slight improvement in negative symptoms and cog-
nitive function with SGAs that is not seen with FGAs.
At this time, the US Food and Drug Administration
has approved the FGAs haloperidol and chlorpromazine
and the SGAs risperidone, olanzapine, quetiapine, and
aripiprazole for first-line treatment of EOS. Off-label
use of antipsychotics for treatment of EOS is common
practice, given the paucity of available trials conducted
in this population.
Treatment guidelines for EOS mimic those available
for the adult population. (13) Recommended practice
at this time for VEOS and EOS is to use the first-line
SGAs. Selection of the SGA at this time depends on care-
ful consideration of the health status of the patient, se-
verity of symptoms, and sensitivity to adverse events.
Clozapine is considered the “gold standard” approach
for treatment-resistant patients; however, use is restricted
and requires active monitoring with regular blood mon-
itoring because of the associated risk of seizures, agranu-
locytosis, and leukopenia.
Pediatrics in Review Vol.34 No.7 July 2013 303
behavioral and mental health issues psychosis
It is strongly recommended that prescribers of antipsy-
chotic drugs practice routine monitoring for metabolic
and neurologic adverse events, with active attention paid
to risks of negative outcomes. Practice always involves us-
ing monotherapy if possible and, certainly in youth, using
the lowest effective dose of medication.
In youth who are compliant, pharmacotherapy is ef-
fective in treating psychotic symptoms in 90% of cases.
With remission of symptoms, it is recommended that pa-
tients continue to take the medication for 2 years before
consideration of discontinuation. Only approximately
20% of patients are able to discontinue use of the medi-
cation, whereas most will require long-term treatment.
Augmentation therapies to medication are numerous.
There are many specialized early psychosis programs in
the world that focus on treatment of EOS. These clinics
often are multidisciplinary and may offer therapies spe-
cific and sensitive to the needs of youth. Occupational
therapy, recreational therapy, art therapy, and health
and wellness clinics are useful in helping youth monitor
their risks and adverse medication effects while maintain-
ing healthy lifestyles.
Psychological therapies, such as cognitive therapy
specific to psychosis, help to treat comorbid symptoms
of depression and anxiety and aid navigation of the de-
velopmental challenges that come with illness onset
early in life. Collaboration with substance abuse pro-
grams often is essential to minimize risks of relapse. Fam-
ily education, therapy, and support help to ease the
burden of illness often placed on primary caregivers of
youth who have serious mental illness.
Advocacy for these youth in schools and work can help
with reintegration into daily activities. Youth support
programs and clubhouse models provide peer support
networks that are integral to helping patients recover. Of-
ten, in particularly chronic and severe cases, outreach pro-
grams and residential rehabilitation programs are useful
in helping youth who have severe EOS achieve some level
of independence and a better quality of life.
Barriers to Recovery
Despite the fact that compliance with medication use may
be enough to manage the symptoms of the illness and
foster benefit from recovery programs, many youth refuse
to take the medication, are poorly compliant with the
medication use, or refuse follow-up. Many issues have
been identified that help to explain this behavior in terms
of barriers to illness recovery (Table).
Lack of insight is thought to be an inherent symptom
of the illness that exists in some patients in whom there is
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no acknowledgement or recognition of having an illness,
either in the acute stage or when the symptoms have re-
solved. Patients often refuse medication soon after feeling
well, with the misperception that the symptoms will never
recur. Some clinicians believe this apparent lack of insight
is a form of denial; however, others differentiate the de-
ficiency as an aspect of psychosis itself. Certainly, those
patients who lack insight at any stage of the illness carry
the burden of a poorer prognosis.
Stigma on the part of friends and family, the patient,
clinician and society presents as an ongoing barrier to
recovery. The negative connotations associated with
schizophrenia are significant and impairing. Many youth
will have lost friends during their illness because of
stigma. Education designed to battle such misperceptions
and support offered to patients, family, and friends is
essential.
Of particular importance in any treatment program is
engaging the youth in all aspects of the treatment plan,
enabling him or her to make reasonable decisions about
treatment and recovery. Reassurance and education help
them to become more knowledgeable about their illness
and to gain some sense of independence and control over
outcomes.
Furthermore, a regular review of medication and ad-
verse effects with the patient is crucial to ensure that there
exists a meaningful and safe balance that is clinically ac-
ceptable to the youth. Meeting youth “where they’re
at” in terms of their developmental stage and readiness
for change is important, recognizing that for some recov-
ery might happen in slow, small, but meaningful steps.
Those youth who remain engaged in the treatment pro-
cess fare much better.
Prognosis
Research and clinical experience confirm that the earlier
treatment is initiated for EOS, the better the outcomes.
Certainly, for those youth who present with a more se-
vere form of the illness marked by cognitive deficits,
disorganized thinking, and negative symptoms, the out-
come may be less favorable. For those who present with
primarily positive or psychotic symptoms without the
other deficits, the prognosis is much better, particularly
with earlier attention. Most patients (40%-60%) will re-
cover in the first year if they maintain compliance. Over
time, more than two-thirds of patients who are compliant
have complete remission of positive symptoms and are
able to manage their daily activities. More than 50% of
these youth are able to return to age-appropriate social
and academic roles.
 behavioral and mental health issues psychosis

3. Masi G, Mucci M, Pari C. Children with schizophrenia: clinical

Summary
• On the basis of strong research evidence (1)(3) very
early onset (VEOS) and early onset schizophrenia
(EOS) carry significant morbidity and mortality risks
for children and adolescents.
• On the basis of strong research evidence, the
pathogenesis of EOS is linked to a dysregulation of
dopamine and morphologic brain changes. (6)(7)
• On the basis of some research evidence and consensus,
development of schizophrenia is the result of the
interplay between genetic and environmental risk
factors. (4)
• On the basis of strong research evidence,
antipsychotic medications are the cornerstones of
treatment for EOS. (11)(12)(13)
• On the basis of some research evidence and consensus,
(13) treatment for schizophrenia should be timely,
multimodal and multidisciplinary, including both
pharmacologic and nonpharmacologic modalities to
optimize recovery.
References
1. Algon S, Yi J, Calkins ME, Kohler C, Borgmann-Winter KE.
Evaluation and treatment of children and adolescents with psy-
chotic symptoms. Curr Psychiatry Rep. 2012;14(2):101–110
2. American Psychiatric Association. Diagnostic and Statistical
Manual for Mental Disorders, Fourth Edition, Text Revision.
Washington, DC: American Psychiatric Association; 2000
picture and pharmacological treatment. CNS Drugs. 2006;20(10):
841–866
4. van Os J, Kapur S. Schizophrenia. Lancet. 2009;374(9690):
635–645
5. McGrath J, Saha S, Chant D, Welham J. Schizophrenia: a concise
overview of incidence, prevalence, and mortality. Epidemiol Rev.
2008;30:67–76
6. Guillin O, Abi-Dargham A, Laruelle M. Neurobiology of
dopamine in schizophrenia. Int Rev Neurobiol. 2007;78:1–39
7. Vita A, De Peri L, Silenzi C, Dieci M. Brain morphology in first-
episode schizophrenia: a meta-analysis of quantitative magnetic
resonance imaging studies. Schizophr Res. 2009;108:3–10
8. McGuire PK, Jones P, Harvey I, Williams M, McGuffin P, Murray
RM. Morbid risk of schizophrenia for relatives of patients with
cannabis-associated psychosis. Schizophr Res. 1995;15(3):277–281
9. Andréasson S, Allebeck P, Engström A, Rydberg U. Cannabis
and schizophrenia: a longitudinal study of Swedish conscripts.
Lancet. 1987;2(8574):1483–1486
10. Henquet C, Murray R, Linszen D, van Os J. The environment
and schizophrenia: the role of cannabis use. Schizophr Bull. 2005;31
(3):608–612
11. Lieberman JA, Stroup TS, McEvoy JP, et al; Clinical Antipsy-
chotic Trials of Intervention Effectiveness (CATIE) Investigators.
Effectiveness of antipsychotic drugs in patients with chronic
schizophrenia. N Engl J Med. 2005;353(12):1209–1223
12. Findling RL, Johnson JL, McClellan J, et al. Double-blind
maintenance safety and effectiveness findings from the Treatment of
Early-Onset Schizophrenia Spectrum (TEOSS) study. J Am Acad
Child Adolesc Psychiatry. 2010;49(6):583–594, quiz 632
13. The Canadian Psychiatric Association Working Group. Clinical
practice guidelines for the treatment of schizophrenia. Can J
Psychiatry. 2005;50(13 suppl 1):7S-57S.

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1. A 10-year-old boy was recently diagnosed as having attention-deficit/hyperactivity disorder. His paternal
uncle has schizophrenia. The boy has great difficulty falling asleep, and he frequently does not go to sleep until
midnight. He is prescribed extended-release methylphenidate to improve his attention. On the second day
taking the medication, he is describes seeing spiders on his bedroom wall and says he is afraid to go to sleep.
What is the MOST likely explanation for his symptoms?
A. Early-onset schizophrenia.
B. Extrapyramidal adverse effects of stimulant medication.
C. Psychotic reaction to stimulant medication.
D. Sleep deprivation.
E. Stimulant medication overdose.

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behavioral and mental health issues psychosis

2. A 6-year-old boy washes his hands compulsively. He started this behavior during the past year. He organizes his
belongings by color and is particularly obsessed with the color blue. He is empathetic with his family members,
tells his mother that he has friends at school, but his teacher relates that he is easily upset in the classroom
when other children touch his belongings. He states that he hears someone telling him to keep his toy cars in
order by size and color. What is the MOST likely diagnosis for this child’s condition?
A. Anxiety.
B. Auditory hallucination.
C. Autism.
D. Obsessive-compulsive disorder.
E. Very early-onset schizophrenia.

3. A 17-year-old boy recently diagnosed as having schizophrenia returns to review brain magnetic resonance
imaging findings. What is the MOST likely finding to be seen on the brain magnetic resonance image?
A. Basal ganglia atrophy.
B. Cerebellar hypertrophy.
C. Increased cortical sulci.
D. Gray matter atrophy.
E. Slit ventricles

4. An 18-year-old woman is a senior in high school. She has had several episodes of auditory hallucinations in the
past year. She was very active in sports and social activities during her first several years of high school, but she
now spends most of her time in her bedroom. She began using cannabis 1 year ago and now uses the drug daily.
Her great grandfather had schizophrenia. Her parents divorced when she was 10 years old, and she received
counseling for several years. She lives with her mother, who has been depressed since the divorce. The girl is
now seeing a psychiatrist, who is concerned that she may have schizophrenia. For this young woman, what is
the MOST likely association with her potential diagnosis?
A. Cannabis use.
B. Early trauma from parental divorce.
C. Family history of schizophrenia.
D. Maternal depression.
E. Social isolation.

5. A 16-year-old boy recently has been diagnosed as having schizophrenia. His parents relate that he seems more
disorganized, has difficulty maintaining friendships with peers, and misinterprets his mother’s worry about him
as criticism of his recent diagnosis. What is the MOST likely cause of these social symptoms?
A. Executive function deficits associated with schizophrenia.
B. Lack of adequate social support in school.
C. Maternal anxiety.
D. Misdiagnosis of schizophrenia with correct diagnosis of attention-deficit/hyperactivity disorder.
E. Stigma associated with schizophrenia.

Parent Resources From the AAP at HealthyChildren.org

The reader is likely to find material relevant to this article to share with parents by visiting these links:
http://www.healthychildren.org/English/health-issues/conditions/emotional-problems/Pages/Schizophrenia.aspx

306 Pediatrics in Review Vol.34 No.7 July 2013

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 Psychosis in Children and Youth: Focus on Early-Onset Schizophrenia
Sabina Abidi
Pediatrics in Review 2013;34;296
DOI: 10.1542/pir.34-7-296

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http://pedsinreview.aappublications.org/content/34/7/296#BIBL
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