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Sabina Abidi MD FRPCP

Head, Youth Psychosis Program

Division Head of Outpatient Services

IWK Mental Health & Addictions Program

Division of Child & Adolescent Psychiatry

Dalhousie University

Halifax Nova Scotia

No disclosures or conflicts to report

Objectives

To review the diagnostic phenomenology of psychosis and psychotic disorders in children and youth

To differentiate between the phenotypes of psychotic disorders in children and youth

To review the history, epidemiology and etiology of psychotic disorders in children and youth

To recall the recommended treatment approach for psychotic disorders in children & youth

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What is psychosis?

“psych” : the mind

“-osis”: abnormal condition

Psychotic symptom or experience Disturbances of perception or thought that occur in the absence

of cause or stimulus and out of keeping with common experience○ Can arise secondary to many causes

○ Many neuropsychiatric illnesses present with symptoms of psychosis

○ Many medical illnesses can present with psychosis as a primary symptom

○ Primary psychotic spectrum disorders should be diagnoses of exclusion (not used interchangeably with the word “psychosis”)

loss of contact w reality

Psychosis as a symptom of illness

Other conditions that can present with psychosis medical conditions include central nervous system processes; autoimmune and

infectious diseases; genetic, endocrine, and metabolic disorders; electrolyte imbalances; and prescription medications and drugs of abuse

Autoimmune Post-streptococcal acute disseminated encephalomyelitis, anti-NMDA receptor encephalitis, MS in childhood, SLE in adolescence

Neuropsychiatric Epilepsy (10-15% prevalence of psychosis) esp TLE, brain tumor, Wilson’s, Huntington’s, Freiderich’s ataxia, head trauma

Chromosomal/Congenital Turners, DiGeorge, Fragile X, PKU

Metabolic/Endocrine Thyroid disease, electrolyte abnormalities (Ca, Mg), B12 deficiency, disorders of copper (Wilson’s), lead metabolism (heavy metals)

Infectious HIV, syphilis, lyme disease, encephalitis, brain abcess

Drugs/Medication psychedelic/hallucinogenics (PCP, MDMA, amphetamine), psychostimulants, opiates, hypnotics, benzodiazepines, barbiturates, antidepressants, herbals (St John’s Wort), polypharmacy

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Psychosis as an experience

In children can be common and transient Most children who present with psychotic experiences (PE) do

not have a psychotic disorder

Associated with:○ Imaginative play in young children or those with lower intellectual function

○ Children and youth with a tendency towards concrete thinking

○ Experience of distress, anxiety, mood abnormalities (PTSD)

About 8% of a community sample of children report PE and do not develop psychotic disorder

About 15-20% of adolescents/adults reports PEs and do not develop psychotic disorder

Psychosis as an experience

Historically and currently very difficult to interpret given children’s changing concept of reality

< age 5, psychotic symptoms are uncommon Stress, anxiety, transient, benign

• > age 5 (school age), persistent psychotic symptoms may be a marker for increased risk for illness later in life

(Poulton R et al. 2000)

By early-mid adolescence, persistent psychotic symptoms are more predictive of later onset of schizophrenia

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Psychosis as a symptom

Longitudinal studies show that children who present with PEs (age 11) are (25%) more likely to develop schizophreniform disorder as adults (age 26) (Poulton et al 2000).

About 1/3 of adult patients with schizophrenia say their symptoms began before age 20.

How can we predict the clinical relevance and significance of the psychotic symptom in children and youth?

Psychosis as an illness

In children and youth psychotic symptoms are seen in*

OCD (experience of obsessive thoughts)

Other anxiety disorders (paranoid ideation vs social anxiety)

PTSD (auditory hallucinations, dissociation, paranoia)

Depression/Mood (negative cognitive distortions as hallucinations)

Bipolar disorder with psychotic features

Substance use disorders (intoxication/withdrawal)

ADHD/disruptive behavior disorders

Autism spectrum disorders (hallucinations, delusional content)

Medical illness (disintegrative disorder)

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Psychosis as an illness

Psychotic symptoms can be manifestations of various psychiatric illnesses seen in adults (implies existence of other required criteria)*

Schizophrenia Schizophreniform Disorder Brief Psychosis Schizoaffective Disorder Psychosis NOS Delusional Disorder Drug Induced Psychosis Bipolar Disorder (with psychotic features) Psychotic Depression Secondary to a medical condition

Psychosis as an illnessSchizophrenia in children – a history

Kraeplin’s concept of dementia praecox originally extended to children (praecosisma) by virtue of including all severe childhood disturbance as a form of schizophrenia

Infantile autism described by Kanner thought to be the first manifestations of childhood schizophrenia

Not until work of Kolvin (1970s) concept of autism differentiated from childhood schizophrenia (prevalence, age of onset, pathognomonic features)

First included in DSMIII in 1980 a category for childhood schizophrenia separated from infantile autism

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Psychosis as an illnessSchizophrenia in children – a history

DSMIVTR defines schizophrenia similarly for children, adolescents and adults

Overall psychotic disorders can be characterized by psychopathological syndromes characterized by:

1) Marked disturbance in perception of reality2) Representation from at least one of four symptoms domains

(positive, negative, cognitive and secondary mood)3) Fluctuating temporal course4) Disease interrupts the course and continuity of development,

experience, behavior and ultimate potential in terms of function without attention and treatment

DSM IVTR criteria for schizophrenia*

A. Characteristic symptoms Two (or more) of the following, each present for a significant portion of time during a 1-month period (or less if successfully treated):

(1) delusions(2) hallucinations(3) disorganized speech (4) grossly disorganized or catatonic behavior(5) negative symptomsNote: Only one Criterion A symptom is required if

delusions are bizarre or hallucinations consist of a voice keeping up a running commentary on the person's behavior or thoughts, or two or more voices conversing with each other.

B. Social/occupational dysfunction: For a significant portion of the time since the onset of the disturbance, one or more major areas of functioning such as work, interpersonal relations, or self-care are markedly below the level achieved prior to the onset (or when the onset is in childhood or adolescence, failure to achieve expected level of interpersonal, academic, or occupational achievement).

C. Duration: Continuous signs of the disturbance persist for at least 6 months. This 6-month period must include at least 1 month of symptoms that meet Criterion A and may include periods of prodromal or residual symptoms.

D. Schizoaffective and Mood Disorder exclusion: Schizoaffective Disorder and Mood Disorder With Psychotic Features have been ruled out.

E. Substance/general medical condition exclusion:

F. Relationship to a Pervasive Developmental Disorder: If there is a history of Autistic Disorder or another Pervasive Developmental Disorder, the additional diagnosis of Schizophrenia is made only if prominent delusions or hallucinations are also present for at least a month (or less if successfully treated).

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Schizophreniasymptom domains

Cognitive deficits

Mood disturbance

Positive symptoms

Negativesymptoms

Memory deficitsPoor attentionPoor organizationConcrete thinking

Lack of:Energy

MotivationDrive

SocializationreactivityEmotionSlowed

thoughts or speech

HallucinationsDelusionsDisorganized andBizarre behavior

AnxietyDepressionIrritabilityRapid swingsanger

Schizophreniacriteria specific to children/adolescents

Failure to achieve social, academic outcomes (as opposed to loss of function)

Less elaborate hallucinations and delusions

Less complex, bizarre delusions

More in keeping with developmental age (monsters, kidnapping, toys; less violent or sexual themes)

Negative symptoms and disorder of thought form less common in children (worsen over time)

Auditory hallucinations in 80%

Somatic and visual hallucinations less frequent

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Schizophreniacourse

Schizophreniapresentation by age

Differentiation of schizophrenia in childhood, adolescence and adulthood is based on chronological age: Very Early Onset Schizophrenia (VEOS) with onset < age 13 Early Onset Schizophrenia (EOS) with onset between 13-18 Adult Onset Schizophrenia (AOS) with onset > 18

Other designations that overlap but are used in parallel: Childhood onset schizophrenia or COS (Rapoport et al) with onset 12

years or younger Adolescent onset schizophrenia with onset 13-17

not based on puberty onset or other developmental milestones There are significant differences in illness presentation

depending on age of onset

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Schizophreniachildhood onset (COS)

Longitudinal study of large research cohorts have informed our learning about this illness Childhood onset schizophrenia study NIMH early 90s(Rapoport & Inoff-Germain, 2000; Rapoport et al. 2012 update)

Strict inclusion criteria○ Onset < age 12

○ IQ 70

○ No neurological abN

○ No other significant Axis I disorder

○ Exhaustive screening process E.g. of 250 screened (help seeking), 89 accepted with COS

○ Avg age onset 10 +/- 2.1 years *


COS is a more severe, persistent form (presentation, outcomes) of the late adolescent/adult onset illness with worse outcomes

Rare; insidious onset with cognitive deterioration early

Early neuroanatomical changes

Significant early signs impairment preceding onset of illness reflecting early compromised brain development

Can qualify premorbid, prodromal, active and recovery phases of COS

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Developmental impairments may be noticed in the first years of life (premorbid phase)*

○ Motor delay/disturbance (50%), speech delay (50%), language abnormalities, social skill abnormalities (87%)

○ Lower premorbid IQ (sometimes below 70)*○ Mistaken as ASD due to similarities – echolalia, stereotypies,

social withdrawal

COS prodromal phase (years before active phase) deterioration in school performance, social withdrawal, disorganized or unusual behavior decreased ability to perform regular activities, Poor attention to self-care and hygiene change in behavior sometimes marked by aggression or hostility


COS active psychotic phase 80% auditory hallucinations (simple); visual are less frequent Non complex delusions with age-related concerns (monsters, paranoia,

kidnapping) but may still have Schneiderian symptoms* May not exhibit classic negative symptoms initially (flat, odd affect) Thought form abnormalities may not be apparent initially – worsen over

time Catatonia is rare

Outcomes: recovery phase 70% living a dependent life into adulthood. More than half have impaired social outcomes Approximately 15% to 30% may experience remission with treatment, but

the illness tends to relapse worsening prognosis over time. – EOS has high diagnostic stability

supporting the continuity of the illness into adulthood

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Differential Diagnosis of COS

Multidimensionally Impaired Group (MDI) (Rapoport, Ngtay, 2007)

Different from COS/VEOS Brief, transient episodes of psychosis,

usually in response to stress Age onset 7.7 +/- 2.2 Daily emotional lability Impaired interpersonal skills despite

being pro-social Multiple deficits in information

processing on cognitive assessment Comorbid ADHD No formal thought disorder Do not progress to schizophrenia

Multiplex Developmental Disorder (MDD) (Rapoport, Ngtay, 2007)

• Earlier age of onset, age 5 -More ASD-like symptoms- Daily affect dysregulation- Poor social behavior skills


Epidemiology

1% of all cases have onset before age 10

About 1/3 of all cases have onset before age 18

Description Age Frequency Sex ratio (boys: girls)

VEOS/COS <13 0.0019% 1.4:1

EOS 13-18 0.23% =

Adult onset >18 1-1.5% Boys earlier(males 15-25; females 19-35)

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Adapted from Table 2. Waddell et al. 2002. Child Psychiatric Epidemiology and Canadian Public Policy-Making. The state of the science and the art of the possible. Can J Psychiatry

Prevalence of mental illness in children & youth in Canada

Age

Boys

Girls

Prevalence of Psychotic spectrum disorders per 1000 children/adolescents

(Reprinted) Spady et al. Prevalence of Mental Disorders in Children Living in Alberta, Canada, as Determined from Physician Billing Data. 2001.Arch Pediatr AdolescMed. 155: pp.1156.

0 3 6 9 12 15 18

8

6

4

2

0

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10 20 30 40 50

GOOD

Function

POOR

Age

Course of Schizophrenia

SchizophreniaGenetic Risk

Genetic Risks

Schizophrenia is highly heritable Concordance rate between monozygotic twins 88.2%; dizygotic 22.7% Discordant twins can transmit risk to their offspring at the same rate despite

not expressing the illness themselves Adopted out children of a parent with schizophrenia develop the illness at rates

higher than 1%

Adult form of schizophrenia risk by familial history One parent: 13%; ranges from 2-35% depending on severity and number of

affected relatives Both parents, risk for offspring: 46% Sibling: 8% (if no other relatives are affected) Risk increases markedly with degree of genetic relatedness Identical twins: 48%; fraternal twins: 17%

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SchizophreniaPathophysiology

Multiple neurotransmitter systems appear to be abnormal

Subcortical dopamine hyperactivity is a common feature○ DA abnormalities are tightly interwoven with Glutamate and GABA deficits

also thought to play a role

The Presynaptic DA system is dysregulated:○ Increased presynaptic DA synthesis

○ Elevated DA release into synapse (also seen in schizotypal PD)

○ Increased occupancy of DA receptors in striatum (resting concentration of DA is higher)


Increased striatal presynaptic dopamine function is a phenomenon shared by unaffected siblings of patients with schizophrenia, and is therefore likely related to vulnerability than full clinical expression of the illness○ Unaffected identical twins have higher D2 receptor densities in the caudate

nucleus, negatively correlating with cognitive performance○ There are distinct vulnerability and disease-related contributions to cortical D1

receptors: receptors are increased in individuals at genetic risk, but decreased in patients who express the illness, possibly due to chronic antipsychotic medications. COMT polymorphism increased influence when exposed to specific risk

factors

Decreased 5HT2a receptor binding (major serotonin excitatory) in cortical neurons in persons at risk correlating with the severity of the prodromal state* Altered binding of 5HT2 receptors may predate onset of schizophrenia

but is also dependent on illness state

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fMRI shows hyper/hypo- activity in different brain regions Decreased brain response to specific stimulus Decreased ability to suppress brain activation in response to other

repeated stimuli

How does altered concentration of dopamine (and other neurotransmitters) lead to weighting of salience of symptoms in schizophrenia?* ?aberrant firing of the DA system may lead to aberrant

assignment of salience to objects, people, actions○ In combination with a cognitive schema, psychosis proneness or

other factors dictating whether one is at clinical risk

SchizophreniaRisk

Stress/vulnerability model Longitudinal studies support the dimensional nature of psychotic

symptoms and risk

How can we predict which youth with psychotic experiences are at risk for developing chronic psychotic disorder?

What are the risk factors for developing schizophrenia and how do they interact with the genetic risk to lead to manifestation of this illness?

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The psychosis continuum orspectrum of symptoms

Psychotic like experiences(normal variant)

Psychotic disorder(schizophrenia)

PLEs associated with other disorders

PLEs + markers of risk

What factors convey increased risk from genes to the identified phenotype?

SchizophreniaRisk

Comparison of a Selected Set of Relatively Well-Established Risk Factors for Schizophrenia, Focusing Mainly on Pre- and Antenatal Factors [6] (abbreviations: CNS, central nervous system; depr, depression; Rh, Rhesus) Sullivan PF The Genetics of Schizophrenia 2005.

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SchizophreniaRisk Factors

Pre/perinatal risk Genetic risk Infection/famine

○ Toxoplasmosis Gondii○ Infants born in utero during the Dutch Hunger Winter showed increased

rates of brain abn, depression and schizophrenia Placental pathology

○ Obstetrical events may be causal or reflect other causal processes

Premorbid risk Urban environment

○ Nonspecific (mood and anxiety disorders also elevated)○ Controlled for urban drift and minority status (rates decrease with rural move)

Childhood trauma Cannabis exposure Social isolation/immigrant status*

○ Social defeat/depression○ Best documented and strongest environmental risk factors

SchizophreniaRisk FactorsSubstance abuse

Cannabis use and risk for psychotic disorder Delta-9-THC can produce transitory psychotic experiences in 10-15%

of healthy controls

Those with genetic vulnerability to psychosis experience an exaggerated response further predisposing them to risk

The relationship may be circular: psychosis proneness induces cannabis use and cannabis use induces psychosis proneness

The association between cannabis use and psychotic outcome has been replicated several times Cognitive outcomes, sibling birth cohort studies, neuroimaging,

prospective comparisons among probands, sibs, relatives

Caspi et al 2005*,

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Cannabinoid receptors (CB1) in basal ganglia, cerebellum, hippocampus and cortex (involved in regulation of dopamine and glutamate stimulation)

THC can bind to the CB1 receptor thereby disrupt the regulation of neurotransmitter release during critical periods of synaptic pruning

The neurotoxicity theory of THC alone is not sufficient to prove causality There are differential effects on CB1receptors in adults compared to

adolescents

Adolescence may be a vulnerable period to exposure with increased susceptibility to disturbance

Pre-existing risk for psychotic disorder may also be a vulnerable brain condition more susceptible to changes at the CB1 receptor level (but who are these kids?)


Is there evidence for vulnerable subgroups?

Exposure to urban environment, cannabis use, developmental trauma and minority group position may be a common occurrence but the rate of psychotic syndrome is low. Thus are there vulnerable subgroups that are more sensitive to the E risks?○ ?mediated by genetic factors

○ ?mediated by personality/cognitive factors, social cognition & psychosis proneness*

○ ?mediated by disruption of neuronal connectivity related to exposure to environmental insult at developmentally critical periods*

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Schizophreniaearly identification of at risk states

- In keeping with the staging model of schizophrenia, research is focused on identifying those at clinical risk

- There are known clinical factors associated with elevated risk for developing schizophrenia1) family history2) psychotic experiences in attenuated form3) functional deterioration in the year prior4) schizophrenia proneness/schizotypal personality

- Structured instruments designed to identify youth at risk or potentially in prodrome stage using these criteria: 1) Structured Interview for Prodromal Syndromes (SIPS) (McGlashan et al, 2004)2) Bonn Scale for Assessment of Basic Symptoms (BASBS) (Gross et al, 1987)3) Comprehensive Assessment of At Risk Mental States (CAARMS) (Yung et al 2004)

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Schizophreniaearly identification of at risk states

Longitudinal studies following high risk youth have evaluated risk factors associated with conversion from prodrome stage to first episode: 1) family history 2) poor GAF 3) substance abuse 4) increased abnormal thought content 5) greater psychosocial impairment

North American Prodromal Longitudinal Study (Canon et al 2008) Conversion rates of 35% over 2.5 years with declining rates thereafter

Biomarkers (indicative of vulnerable subgroups) There is a definite continuity of some biomarkers in those identified in the

prodrome phase who have converted; data still inconclusive

Management No evidence for pharmacotherapy in high risk patients Cochrane review supports psychotherapeutic effort in this phase however

unable to support one modality over another (e.g. CBT, supportive, education, etc)

Neurodevelopmentalmodel of schizophrenia

Cohort studies provide information on the link between forms of illness and support the neurodevelopmental model of schizophrenia (sheds light on the crucial need for early ident)

Neuropsychological Function in COS Deficits in attention, short term memory, recent long term memory

Deficits in tasks requiring fine motor speed

Deficits are not more severe than that seen in adult onset, but

As per adults, children with schizophrenia experience a deterioration in cognitive function between the premorbid period and after the onset of psychosis; this deterioration seems to plateau in adults after episode onset. In children however the intellectual deterioration seems to continue until 24-4 months after onset of psychosis*.

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Neuroimaging Findings support the concept of biological continuity between

child onset and adult onset forms of the illness

Brain morphology○ most consistent finding in adult onset schizophrenia is decreased total cerebral volume (not due to neuronal loss)* increased (third) ventricular volume decreased grey matter volume (localized to prefrontal/temporal

cortices by adulthood) decreased volume of medial lobe structures (hippocampus)

○ Many of these abnormalities exist prior to the frank manifestations of the illness


Brain morphology – studies of non-psychotic sibs Full sibs of COS patients show prefrontal and temporal grey

matter deficits in childhood that seem to normalize by late adolescence

This pattern of resilience is not seen in COS patients (where early GM loss persists into adulthood) suggesting a two-hit hypothesis:

Early GM loss is due to genetic vulnerabilities but expression of the illness requires a second hit at a critical period of brain development (that is absent in healthy sibs/controls)○ Environmental trigger

○ Cytogenetic abnormality

○ Copy number variant

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Molecular Psychiatry (2012) 17, 1228-1238;doi:10.1038/mp.2012.23

Figure 2


Brain morphology○ White matter integrity also changes throughout the course of

the illness especially in the prefrontal cortex These changes may progress with onset of illness

Lack of WM growth seen in adolescent years of COS patients

Schizophrenia is increasingly thought to be a disorder of cortical connectivity (not loss)○ Studies from anatomical and functional imaging show that the

tendency for normal brains to maximize communication efficiency via extension of cortical networks among brain regions is altered in COS and schizophrenia This property is thought to be under genetic influence

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Eye Tracking Eye tracking abnormalities (smooth pursuit eye movements

SPEM) seen in adults patients with schizophrenia also seen in COS○ Greater catch-up saccade (fast eye movements bringing the eye closer to the

target) amplitude

○ Abnormalities seem to be more salient in COS than AOS*

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Epigenetic Studies

Schizophrenia is highly heritable however is neither purely genetic or caused by a single gene

Link between risk alleles and resulting brain abnormalities in schizophrenia○ In COS patients and normal sibs VAL158/MET gene coding for COMT Increased VAL dosing resulted in increased cortical grey matter loss in PFC

in both COS and healthy sibs The MET/MET genotype appeared to normalize this GM loss but this

normalization occurred at an earlier age in sibs and later in COS probands

Caspi et al 2005 study shows in those with the VAL/MET heterozygotes, exposure to cannabis may be the “second hit” resulting in genotype expression of the schizophrenia trait (10-fold increased risk)


Copy number variants○ Rare DNA CNVs are risk factors for schizophrenia

○ Immunological and brain developmental pathways are implicated

○ CNVs may be more frequent in COS/VEOS

○ A “second hit” could be another CNV or an environmental event influencing expression of the phenotype

○ The best supported loci are deletions at: 1q21, 2p53, 3q29, 15p11.2, 15q11.3, 17q12, 22q11.2 *and Neurexin 1 and duplications at 7q36.3, 25q11-13, 16p11.2, 16p13.1

Velocardiofacial syndrome (1/4000, 4% of COS, risk for schizophrenia is 20-25%)

Mosaic Turner Syndrome – higher number of females in COS cohort

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Schizophreniatreatment

Treatment includes both pharmacotherapy and psychotherapeutic models

Pharmacotherapy

Antipsychotic medication is the cornerstone of treatment of the symptoms of EOS despite the paucity of evidence based studies (mimic adult world)

While First generation antipsychotics (FGA) improve positive symptoms, the risk of extrapyramidal side effects, tardive dyskinesia, prolactin elevation favors the use of SGA.

There is no evidence showing increased efficacy of SGAs over FGAs or among the SGAs* with the exception of Clozapine.

In treatment-resistant adolescents with schizophrenia, Clozapine is superior to Haloperidol and Olanzapine (NNT 3).

*The Treatment of Early Onset Schizophrenia Study (TEOSS) (2008) showed that Risperidone, Olanzapine were not more efficacious than Molindone. Weight gain were significant with the SGA while akathisia was seen with the FGA.


Clozapine has a favored response profile over Haloperidol and Olanzapine in treatment-resistant EOS.

Clozapine showed a modest improvement in negative/cognitive symptoms in 2 RCTS of EOS followed for 8 weeks in comparison to Olanzapine.

Clozapine has shown good efficacy in COS in case reports

The concern however is the side effect profile of Clozapine and the other antipsychotics Pediatric populations are more sensitive to adverse effects especially

weight gain, lipid abnormalities, sedation, EPSE, akathisia, prolactinabnormalities and other metabolic abnormalities○ Medicine naïve○ More premorbid abnormalities○ Increased severity of illness

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The 7 second-generation antipsychotics (SGA) available for use in Canada are: Risperidone, Aripiprazole, Olanzapine, Ziprasidone, Quetiapine, Paliperidone and Clozapine

Reciprocal inhibition of D2 receptors by increased affinity and blockade of serotonin receptors. Also rapid dissociation from D2 receptors

Outside of Aripirazole all SGA use in Canada in children & adolescents is “off label”

There is evidence however for use of SGAs in EOS

2011 – Aripiprazole approved for use in treatment of schizophrenia for adolescentsAge 15-17.

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© 2013 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc.

7

Treatment of adolescents with early‐onset schizophrenia spectrum disorders: in search of a rational, evidence‐informed approach.Schimmelmann, Benno; Schmidt, Stefanie; Carbon, Maren; Correll, Christoph

Current Opinion in Psychiatry. 26(2):219‐230, March 2013.DOI: 10.1097/YCO.0b013e32835dcc2a

Table 2 Overview of side effect profiles comparing second‐generation antipsychotic medications in children and adolescents*

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SchizophreniatreatmentPsychotherapeutic treatment of EOS

• Several different modalities have been reviewed: Cognitive behavioral therapy, cognitive remediation therapy (3 RCTs in youth with FEP), family intervention/psychoeducation/support

•Psychoeducation and family intervention has been shown to improve cognitive, clinical and psychosocial measures of outcome

•Evidence for CBT in EOS is inconclusive •Recent Cochrane review was unable to show superiority of CBT over other treatment modalities in adult onset schizophrenia

•Use of integrated intervention (CBT, group skills, CRT, family education) in a prodrome population was more effective than traditional supportive counseling in delaying psychosis over a 2 year period

• not enough evidence to support one treatment modality over another

Schizophreniarecovery and outcomes

Best predictor of outcome*: premorbid functioning on domains of social function and

cognitive development

Severity of symptoms (negative and cognitive)

Duration of untreated psychosis (DUP)

Prolonged duration of first hospital admission

Other factors associated with poor prognosis: male, early onset, insidious onset, negative/cognitive

symptoms, substance use (cannabis), multiple episodes, strong familial history, severity of illness at first episode

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COS EOS Adult OS

Episodes/illness duration

Non episodic, diagnostic stability maintained into adulthood

(late adolescent onset): 20% will only have one episode; 80% episodic course

Comorbidities Lower GAF, anxiety disorder, depression (mood disorder), DBD, ADHD

Social anxiety persists despite improvement in someDepressionSubstance abuse disorder

Prognosis 15-30% experience remission with treatment70% dependent lives50% impaired social outcomeUnfavorable course of illness

(later adolescent onset): 20-30% may remit after 2 years without need for further treatment80% will remit with treatment in first year 40-60% will achieve close to pre-illness onset potential in first year30- 40% treatment resistant

Lifespan Unknown 5% die by suicide in first year

<20-25 years less (suicide (10-15%), cardiovascular, metabolic abn assoc with treatment)

Predictors of Recovery

Premorbid social adjustment - stigma, insight, compliance, DUP, cost, adverse effects, supportive networks, severity of symptoms (more modifiable)

References

1. Rapoport JL, Giedd JN, Gogtay N. 2012. Neurodevelopmental model of schizophrenia: update 2012. Molecular Psychiatry 17, 1228-1238.

2. Vyas NS., Gogtay N. 2012. Treatment of Early Onset Schizophrenia: recent trends, challenges and future considerations. Frontiers in Psychiatry 3(29): 1-5.

3. Schimmelmann, BG., Schmidt S., Carbod M., Correll C. 2013. Treatment of adolescents with early-onset schizophrenia spectrum disorders: in search of a rational, evidence-informed approach. Curr Opin Psychiatry 26: 219-230.

4.Van Os, J., Krabbendam L., Myin-Germeys I., Delespaul P. 2005. The Schizophrenia Envirome. Curr Opin Psychiatry 18: 141-145.

5. Van Os J., Kapur S., 2009. Schizophrenia. The Lancet 374: 635-644.6. Vyas N, Patel NH., Puri BK. 2011. Neurobiology and phenotypic

expression in early onset schizophrenia. Early Intervention in Psychiatry 5: 3-14.

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