"Psychosis in Youth" Portland, Maine; March 30, 2004 Psychiatry Grand Rounds at Maine Medical Center *Learn clinical assessment of psychosis in youth *Learn neurobiology of psychosis *Learn course and prognosis of psychosis *Learn treatment of psychosis in youth

1. Psychosis in YouthPsychosis in Youth
Carlo G. Carandang, M.D.Carlo G. Carandang, M.D.
Pediatric Affective Disorder ServicesPediatric Affective Disorder Services
Maine Medical CenterMaine Medical Center
Clinical Assistant Professor of PsychiatryClinical Assistant Professor of Psychiatry
University of Vermont College of MedicineUniversity of Vermont College of Medicine

2. ObjectivesObjectives
Learn clinical assessment of psychosis inLearn clinical assessment of psychosis in
youthyouth
Learn neurobiology of psychosisLearn neurobiology of psychosis
Learn course and prognosis of psychosisLearn course and prognosis of psychosis
Learn treatment of psychosis in youthLearn treatment of psychosis in youth

3. What is psychosis?What is psychosis?
Thought Disorder/Disorganized ThinkingThought Disorder/Disorganized Thinking
(core deficit)(core deficit)
Hallucinations (accessory symptom)Hallucinations (accessory symptom)
Delusions (accessory symptom)Delusions (accessory symptom)
Disorganized/Bizarre BehaviorDisorganized/Bizarre Behavior
Impaired reality testingImpaired reality testing

4. Thought DisorderThought Disorder
Disturbance in the form or manner that one presentsDisturbance in the form or manner that one presents
their thoughts to otherstheir thoughts to others
No consensus definition: includes loosening ofNo consensus definition: includes loosening of
associations, illogical thinking, incoherence, tangentiality,associations, illogical thinking, incoherence, tangentiality,
circumstantiality, poverty of speechcircumstantiality, poverty of speech
Must account for developmental level (normal youth <Must account for developmental level (normal youth <
age 7 exhibit illogical thinking and loosening ofage 7 exhibit illogical thinking and loosening of
associations)associations)
R/O language d/o’s, PDDR/O language d/o’s, PDD
Usually more bizarre or marked in youth withUsually more bizarre or marked in youth with
schizophrenia vs. youth with affective psychosisschizophrenia vs. youth with affective psychosis
Mild forms can present in youth with ADHDMild forms can present in youth with ADHD

5. HallucinationsHallucinations
Perceptions in the absence of external stimuliPerceptions in the absence of external stimuli
Any sensory modality (auditory most often)Any sensory modality (auditory most often)
Distinguish from hypnogogic (falling asleep) andDistinguish from hypnogogic (falling asleep) and
hypnopompic (awakening) hallucinationshypnopompic (awakening) hallucinations
Differentiate from illusions (misperceptions ofDifferentiate from illusions (misperceptions of
external stimuli) and elaborate fantasyexternal stimuli) and elaborate fantasy
Hearing a voice calling name once or twice notHearing a voice calling name once or twice not
likely to be pathologic hallucinationlikely to be pathologic hallucination

6. DelusionsDelusions
Fixed false belief that is not consistentFixed false belief that is not consistent
with person’s subculture and cannot bewith person’s subculture and cannot be
changed by evidence against itchanged by evidence against it
Distinguish from magical thinking, fantasyDistinguish from magical thinking, fantasy
Can be somatic, grandiose, guilt,Can be somatic, grandiose, guilt,
persecutory, referentialpersecutory, referential
Less systematized in younger agesLess systematized in younger ages
Anxiety (excessive worry) sometimesAnxiety (excessive worry) sometimes
mistaken for paranoid delusionmistaken for paranoid delusion

8. Psychotic-like phenomenaPsychotic-like phenomena
Developmental delays causing idiosyncraticDevelopmental delays causing idiosyncratic
thinking and perceptionsthinking and perceptions
Speech and language disordersSpeech and language disorders
Exposure to traumatic eventsExposure to traumatic events
– Dissociation/DerealizationDissociation/Derealization
– FlashbacksFlashbacks
Obsessions in OCD (ego dystonic)Obsessions in OCD (ego dystonic)
Hypnogogic and hypnopompic hallucinationsHypnogogic and hypnopompic hallucinations
Overactive imagination (intact reality testing)Overactive imagination (intact reality testing)

9. Screening psychosis in youthScreening psychosis in youth
Use age-appropriate language (does yourUse age-appropriate language (does your
mind ever play tricks on you?)mind ever play tricks on you?)
Normalize the experience to make lessNormalize the experience to make less
threatening (some children tell me…)threatening (some children tell me…)
How pervasive are the experiencesHow pervasive are the experiences
(transient vs. frequent)(transient vs. frequent)
Make sure symptoms occur while awakeMake sure symptoms occur while awake

10. Diagnoses associated withDiagnoses associated with
psychosispsychosis
Affective DisordersAffective Disorders
SchizophreniaSchizophrenia
Delirium/encephalopathyDelirium/encephalopathy
Substance use (stimulants, hallucinogens,Substance use (stimulants, hallucinogens,
cocaine, etc.)cocaine, etc.)
Stress-InducedStress-Induced
Pervasive Developmental DisorderPervasive Developmental Disorder
““Multi-dimensionally impaired”Multi-dimensionally impaired”

11. Organic PsychosisOrganic Psychosis
Delirium/encephalopathyDelirium/encephalopathy
Seizure disorders (complex partial seizures)Seizure disorders (complex partial seizures)
CNS lesions (***always get brain imaging forCNS lesions (***always get brain imaging for
new onset psychosis***)new onset psychosis***)
Neurodegenerative diseasesNeurodegenerative diseases
Metabolic DisordersMetabolic Disorders
Infectious diseases (i.e. HIV)Infectious diseases (i.e. HIV)
***Rule-out organic etiology before diagnosing***Rule-out organic etiology before diagnosing
psychosis***psychosis***

12. Workup for New-Onset PsychosisWorkup for New-Onset Psychosis
MRI-brainMRI-brain
CBCCBC
Electrolytes, BUN, Creatinine, Ca, MgElectrolytes, BUN, Creatinine, Ca, Mg
Hepatic panelHepatic panel
Sed RateSed Rate
RPRRPR
Vit B12, RBC and serum FolateVit B12, RBC and serum Folate
Urine PorphyrinsUrine Porphyrins
CeruloplasminCeruloplasmin
TSH, free T4TSH, free T4
Heavy metalsHeavy metals

13. Schizophrenia DSM-IV criteriaSchizophrenia DSM-IV criteria
Two or more of: 1) delusions; 2)Two or more of: 1) delusions; 2)
hallucinations; 3) disorganized speech; 4)hallucinations; 3) disorganized speech; 4)
grossly disorganized behavior; or 5)grossly disorganized behavior; or 5)
negative symptoms (four A’s: flat Affect,negative symptoms (four A’s: flat Affect,
Alogia, Avolition, Autism-like social W/D)Alogia, Avolition, Autism-like social W/D)
Impairment of functioningImpairment of functioning
At least 6 months continuous disturbanceAt least 6 months continuous disturbance
< 6 months but > 1 month =< 6 months but > 1 month =
Schizophreniform d/oSchizophreniform d/o

14. Schizophrenia in YouthSchizophrenia in Youth
Early-Onset Schizophrenia (EOS): OnsetEarly-Onset Schizophrenia (EOS): Onset
before age 18before age 18
Very Early-Onset Schizophrenia (VEOS):Very Early-Onset Schizophrenia (VEOS):
Onset before age 13Onset before age 13
Usually family history of schizophreniaUsually family history of schizophrenia
Prevalence:Prevalence:
– VEOS: 1/5000 (NIMH est. 1/40,000)VEOS: 1/5000 (NIMH est. 1/40,000)
– EOS: 4/5000EOS: 4/5000
– Adult-onset Schizophrenia: 1/100Adult-onset Schizophrenia: 1/100

16. Clinical PresentationClinical Presentation
VEOS: insidious onsetVEOS: insidious onset
EOS: insidious or acute onsetEOS: insidious or acute onset
Pre-morbid abnormalities occur in 90% ofPre-morbid abnormalities occur in 90% of
youth with schizophrenia (especiallyyouth with schizophrenia (especially
VEOS)VEOS)

17. Premorbid AbnormalitiesPremorbid Abnormalities
Disruptive Behavior Disorders (ADHD,Disruptive Behavior Disorders (ADHD,
Conduct D/O)Conduct D/O)
Autistic features (social withdrawal,Autistic features (social withdrawal,
unusual peer relationships, developmentalunusual peer relationships, developmental
delays)delays)
Speech and language problemsSpeech and language problems
Academic difficultyAcademic difficulty

18. SymptomatologySymptomatology
Most common: Thought Disorder,Most common: Thought Disorder,
Hallucinations, Flattened AffectHallucinations, Flattened Affect
Less common: Delusions, CatatoniaLess common: Delusions, Catatonia
Types of Thought Disorder:Types of Thought Disorder:
– More common: loosening of associations,More common: loosening of associations,
illogical thinking, impaired executive skillsillogical thinking, impaired executive skills
– Less common: incoherence, poverty ofLess common: incoherence, poverty of
speechspeech

20. Neurobiological AbnormalitiesNeurobiological Abnormalities
None are diagnosticNone are diagnostic
Neuroimaging findings:Neuroimaging findings:
– Progressive increase in lateral ventricular sizeProgressive increase in lateral ventricular size
– VEOS:VEOS: ↓↓ brain volume,brain volume, ↓↓ total grey matter,total grey matter,
andand ↓↓ frontal grey matter compared to ADHDfrontal grey matter compared to ADHD
controls and normal controls (longitudinalcontrols and normal controls (longitudinal
NIMH study following schizophrenic childrenNIMH study following schizophrenic children
into adolescence)into adolescence)

21. MRI Twins (Source: NIMH)MRI Twins (Source: NIMH)

22. PET Scans (Source: NIMH)PET Scans (Source: NIMH)

23. Brain Tissue Slide (Source: NIMH)Brain Tissue Slide (Source: NIMH)

24. Human Genome (Source: NIMH)Human Genome (Source: NIMH)

25. Neurodegenerative IllnessNeurodegenerative Illness

26. Neuropsychological AbnormalitiesNeuropsychological Abnormalities
Deficits in smooth eye pursuit movementsDeficits in smooth eye pursuit movements
Abnormal autonomic reactivityAbnormal autonomic reactivity
Frontal-lobe dysfunctionFrontal-lobe dysfunction

27. Longitudinal CourseLongitudinal Course
Rarely complete remission (<20%)Rarely complete remission (<20%)
80-90% had more than one psychotic episode80-90% had more than one psychotic episode
over 5-year follow-upover 5-year follow-up
Long term follow-up into adulthoodLong term follow-up into adulthood
– 50-75% had moderate or severe impairment50-75% had moderate or severe impairment
– Good prognosis: later age of onset, good premorbidGood prognosis: later age of onset, good premorbid
functioning, acute onsetfunctioning, acute onset
– Poor prognosis: early age of onset, poor premorbidPoor prognosis: early age of onset, poor premorbid
functioning, insidious onset (VEOS has worstfunctioning, insidious onset (VEOS has worst
outcome)outcome)
– Prognosis for affective psychosis much betterPrognosis for affective psychosis much better

30. Complications of SchizophreniaComplications of Schizophrenia
Functional DisabilityFunctional Disability
Family Distress and DisruptionFamily Distress and Disruption
Increased MortalityIncreased Mortality
SuicideSuicide
Substance AbuseSubstance Abuse
ViolenceViolence
Criminal BehaviorCriminal Behavior

31. Differentiating from Psychosis dueDifferentiating from Psychosis due
to Substance Useto Substance Use
Substance-induced psychosis not likely ifSubstance-induced psychosis not likely if
symptoms persist 1 week beyondsymptoms persist 1 week beyond
discontinuationdiscontinuation
Substance use often occurs duringSubstance use often occurs during
prodromal phaseprodromal phase
Substance use may trigger active phase ofSubstance use may trigger active phase of
schizophreniaschizophrenia

32. Differentiating Psychosis from PDDDifferentiating Psychosis from PDD
Psychotic symptoms more transient andPsychotic symptoms more transient and
less prominent in PDDless prominent in PDD
Language, social deficits,Language, social deficits,
restricted/bizzare interests morerestricted/bizzare interests more
prominent in PDDprominent in PDD
PDD has earlier onset (usually before agePDD has earlier onset (usually before age
3) and more severe developmental delays3) and more severe developmental delays

33. Treatment for SchizophreniaTreatment for Schizophrenia
Antipsychotic medications (cornerstone ofAntipsychotic medications (cornerstone of
treatment)treatment)
Psychoeducation (patient and family)Psychoeducation (patient and family)
Educational/Vocational Support ProgramsEducational/Vocational Support Programs
PsychotherapyPsychotherapy
– SupportiveSupportive
– Social Skills trainingSocial Skills training
– Family Therapy (reduce expressed emotions)Family Therapy (reduce expressed emotions)

34. AntipsychoticsAntipsychotics
All exert blockade of post-synaptic dopamineAll exert blockade of post-synaptic dopamine
receptors (Dreceptors (D22))
Relative overactivity of dopaminergic mesolimbicRelative overactivity of dopaminergic mesolimbic
circuits (axonal projections from midbrain tocircuits (axonal projections from midbrain to
limbic area) produces positive symptomslimbic area) produces positive symptoms
(thought d/o, hallucinations, delusions)(thought d/o, hallucinations, delusions)
Relative hypoactivity of mesocortical circuitsRelative hypoactivity of mesocortical circuits
(esp. prefrontal) leads to negative symptoms(esp. prefrontal) leads to negative symptoms
(four A’s: flat Affect, Alogia, Avolition, Autism-like(four A’s: flat Affect, Alogia, Avolition, Autism-like
social withdrawal)social withdrawal)

37. Randomized Controlled TrialsRandomized Controlled Trials
Psychosis in YouthPsychosis in Youth
Loxapine = Haldol > placeboLoxapine = Haldol > placebo (Pool et al., 1976)(Pool et al., 1976)
Thiothixene = thioridazine (50% showedThiothixene = thioridazine (50% showed
improvementimprovement (Realmuto et al., 1984)(Realmuto et al., 1984)
Haldol > placeboHaldol > placebo (Spencer et al., 1992)(Spencer et al., 1992)
Clozapine > Haldol in treatment-resistantClozapine > Haldol in treatment-resistant
schizophreniaschizophrenia (Kumra et al., 1996)(Kumra et al., 1996)

38. Mean BPRS Total Scores During
6 Weeks of Risperidone Treatment
Monotherapy in AdolescentsMonotherapy in Adolescents
With Schizophrenia: RisperidoneWith Schizophrenia: Risperidone
6-week, open-label, pilot6-week, open-label, pilot
study in 10 adolescents,study in 10 adolescents,
aged 11-18 yearsaged 11-18 years
Nonresponders to typicalsNonresponders to typicals
or neuroleptic-naor neuroleptic-naiiveve
Mean daily risperidoneMean daily risperidone
dose, 6.6 mgdose, 6.6 mg
Clinically and statisticallyClinically and statistically
significant improvementssignificant improvements
on BPRS, PANSS foron BPRS, PANSS for
schizophrenia, and CGIschizophrenia, and CGI
Well tolerated; meanWell tolerated; mean
weight gain, 4.85 kgweight gain, 4.85 kg
BPRS = Brief Psychiatric Rating Scale; PANSS = Positive and Negative Syndrome Scale for schizophrenia; CGI = Clinical Global Impression
Adapted with permission from Armenteros JL, et al. J Am Acad Child Adolesc Psychiatry. 1997;36:694-700. Copyright © 1997 American
Academy of Child and Adolescent Psychiatry.
All rights reserved.
MeanBPRSTotalScores
43
38
33
28
23
18
Baseline 1 2 3 4 5 6
Study Week

39. PANSS = Positive and Negative Syndrome Scale for schizophrenia (range, 30-210)
Adapted with permission from Findling RL, et al. J Am Acad Child Adolesc Psychiatry. 2003;42:170-175. Copyright © 2003
American Academy of Child and Adolescent Psychiatry. All rights reserved.
Monotherapy in AdolescentsMonotherapy in Adolescents
With Schizophrenia: OlanzapineWith Schizophrenia: Olanzapine
8-week, open-label trial in8-week, open-label trial in
16 adolescents, aged 12-1716 adolescents, aged 12-17
years, given olanzapineyears, given olanzapine
(mean final dose, 11.9 mg/d)(mean final dose, 11.9 mg/d)
Statistically significantStatistically significant
reductions in positive andreductions in positive and
negative symptoms on thenegative symptoms on the
PANSSPANSS
Well tolerated; weight gain,Well tolerated; weight gain,
increased appetite, andincreased appetite, and
sedation most common sidesedation most common side
effectseffects
PANSS Total Scores at Baseline and Following
Treatment With Olanzapine
in Adolescents With Schizophrenia
or a Related Disorder
90.6
74.2*
0
20
40
60
80
100
Baseline Endpoint
PANSSTotalScore
*P<.0005

40. Mean Changes in PANSS, BPRS, and YMRS
Scores During 8 Weeks of Quetiapine
Treatment
Monotherapy in AdolescentMonotherapy in Adolescent
Psychosis: QuetiapinePsychosis: Quetiapine
8-week, open-label8-week, open-label
trial in 15 patients,trial in 15 patients,
aged 13-17 yearsaged 13-17 years
Final average dose,Final average dose,
467 mg/d467 mg/d
Significant improvementSignificant improvement
on PANSS, BPRS, andon PANSS, BPRS, and
YMRSYMRS
Well tolerated; meanWell tolerated; mean
drug-related weightdrug-related weight
gain, 3.4 kggain, 3.4 kg
RatingScaleScore
95.0
85.0
75.0
65.0
55.0
45.0
35.0
25.0
15.0
5.0
Time 1
(Baseline)
Time 2
(Week 1)
Time 3
(Week 2)
Time 4
(Week 4)
Time 5
(Week 6)
Time 6
(Week 8)
85.7
74.8
64.7
55.5
52.0 50.3
35.9
29.0
22.4
17.6
15.0 13.7
19.7
13.8
9.9 8.2 7.1
5.7
PANSS
BPRS
YMRS
Adapted with permission from Shaw JA, et al. J Child Adolesc Psychopharmacol. 2001;11:415-424.
PANSS = Positive and Negative Syndrome Scale for schizophrenia
BPRS = Brief Psychiatric Rating Scale
YMRS = Young Mania Rating Scale

41. Pappadopulos et al., 2003
Side Effects: AtypicalsSide Effects: Atypicals

42. Dosing in Youth (Pappadopulos et al., 2003)Dosing in Youth (Pappadopulos et al., 2003)

43. Atypicals: DosingAtypicals: Dosing
Abilify 10-30mg dailyAbilify 10-30mg daily
Clozaril 50-600mg dailyClozaril 50-600mg daily
Geodon 20-160mg dailyGeodon 20-160mg daily
Risperdal 0.5-6mg dailyRisperdal 0.5-6mg daily
Seroquel 50-600mg dailySeroquel 50-600mg daily
Zyprexa 2.5-20mg dailyZyprexa 2.5-20mg daily

44. ConclusionConclusion
Consider broad differential diagnosis ofConsider broad differential diagnosis of
psychosis in youth: most youth will notpsychosis in youth: most youth will not
have schizophrenia (very rare)have schizophrenia (very rare)
Evaluate potential psychotic symptoms inEvaluate potential psychotic symptoms in
developmental contextdevelopmental context
Treatment with atypical antipsychoticsTreatment with atypical antipsychotics
first-line, given less adverse effectsfirst-line, given less adverse effects