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Psychosis in Youth


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"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

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Psychosis in Youth

  1. 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. 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. 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. 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. 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. 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
  7. 7. 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)
  8. 8. 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
  9. 9. 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”
  10. 10. 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***
  11. 11. 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
  12. 12. 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
  13. 13. 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
  14. 14. 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)
  15. 15. 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
  16. 16. 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
  17. 17. 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)
  18. 18. MRI Twins (Source: NIMH)MRI Twins (Source: NIMH)
  19. 19. PET Scans (Source: NIMH)PET Scans (Source: NIMH)
  20. 20. Brain Tissue Slide (Source: NIMH)Brain Tissue Slide (Source: NIMH)
  21. 21. Human Genome (Source: NIMH)Human Genome (Source: NIMH)
  22. 22. Neurodegenerative IllnessNeurodegenerative Illness
  23. 23. Neuropsychological AbnormalitiesNeuropsychological Abnormalities Deficits in smooth eye pursuit movementsDeficits in smooth eye pursuit movements Abnormal autonomic reactivityAbnormal autonomic reactivity Frontal-lobe dysfunctionFrontal-lobe dysfunction
  24. 24. 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
  25. 25. 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
  26. 26. 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
  27. 27. 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
  28. 28. 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)
  29. 29. 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)
  30. 30. 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)
  31. 31. 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
  32. 32. 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
  33. 33. 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
  34. 34. Pappadopulos et al., 2003 Side Effects: AtypicalsSide Effects: Atypicals
  35. 35. Dosing in Youth (Pappadopulos et al., 2003)Dosing in Youth (Pappadopulos et al., 2003)
  36. 36. 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
  37. 37. 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