By: Haydee Cantu and Jennifer Nichols - the UIC Department of ...

By: Haydee Cantu and Jennifer Nichols

Definition• Childhood Onset Schizophrenia: Onset prior to 13years• Early Onset Schizophrenia: Onset prior to 18 years• Same diagnostic criteria in youth as in adults;continuous with adult-onset in terms of symptoms,course of illness, outcome, and neurobiologicalfeatures.

DSM-IV Criteria• Same criteria as for adults:• 2 or more of the following for at least 1 month:• Delusions, hallucinations, disorganized speech, grosslydisorganized or catatonic behavior, negative symptoms(such as flat affect, anhedonia, apathy, alogia, lack ofinterest in socialization)• Only one of the above is required if delusions are bizarreor hallucinations consist of a voice keeping a runningcommentary, or 2 or more voices conversing with eachother• Must cause significant social or occupational functionaldeterioration• Duration for at least 6 months (including prodromal orresidual periods where above criteria may not be met)

Epidemiology• Onset prior to 13 years is very rare• Rate of onset increases during adolescence and peaksbetween 15 and 30 years old• In general male onset of schizophrenia isapproximately on average 5 years younger than infemales; therefore COS and EOS are predominantlyfound in males and in adults the gender ratio is moreeven.

Etiology - Genetics• Genetics and environment both play a role• Strong genetic component evidenced by family, twin, andadoption studies with 5-20 times increased risk in firstdegreerelatives of affected individuals. 40-60%monozygotic twin concordance vs. 5-15% sibling anddizygotic twin concordance• “Common disease-common allele” model: multiplecandidate genes interact to predispose an individual todevelopment of schizophrenia, but the associations areunclear and not replicable and are often family-specific (linked to highly penetrant, individually rare genes)• The same genes are implicated in youth onset as adultonset, but COS especially is associated with higher rates ofcytogenetic abnormalities (especially DiGeorge syndrome –10-30% of these individuals develop schizophrenia-likepsychotic disorders)

Etiology – Environmental Factors• Best replicated risk factors: paternal age and in uteroexposure to maternal famine• Proposed mechanisms: direct neurological damage,gene-environment interactions, epigenetic effects, denovo mutations

Etiology - Neuroanatomical Abnormalities• Brain volume reductions in multiple regions (trueregardless of age)• Increased lateral ventricle volumes• Reduced hippocampal, thalamic, and frontal lobe volumes• Cortical thickness changes in prefrontal temporal andparietal regions• COS-specific changes: more rapid progressive loss of graymatter in a parietal-to-frontal pattern during adolescence.Plateaus in early adulthood.• Cortical thinning could be a result of increased pruning inadolescence of synaptic projections, affecting thematuration of complex processes. It could also be due todecreased myelination of neurons.• The amount of volume reduction in the brain has nocorrelation with symptom severity

Etiology - Neurochemistry• Dopamine hypothesis• Sx’s due primarily to hyperactive dopamine system inlimbic regions and hypoactive frontal regions• Reason why antipsychotics (D2 antagonist) worked sowell• Reason why dopamine agonists worsened schizophreniasymptoms• The newer atypical antipsychotics introduce a 5-HT role• Glutamate hypothesis• xs glutamate released causes a neurotoxic effect leadingto schizophrenia

“Cerebellar development in childhood onsetschizophrenia and non-psychotic siblings”(Greenstein et al, Psychiatry Research, 2010)• Longitudinal MRI study of regional and totalvolumetric cerebellar differences btwn 3 groups:• Pts dx with COS (COS)• Non-psychotic full siblings of those with COS (SIB)• Typical normal developing brain participants (TD)

Hypothesis• Sibling cerebellar abnormalities in childhood would bediminished by early adulthood to converge withcontrols• COS group would have smaller total and regionalcerebellar volumes and would diverge from controls

Results• COS diverged from TD in total cerebellum, b/l inferior-posterior lobes,and b/l cerebellar hemisphere volumes• SIB diverged from TD in total cerebellum, left inferior-posterior lobe,left superior posterior lobe, and total right cerebellar hemispherevolumes (counter hypothesis).• So familial genetic risk factors may affect brain growth• SIB converged with TD in superior vermis (supporting hypothesis)• So the vermis may mediate a compensatory/adaptive plasticchanges in relation to pathology)• Throughout development, COS had smaller volumes than TD and SIB• Measurements in early adulthood:• COS volume was smaller than TD for all regions• SIB volume was smaller than TD for right cerebellar and leftsuperior-posterior volumes (trend towards smaller totalcerebellum) (counter hypothesis)• Yet, if data was limited to ONE scan per person after 20 years,results did not show any SIB abnormalities compared to TD

Phases• Same in youth and adults• Prodromal (decline in functioning; days to weeksor years; chronic – COS, variable - EOS), acute(significant positive symptoms), recovery (shift tonegative symptoms, 1-6 months or more), residual(disordered thinking, negative symptoms,functional deficits)• Patients cycle through the last 3 onceschizophrenia is established• In youth recovery is often incomplete• Greater functional impairment over time ifpsychosis goes untreated longer and negativesymptoms are more severe

Clinical Presentation• Negative symptoms are the most specificallyassociated with EOS• Loose associations and illogical thinkingcharacteristic• Hallucinations, disordered thought, affectiveflattening frequent; complex delusions andcatatonia less frequent• Majority of EOS patients have premorbidproblems: intellectual deficits (10-20%), ADHD,disruptive behavior disorders, anxiety and mooddisorders, substance abuse• Family history of depression is common in youthwith schizophrenia

“Childhood Onset Schizophrenia: High Rateof Visual Hallucinations” (Christopher N. David et al, Journalof the American Academy of Child and Adolescent Psychiatry, July 2011)• Studies in adult onset schizophrenia report visualhallucination rates ranging from 12% to 72% with mostratings less than 35%. Studies of COS suggest rates ashigh as 69% from chart review and 48% usingstandard rating scales.• Hypothesis: COS patients will show higher rates ofvisual and other nonauditory hallucinations thanadults, and COS patients that experience both visualand auditory hallucinations will be more severely illthan those with auditory hallucinations alone.

Methods• Subjects: 117 patients with onset of psychosis before age 13,premorbid IQ of 70 or above, and absence of significantneurological illness. Age range from 6.5 to 17 years (meanage 13.6 years), 67 male and 50 female. Pts were admittedfor inpatient observation which included a 2-3 week drugfree period (if pts were not drug free at admission).• Ratings: The Scale for the Assessment of PositiveSymptoms (SAPS) and the Scale for the Assessment ofNegative Symptoms (SANS) were used – intensity ofsymptoms was rated. Children’s Global Assessment Scale(CGAS) was used to assess overall behavior (hallucinationratings not included).• Rating scales used at screening, during inpatient period,and at follow-up

Results• 95% (111) of patients reported auditory hallucinations, 80.3% (94) reportedvisual hallucinations, 60.7% (71) reported somatic/tactile hallucinations, and30% (35) reported olfactory hallucinations• These rates are higher across all hallucination subtypes when comparedto adults• Girls were more likely to experience olfactory hallucinations• Generally, visual hallucinations only occurred in pts experiencing auditoryhallucinations, and both auditory and visual hallucinations were alwayspresent if tactile or somatic hallucinations occurred• This supports an additive model of hallucination modalities (the moretypes of hallucinations the more rare, the more severe the illness, and thelower the verbal IQ of the patient)• Visual hallucinations were linked to earlier age of psychosis onset, lower IQscore, lower CGAS scores, and shorter duration of illness• Overall, visual hallucinations predicted more severe illness: greaterclinical impairment and greater compromise in general brain functioning

Psychosocial Factors• Interact with biological risk factors to influence the timingof onset, course, and severity of schizophrenia• Positive remarks from caregivers are associated with fewernegative symptoms and better social functioning inadolescents and young adults• Criticism, emotional over-involvement, and hostility infamilies (high expressed emotion) are associated withworse outcomes• Strong predictor of future relapse of hospitalized patients• Could be a response to a severely ill family member vs. acausal factor• Cultural context is important – in African American families,high expressed emotion is not a predictor of relapse; highlevels of critical and intrusive behavior are associated withimproved outcomes

Peers and Culture• Youth with schizophrenia are especially vulnerable tointerpersonal relationship difficulties. Prodromal period –relationship difficulties and withdrawal• Potential symptoms should always be evaluated in thecontext of one’s culturally and environmentally sanctionedbeliefs – symptoms should be incongruent• Prevalence rates of schizophrenia are similar crossculturally• Transitioning to a new culture may be associated withonset of illness – first and second generation immigrantsare at higher risk, especially if from developing countries• Urban environments and increased life stressors may alsoincrease risk of development

Treatment• Combines medication with psychosocial interventions(addresses cognitive, behavioral, familial, and socialfunctioning); very similar to adult treatment withadded emphasis on family and developmental issues• Medication: guidelines based on adult literature;risperidone and aripiprazole have been approved bythe FDA for adolescents. Clozapine is used in youthwith treatment resistant schizophrenia who havefailed other agents (significant side effect profile)• Acute phase treatment: treatment based on side effectprofile, insurance, and what has worked in the past (forpatient or family members)• 4-6 weeks needed to determine effectiveness – switchafter 6 weeks if no improvement

Treatment Continued• Family therapy• Educate more about the nature of the illness (cause, prognosis, treatments)• Learn how to improve communication with their schizophrenic relative• Minimize criticism• Minimize “high expressed emotion”• Results: improvements in relapse rates and global functioning; moreeffective in youth with greater premorbid functional deficits• Cognitive rehab• Remediate the abnormal thought process• Improve information processing skills (attention, memory, vigilance)• Changing the thoughts, responses to the thoughts by incorporating copingstrategies• Results: improved symptom management and medication compliance• Psychosocial Rehab• Day treatment programs, assertive community treatment programs, etc tohelp integrate the patient back into his/her community• Peer support• Companionship• Vocational interventions• Interpersonal skills training - Results: improved role functioning, selfefficacy,patient satisfaction. Targets social skills deficits, decreases stress.Modified in youth to account for developmental level.