0521850568c03 39.58

File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Childrenand Adolescents Jason SchiffmanAssistant Professor, Department of Psychology, University of Hawaii at Manoa Note: Age of onset received an A- because this is the defining characteristic of childhood onset schizophrenia relative to adulthood. It should be noted, however, that the age of onset varies among youth and can range from as early as 5 until 18.
Treatment received a B, but the strength of the evidence is among psychopharmacological treatments. To date, psycho- social interventions have not been systematically examined to the degree psychopharmacological treatments have, and would therefore receive a C if rated independently.
Schizophrenia among young people is a devastating and costly mental illness.
Considered a more severe variant of adult schizophrenia, childhood schizophreniacan be a terrifying and debilitating condition for youth and family. Although thedisorder is rare, interest in schizophrenia among children and adolescents has File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d grown as researchers and clinicians recognize the benefits of understanding thedisorder. Continued research promises to increase the ability to diagnose and treatearly forms of schizophrenia. Additionally, the study of early-onset variants ofdisorders often enables the examination of a more genetically homogeneous andless environmentally influenced disease condition. As such, understanding early-onset schizophrenia may possibly provide useful information about the etiologyand course of adult-onset schizophrenia (Kumra et al., 2000). Despite growinginterest, however, research on schizophrenia among children and adolescentsis limited. Several research groups currently pursue studies of individuals withearly schizophrenia to discern functional and structural deficits associated with thedisorder (e.g., Asarnow & Asarnow, 2003). While ongoing research continues toincrease our understanding of biological and environmental factors associatedwith and contributing to the disorder, the rarity of the condition has resulted inonly modest gains in understanding.
Factors associated with early-onset schizophrenia such as basic demographics (e.g., prevalence, gender distribution, comorbidity), presentation, course andoutcome, neuropathology, genetic factors, and treatment remain areas of relativemystery. Increased knowledge of the general portrait presented by children andadolescents with schizophrenia may increase understanding and have implicationsfor mental health care provision.
Very few studies have tracked rates of schizophrenia among youth in the generalpopulation. Gillberg and Steffenburg (1987) estimated very early onset schizo-phrenia (10 years of age or younger) rates at 1.6 per 100,000 in western Sweden.
Remschmidt et al. (1994) suggested that approximately one in 10,000 childrendevelop schizophrenia before 18 years of age. Among slightly older (12 to 19 years)youth receiving psychiatric outpatient services, Evans and Acton (1972) reportedthat the rate of a more inclusive condition of psychosis was approximately onepercent.
A study by Thomsen (1996) looked at childhood and adolescent onset schizophrenia throughout Denmark from 1970 to 1993. Findings indicated that32 children younger than 15 met criteria for schizophrenia between 1970 and 1993comprising 86% of the psychiatric in-patient population in this age group.
As would be expected, the occurrence of schizophrenia increased with age.
Between ages 15 and 17, 284 adolescents with schizophrenia were hospitalizedfrom 1970 to 1993. Although informative, this Danish study did not include youth File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Children and Adolescents served in non-hospital settings. Given a trend towards least restrictive care in theUnited States, many children and adolescents with schizophrenia in the USAprobably receive treatment outside of the hospital.
While prevalence estimates in the USA are rare, we recently completed a study of youth with schizophrenia spectrum disorders served by the state mental healthsystem of Hawaii (Schiffman & Daleiden, in press). Schizophrenia spectrumdisorders (e.g., schizophrenia, schizoaffective disorder, psychotic disorder NOS)may be of particular interest to researchers and clinicians because they aregenetically linked to schizophrenia and are slightly more available for study.
Among other findings assessing children and adolescents seeking services throughboth hospitalization and community clinics served by the state mental healthsystem in Hawaii, we estimated an observed prevalence of 5% among all youthregistered for mental health services. As might be expected, the Hawaii analysis,which included home and community services, yielded a slightly lower prevalencerate estimate than that reported in a psychiatric in-patient population (Thomsen,1996).
In general, most studies of the epidemiology of early-onset schizophrenia converge to suggest low rates of the disorder attesting to the rarity of this conditionamong youth. Additional epidemiological reports are needed to augment thecurrent understanding of schizophrenia in children and adolescents. Overall,Asarnow and Asarnow (2003, p. 461) note that current ‘‘prevalence figures mustbe viewed as highly tentative until more representative data become available’’.
Previous research suggests a male-to-female ratio ranging from 2:1 to 5:1(Beitchman, 1985; Evans & Acton, 1972; Green et al., 1992; Hollis, 1995;Thomsen, 1996; Werry, 1992). Findings from the Hawaii study suggest a male-to-female ratio of 1 to 2.38 among youth with schizophrenia spectrum disorders.
This range of gender ratios conflicts with general prevalence estimates of adultschizophrenia that suggest approximately equal gender distribution, butis consistent with the notion that males typically have an earlier age of onsetthan females. Kolvin et al. (1971) suggested that the predominance of malesamong youth with schizophrenia is a distinguishing characteristic of early-onsetschizophrenia.
Youth with schizophrenia typically have multiple diagnoses. A study by Russell,Bott and Sammons (1989) reported that 68% of children with schizophrenia intheir sample met criteria for another mental illness. Reports from the literatureindicate that externalizing disorders such as conduct or oppositional defiant File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d disorders as well as internalizing disorders such as depression are commonlydiagnosed along with a schizophrenia spectrum diagnosis (Eggers, 1989; Nicolsonet al., 2001; Werry, McClellan, & Chard, 1991). Among youth with psychosis,a study by Biederman et al. (2004) indicated that 131 of 132 identified youthwith psychosis had a comorbid disorder.
In the Hawaii study, disruptive behaviors and attentional problems were the most frequently diagnosed comorbid conditions for both youth with and withoutspectrum disorders. The rate of comorbid disruptive behavior and attentionalproblems among the comparison group of all youth in the system without aschizophrenia spectrum disorder (‘‘non-spectrum youth’’), however, was signifi-cantly greater than among youth with spectrum disorders. This pattern of resultssuggests that youth with disruptive and attentional disorders are more likely to beregistered with the Department of Health than youth with any other diagnosis,but this effect was not as pronounced for youth with schizophrenia spectrumdisorders.
Youth with schizophrenia are also more likely to have mental retardation (Aylward, Walker, & Bettes, 1984). Consistent with that finding, youth in theHawaii study with spectrum disorders were more likely to have a diagnosis ofmental retardation than non-spectrum youth. Aylward et al. (1984) suggested thatmental retardation can serve as a premorbid feature of early-onset schizophreniaand may relate to the course of the illness. This link between mental retardationand early-onset schizophrenia, however, may be underrepresented as someresearch groups exclude youth with severe intellectual disabilities from theirstudies of childhood schizophrenia (Friedlander & Donnely, 2004).
Given the rarity of the condition, research does not provide a clear descriptionof the ethnic breakdown of youth with schizophrenia. Studying youth in Hawaiioffered the advantage of a large multi-ethnic sample. This is particularly beneficialwith childhood-onset schizophrenia as demographics in general are poorlyunderstood and under studied. In the Hawaii study, ethnic background didnot significantly differ between the spectrum and non-spectrum groups, withthe exception of Asian youth (Schiffman & Daleiden, in press). Our findingsindicated that Asian youth accounted for a larger proportion of the spectrumdisorder group than the non-spectrum control group of all other registered youth.
The proportion of Asian youth in the non-spectrum group (18.2%) was less thanthe proportion of Asian youth (29.9%) in the general Hawaii population (USCensus Bureau, 2000). The proportion of Asian youth in the spectrum group(30.2%) resembled the general population of Asian youth in Hawaii. Studies havereported lower representation among Asian Americans in hospital-based and File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Children and Adolescents community mental health service populations than expected based on censusestimates (Leong, 1994). The source of underutilization is unclear, however,cultural factors may partially account for this finding (Leong, 1994; Sue &Morishima, 1982). The closer approximation to census estimates in the group ofyouth with schizophrenia spectrum disorders may suggest that, among otherpossibilities, the severity of spectrum disorders may contribute to the increasedlikelihood that Asian youth with schizophrenia spectrum disorders receive mentalhealth services.
The modal age of onset of typical schizophrenia is in early adulthood, usuallybefore 25 years of age. While specific age cutoffs for early onset vary in theliterature, researchers generally consider schizophrenia diagnosed before age 18 asearly onset. Diagnoses before age 13 are rare and often labeled as ‘‘very earlyonset.’’ Given the low base rate of the phenomenon and normal developmentalprocesses (e.g., childhood imagination), diagnosing schizophrenia prior to ageseven is extremely uncommon. As might be expected, the rate of schizophreniaamong youth increases with age. Among youth in Hawaii, registered youth with adiagnosis of a schizophrenia spectrum disorder in the mental health system weresignificantly older in relation to all other registered youth (14.6 years versus12.0 years; Schiffman & Daleiden, in press).
Current DSM-IV-TR diagnostic criteria for childhood-onset schizophrenia are thesame as those used for adult schizophrenia. As with adults, the hallmark symptomsinclude delusions and hallucinations. When sufficiently severe, only one of thesesymptoms is required for a diagnosis. Other symptoms include disorganizedspeech, disorganized or catatonic behavior, and negative symptoms. In additionto the characteristic symptoms, DSM-IV-TR (American Psychiatric Association,1994) also requires social or occupational dysfunction (generally schoolperformance for young people), symptoms for at least six months, and symptomsnot better accounted for by mood disorders, schizoaffective disorder, substanceuse, a general medical condition, or a pervasive developmental disorder (forpervasive developmental disorders, schizophrenia is given if delusions orhallucinations are present for at least a month).
File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Specific patterns of symptom presentation among youth with schizophrenia are not well studied. Russell et al. (1989) reported hallucinations in 80% of theirsample of 35 children with schizophrenia, with auditory hallucinations the mostcommon form, followed by visual. Delusions were reported in approximately63% of cases from this sample. In a descriptive account of 33 youth withschizophrenia, Werry et al. (1994) indicated that 61% of their sample reportedhallucinations (57% auditory), and 55% of their sample reported delusions.
The authors also noted that delusions tended to be less well-formed relativeto adults. Communication may be impaired in youth with schizophrenia,with Caplan (1994) noting three patterns of deficits among 31 children withschizophrenia including impaired discourse skills, loose associations, and illogicalthinking.
In a relatively large study of 132 youth with psychosis, Biederman et al. (2004) reported that 44% of the sample suffered from delusions, and 85% hallucinations.
Auditory hallucinations were most common (79%), followed by visual (54%),tactile (23%), and olfactory (13%). Within delusions, delusions of persecution andreference were most common (27% and 23% respectively). Approximately 20% ofyouth expressed other symptoms such as incoherence, loosening of associations,flat affect, and inappropriate affect.
Developmental considerations may influence diagnostic decisions when evaluat-ing children for schizophrenia, as the presentation quality of symptoms may differfrom those seen in adulthood. For instance, some researchers suggest that negativesymptoms are less common among children with schizophrenia, and delusionsand hallucinations may be less well developed and involve more childlike themes(monsters or toys versus religious or sexual themes) (Volkmar, 2001). Evidencesuggests that when accounting for developmental considerations, schizophrenia inchildren can be reliably diagnosed (Werry, 1992). Diagnostic interviews such asthe Schedule for Affective Disorders and Schizophrenia for School-Age Childrenare useful in increasing the reliability and validity of the diagnosis (Kaufman et al.,1997). This interview provides the assessor developmentally tailored questionsassessing for symptoms associated with schizophrenia and other disorders asexpressed in childhood.
In addition to symptom presentation, youth with schizophrenia demonstratea host of neuropsychological deficits. Most of these deficits are similar to thoseseen in adult schizophrenia. Kumra et al. (2000) reported that children withschizophrenia (average age 14.4 years) consistently demonstrated one to two File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Children and Adolescents standard deviation impairment across a range of neuropsychological tests (generalIQ, achievement, attention, executive functioning, memory, motor skills, etc.).
Likewise, in a review, Asarnow and Asarnow (2003) reported a similar array ofneurocognitive deficits among children with schizophrenia (attention, visual-motor coordination and fine motor speed, executive functioning, and variousforms of memory).
Several studies have looked at particular patterns of neurocognitive deficits among young people with schizophrenia. A study of 17 adolescents withschizophrenia supported the global cognitive dysfunction findings, and specifi-cally noted larger differences between cases and controls on working memory andattention (Kenny et al., 1997). Oie and Rund (1999) also reported similar globalimpairment among 19 adolescents with schizophrenia compared to controlgroups with and without other psychiatric conditions (Attention-DeficitHyperactivity Disorder). The authors indicated particular deficits in the areas ofabstraction, visual memory, and motor functioning. Among never medicated, firstepisode adolescents with psychosis (most of whom either subsequently developedschizophrenia or were deemed to have the disorder after further review of history),Brickman et al. (2004) reported global neuropsychological deficits, with thegreatest deficits observed in executive functioning, attention, and memory.
The authors also reported relatively intact language functioning, a finding alsoreported by Kenny et al. (1997). The findings from Brickman et al. (2004) are ofparticular interest as subjects were free of the potentially confounding impacts ofneuroleptic treatment and long duration of illness. Collectively, these findingsstrongly support global neurocognitive impairment among youth with schizo-phrenia, with specific areas of relative deficits seeming to fall in the domains ofmemory (of varying type), attention, executive functioning, and perhaps motorfunctioning.
Interestingly, studies of neurocognitive functioning reveal that youth withschizophrenia resemble a potentially related group of youth not meeting full cri-teria for the disorder. As with adults, youth with psychotic symptoms not reachingdiagnostic threshold for full schizophrenia are often diagnosed with psychoticdisorder NOS. Neurocognitive reports comparing youth with childhood-onsetschizophrenia to a group of youth with psychotic disorder NOS suggest fewmeaningful differences in neurocognitive profiles (McClellan et al., 2004).
Given similarities in neurocognitive performance and symptoms presentations,some researchers speculate that psychotic disorder NOS may be a less severecondition genetically related to childhood-onset schizophrenia (Kumra et al.,2000).
File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d The premorbid course of childhood-onset schizophrenia appears associated withan array of functional deficits. Kolvin et al. (1971) as well as others (Alaghband-Rad et al., 1995; Hollis, 1995; Nicolson et al., 2000; Russell et al., 1989) reporthigh rates of developmental delays including speech and language and socialpeculiarities. A more recent study by Nicolson and colleagues (2000) reported thatover half of the 49 children with schizophrenia in their sample had premorbidimpairment in motor, social, and speech and language functioning. While therewas no comparison group in this study, the rate of impairment seems strikinglyhigh and suggests a developmentally deviant premorbid course.
The course of childhood schizophrenia once diagnosed is understudied and varies by individual. As seen in adult schizophrenia, it is believed that theprogression roughly follows a period of deterioration, followed by stabilization,and hopefully improvement (Merry & Werry, 2001, p. 280). Based on a review ofseveral studies of varying methodology tracking outcome among youth with aschizophrenia diagnosis, reviews by Asarnow, Tompson, and McGrath (2004)and McClellan et al. (2001) indicate that about one half of youth withschizophrenia remain severely impaired over time, with the other half showinga variable course with some improvement in psychotic symptoms. A longitudinaldescriptive report of psychosocial outcome among adolescents with schizophreniaby Lay et al. (2000) indicated that, among those available for follow-up at ten ormore years, 83% had at least one re-hospitalization, 57% showed at leastmoderately vocational impairment, and 75% were supported by either theirparents or public means.
Generally, most evidence suggests that the majority of youth with schizophrenia show a slower onset and chronic pattern as opposed to an acute psychotic break(Asarnow et al., 2004). While difficult to compare directly, Nicolson et al. (2000)suggest that the premorbid course for individuals with childhood-onset schizo-phrenia may be worse than the premorbid course for adult-onset schizophrenia.
Additionally, it seems that the earlier the onset, the worse the prognosis (Merry &Werry, 2001, p. 294).
Among youth with psychotic disorders, those with worse premorbid characteristics and earlier onset tend to have worse outcomes. McClellan andcolleagues note that poor premorbid adjustment, negative symptoms, and low IQpredicted poor outcome among youth with psychotic disorders (McClellen et al.,1999; Werry & McClellan, 1992). Similarly, Nicolson et al. (2001) reported thathigh levels of psychopathology, cognitive deficits, and motor impairmentspredicted poor outcome among a sample of 26 youth with psychotic disorderNOS. Collectively, these findings suggest that schizophrenia spectrum disorders File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Children and Adolescents in childhood appear associated with poor long-term outcome with the worstoutcomes associated with earlier onset, poor premorbid functioning, andimpairment at intake (Asarnow et al., 2004; Gillberg, Hellgren, & Gillberg, 1993;Werry et al., 1991;).
A series of studies from the Child Psychiatry Branch of the National Institute ofMental Health (NIMH) suggest reduction in cerebral volume and pervasivepattern of brain deterioration in childhood-onset schizophrenia. Similar to adultschizophrenia, individuals with childhood-onset schizophrenia tend to haveventricular enlargement and progressive loss of gray matter (4% reduction incerebral volume) (Rapoport et al., 1997; Rapoport et al., 1999). Confirming initialfindings, Sowell et al. (2000) identified a similar reduction in gray matter andenlarged ventricles in an independent sample. Although limited in number,a handful of imaging studies suggest various other brain abnormalities seen inchildhood-onset schizophrenia. Findings include abnormalities in the corpuscallosum (Jacobsen et al., 1997; Keller et al., 2003; Sowell et al., 2000), andsubcortical structures such as the vermis (Jacobsen et al., 1997) and basal ganglia(Blanton et al., 1999).
Several follow-up studies from the NIMH group identify brain deterioration over time among youth with schizophrenia. For instance, Giedd et al. (1999)reported progressive brain deterioration among youth with schizophrenia,noting decreases in cerebrum and hippocampus volume, and increases inthe lateral ventricles. The rates of deterioration appeared to level off as youthentered adolescence. Thompson (2002), discussing data from this project, noteda relation between rate of temporal cortical loss and positive symptoms, as wellas a relation between gray matter loss in the frontal cortices and negativesymptoms.
In a more detailed and recent analysis including additional subjects from the NIH project, Sporn et al. (2003) identified progressive loss in the frontal andtemporal cortices across multiple assessments, suggesting neural deteriorationspreading from parietal regions towards the cortex. Similar to the earlier study, theauthors also noted that gray matter loss appeared to level off with age. Gray matterloss was related to premorbid impairment but, in contrast to an earlier report byThompson (2002), it was also related to greater clinical improvement as measuredby the Brief Psychiatric Rating Scale and the Scale for the Assessment of NegativeSymptoms scores. The authors speculate that perhaps ‘‘compensatory ‘pruning’of malfunctioning neural circuits’’ might in part begin to explain the relation File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d between clinical improvement and brain volume loss (Sporn et al., 2003, p. 2188).
Future imaging work among youth with schizophrenia is needed to replicate theseearly studies, as well as provide additional findings with respect to brain structure,function, and change over time.
Related to imaging studies of neuropathology is the study of neurological functioning. Using a subsample from the above-described NIH study, Karp et al.
(2001) noted high rates of neurologic abnormalities, including elevated rates ofprimitive reflexes and other abnormalities relative to controls, that persisted withage among youth with childhood-onset schizophrenia. These deficits suggesthemispheric inhibition of the brainstem, and strongly support general deficienciesin normal maturation. According to the authors, results from the study highlightthe role of genetically mediated early central nervous system insults in the etiologyof childhood-onset schizophrenia.
Little is known about specific neurochemical abnormalities underlying schizo-phrenia in childhood. Perceiving childhood-onset schizophrenia as a related andcontinuous disorder with adult schizophrenia allows speculation that neuro-chemical abnormalities present in adult schizophrenia are similar to those foundin childhood schizophrenia (e.g., dopamine, glutamate, serotonin). Much of theevidence for the influence of dopamine in adult schizophrenia comes from thefact that patients respond favorably to anti-dopaminergic medications and thatdopamine agonists can cause psychotic symptoms among non-psychiatricindividuals. This same pattern is true in children. While enough evidence existsto suggest that dopamine plays a role in childhood schizophrenia, specifics of thatrole are not understood. The few studies conducted in this domain with childrenreport similar patterns of results as those typically found in adult schizophrenia(Asarnow & Karatekin, 2001).
Early onset of schizophrenia seems associated with high genetic loading forthe disorder. Research has borne out this relation, noting an increased riskof schizophrenia among the relatives of children with schizophrenia (Asarnowet al., 2001; Sham, MacLean, & Kendler, 1994). Asarnow et al. (2001) reportedthat the relatives of children with schizophrenia in their study were 17 times morelikely to have a schizophrenia spectrum disorder in relation to controls. This riskis obviously far greater than the risk in the general population, as well as greaterthan that found in similar studies of relatives of adults with schizophrenia File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Children and Adolescents (three to six times more likely among relatives of adults with schizophrenia).
Findings from this report suggest an increased genetic component to schizo-phrenia in childhood over and above that found in adult schizophrenia.
In a similar report, Nicolson et al. (2003) advanced this line of study by includingrelatives of patients with adult-onset schizophrenia as a control group. Findingsconfirmed speculations made by Asarnow et al. (2001) that youth with schizo-phrenia are more likely to have relatives with a schizophrenia spectrum disorderin relation to adults with typical-age-of-onset schizophrenia. Collectively, thesefindings support the strong role of genetic contributions to early-onsetschizophrenia.
In two independent samples, Matsumoto et al. (1999; 2001) reported an increasein obstetrical complications (OCs) associated with early-onset schizophrenia(16 years old and younger) in relation to control subjects. In both studies,individuals with obstetrical complications were over three times more likely todevelop childhood-onset schizophrenia relative to psychiatric controls. Thisfinding is consistent with other reports suggesting a link between OCs and earlierage of onset in adult schizophrenia (Rosso & Cannon, 2003), and a wealth ofliterature suggesting increased OCs among individuals with schizophrenia ingeneral. As seen with other correlates, Matsumoto and colleagues suggest that thesimilarity in the relation between childhood and adult schizophrenia and OCsindicate continuity between the two disorders.
Contrary to the findings from Matsumoto et al. (1999, 2001), Nicolson and Rapoport (1999) did not find an elevation in OCs among individuals withchildhood-onset schizophrenia. The comparison group employed by Nicolsonand Rapoport, however, was composed of the siblings of the patients who mayshare genetic risk for OCs, rather than genetically independent controls.
Interestingly, however, the percentage of individuals with childhood-onset schizo-phrenia who had OCs were similar in both studies (34.3% in the Matsumoto et al.
(2001) sample, 27.7% in the Nicolson and Rapoport (1999) sample).
Schizophrenia in adulthood is associated with high levels of care and high costfor services (Cuffel et al., 1996; King, Singh, & Shepherd, 2000). In our analysis File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d of youth with schizophrenia spectrum disorders in Hawaii, we found above-average use of more restrictive levels of care. More restrictive levels of care mayreflect that youth with schizophrenia spectrum disorders struggle with more severeproblems. Problems faced by these youth may require great environmentalresources and possibly put these individuals in danger. It is important to note,however, that results from the service analyses in the Hawaii study suggest thatapproximately four out of five youth with services procured for schizophreniaspectrum problems were treated in home or community settings. Approximatelyone half received intensive home and community services and almost all receivedless intensive outpatient services.
In addition to requiring more services, we found that youth with spectrum disorders are financially expensive relative to other youth in the system. Theaverage annual cost per youth with a schizophrenia spectrum disorder in Hawaiiwas $16,420, a rate nearly twice as high as the average annual cost per youth ofothers in the system. Schizophrenia is an expensive illness to manage, especiallyamong young people.
The above-average use of more restrictive services would seem to highlight an opportunity for the development of evidence-based strategies that supportmanagement of schizophrenia spectrum disorders in home and communitysettings. Presently, intervention with neuroleptic medication is the onlyempirically supported treatment for early-onset schizophrenia. Although thebenefits of psychopharmacology are well documented, the intervention is globaland does not specifically target individual areas of concern. Mental healththerapists are likely to benefit from structured psychosocial strategies effec-tive in helping youth with schizophrenia spectrum disorders. The efficacy ofstructured psychosocial interventions for early-onset schizophrenia has not yetbeen systematically assessed. Evidence from a range of areas, however, suggeststhat a psychosocial intervention targeting specific symptoms might benefit youthwith early-onset schizophrenia (discussed below), especially when used as anadjunct to psychopharmacological intervention.
Atypical neuroleptics seem to be the most effective means of treating childhoodschizophrenia. Most research has focused on clozapine, with more recent studiesbeginning to investigate other atypical neuroleptics (Zalsman et al., 2003). As inadults, clozapine seems to offer the advantages of effectively treating both positiveand negative symptoms with less extrapyramidal side effects relative to typicalneuroleptics. Less side effects, particularly attenuated extrapyramidal symptoms,generally lead to increased tolerability and medication compliance. Potentiallyfatal risk, however, is associated with clozapine (e.g., agranulocytosis), and File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Children and Adolescents therefore clozapine is not recommended as the first option in treating early-onsetschizophrenia. Rather, non-clozapine atypical neuroleptics, not associated withfatal risk, are generally recommended. Two open-label studies of other atypicalneuroleptics (one of risperidone and the other of olanzapine) have beenconducted with youth with schizophrenia, with promising results. While thesemedications are not associated with life-threatening side effects, most do havesome significant side effects including, among others, some extrapyramidalsymptoms, and significant and sometimes distressing weight gain and sedation.
Given the rarity of the disorder, medication trials pose formidable methodo- logical barriers that have slowed research in this area. In a recent review ofthe existing literature, Cheng-Shannon et al. (2004) concluded that atypicalantipsychotic medications are in fact useful in treating psychosis among youth.
The American Academy of Child and Adolescent Psychiatry practice parametersfor the treatment of childhood schizophrenia also express this sentiment. Despitethese positive conclusions, Remschmidt et al. (2001) estimated that approximately15% of childhood-onset patients do not respond to typical or atypicalneuroleptics. Additionally, while it appears that pharmacological therapy isuseful for youth struggling with psychotic symptoms, little is known about thelong-term effects of these medications. Frequent and regular contact with thetreating psychiatrist is recommended.
Practice parameters for the treatment of childhood schizophrenia established bythe American Academy of Child and Adolescent Psychiatry call for a two-prongedsymptom-specific and general-functioning approach to treatment. Specificsymptom targeting includes addressing positive and negative symptoms directly,while general functioning refers to more broad social, academic, and family needs.
The practice parameters call for a ‘‘comprehensive multimodal approach’’ totreatment (McClellan et al., 2001, p. 145) taking into consideration comorbidconditions and developmental considerations. This position is consistent with onestudy that systematically investigated a comprehensive community treatmentapproach for a small group of adolescents with schizophrenia reporting positiveeffects of working with parents, problem solving skills, and re-integration efforts(Rund et al., 1994).
University of Hawaii Child and Adolescent Thought Disorders Program The Child and Adolescent Thought Disorders Program at the University of Hawaiiat Manoa was established in 2003 to provide comprehensive assessment andpsychosocial interventions to youth with schizophrenia spectrum disordersin Hawaii. The program is also designed to increase the understanding of thought File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d disorders in youth through systematic collection of information from thispopulation. Funding for this program is provided by the Hawaii Department ofHealth Child and Adolescent Mental Health Division. The clinic was designedwith the American Academy of Child and Adolescent Psychiatry practiceparameters in mind and serves as an example of the assessment and psychosocialtreatments available for youth with schizophrenia.
Youth with suspected thought disorders eligible for services in our programparticipate in a thorough mental health examination. The initial assessmentbattery provides a thorough diagnostic and neuropsychological evaluation toverify diagnosis and identify relative strengths and weaknesses in functioning.
The clinic employs a semi-structured interview designed to assess an array ofpsychopathology in youth, including psychotic processes (Kaufman et al., 1997).
To provide more accurate and complete information, we interview the child,parent, and relevant adults in the child’s life (e.g., teacher, treating therapist,psychiatrist, etc.). Self-report questionnaires from various informants supplementinterview information. Assessments particularly focus on identifying behaviors ofimpairment through interview as well as direct observation to help determinespecific treatment goals for subsequent intervention.
In addition to the diagnostic and functional components, we also offer a screening of neurocognitive functioning. Domains of functioning assessed includeareas identified in the literature as potential deficits for youth with schizophrenia.
We employ tests of executive functioning, attention, various forms of memory,and an abridged test of intelligence. The neurocognitive examination allows for anassessment of relative strengths and weaknesses in cognitive functioning andprovides information useful for recommendations and treatment planning.
As mentioned above, there are currently no identified evidence-based psychosocialinterventions for schizophrenia among youth. We attempt to systematicallystudy our on-going treatment cases to provide useful approaches to treating otheryouth with similar conditions. The heterogeneity of the disorder, however, makesgeneralization from one case to the next difficult. To address the issue of variabilityof individual presentation, we employ a modular approach to therapy containingspecific sections for specific problem behaviors. This approach provides ourclinicians with a range of strategies to address target behaviors. Our modulesare derived from a range of areas including: cognitive and behavioral treat-ment for adult schizophrenia; empirically supported therapies for childhoodanxiety, depression, and disruptive behavior disorders; social skills training; File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Children and Adolescents behavioral treatment for autism; community involvement; and motivationalinterviewing. Even if symptoms directly associated with symptoms of schizo-phrenia (e.g., hallucinations and delusions) are resistant to treatment, a modularapproach is often effective in treating comorbid and related conditions (e.g.,specific phobia of water caused by the delusional fear that evil creatures will drownthe client).
Additionally, our clinic also offers family therapy and multifamily therapy(McFarlane et al., 1995). Collateral work with parents and close relatives isessential for the complete care of youth with schizophrenia spectrum disorders.
Additionally, multifamily therapy has been demonstrated effective in thetreatment of adult schizophrenia. These groups focus on problem-solvingstrategies and community building between families struggling with similar issues.
Family work has an underlying goal of reducing critical or over-protective comments from family members, referred to as ‘‘expressed emotion’’. High levelsof expressed emotion are associated with relapse among adults with schizophrenialiving with their families (Leff & Vaughn, 1985). The role of families in the livesof youth with schizophrenia spectrum disorders is possibly even more powerfuland relevant than among adults with schizophrenia, as young people may beeven more dependent on family for support.
Related to work with the family is the importance of interdisciplinary coordination of services. Youth with schizophrenia often have many healthcare providers as team members. In addition to the parent(s), psychiatrists,psychologists, teachers, nurses, social workers, individual skills trainers, occupa-tional therapists, and others are often involved in cases. Working collaborativelywith all treatment team members is crucial to the functioning and outcome ofthe child.
For all of our cases, we provide ongoing structured single-case evaluation protocols involving multiple informants for therapists to track the effectiveness ofspecific interventions. Ongoing monitoring and assessment of progress through-out the course of treatment enhances the ability to determine the most effectivetechniques for specific symptoms in a particular client and enables the monitoringof overall progress.
The field of early-onset schizophrenia holds far more questions than answers.
While interest and understanding of the disorder continue to grow, many File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d unanswered questions remain. By definition, schizophrenia in childhood is similarto adult-onset schizophrenia in terms of defining symptomatology. Certaincorrelates and expression of the disorder in youth, however, vary relative totypical-onset schizophrenia.
Although rates increase with age, the prevalence of early-onset schizophrenia is rare. This fact, perhaps more than any other, contributes to the limitations inunderstanding the disorder. Despite the rarity of the condition, schizophrenia inyoung people can be reliably diagnosed and researched. Research has revealeda preponderance of males relative to females and high rates of comorbidity.
Additionally, the course of childhood-onset schizophrenia typically appears worserelative to the adult-onset variant of the disorder, with estimates of nearly half ofyouth diagnosed having poor outcomes. In line with poor prognosis, in vivoneuroimaging studies tend to show progressive deterioration in the brains ofyouth with schizophrenia. While research has yet to uncover all causal factors,genetics seem to play a large role in the etiology of the disorder.
Consistent with our lack of understanding of the disorder, the field has only begun to identify effective treatments for schizophrenia among youth.
Psychopharmacological treatment is an essential component to managing thedisorder, but is rarely a cure. Comprehensive wrap-around psychosocial servicesfor the youth and family are also important in helping individuals with thiscondition. Further research investigating all factors associated with childhood-onset schizophrenia, including the etiology, demographic profile, neurologicalcorrelates, and course and progression, may provide hope for future treatment of,and recovery from, this devastating condition.
Alaghband-Rad, J., McKenna, K., Gordon, C. T., et al. (1995). Childhood-onset schizophrenia: The severity of premorbid course. Journal of the American Academy of Child and Adolescent American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Association.
Asarnow, J. R. & Asarnow, R. F. (2003). Childhood-onset schizophrenia. In Child Psychopathol- ogy, 2nd edn., ed. E. Mash and R. Barkley. New York: Guilford Press, pp. 486À519.
Asarnow, R. F. & Karatekin, C. (2001). Neurobehavioral perspective. In Schizophrenia in Children and Adolescents, ed. H. Remschmidt. Cambridge: Cambridge University Press, Asarnow, R. F., Nuechterlein, K., Fogelson, D., et al. (2001). Schizophrenia and schizophrenia- spectrum personality disorders in the first-degree relatives of children with schizophrenia: The UCLA family study. US Archives of General Psychiatry, 58(6), 581À8.
File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Children and Adolescents Asarnow, J. R., Tompson, M. C., & McGrath, E. P. (2004). Annotation. Childhood-onset schizophrenia: Clinical and treatment issues. Journal of Child Psychology and Psychiatry, Aylward, E., Walker, E., & Bettes, B. (1984). Intelligence in schizophrenia: Meta-analysis of the research. Schizophrenia Bulletin, 10, 430À59.
Beitchman, J. (1985). Childhood schizophrenia: A review and comparison with adult-onset schizophrenia. Psychiatric Clinics of North America, 8, 783À814.
Biederman, J., Petty, C., Faraone, S., et al. (2004). Phenomenology of childhood psychosis.
The Journal of Nervous and Mental Disease, 192, 607À14.
Blanton, R. E., Levitt, J., Thompson, P. M., et al. (1999). Average 3-dimensional caudate surface representations in a case of juvenile-onset schizophrenia. Archives of General Psychiatry, 53, Brickman, A., Buschsbaum, M., Bloom, R., et al. (2004). Neuropsychological functioning in first-break, never-medicated adolescents with psychosis. The Journal of Nervous and Mental Caplan, R. (1994). Communication deficits in children with schizophrenia spectrum disorders.
Cheng-Shannon, J., McGough, J. J., Pataki, C., et al. (2004). Second-generation antipsychotic medications in children and adolescents. Journal of Child and Adolescent Psychopharmacology, Cuffel, B., Jeste, D., Halpain, M., et al. (1996). Treatment costs and use of community mental health services for schizophrenia by age cohorts. American Journal of Psychiatry, 153, 870À76.
Eggers, C. (1989). Schizoaffective disorders in childhood: A followup study. Journal of Autism and Developmental Disorders, 19, 327À42.
Evans, J. & Acton, W. (1972). A psychiatric service for the disturbed adolescent. British Journal Friedlander, R. I. & Donnely, T. (2004). Early-onset psychosis in youth with intellectual disability. Journal of Intellectual Disability Research, 48, 540À47.
Giedd, J., Jeffries, N., Blumenthal, J., et al. (1999). Childhood-onset schizophrenia: Progressive brain changes during adolescence. Biological Psychiatry, 46, 892À8.
Gillberg, C., Steffenburg, S. (1987). Outcome and prognostic factors in infantile autism and similar conditions: A population-based study of 46 cases followed through puberty. Journal of Autism and Developmental Disorders, 17, 273À87.
Gillberg, I. C., Hellgren, L., & Gillberg, C. (1993). Psychotic disorders diagnosed in adolescence: Outcome at age 30 years. Journal of Child Psychology and Psychiatry, 34(7), 1173À85.
Green, W., Padron-Gayol, M., Hardesty, A. S., et al. (1992). Schizophrenia with childhood onset: A phenomenological study of 38 cases. Journal of the American Academy of Child and Hollis, C. (1995). Child and adolescent (juvenile onset) schizophrenia: A case control study of premorbid developmental impairments. British Journal of Psychiatry, 166, 489À95.
Jacobsen, L. K., Giedd, J. N., Rajapakse, J. C., et al. (1997). Quantitative magnetic resonance imaging of the corpus callosum in childhood-onset schizophrenia. Psychiatry Research, 68, File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Karp, B., Garvey, M., Jacobsen, L., et al. (2001). Abnormal neurologic maturation in adolescents with early-onset schizophrenia. American Journal of Psychiatry, 158, 118À22.
Kaufman, J., Birmaher, B., Brent, D., et al. (1997). Schedule for affective disorders and schizophrenia for school-age children. Present and lifetime version (K-SADS-PL): Initial reliability and validity data. Journal of the American Academy of Child and Adolescent Keller, A., Jeffries, N. O., Blumenthal, J., et al. (2003). Corpus callosum development in childhood-onset schizophrenia. Schizophrenia Research, 62(1À2), 105À14.
Kenny, J., Friedman, L., Findling, R., et al. (1997). Cognitive impairment in adolescents with schizophrenia. American Journal of Psychiatry, 154, 1613À15.
King, C., Singh, K., & Shepherd, G. (2000). An analysis of process and outcomes for new long-stay patients in a ‘‘ward-in-a-house.’’ Journal of Mental Health, 9, 179À91.
Kolvin, I., Ounsted, C., Humphrey, M., et al. (1971). Studies in the childhood psychoses, II: The phenomenology of childhood psychoses. British Journal of Psychiatry, 118, 385À95.
Kumra, S., Giedd, J. N., Vaituzis, A. C., et al. (2000). Childhood-onset psychotic disorders: Magnetic resonance imaging of volumetric differences in brain structure. American Journal Kumra, S., Wiggs, E., Bedwell, J., et al. (2000). Neuropsychological deficits in pediatric patients with childhood-onset schizophrenia and psychotic disorder not otherwise specified.
Schizophrenia Research, 42, 135À44.
Lay, B., Blanz, B., Hartmann, M., et al. (2000). The psychosocial outcome of adolescent-onset schizophrenia: A 12-year follow-up. Schizophrenia Bulletin, 26, 801À16.
Leff, J. & Vaughn, C. (1985). Expressed Emotion in Families: Its Significance for Mental Illness.
Leong, F. (1994). Asian Americans’ differential patterns of utilization of inpatient and outpatient public mental health services in Hawaii. Journal of Community Psychology, 22, Matsumoto, H., Takei, N., Saito, H., et al. (1999). Childhood-onset schizophrenia and obstetric complications: A case-control study. Schizophrenia Research, 38(2À3), 93À9.
Matsumoto, H., Takei, N., Saito, H., et al. (2001). The association between obstetric complications and childhood-onset schizophrenia: A replication study. Psychological McClellan, J., McCurry, C., Snell, J., et al. (1999). Early-onset psychotic disorders: Course and outcome over a 2-year period. Journal of the American Academy of Child and Adolescent McClellan, J., Werry, J., Bernet, W., et al. (2001). Practice parameter for the assessment and treatment of children and adolescents with schizophrenia. Journal of the American Academy of Child and Adolescent Psychiatry, 40(Suppl. 7), 4À23S.
McClellan, J., Prezbindowski, A., Breiger, D., et al. (2004). Neuropsychological functioning in early onset psychotic disorders. Schizophrenia Research, 68, 21À6.
McFarlane, W., Lukens, E., Link, B., et al. (1995). Multiple family group and psychoeducation in the treatment of schizophrenia. Archives of General Psychology, 52, 679À87.
File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Schizophrenia among Children and Adolescents Merry, S. & Werry, J. (2001). Course and prognosis. In Schizophrenia in Children and Adolescents, ed. H. Remschmidt. Cambridge: Cambridge University Press, pp. 268À97.
Nicolson, R. & Rapoport, J. (1999). Childhood-onset schizophrenia: Rare but worth studying.
Biological Psychiatry, 46(10), 1418À28.
Nicolson, R., Lenane, M., Singaracharlu, et al. (2000). Premorbid speech and language impairments in childhood-onset schizophrenia: Association with risk factors. American Journal of Psychiatry. 157(5), 794À800.
Nicolson, R., Lenane, M., Brookner, F., et al. (2001). Children and adolescents with psychotic disorder not otherwise specified: A 2- to 8-year follow-up study. Comprehensive Psychiatry, Nicolson, R., Brookner, F. B., Lenane, M., et al. (2003). Parental schizophrenia spectrum disorders in childhood-onset and adult-onset schizophrenia. American Journal of Psychiatry, Oie, M. & Rund, B. (1999). Neuropsychological deficits in adolescent-onset schizophrenia compared with attention deficit hyperactivity disorder. American Journal of Psychiatry, 156, Rapoport, J., Giedd, J., Kumra, S., et al. (1997). Childhood-onset schizophrenia: Progressive ventricular change during adolescence. Archives of General Psychiatry, Rapoport, J. L., Giedd, J. N., Blumenthal, J., et al. (1999). Progressive cortical change during adolescence in childhood-onset schizophrenia: A longitudinal magnetic resonance imaging study. Archives of General Psychiatry, 56, 649À54.
Remschmidt, H., Schulz, E., Martin, M., et al. (1994). Childhood-onset schizophrenia: History of the concept and recent studies. Schizophrenia Bulletin, 20, 727À46.
Remschmidt, H., Martin, M., Henninghausen, K., & Schulz. (2001). Treatment and rehabi- litation. In Schizophrenia in Children and Adolescents, ed. H. Remschmidt. Cambridge: Cambridge University Press, pp. 192À267.
Rosso, I. & Cannon, T. (2003). Obstetric complications and neurodevelopmental mechanisms in schizophrenia. In Neurodevelopmental Mechanisms in Psychopathology, ed. D. Cicchetti and E. Walker. New York, NY: Cambridge University Press, pp. 111À37.
Rund, B. R., Moe, L., Sollien, T., et al. (1994). The psychosis project: Outcome and cost- effectiveness of a psychoeducational treatment programme for schizophrenic adolescents.
Acta Psychiatrica Scandinavica, 89, 211À18.
Russell, A. T., Bott, L., & Sammons, C. (1989). The phenomenology of schizophrenia occurring in childhood. Journal of the American Academy of Child and Adolescent Psychiatry, 28, Schiffman J. & Daleiden, E. (in press). Population and service characteristics of youth with schizophrenia-spectrum diagnoses in the Hawaii system of care. Journal of Child Psychology Sham, P. C., MacLean, C. J., & Kendler, K. S. (1994). A typological model of schizophrenia based on age at onset, sex and familial morbidity. Acta Psychiatrica Scandinavica, 89(2), File: {CUP_FPP}Fuji-0521850568/0521850568c03.3d Sowell, E. R., Levitt, J. T., Thompson, P., et al. (2000). Brain abnormalities in early-onset schizophrenia spectrum disorder observed with statistical parametric mapping of structural magnetic resonance images. American Journal of Psychiatry, 157(9), 1475À84.
Sporn, A. L., Greenstein, D. K., Gogtay, N., et al. (2003). Progressive brain volume loss during adolescence in childhood-onset schizophrenia. American Journal of Psychiatry, 160(12), Sue, S. & Morishima, J. (1982). The Mental Health of Asian Americans. San Francisco, CA: Thompson, P. (2002). Brain deficit patterns may signal early-onset schizophrenia. Psychiatry Thomsen, P. H. (1996). Schizophrenia with childhood and adolescent onset: A nationwide register-based study. Acta Psychiatrica Scandinavica, 94, 187À93.
US Census Bureau (2000). Census 2000 Redistricting Data, Public Law 94À171, Summary File, Volkmar, F. R. (2001). Childhood schizophrenia: Developmental aspects. In Schizophrenia in Children and Adolescents, ed. H. Remschmidt. Cambridge: Cambridge University Press, Werry, J. S. (1992). Child and adolescent (early onset) schizophrenia: New directions. Journal of Autism and Developmental Disorders, 22, 601À24.
Werry, J. S. & McClellan, J. M. (1992). Predicting outcome in child and adolescent (early onset) schizophrenia and bipolar disorder. Journal of the American Academy of Child & Adolescent Werry, J. S., McClellen, J. M., & Chard, L. (1991). Childhood and adolescent, bipolar, and schizoaffective disorders: A clinical and outcome study. Journal of the American Academy of Child and Adolescent Psychiatry, 30, 457À65.
Werry, J. S., McClellen, J. M., Andrews, L. K., et al. (1994). Clinical features and outcome of child and adolescent schizophrenia. Schizophrenia Bulletin, 20, 619À30.
Zalsman, G., Carmon, E., Martin, A., et al. (2003). Effectiveness, safety, and tolerability of risperidone in adolescents with schizophrenia: An open-label study. Journal of Child and Adolescent Psychopharmacology, 13(3), 319À27.

Source: http://moodle.telhai.ac.il/pluginfile.php/45033/mod_resource/content/0/Schizophrenia_in_Children_2006.pdf