Childhood-Onset Schizophrenia:

The Severity of Premorbid Course

JAVAD ALAGHBAND-RAD, M.D., KATHLEEN McKENNA, M.D., CHARLES T. GORDON, M.D.,
KATHLEEN E. ALBUS, B.A., SUSAN D. HAMBURGER, M.A., M.S., JUDITH M. RUMSEY, PH.D.,
JEAN A. FRAZIER, M.D., MARGE C. LENANE, M.S.W.,
AND JUDITH L. RAPOPORT, M.D.

ABSTRACT
Objective: To review the premorbid histories of 23 children meeting DSM-II/-R criteria for schizophrenia with onset
before age 12 years and to compare these with childhood data of later-onset schizophrenics. Method: Premorbid
features up to 1 year before onset of first psychotic symptoms were rated from hospital and clinic records, clinical
interviews, rating scales, and tests. Results: In keeping with previous studies, specific developmental disabilities and
transient early symptoms of autism, particularly motor stereotypies, were common. Comparison with the childhood of
later-onset schizophrenics showed greater delay in language development, and more premorbid speech and language
disorders, learning disorders, and disruptive behavior disorders. (Sixty percent had received or were estimated to meet
criteria for one or more clinical diagnoses.) Conclusions: Childhood-onset schizophrenia may represent a more malig-
nant form of the disorder, although selection and ascertainment bias cannot be ruled out. The presence of prepsychotic
language difficulties focuses attention on the importance of early temporal and frontal lobe development; early transient
motor stereotypies suggest developmental basal ganglia abnormalities and extend previous findings seen in the child-
hood of later-onset patients. J. Am. Acad. Child Ado/esc. Psychialry, 1995,34,10:1273-1283. Key Words: childhood-
onset schizophrenia, premorbid, prodrome, prepsychotic.

The conceptualization ofschizophrenia as a neurodevel- neurological development in the childhood of pre-

opmental disorder has drawn increasing attention. A
primary cerebral insult during the early brain develop-
ment of schizophrenics is hypothesized (Bloom, 1993;
Bogerts, 1989; Crow et a!" 1989; Feinberg, 1982;
Fish, 1977; Keshavan et al., 1994; Lewis, 1989; Med-
nick et al., 1991; Murray and Lewis, 1987; Murray
et al., 1992; Waddington, 1990, 1993; Weinberger,
1987; Weinberger et al., 1986). One of several ap-
proaches to a neurodevelopmental basis for schizophre-
nia assumes that abnormal cognitive, behavioral, or
Acceptedjanuary 19, 1995.
From the Child Psychiatry Branch. National Institute o/Mental Health,
Bethesda. MD.
Reprint requests /0 Dr. Alaghband-Rad, Child Psychiatry Branch, NIMH,
Building 10, Room 6N240, Bethesda, MD 20892; telephone: (301) 496-
6081; fax: (J0J) 402-0296
0890-8567/95/341 0-1273$03.00/0© 1995 by the American Academy
of Child and Adolescent Psychiatry.
schizophrenic subjects reflects subtle abnormalities early
in brain development.
Several studies of the childhood of adult-onset
schizophrenia, retrospective in one form or another,
have found abnormal premorbid social, intellectual,
and neurological development, providing indirect sup-
port for the neurodevelopmental hypothesis (Garmezy
and Rodnic, 1959; Offord, 1974; Offord and Cross,
1969; Philips, 1953; Watt, 1972, 1978; Watt and
Saiz, 1991; Westermeyer and Harrow, 1986; Zigler
and Phillips, 1961). Lower premorbid IQ (Offord,
1974; Pollack et al., 1970), cognitive-developmental
delays, and premorbid social abnormalities have been
consistently seen, particularly in males (Aylward et aI.,
1984, Walker and Lewine, 1990, 1993; Watt, 1972,
1978, 1979; Watt and Lubensky, 1976). Most recently,
two large prospective community cohort studies (Done
et aI., 1994; Jones et aI., 1994) found that children
who developed schizophrenia as adults had mild devel-

]. AM. ACAD. CHILD ADOLESC. PSYCHIATRY. 34:10, OCTOBER 1995 1273

A LACHBAND - RAD ET A I..
op mc nra l delays an d poor er soc ial adj us tme nt th an
controls; in general, th ese features we re m ore ap pa rent
in males.
The st udy of childhood-onset sch izo phren ia rep re-
sen ts a unique app roach to the neurod evelopmental
understanding of th e d isorder. Very early on set cases
ma y rep resent a m ore h omogen eou s or m ore severely
affected gro up, th at received a " bigger do se" of a
hypo th et ical etiolog ical age nt suc h as early brain insult.
Alt ern at ively, a relati vely beni gn p rem orbid course
wo uld foc us interest mo re on facto rs respo nsi ble for
acti vation of the di so rd er, e.g. , pr ecocious pu bertal
devel opment, in whi ch an identical diso rder and co u rse
is manifest ed but sim ply initiated at an earlier po int
in time.
Only a sma ll number of repo rts on ch ild hood -o nset
sch izoph ren ia d escribe even briefly the pr epsych otic
and /or p rodromal co urse. These are su m marized in
T abl e I .
As see n, Kolvin et a!. (19 7 1) exa mi ned the p rem orb id
period of 33 sch izoph ren ic child ren whose illnesses
developed before age 15 years, finding behavioral abn or-
malities in 87(Yo and m ajor milestone delays in 49%
o f cases. Kydd and Werry ( 1982) d escribed 15 ch ildre n
in who m schizo ph renia developed befo re age 16 years,
for who m o nset was rated as insidious in onl y fou r.
Prodromal depressive sym pto ms pr ed ated th e onset of
schizo ph ren ia by a period of 1 month to 2 years in
th ese chi ld ren. Asarn ow and Ben-Meir ( 198 8) repo rte d
poorer p remorbid ad ju stm ent and mo re insi d ious o nset
in children with schi zo phrenia spectrum disorders co m-
pared with children who had depressive disorders.
Green and co lleagues ( 1984) examined 24 children in
who m sch izo ph renia developed befo re th ey were 12
years of age, and an enlarged sam ple of 38 cases (Green
et al., 1992 ), and th ey found insidi ous onse t to be the
rul e. W atkins and co lleag ues (19 88) , in the mo st carefu l
stu dy to date, of 18 schizo ph renic chi ldren, all psych oti c
by age 10 , found severe language deficits and delayed
motor development in 72%. Thi rt y-n ine percent of
the sample had met criter ia for in fantile autism before
the on set of sch izo phre n ia, with m or e disturbance in
ma les. Ru ssell and co lleagues ( 1989) , in a separate
study fro m th e same cen ter, found th at 9 (26%) of
3 5 ch ild ren with sch izophren ia had exh ibited clear
sym pto ms of pervasive developmental d isorder (P O D),
altho ugh non e had met full cr iter ia.
1274 j . AM. AC AD . C H IL D ADO l. ESC . PSYCHIAT RY, .14: 10 , OCT O BE R 19 9 5
T he clinical and neurob iolo gical character iza tio n of
ch ild hood- onse t schizo p h ren ic pat ients is on going at
th e N ational Institute of Mental H ealth (NIMH) (Fra-
zier er al., 1994; Gordon et al., 1994; McKenna
et al., 1994a ,b) . In th e present study, the prep sych otic
development of th is sam ple of 23 chi ld ren and adoles-
cents me eting DSM -III-R criter ia for schizophren ia,
with onse t of first psychotic sym ptoms by or before
age 12 years, was exam ined . The pr esent rep ort is of
thi s gro u p's prem orbid dev elo pme ntal course in relatio n
to othe r stud ies of ch ild ho od-o nse t sch izophren ia and
to studies of childhood abnorm aliti es seen in patients
with later-onset sch izoph ren ia.
METHOD
SUBJECTS
T he premorb id and prodromal histo ries of 23 children (15 boys
and 8 girls) diagnosed using DSM -fll-R criteria for schizophrenia
(American Psychiatric Associa tio n, 1987) are th e subject of this
stud y. W hen seen at the N IM H , they had a mean age of 14 years
(range, 10 through 19). Patients had been recruit ed natio nally
throu gh an no un cements to profession al and patient ad voc acy
groups. T he advertisem ent s sought referrals of children meeting
DSM-lIf-Rcriteria for schizophrenia with o nset of psychot ic symp-
tom s prior to or by age 12 years. Early history from preschoo l
and kindergart en had to suppo rt an estima ted no rmal intelligence.
More th an 350 charts were reviewed, from which 98 subjects and
their families were screened in person and 28 were diagnosed as
sch izo p h ren ic. T wenty-t hr ee of the se patient s have partici pated in
the study to date. More com plete descrip tions of this o ngoing
stu dy are available elsewhere (Go rdo n ct al., 1994; McKenna
er aI., 1994a,b).
At th e NIMH , all partic ipants und erwent a com prehensive
screening process inclu ding clinical int erview by two child psychia-
trists and structu red int erviews with the Schedule for Affective
Disorders and Sch izophreni a for School-Age C hild ren-E pidem io-
logic Version (K-SADS -E) (O rvaschel er al., 1980); selected portions
of the Diag nostic In terview for C hildren and Ado lescents-Parent
Versio n (DICA-P) and C hild Version (DICA-C) for disrup tive
behavior disorder s, substance abuse, and child psychosis (H erjanic
and Ca mpbell, 1977); th e Prcmo rbid Adj ustme nt Scale (PAS)
(Ca nno n-Spoo r er al., 1982); and the Auti sm D iagnostic Inte rview-
R (Lord , 1991 ).
RATING OF PREMORBID AND PRODROME PERIODS
Two psychiatrists (l.A, K.M.) independently reviewed the pre-
mo rbid and prodromal histo ries of th e 23 patients usin g all available
past records, includin g charts from previou s hospitals and clinics,
clinical and structured psych iatric interviews at the NIMH , and
all available tests. T he records reviewed and nu mber availab le for
each measure are shown in Table 2. As expecte d, hospital/clinical
evaluation s varied co nsiderably.
Raters were instructed to rate only those sym pto ms fo r which
dea r behaviora l descript io ns existed in th e records. In case of
 CHILDHOOD-ONSET SCHIZOPHRENIA

TABLE 1
Studies of Premorbid History of Childhood-Onset Schizophrenics
Age at Onset Findings
Study Sample Method of Psychosis Premorbid Prodrome

Kolvin et al., 197 I 33 Unstructured < 15 yr (10 29 (87%) "odd or un- Insidious onset in 29 (87%)
interview were < 12 usual"; 16 (49%) any
yr) major milestone delay
(mainly speech delay:
15 [46%]); 2 (6%)
echolalia
Kydd & Werry, 1982 15 (8 M/7 F) Chart review <16 yr Insidious onset in 4 (26%)

Green ct al., 1984, 24 (15 M/9 F), CBCL and <12 yr Insidious onset in 29 (87%)
1992 expanded to chart review
38 (26 M/
12 F)
Asarnow & Ben-Meir, 31 (I I M/6 F K-SADS and <13 yr Very poor scores on PAS, Insidious onset in 16 (52%),
1988 schizophrenic, interview means (± SD): schizo- chronic course in
10 M/4 F (DSM-III) phrenics, 4.11 (1.0); less 14 (45°/<,)
schizo typal) premorbid sociability,
much more disturbed
than depressive contrast
group (p < .000 I);
FSIQ = 89.7 (11.99);
VIQ = 92.2 (14.3):
PIQ = 87.2 (10.5)
Watkins et al., 1988 18 (13 M/5 F) DSM-lll and <12 yr 39% infantile autism; 17%
CBCL PDD NOS; 72% severe
language deficits; 72%
developmental motor
abnormalities
Russell et al., 1989 35 (24 Mill F) Semistructured < 12 yr ADHD features, 14 (40%); Behavioral disturbance in
interview conduct disorder, 30 (86%)
(DSM-IIl) 6 (17%); PDD features,
9 (26%); none met full
criteria

Note: Higher PAS scores reflect greater impairment (maximum = 6). Insidious = slow, continuous decline. CBCL = Child Behavior
Checklist; PAS = Premorbid Adjustment Scale; K-SADS = Schedule for Affective Disorders and Schizophrenia for School-Age Children;
FSIQ = Full Scale IQ; VIQ = Verbal IQ; PIQ = Performance IQ: PDD = pervasive developmental disorder; NOS = not otherwise
specified; ADHD = attention-deficit hyperactivity disorder.

discrepancies, "positive" clear symptoms took precedence over
negative statements, and symptoms recorded at the time they were
observed took precedence over recollection.
Prodrome was defined as any new symptoms during the I-year
period before the onset of first psychotic symptoms. All childhood
years before that were considered the premorbid period, the focus
of this study. All measures were not available for every subject,
and a combination of data from available sources (psychological
tests, hospital records, school records, parents' reports, interview
notes) were used, usually giving most weight to positive statements.
Because of the varied amount and quality of information, a diagnosis
of absent/probable/definite was used in denoting the presence or
absence of characteristics.
Establishment of Interrater Reliability
After five practice chart reviews, reliability between the two
psychiatrists was assessed on 10 subsequent charts rated independ-
ently. Interrarer reliability was then checked periodically throughout
the remainder of assessment. Interrarer reliability was calculated
using the K statistic if ratings were on a categorical scale or intraclass
correlation coefficients (ICCs) if on a continuous scale (Bartko
and Carpenter, 1976; Flciss, 198 I). Agreement on the following
variables was excellent: speech (K = .81), attention-deficit hyperactiv-
ity disorder (ADHD) (K = .80), motor development (K = .80),
PDD symptoms (K = 1.0), sociability (ICC = .96), peer relationships
(ICC = .98), interests (ICC = .89), scholastic performance (ICC =
.93), and adaptation to school (ICC = 1.0). Agreement on language,
type of onset, and prodrome was fair to good: language (K = .64),
type of onset (K = .4 I), impulsivity (K .44), and prodrome
(K = .55).
Two reasons may explain the higher K for speech than for
language. Speech disorders were diagnosed if a significant degree
of stuttering, articulation problems, or dysfluencies were described
in the records or clinical interviews. These are somewhat easier to

]. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 34:10. OCTOBER 1995 1275

ALAGHBAND-RAD ET AL.

TABLE 2
Basis for Ratings of Prodromal Behavioral Status for 23 Childhood-Onset Schizophrenics
Data Source/Number Available
Speech &
Psychiatric School Language Hospital Parent
Measure/Diagnosis Testing Reports Evaluation Records Interview D!CA AD! PAS K-SADS

IQ 7 16
Developmental
milestones 20 21 22
Specific develop-
mental disorders 21 7 20 23 23
Disruptive behavior
disorders 21 20 23 23
Pervasive develop-
men tal disorders 21 20 23 22
Social development 21 23 23 22 23
Prodrome 21 20 23 23

Note: Type of onset (acute, subacute or insidious) was rated on the basis of all available charts, records, and past interviews. DICA =
Diagnostic Interview for Children and Adolescents; ADI = Autism Diagnostic Interview; PAS = Premorbid Adjustment Scale; K-SADS =
Schedule for Affective Disorders and Schizophrenia for School-Age Children.

specify and code than the results of the language testing, which
included some contradictory findings and discrepant test results
which were not simple to interpret.
PREMORBID PERIOD
Developmental Milestones
Developmental milestones were examined through the Autism
Diagnostic Interview, medical, and educational records and other
parental reports. Where sources conflicted, data were rated as
missing. The Denver Developmental Screening Test (Frankenburg,
1969) was used to determine developmental milestones (below
l Oth percentile was considered a significant delay).
Premorbid IQ
Test scores were available for seven patients; for cases where
more than one premorbid IQ test was available, the highest score
was used. Where repeated IQ scores and/or other indices of
cognitive level were available, the data were scrutinized for evidence
of intellectual deterioration. In other cases intelligence estimates
were based on school performance using the scale developed by
Kydd and Werry (1982): level 1 and 2 = above average intelligence,
level 3 = average, level 4 to 7 = below average.
Social Development
Premorbid social functioning, assessed using the PAS, was based
on information from the patient, the patient's family, and previous
records. In the PAS, "prernorbid" is defined as the period ending
6 months before evidence of overt psychosis. It has four sections
(childhood, up to 11 years), early adolescence (12 through 15
years), late adolescence (16 through 18 years), and adulthood (19
years and older). Norms are provided for each age group from a
large normarive database but only for total score, and without
standard deviations. The appropriate premorbid life periods are
rated using this scale regardless of the present age of the subject.
Thus, for this study, only the childhood section was used. There
is a 7-point scale for each item (0 through 6 = normal-severely
impaired); individual items were social withdrawal (as defined by
avoidance of social interaction and social contexts, i.e., a reduction
in the rate of interpersonal interaction), peer relationships, interests,
scholastic performance, and school adaptation. Finally, an overall
PAS score was generated by adding the scores for each item and
dividing this sum by the number of items rated. Premorbid
impulsivity was rated separately using items in the DleA, which
reflect items 4, 5, and 12 of criterion A from the DSM-III-R
ADHD criteria. These were difficulty awaiting turn in games or
group situations, blurting out answers to questions before they
had been completed, and not listening to what is being said to
him or her. A -i-poinr scale was used representing 3, 2, 1, or no
items endorsed.
Specific Developmental Disorders
Speech and Language Disorders. Psychological reports, school
records, and medical records were examined by two psychiatrists to
determine the presence or absence of language disorders, including
expressive, receptive, or speech and articulation disorders. Full
DSM-III-R criteria were required for "definite" diagnosis. For those
with definite diagnoses, the following IQ and language tests were
available: Verbal subscale ofWISC (seven cases), Token Tests for
Children (two cases), Clinical Evaluation of Language Fundamen-
tals-Revised (three cases), Experience One Word Picture Vocabulary
Test (two cases), Peabody Picture Vocabulary Test-Revised (five
cases), Structured Clinical Interview for DSM-III-R (one case),
Developmental Sentence Analysis (one case), Carrow Receptive
Language Test (one case), Test of Language Development (one
case), Test for Auditory Comprehension of Language-Revised (one
case), Bankson Language Screening (one case), Boston Naming
(one case), One Word Receptive Picture Vocabulary Test (one
case), Test of Problem Solving (one case), and Language Screening
Test (one case). Cases had a mean number of 3.5 tests (range, 1
through 5).

1276 J. AM. ACAD. CHIl.D ADOl.ESC. PSYCHIATRY, 34:10, OCTOBER 1995


Motor Ski lls Disorder. Cri terion A of DSM-IIl- R develop ment al
co ordi na tio n d isor der was used :"The person's performan ce in daily
acriviries req uiri ng m ot o r coordination is marked ly below the
expected level, given th e person 's chro no logical age an d int ellect ual
capac ity . T his may be man ifested by ma rke d del ays in achieving
mo to r mil eston es, d rop pin g th ings, clu msiness, poor perform an ce
in sports , or poor handw riti ng." Reports by pa rents or reach ers of
suc h prob lems were take n as diagnostic.
Academic Skills Disorders. T hree school record ite ms were exam-
ined : repe titio n of a grade before o nset of psych oti c sym ptoms,
p laceme nt in a specia l ed ucation class or assign me nt to specia l
classes, and any test-based reports of specific learn ing disabilities
such as readin g, ar ithmetic, etc .
Premorbid Pervasive Developmental Disorders
Selected parts of the Autism Diagnostic Interview (commun ica-
tio n, soc ial development and play, int erests and behaviors) and all
availab le charts 'and records were exam ine d. C hildren with a histo ry
of PO D sym pto ms were classified by whe the r they met th e full
DSM- IlI-R criteria for PO D (t hree criteria) or met two of the
th ree DSM-IIl-R crit er ia for POD. Those meeting one criteria for
POD m ost typ ically exhib ited stereo typy, echo lalia, or Rapping.
Disruptive Behavior Disorders
ADHD. Medical, psychological, and school records were exam-
ined as well as scor es for D IC A-P. T he di agnosis of AD HD was
mad e using DSM -IlI-R criteria (Ame rica n Psych iat ric Associa-
tion, 1987).
Conduct D isorder. Pare nt and Child DI CA sections on disrup tive
behavior d isord ers were exami ned and teachers' comments were
recorded whe n available: C h ild ren were co nsidered to have had
co nduct disorder features if any th ree of th e DSM -IlI-R co nd uct
disor der criteria were m et up to 1 year befo re the o nset of
psych oti c sym pto m s.
PRODROME
Sym p to ms during th e yea r before o nset of psychotic symptoms
were evalua ted using th e p rodrome section of the K-SAD S w ith
respect to withdrawal, school pe rfor ma nce , markedly peculiar be-
havior , impaired hygiene, blunted or ina pprop riate affect, vagu e/
digressive speech or pov erty of speech, odd or magical thinking,
od d perceptual experiences, and marked lack of initiative. C ha rts
were also reviewed to evaluate oppositional or negativistic beh avior
versus socia l wi thdrawal or inhibitio n.
TYPE OF ONSET
T ype of o nset was classified by the two rating psych iatr ists as
subacut e (6 months or less between change from baseline, i.e.,
in itial no nspec ific sym p toms to first psychotic symp to ms) or insid i-
ous (more th an 6 m onths between change fro m baseline to first
p sych otic sy m p to m s) , Co urse of ill" ess wa s ra te d as epi sodi c if
charac terist ic psycho tic sym pto ms (such as delusions, hallucinat ions,
or for ma l th ou ght disorder) had ever occ urred in discrete ep isode s
lastin g 6 months or lon ger.
ADULT STUDIES
All available stu dies of the childhood o f adul t schi zop h ren ics
w ith at least so mewhat compa rab le measures were selected . Me thod-
ologica lly, these varied co nsiderably and no ne had pr ecisely compa-
rable ch ild hoo d beh avioral measures.
j . AM , ACAD, CHILD AD O L ESC . PSYC H IAT RY, 34:10. O C T O BE R 19 9 5
C H ILD HOOD-ON SET SC H IZO P HREN IA
RESULTS
T he premorbid and prod romal histories of 23 pa-
tient s (males: n = 15, mean = 14. 5 ± 1.5; females:
n = 8, mean = 13.9 ± 1.8) with a mean age on
adm ission of 14.3 (± 1.8) years (range, 10 to 19 years)
are summarized in T able 3. T he gro up had considera ble
premorbid develop mental delay and psychop ath ology,
in keeping with other reports of premorbid develop -
ment in childhoo d schizop h renia .
Statistical Analysis
Chi-square, Student's t test, or paired t test were
used to compare groups or child/adult-onset studies
differences, depending on th e distribution of th e vari-
ables. Spearman or Pearson correlations were used to
examine the relation ships amo ng variables.
Developmental Milestones
Delays, as repo rted retros pectively, were seen for
one quarter to one half of the subjects. There were
more delays for crawling in males (t = 10.0 , P = .04).
Delays were most striking for language development,
since 9 (43%) of th e 2 1 for who m dat a were available
had had prominent delay; th e mean age of first sente nce
was 26 .5 months (±7.4) , which is significantly delayed
compared with the adult cases in Jones and cowo rkers'
(1994) repo rt (t = 6.30 , P < .000 1), alth ough it is
not clear whether we had the exact comparable data.
Early developmental delays in talking had no significant
relationship to IQ as obtained for 17 subj ects on
admission to the NIMH (r = - .25, P = not signifi-
cant [NS]).
Premorbid IQ
T he mean prepsychotic Full Scale IQ score, available
for only seven pat ient s, was 87.7 (25.4), wit h a range
of 64 to 134, which correspo nds to borderlin e to low-
normal range of IQ and is significantly lower than
Offord's (1974) report (X 2 = N S, P < .000 1). T he
m ean sco res on the Ve rba l a nd Performance su bs ca les
were 86.83 (29.1) and 93.42 (19.0), respectively. For
th e 16 cases witho ut premorbid IQ tests, school per-
form ance-based inte lligence estimate s showed low-n or-
mal IQ as a rule. For those who had both pre- and
postp sychot ic IQ test ing, multiple test ing between
high est prem orb id IQ and NIMH IQ revealed no
consistent cognitive decline. (Prepsychotic mean = 87.7
1277
ALAGI-lBAND-RAD ET AL.
[25.4], postpsychotic mean = 83.7 [17.3], paired t= .77,
P = .48.) Further assessment of pre- and postpsychotic
language tests for seven subjects, with particular atten-
tion to reading or vocabulary subscales, also did not
suggest significant cognitive decline.
Social Development
The mean overall total PAS score was 2.33 ± 1.60.
The total norm for this age group is 0.23.
The mean for impulsivity was 0.86 ± 1.17 and
there were no sex differences (p = NS). Approximately
half the sample had significant impulsivity (see below
and Table 3), and approximately half were relatively
withdrawn and asocial.
Specific Developmental Disorders
Speech and Language Disorders. Ten (43%) patients
had definite and two (9%) had probable histories of
articulation disorders. All 12 cases had articulation
delays (failure to use developmentally expected speech
sounds), and stuttering was recorded for two. Using
DSM-III-R criteria, expressive, receptive, or mixed re-
ceptive/expressive language disorders were found in
eight patients (33%). Of these, three had mixed re-
ceptive/expressive, four expressive, and one receptive
language disorders. In addition, two patients had proba-
ble language disorders. Comparison with a large pro-
spective study of the childhood of a community-based
adult sample Oanes et al., 1994) showed a significant
delay in spoken language for our group (t = 6.3, P
< .0001).
Motor Skills Disorder. Using criterion A of the DSM-
III-R, coordination disorder, significant symptoms were
recorded for six cases (27%), while two (9%) had
probable histories of motor disorder. All had signifi-
cantly delayed motor milestones. Two had difficulty
with handwriting, one had poor performance in sports,
and one was identified as very clumsy.
Academic Skills Disorders. Twelve patients (52%) had
repeated at least one grade before the onset of psychotic
symptoms, which was not significantly different from
Offord's (1974) report. Fifteen cases (65%) had had
placement in special education classes, and specific
learning disabilities had been diagnosed in seven (30%)
patients: reading for three (13%) and arithmetic for
four (17%).
Pervasive Developmental Disorders
Nine (36%) patients had had at least some feature
of POD: three (13%) patients met full criteria for
1278 J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 34:10, OCTOBER 1995
infantile autism, one (4%) had met two of three, and
four (17%) had met one of three criteria for infantile
autism (Table 3). Of great interest were the transient
motor features of POD, namely hand flapping (5 cases),
head banging (1 case), and hand flicking (1 case).
Children with any features of POD were more likely
to be male (X 2 = 7.2, P < .01), to have insidious onset
(X 2 = 8.6, P = .003), and to have more developmental
motor delays (X 2 = 6.8, P = .03). Thus, as expected,
children without a history of autism or autistic features
were less abnormal premorbidly.
Disruptive Behavior Disorders
Seven (30%) patients were considered to have had
definite AOHO and two (9%) had met criteria for
conduct disorder.
Type of Onset/Prodrome
As reported in other childhood studies, insidious
onset was most frequent; 15 patients (62%) had insidi-
ous onset of psychosis, whereas in 8 (35%) the onset
was subacute. Only one (possible) case was rated as
episodic in course.
A variety of prodromal symptoms were indicated
by the K-SAOS. Scores from the prodrome section of
the K-SAOS (a dichotomous scale) for 17 subjects
were as follows: withdrawal, 65%; impaired school
performance, 65%; markedly peculiar behavior, 59%;
impaired hygiene, 29%; blunted/inappropriate affect,
71 %; vague/poverty of speech, 47%; odd/magical
thinking, 35%; odd perceptual experience, 35%; and
marked lack of initiative, 53%.
The change in behavior indicated by previous clinical
records during the prodrome (that is, during the year
prior to the onset of psychotic symptoms) similarly
showed 10 (43%) patients to have exhibited opposi-
tional or negativistic behavior. Social withdrawal or
inhibition was also recorded in 10 (43%) patients. In
3 (13%) there had been no change.
Summary of Childhood Findings for NIMH Sample
In general, as seen in Table 3 the present sample
showed quantitative and qualitative abnormalities simi-
lar to those in previous reports on very early onset
schizophrenia (no statistical differences were found
by X2 analysis). Delayed milestones were prominent,
particularly for language. In agreement with other
pediatric studies, transient early symptoms of POD
had been common.
 CHILDHOOD-ONSET SCHIZOPHRENIA

TABLE 3
Premorbid Developmental Milestones, Developmental Disorders, and Psychiatric Disorders for 23 Childhood-Onset Schizophrenics
Age Reached Milestone Percent with Delay
Age at First: Mean (SO) Range (>95% on DDST) Comments

Smile (wk) 7.0 (5.2) 1-16 38 (7/18)

Sit (rno) 6.9 (1.9) 5-12 38 (8/21)
Crawl (mo) 8.44 (2.8) 5-12 37 (7/19) Delays for crawling more in males
(p = .04)
Walk (mo) 13.05 (2.5) 10-18 17 (4/23) Greatest delays for language
Words (mo) 17.55 (7.6) 6-36 48 (10/21) Similar to Kolvin et al. (197 I) and Watkins
ct al. (1988) showing major
developmental delay, including speech
and language
Sentence (rno) 26.55 (7.4) 12-36 43 (9121)

Developmental Definite Probable Total

Disorders" No. (%) No. (%) No. (%) Comments

Speech disorders 10 (43) 2 (9) 12 (52) Comparable to Kolvin et al. (I 971), who
found 46% (16/33) (X' = NS)
Language disorders 8 (35) 2 (9) 10 (43) 72% reported by Watkins et al. (1988)
(X' = NS)
Motor coordination disorder 6 (27) 2 (9) 8 (36) 72% reported by Watkins er al. (1988)
(X' = NS)
Specific learning disability 7 (30) No data given in other studies
Reading 3 (13)
Arithmetic 4 (17)
Repeating a grade 12 (52) 12 (52)
Special educational 15 (65) 15 (65)
placement

Psychiatric Definite
Disorder No. (%) Probable Comments

ADHD 7 (30) 7 (30%), 6 were male

Conduct disorders
POD
Met full criteria
Met two criteria
Met one criterion
2 (9) 10 (43%) had any disruptive behavior
disorder; Russell et al. (1989) reported
40% ADHD and 17% conduct disorder
8 (35%) had had any autistic fearurcs,
3 (13) comparable to Russell et al, (1989), who
1 (4) found 26% with "features" or Watkins ct
4 (17) al. (1988), wirh 39% having met full
criteria

Note: DDSI' = Denver Developmental Screening Test; NS = not significant; ADHD = attention-deficit hyperactivity disorder; POD =
pervasive developmental disorder.
"Ten (43%) had at least one definite premorbid developmental disorder.

Comparison with Childhood of Adult-Onset
Schizophrenics
Table 4 shows a highly condensed summary of
childhood studies of later-onset schizophrenia with
comparison to the present study.
The present data would indicate a more severe
premorbid course for childhood-onset cases. Most in-
teresting is how this is true for only some measures.
For example, the lack of cognitive deterioration seen
in our sample is similar to findings in adult-onset
schizophrenia (Goldberg and Weinberger, 1988).
In general, girls had better premorbid histories than
boys and less insidious onset, consistent with findings
in adults. However, unlike reports in adults, there were
no statistical differences between girls and boys on
social maladjustment as measured by the PAS and

]. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 34:10, OCTOBER 1995 1279

ALA GHBAND -RAD ET AL.

TABLE 4
Child hood Status of Adult-Onset Schizophrenics
Co m pa rison with Premorbid
H istory for N IM H
C h ild hoo d-O nset Schizophrenics
Study Sam ple Me thods Findings (n = 23)

O fford, 1974 116 (51 MI65 F) Schoo l records Rep eating a grade 32%; mean Repeating a grade 52% (Xl =
FSIQ = 92.65 N S); mean FSIQ = 87.7
(p < .000l)
Wan & Luben- 54 (27 M/27 F) School records M ean IQ = 102.86. M ales: em o- No sex differences for impulsiv-
sky, 1976 (age 15-34) tionall y unstable in grades i ry (Xl = N S); special class:
7-12; fema les: introverted, 65% (selective difficulties with
crno rio nally u nst able and pas- math and read ing)
sive in kindergarten-grade 6
(earlier than expect ed); learn -
ing difficu lties based on grad es
(especia lly ma th)
W alker & Lew- 5 Siblings Home movies from C ompared ro nonpsychotic sib- N o home mov ies availabl e; mile-
inc, 1990 (4 M Il F) infancy and lings: poor eye contact, less sto ne delays compatible; tran -
(age 17-24 ) child hood positive affect. poorer fine and sient PDD motor may be
gross motor coordination , less similar ph enomena
inte rpersonal responsiveness
Walker er al., 25 Sibl ings Home mo vies from G reater negat ive affecr than sib- N o sex differences for opposi-
1993 (25 M/7 F) infancy and lings, especially for fem ales tion al or negativistic behavior
(mea n agc: childhood (Xl = N S)
34 ::!: 6.27)
Jones et al., 1994 30 (20 Mil 0 F) Pro spective data Late mi lestones (walking and W alkin g 13.1 (t = N S); talk ing
from British talkin g with d ifference s in 26.5 (t = 6.30; P < .000 1)
1946 birth co- means 1.2 months):
hort (N = 5.362) walkin g (mea n) = 14.7 mo;
ralking (mean) = 15.5 rn a
Done cr al., 1994 33 (20 M/ 13 F) Prospective data Age 7: more social maladjust- N o gender differences for with -
from Brit ish ment than controls (p < .0 1); dr awal (Xl = NS ); o nly moder-
1958 cohort male: overreaction > ate withdrawal prob lem s for
(N = 15,398 underreaction group
in 1965) (F = 3.2, P = .02) (F = 12.1,
P < .001)
Note : N IM H = N ational Institute of Mental Health; FSIQ = Full Scale IQ; PDD = pervasive developmental disor der; N S = not
significant.

ratings of wit hdrawn/oppositional behaviors. In con-
trast to reports on adults, three reports of childhood-
onset schizophrenia (including this study) find a
substant ial minority of cases to have had at least one
symptom of PDD, although none met criteria for
PDD at the time of the study. Such observation was
not noted for any adult-onset studies. Furthermore,
the majority of childhood cases appear to have had
insidious onset, without episodic course , in contrast
to first-episode adult cases (Lieberman et al., 1993).
Although we did not find the same severe premorbid
poor adjustment using the PAS as did Asarnow and
Ben-Meir (1988) , our data indi cate significant premor-
bid social maladjustment in this population compared
with at least first-episode adults (e.g., Lieberman er al.,
1992), altho ugh PAS scores are not directly comparable
across studies.
DISCUSSION
These findings support and extend previous reports
on the preps ychotic development of very early onset
schizophrenia. A more chronic course, more typically
insidious onse t, more severe abnormalities in language

1280 J. AM . ACAD. CH IL D AD O LESC . PS YCH IAT RY. 34 :1 0 , O C T O BE R 19 9 5


and motor development, and a high proportion of
clinically significant premorbid psychiatric disorders
appear more characteristic of childhood-onset cases.
Evidence of disruptive behavior disorders in 43% of
children, school performance problems and learning
disabilities in almost 50%, language difficulties in about
50%, and mean IQ in the borderline to low-average
range are consistent with other studies.
The comparison with adult-onset schizophrenia (Ta-
ble 4) is of interest. Where quantification is available,
particularly for the prospective studies of Jones et al.
(1994) and Done et al. (1994), the findings indicate
greater premorbid abnormalities in childhood-onset
schizophrenia, most notable for delays and abnormalit-
ies in speech and language development, for specific
learning disabilities and disruptive behavior disorders.
Only a minority of our cases were not a focus of
clinical concern before the onset of psychosis. This,
together with the chronicity and severity of childhood
cases (Gordon et al., 1994), indicates that childhood-
onset schizophrenia may be a more malignant form
of the disorder. However, selection and ascertainment
biases together with our small sample make these
conclusions tentative.
The somewhat focused areas of greater severity such
as language abnormalities may be indicators of left
brain dysfunction, appearing earlier in development
(David, 1994; McGuire et al., 1993; Watkins et al.,
1988). We did not, however, have sufficient informa-
tion to further characterize the pattern of preschizo-
phrenia language difficulties. Clinically premorbid
patterns of language development may be of great
predictive value for later psychosis. Diagnostic evalua-
tion of childhood schizophrenics should attempt careful
characterization of underlying speech and language
abnormalities.
A particularly intriguing finding, consistent across
three of six studies, is that symptoms of POD occur
premorbidly in childhood-onset schizophrenia (Russell
et al., 1989; Watkins et al., 1988). The possible conti-
nuity between schizophrenia and autism has been a
matter of controversy in the past (Cantor et al., 1982;
Petty et al., 1984), but in general the two are well
established as distinct disorders (Volkmar et al., 1988;
Volkmar and Cohen, 1991). The present findings raise
the possibility that at least some transient forms of
POD features may reflect a more severe early brain
insult, and in fact the motor abnormalities seen in our
J. AM. ACAD. CHILD ADOLESC. PSYCHIATRY, 34:10, OCTOBER 1995
CHILDHOOD-ONSET SCHIZOPHRENIA
sample may be an exaggerated form of the transient
abnormalities described by Fish (1984; Fish et al.,
1992) for high-risk infants who later became schizo-
phrenic and by Walker et al. (1994a,b) based on home
movies. It is tempting to speculate that our early-onset
cases suffered more severe early brain insult so that
these transient disturbances were more striking and
came to clinical attention. Alternatively, the retrospec-
tive nature of the adult studies may have obscured
such early history, while the present study used parent
interviews and the Autism Diagnostic Interview to
obtain such data more systematically than is likely in
most studies of later-onset cases. Diagnostically, it is
clear that early transient "POD" should not preclude
a later diagnosis of childhood-onset schizophrenia.
A number of methodological limitations make these
conclusions tentative. Because of the rarity of schizo-
phrenia in childhood, these patients were recruited by
national search and, in fact, more than 100 children
referred as schizophrenic were seen in person to identity
these 23 cases. Thus we cannot evaluate the selection
bias inherent in this study. Because these cases were
referred for participation in an inpatient trial of cloza-
pine offered to nonresponders to typical neuroleptics
(Frazier et al., 1994), only more severe cases would
have been referred. Just as important, retrospective
studies of later-onset schizophrenia either did not or
could not obtain the detailed childhood records avail-
able for very early onset cases. It is unclear, therefore,
whether the increased rate in childhood cases reflects
ascertainment and/or recording bias. In spite of this,
our findings agree with those of previous reports from
groups that were not carrying out extensive inpatient
evaluation or drug treatment (Russell et al., 1989;
Watkins et al., 1988), indicating similar high chronicity
and high rate of premorbid disorders when compared
to later-onset subjects.
In conclusion, as expected, patients with childhood-
onset schizophrenia have a more disturbed premorbid
history as a group, particularly as evidenced by the
presence of speech and language disorders. The major
findings, however, highlight the similarity in develop-
mental pattern for childhood and later-onset disorder.
Ongoing neurobiological studies including quantitative
magnetic resonance imaging will seek evidence of more
severe CNS alteration or evidence of precocious brain
development for these unexplained vety early onset
cases.
1281
A I.AC HBAN D-RA D ET At.
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