Amann-Zalcenstein et al.
Supplementary Material
Detailed description of family sample and diagnostic methods
Families of Arab Israeli origin with two or more members affected with schizophrenia
were systematically recruited from the catchment area of the Taibe Regional Mental
Health Center1, 2. This clinic serves a population of ~66000 living in adjacent Arab
Israeli towns and villages in the central region of Israel. The project was approved by
the Helsinki Committee (Internal Review Board) of the Hadassah - Hebrew University
Medical Center and written informed consent was obtained from all subjects. For the
present study, one nuclear family was selected from each family with more than one
branch included in the genome scan or recruited subsequently, based on having the
largest number of affected offspring and at least one parent, preferably both, recruited.
Including the families recruited subsequent to the genome scan, the sample available to
us for family based association studies consists of 53 families (190 individuals with DNA
of whom 85 are affected); 34 are “triad” families (affected proband plus both parents)
while 19 families have 2 or more affected offspring (10 with 2 affecteds, 6 with 3
affecteds, 2 with 4 affecteds and 1 with 5 affecteds). Of these 19 families, 10 have both
parents recruited and 9 have one parent recruited (plus one or more unaffected
siblings).
To establish psychiatric diagnosis, subjects were interviewed with the Schedule
for Affective Disorders and Schizophrenia- Lifetime Version (SADS-L)3 and were
questioned about psychiatric symptoms in the family according to the Family History
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Research Diagnostic Criteria (FH-RDC)4. Medical records of hospitalizations and clinic
care were obtained for affected individuals. The completed SADS-L interview form, FHRDC information and medical records were reviewed by two experienced members of
the research team and, in cases where consensus was not achieved, by the principal
investigator (BL). Lifetime diagnoses were established according to the Research
Diagnostic Criteria (RDC)3 and the Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition (DSM-IV)5 using a best estimate consensus procedure6. All
diagnostic evaluations were completed without knowledge of the genotyping data. For
the genome scan and fine mapping, three diagnostic categories were employed –
broad, core and narrow1, 2. For the present study, only the broad category was
employed because this category consistently yielded the strongest results in the
genome scan and subsequent fine mapping and in order to reduce the extent of
correction for multiple testing. In the current sample (termed TKT) this category
encompassed 65 subjects affected with schizophrenia (44 probands and 21 affected
siblings) according to RDC; 17 subjects affected with schizoaffective disorder (9
probands and 8 affected siblings) and 3 siblings affected with unspecified functional
psychosis. Other diagnoses potentially included in the broad diagnostic category are not
in fact represented in the sample.
The replication sample (termed, BT) consists of 209 nuclear families with a total
of 678 individuals, 258 of whom are affected. 177 are trio families; 23 have two
affected offspring, 3 families have 3 affected offspring, 4 families with 4 affected
offspring and there are 2 families with 5 affected offspring. The affected individuals
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were diagnosed with schizophrenia on the basis of interview with the Structured Clinical
Interview for DSM-IV Axis I Disorders (SCID)7 and according to DSM-IV5. This sample is
also of Arab origin, but it is outbred and was recruited from different geographical
regions of Israel and the Palestinian Authority.
In order to insure reliability of diagnoses across the two samples a diagnostic
reliability study was conducted. Ten cases were selected at random from each of the
samples. Selection of cases from the TKT cohort was stratified so as to include cases
with diagnoses other than schizophrenia in their approximate proportion in the sample.
Identically formulated dossiers were prepared that included the SADS-L or SCID
interviews and the additional clinical information available for each subject but not the
best estimate diagnoses. A senior clinician with extensive experience in both semistructured interviews and best-estimate diagnosis received the dossiers and diagnosed
the patients according to DSM-IV criteria. The clinician was not aware of the fact that in
the BT sample, diagnoses were limited to schizophrenia. For both sets of cases there
was complete concordance with the best estimate diagnoses. Thus, reliability of
diagnoses across the two samples is supported by independent assessment.
References for the Supporting Text, Materials and Methods
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Andreasen, N. C., Endicott, J., Spitzer, R. L. & Winokur, G. (1977) Arch Gen
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American_Psychiatric_Association (1994) Diagnostic and Statistical Manual of
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