CONCORDANCE OF AGE AT ONSET AND OTHER CORE CLINICAL CHARACTERISTICS IN SIBLINGS WITH SCHIZOPHRENIC PSYCHOSIS.Yakir A, Kanyas K, Karni O, Turetsky N, Lerer B.Biological Psychiatry Unit, Hadassah -Hebrew University Medical Center, Jerusalem, Israel Linkage analysis of affected sibling pairs is a core strategy in current efforts to establish the molecular genetic basis of schizophrenia. The samples studied generally include probands and affected siblings with schizophrenia (SCZ), schizoaffective disorder (SA) and unspecified functional psychosis (UFP) (according to Research Diagnostic Criteria) or SCZ, SA and schizophreniform disorder according to DSM-IV. This strategy presupposes a shared genetic basis for SCZ, SA and UFP (or schizophreniform disorder). If this is so, it is reasonable to assume that probands and affected sibs with any one of the above diagnoses will resemble each other in core clinical characteristics of their illness. One such characteristic is age at onset of the illness. To explore this question, we have studied 72 pairs of siblings made up of subjects affected with SCZ (n=94), SA (n=47) or UFP (n=3) according to Research Diagnostic Criteria (RDC). Diagnoses were based on semi-structured clinical interview using the Schedule for Affective Disorders and Schizophrenia - Lifetme Version (SADS-L), Family History Research Diagnostic Criteria (FHRDC) and medical records. Data for each individual were also entered into the OPCRIT program. Diagnoses were established by a best estimate procedure taking into account all sources of information. Of the 72 pairs of siblings, 34 pairs (47.2%) were concordant for SCZ and 12 pairs (16.7%) were concordant for SA. 26 pairs (36.1%) were discordant for diagnosis. Age at onset was defined in three different ways: 1) as the age at which the subject first received psychological treatment of any type (AFPT), 2) from the OPCRIT Age at Onset Item (Onset_A), and, 3) as Age at First Psychiatric Hospitalization (AFPH). Considering the entire group of 72 affected sibling pairs, there was no significant correlation for AFPH but there was a trend for AFPT (r=.22, p=.07) and Onset_A (r=.22, p=.06) to be related. When the analyses were confined to sibling pairs concordant for diagnosis (SCZ-SCZ or SA-SA) the relationship between sib pairs for all the variables reflecting age at onset became significant (AFPT r=.34, p=.02; Onset_A r=.36, p=.02; AFPH r=.40, p=..02) while there was no relationship for any of the variables between sibs discordant for diagnosis. We are currently examining concordance of these affected sib pairs for other clinical characteristics including factors derived from the OPCRIT items. Findings from all these analyses will be tested on a separate sample of affected sibling pairs. Our preliminary results for age at onset suggest that concordance of sib pairs for clinical attributes is significantly influenced by concordance for diagnosis. Inclusion of sib pairs discordant for diagnosis (i.e. SCZ-SA, SCZ-UFP or SA-UFP pairs) in linkage analyses could be one factor that contributes to the great variability observed between samples in the results of such analyses. (Supported by the German Israel Foundation for Scientific Research). 
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