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I. Methods, Diagnosis of Probands, and Risk of Schizophrenia in Relatives

Kenneth S. Kendler, MD; Mary McGuire, MB, MRC Psych; Alan M. Gruenberg, MD; Aileen O'Hare, M Soc Sc; Mary Spellman, MB, MRC Psych; Dermot Walsh, MB, FRCPI

Arch Gen Psychiatry. 1993;50(7):527-540.

Abstract
Objectives
We sought to examine, in a rural county in the West of Ireland, the degree of familial relationship between schizophrenia and other nonaffective psychoses and affective illness (AI).

Design
A case-controlled epidemiologic family study using DSM-III-R criteria.

Participants
This study incuded three proband groups: (1) all cases with a clinical diagnosis of schizophrenia from the Roscommon County Case Register born from 1930 onward (n=285); (2) a random sample of cases from the register with a clinical diagnosis of severe AI (n=99); and (3) a matched, random sample of Roscommon residents ascertained from the electoral register (n=150). Face-toface structured interviews were conducted with 86% of traceable, living relatives (n=1, 753) and 88% of traceable, living probands (n=415).

Results
In interviewed relatives, the lifetime risks (±SE) for schizophrenia, as a function of the "blind" proband di- agnosis, were as follows: schizophrenia, 6.5% ± 1.6%; schizoaffective disorder, 6.8%±2.5%; schizotypal personality disorder, 6.9%±3.9%; other nonaffective psychoses, 5.1%±2.4%; psychotic AI, 2.8%±1.2%; nonpsychotic AI, 0.6%±0.6%; and control, 0.5%±0.3%. Individuals with schizophrenia reproduced at a rate about one quarter that of controls and the risk for schizophrenia in parents of probands was much less than that found in siblings.

Conclusions
These results support the following hypotheses: (1) in the West of Ireland, as in other populations, schizophrenia is a strongly familial disorder; (2) schizophrenia shares a familial predisposition with a spectrum of clinical syndromes that includes schizoaffective disorder, other nonaffective psychoses, schizotypal personality disorder, and probably psychotic AI, but not nonpsychotic AI; and (3) the diminished reproductive rates associated with schizophrenia have a large impact on the pattern of risk of illness in relatives.

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