A Follow-up and Family Study of Schizophrenia Samuel B. Guze, MD; C. Robert Cloninger, MD; Ronald L. Martin, MD; Paula J. Clayton, MD \s=b\The Washington University Psychiatry Clinic, St Louis, study began with the systematic clinical evaluation of a cross section of 500 of the clinic's patients. This was followed by a "blind" follow-up of the index subjects and a blind study of first-degree relatives. This report deals with the diagnosis of schizophrenia at index, at follow-up, and among the first- degree relatives. The results indicate that the criteria used for the diagnosis of schizophrenia select patients who show a high degree of diagnostic consistency over many years, al- though not all patients who meet these criteria after follow-up receive the diagnosis of schizophrenia initially. Most impor- tant, the diagnostic criteria select cases associated with a strong familial increase in the risk of schizophrenia (nearly fivefold). The follow-up results indicate also that Feighner- positive schizophrenics often experience intercurrent depres- sions, but that the presence of such depressions does not affect the familial incidence of either schizophrenia or primary affective disorders. (Arch Gen Psychiatry 1983;40:1273-1276) This is a report of a long-term follow-up and family study of schizophrenia, part of a larger investigation of pa¬ tients attending the Washington University Psychiatry Clinic, St Louis, carried out under "blind" conditions. Different persons studied the patients at index and at follow-up and examined the patients' first-degree relatives. Thus, the follow-up and family studies were performed without any knowledge of the findings in the other compo¬ nent or of the findings at index. The overall investigation was designed to evaluate and improve diagnostic criteria for a variety of psychiatric disorders by studying longitudinal course and by identifying patterns of illness in close rela¬ tives of index cases. For many years, we and other colleagues have been concerned with the need to develop widely accepted, valid diagnostic criteria for psychiatric disorders that could be used for research or other purposes, so that all could know with greater confidence which patients were observed or studied. The specific aim has been to identify maximally homogeneous samples. Such specific criteria, including those used in this study, were therefore developed with the deliberate goal of maximizing specificity (ie, reducing false- positives) while keeping sensitivity as high as possible (ie, keeping false-negatives low). In this report, we deal specifically with a number of questions concerning schizophrenia, including the validity of certain diagnostic criteria as measured by consistency of diagnosis over time and the pattern of illness in first-degree relatives and the significance of intercurrent episodes of depression. SUBJECTS AND METHODS Selection of Subjects The selection of the 500 index subjects has been described elsewhere. It was designed to identify and study a representative cross section of outpatients attending the Washington University Psychiatry Clinic. These patients were identified and studied initially during a period of 28 months, from July 1, 1967 to Nov 1, 1969. Information concerning the initial description and psychi¬ atric evaluation of these patients' conditions has been presented in a number of previous publications.1"20 The 1,249 interviews of first-degree relatives were performed between 1969 and 1973. We intended initially to interview an average of three first-degree relatives for each index case. As the number of completed relative interviews grew, progressively greater time and effort were required to locate and interview additional relatives. This led to the decision to stop before the full 1,500 interviews had been achieved. (It appeared as though it might take another two years to interview another 250 relatives.) The follow-up interviews were carried out from 1973 to 1979, Table 1.—The Diagnosis of Schizophrenia Definite Schizophrenia Course Onset before age 35 yr (only applied at index, not at follow-up) One of following must be present: Insidious onset of symptoms over period of at least 6 mo Definite deterioration of social function over period of at least 1 yr Never returned to premorbid level of social function between episodes Positive findings: must have 2*: Hallucinations Delusions Massive passivity Massive catatonic symptoms Thought disorder Silly, senseless behavior that interferes with communication; not manic Negative findings: should not have: Disorientation Marked perplexity about symptoms History allowing diagnosis of alcoholism or addiction beginning at least 2 yr before schizophrenic symptoms Documented family history of affective disorder (not used in family or follow-up study) Affective symptoms (not used in family or follow-up study) Allowing diagnosis of depression More than 1 of cardinal symptoms of mania: hyperactivity, euphoria, flight of ideas Observe caution when there are pronounced affective symptoms whether or not criteria are met for affective disorder Probable Schizophrenia Chronic, progressive disorder characterized by insidious onset, poor prepsychotic adjustment, prominent delusions or hallucina¬ tions, severe disability in interpersonal relationships and job perform¬ ance, minimal, if any, affective symptoms, and clear sensorium, but not meeting criteria for definite schizophrenia 'Originally, a documented family history of schizophrenia was included. It was dropped early in the index study and was not used in the family study or follow-up. Accepted for publication Aug 16, 1983. From the Department of Psychiatry, Washington University School of Medicine (Drs Guze and Cloninger), St Louis, and the Jewish Hospital of St Louis (Dr Cloninger). Dr Martin is now with the University of Kansas Medical Center, Kansas City, and Dr Clayton is now with the University of Minnesota, Minneapolis. Reprint requests to Department of Psychiatry, Washington University School of Medicine, 4940 Audubon Ave, St Louis, MO 63110 (Dr Guze).