Quantifying lifetime risk of psychiatric disorder

doi:10.1016/0022-3956(81)90026-1

Journal of Psychiatric Research

Volume 16, Issue 2, 1981, Pages 113-126

https://doi.org/10.1016/0022-3956(81)90026-1 Get rights and content

Abstract

Lifetime risk for a particular psychiatric disorder is the proportion of a given population that would develop that disorder if no unaffected individual died prior to some specified age. Since it is impossible to quantify risk beyond some normal or maximum lifespan, lifetime risk can only be meaningfully considered “as of some particular age t”. In this paper lifetime risk to age t (LTR_t) is defined in terms of a hazard function and its relationship to other possible measures of risk is examined. The commonlly used morbidity risk ratio (MRR_t) is shown to differ from LTR_t; the value of MRR_t depends not only on the hazard function for onset of the disorder of interest but also on mortality among unaffected individuals. LTR_t, MRR_t and two other measures of risk are also compared in terms of the nature of the sample data that are required in order to estimate them. A numerical example illustrating estimation procedures is discussed in detail.

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Methodologic differences between family studies have the potential to significantly affect these estimates. Early family studies relied almost exclusively on family history data, in which diagnostic information is obtained from one or two family informants ( Luxenburger, 1930; Lewis, 1935; Rüdin, 1953; Kringlen, 1965; Rosenberg, 1967; Insel et al., 1983; Rasmussen and Tsuang, 1986); such ascertainment generally underestimates true rates of illness in families (Thompson and Weissman, 1981; Gershon and Guroff, 1984). Furthermore, these early family studies did not include control families for comparison, so their findings must be interpreted with caution.
Obsessive-compulsive disorder (OCD) is present in 1.5–2.5% of the population and can result in substantial lifelong disability. It is characterized by intrusive thoughts, sensations, and urges and by repetitive behaviors that are difficult to control despite, in most cases, preserved insight as to their excessive or irrational nature. The causes and underlying pathophysiology of OCD are not well understood, which has limited the development of new treatments and interventions. Despite evidence for a substantial genetic contribution to disease risk, identification and replication of genetic variants associated with OCD have been challenging. Decades of candidate gene association studies have provided little insight. They are now being supplanted by modern genomewide approaches to discover both common and rare sequence and structural variants. Studies to date suggest potential novel therapeutic avenues such as modulators of glutamatergic and immune pathways; however, individual genetic findings are not yet statistically robust or replicated. Further efforts are clearly needed to identify specific risk variants and to confirm vulnerable pathways by studying much larger cohorts of patients with comprehensive variant discovery approaches. Mouse knockout models have already made notable inroads into our understanding of OCD pathology; their utility will only increase as specific risk alleles are identified.
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In a study of 229 schizophrenic patients for whom reliable family history information was available, ventricular size and incidence of ventricular enlargement were found to be greater in male cases without a family history of schizophrenia. A significant sex by family history interaction on cerebral ventricular dimension was detected. The age-corrected morbid risk for schizophrenia was lower among first degree relatives of male probands with ventricular enlargement vs. those with normal ventricles, but similar in relatives of females with and without ventricular enlargement. On the other hand, no association was found between family history and degree of cortical atrophy. A meta-analysis of published studies on the issue revealed 20% larger ventricles in patients without any known genetic predisposition for schizophrenia.
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This study begins to test the hypothesis that schizophrenic men and women may be at risk for experiencing different subtypes of the illnes. Given past research, hypotheses predict that schizophrenic men will have an earlier age of onset, poorer premorbid history, lower family morbid risk, and poorer course. Data consist of 332 schizophrenic patients diagnosed according to DSM-III and 713 of their first-degree relatives from the double-blind Iowa 500 and non-500 family studies. Survival analysis was used to estimate age of onset, and Strömgren's abridged method for age correction was used to estimate family morbidity risks. Findings support our hypotheses and suggest that men may be at risk for experiencing a more severe form of schizophrenia.
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^☆: This work was supported in part by USPHS Grant No. 1-RO1-MH28274 from the Center for Epidemiologic Studies, National Institute of Mental Health, ADAMHA. Mr. Thompson was supported by Training Grant No. 1-TO1-MH14235, also from the Center for Epidemiologic Studies.

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Quantifying lifetime risk of psychiatric disorder☆

Abstract

J. Chron. Dis.

J. psychiat. Res.

Epidemiology: Principles and Methods

Survival Distributions: Reliability Applications in the Biomedical Sciences

Causal Thinking in the Health Sciences

The Genetics of Mental Disorders

Manic Depressive Illness

Zum Korrektur des Einflusses der Lebensdauer und Todesauslese auf die Ergebnisse bestimmter Kreuzungen

Arch. Rassen-und Gesellschafts-Biologie

Zum Ersatz des Weinbergschen abgekurzten Verfahrens

Z. ges. Neurol. Psychiat.

Estimating ages-of-onset distributions for disorders with variable onset

Am. J. Human Genetics