A national plan for schizophrenia research: panel recommendations. Research resources.
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Biomedical subjects
Publications and source records attributed to J Endicott.
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Suicidal behavior is a relatively common and serious problem in those with alcohol and drug problems. We compared demographic and clinical characteristics of 123 alcohol rehabilitation patients with and without a history of suicide attempts, using the Schedule for Affective Disorders and Schizophrenia-Lifetime version. Younger age was significantly related to suicide attempts, as were drug disorders, panic attacks, antisocial symptoms, and alcohol-related problems such as violence, withdrawal symptoms, and personal or occupational loss. Untreated suicide attempts were characterized by less serious suicidal intent and medical threat to life. However, alcohol- or drug-abusing individuals who have not sought treatment for suicidal behavior but who continue to drink or use drugs may be at special risk for completed suicide.
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We examined the relationship of major depression, aspects of antisocial personality disorder, family history of alcoholism, treatment history, and onset of alcohol problems to the severity of alcohol dependence and severity of social/occupational problems due to alcohol. Subjects were 111 randomly sampled patients in alcohol rehabilitation. The predictor variables formed different patterns of relationships with alcohol dependence and with social/occupational problems. Implications of the findings for future research are discussed.
A modified version of the Premenstrual Assessment Form (PAF) was administered to 737 military wives as part of a study of stress and well being. A factor analysis of the responses suggests three main subtypes of premenstrual change--hostile depressive, atypical depressive, and anxious--as well as two minor subtypes--organic and hypomanic. Demographic and psychosocial correlates of factor scores are discussed.
Ninety-one patients with panic attacks limited historically to depressive episodes had more severe depressive symptoms and were less likely to recover during a 2-year follow-up than 417 depressed patients who did not have panic attacks. Family study data clearly distinguished another 15 patients with panic disorder and secondary depression; interviewed relatives of panic disorder patients were significantly less likely to have primary depression and significantly more likely to have various anxiety disorders. These data support the hierarchical system by which many of the contemporary diagnostic systems separate panic disorder and major depression.
Family history was examined to determine whether suicide in index patients is associated with suicidal behaviour or mental disorder in their first-degree relatives. Twenty-seven suicides occurred within 5 1/2 years among 955 affectively disordered probands. Among 5042 proband relatives aged 18 years and older, 44 had committed suicide prior to proband entry to the study; however, only one was the relative of a proband suicide. Only two of the relatives who committed suicide were themselves related. As to attempted suicide of relatives, neither the number of attempts nor the severity of attempt was predictive of suicide in probands. Comparison of diagnosis between groups of relatives showed more drug abuse among relatives of proband suicides; this appears to be related to drug abuse among the proband suicides themselves. In contrast to the clustering of suicides within biological families found in other research, these data do not support the use of family history as a clinically useful indicator of suicidal potential in affectively disordered probands.
Concerns about cocaine dependence are increasing, in some ways replacing heroin as the focus of highest concern. We compared cocaine and heroin dependence by levels of cocaine and heroin use in poly-drug users. While dependence indicators differed markedly between regular and sporadic users of these drugs, cocaine dependence indicators did not differ from heroin dependence indicators. Implications of the findings are discussed.
We classified 123 alcohol rehabilitation patients by their histories of lifetime psychiatric comorbidity, and examined the demographic, social, occupational, treatment, and familial variables characterizing the groups. Diagnostic assessments were made with the SADS-L/RDC. High lifetime prevalences of major depressive disorder and drug use disorder were found. Aspects of treatment history distinguished between patient groups with and without lifetime major depression, but not other personal or familial variables. Patients with lifetime drug use disorders were younger and experienced an earlier onset of alcohol problems and treatment. Those with numerous childhood antisocial symptoms were younger, more likely to be male and unmarried, and less educated, and they had presented earlier for treatment. Subjects with two or more adult antisocial symptoms which occurred when subjects were not drinking or using drugs had a significant increase in family history of antisocial personality disorder. However, adult antisocial behaviors which were not separated from the effects of alcohol or drug use were unrelated to a family history of antisocial personality disorder. Implications of these findings are discussed.
Women who report premenstrual dysphoric changes are more likely to have had prior (and are at increased risk for subsequent) episodes of major depressive disorder than are women who do not experience these changes. Women who are currently depressed tend to have premenstrual exacerbations or changes in their symptoms. During the premenstrual period, there is an increased likelihood of suicidal, aggressive, or impulsive behavior and for admission to a psychiatric facility. The authors discuss the possible influence of menstrual cycle phases on the evaluation and treatment of women by investigators and therapists.
As part of the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2225 first-degree relatives of 612 probands. We analyzed 187 families of bipolar patients (149 probands with a diagnosis of bipolar I disorder and 38 with a diagnosis of schizoaffective, manic subtype). Using traditional genetic methods, the morbid risk of bipolar illness in relatives was found to be 5.7% in the relatives of bipolar probands as contrasted with 1.1% in the relatives of probands with major depression. These values compared closely with those obtained using survival analysis. Relatives of probands with early onset were found to have a greater risk than relatives of probands with late onset. The sex of the relative, the sex of the proband, or the subtype of the proband (bipolar I or schizoaffective bipolar) did not influence the risk in the relative. The age at onset was found to be accelerated with birth cohort, with individuals born in more recent cohorts having an earlier onset. Multifactorial analysis found significant heterogeneity for sex-specific sibling correlations (with the brother-sister correlation smaller than the same-sexed correlations), and path analysis estimated transmissibility of liability to be 71%. The mixed model, which allows for a single major locus with a multifactorial background, gave evidence for the presence of a major locus when controlling for the effects of birth cohort and age at onset. However, this evidence is tempered when comparing the mixed model with a more general transmission model.
We examined familial rates of affective disorder and related illness in a cohort of 955 probands studied at five centers in the National Institute of Mental Health Collaborative Study of the Psychobiology of Depression: Boston, Chicago, Iowa City, New York, and St. Louis. Six hundred sixteen of these probands were entered into a family study, and 3423 of their first-degree relatives were evaluated. The probands were divided into five diagnostic groups: schizoaffective-bipolar (n = 37), schizoaffective-depressed (n = 18), bipolar I (n = 151), bipolar II (n = 76), and unipolar (n = 330). The relatives of bipolar I probands had a higher rate of bipolar I illness than the relatives of unipolar probands, but the relatives of unipolar probands did not have a higher rate of unipolar illness than the relatives of bipolar I probands. The relatives of probands with schizoaffective disorder, depressed subtype, had a higher rate of schizophrenia than the relatives of schizoaffective-bipolar probands, suggesting that bipolar schizoaffective disorder may be closer to pure affective disorder while schizoaffective depression may be closer to schizophrenia. An increase in bipolar II illness was also observed in the relatives of bipolar II probands. Overall, these data support the widely accepted distinction between bipolar and unipolar affective disorders.
The Longitudinal Interval Follow-up Evaluation (LIFE) is an integrated system for assessing the longitudinal course of psychiatric disorders. It consists of a semistructured interview, an Instruction booklet, a coding sheet, and a set of training materials. An interviewer uses the LIFE to collect detailed psychosocial, psychopathologic, and treatment information for a six-month follow-up interval. The weekly psychopathology measures ("psychiatric status ratings") are ordinal symptom-based scales with categories defined to match the levels of symptoms used in the Research Diagnostic Criteria. The ratings provide a separate, concurrent record of the course of each disorder initially diagnosed in patients or developing during the follow-up. Any DSM-III or Research Diagnostic Criteria disorder can be rated with the LIFE, and any length or number of follow-up intervals can be accommodated. The psychosocial and treatment information is recorded so that these data can be linked temporally to the psychiatric status ratings.
Afternoon continuous plasma levels of 3-methoxy-4-hydroxyphenylglycol (MHPG) were first shown to be a good representation of the mean 24-hour plasma level of MHPG in 18 normal subjects. Then, after the stability of the procedure was tested and retested, the afternoon continuous test for plasma MHPG levels was performed in 57 normal subjects and 42 endogenously depressed patients. A significant correlation between plasma MHPG levels and age was found in normal subjects and depressive patients. When the variable of age was taken into account, a distinct pattern of increasing plasma MHPG levels with age--the "MHPG per age"--was found in the depressed patients, especially the women, who could be divided into high or low MHPG per age groups. There was almost no association between plasma levels of MHPG or MHPG per age values and clinical symptoms, and the two biologic subgroups did not differ clinically.
Analyses of data from the NIMH-CRB Collaborative Depression Study on age at onset of Major Depressive Disorder (MDD) in 1144 directly interviewed siblings of patients with major affective disorder show a strong secular trend toward increased lifetime risk and earlier onset in successive cohorts of birth since 1930. The proportionate increases in the instantaneous probabilities (hazard) of onset of MDD for each one year difference in year of birth were 5% for brothers and 7% for sisters. Age-period-cohort analysis suggests a powerful period effect may be responsible for this secular trend in rates of MDD, with rates of onset for siblings between 15 and 50 years of age doubling between the 1960s and 1970s. Possible artifacts are investigated.
A difficulty in the interpretation of the reliability/stability of a lifetime diagnosis of mental disorders is the lack of a theoretical perspective. A model expressed in terms of the three unknowns--sensitivity, specificity and true base rate--is problematic due to the lack of a "gold standard", so that only two of these unknowns can be estimated. We extend this model to allow for clinical covariates that increase the likelihood that a positive case at time 1 will be positive at time 2. Under the assumption that all observed cases are true cases at the highest covariate values, we obtain a direct estimate of the sensitivity, so that all unknowns can be estimated. Moreover, we then calculate the likelihood that an observed case with given covariate levels is in fact a true case. The implications of diagnostic error for the estimation of incidence and population rates and the fitting of genetic models are given. These methods are applied to stability data collected as part of the NIMH Psychobiology of Depression Program. A total of 982 relatives have been assessed with interviews separated by a 6 year interval. A logistic function was used to model the stability in 264 relatives with an initial lifetime diagnosis of Major Depressive Disorder. The significant covariate predictors in a step-wise analysis were the number of depressive symptoms in the worst episode, the number of episodes and receiving medication for the worst episode. The sensitivity was estimated to be 0.918 and the specificity was estimated to be 0.940.(ABSTRACT TRUNCATED AT 250 WORDS)
This is a study of the familial transmission of Primary Major Depressive Disorder in the families of 235 probands with this disorder ascertained as part of the NIMH-CRB Collaborative Depression Program. Eight hundred and twenty-six interviewed first degree relatives and 109 spouses are included. Research Diagnostic Criteria have been used and interviews were done using the SADS-L schedule. Prior analyses of these data have established the presence of strong secular trends in the age-of-onset and prevalence of Major Depressive Disorder in these families. Accordingly, new methods for the analysis of family data which incorporate secular variation were developed. Non-parametric Survival Analysis, using the Cox Proportional Hazards Model, guided the formulation of a quantitative family transmission model. Then a family analysis was conducted with the Multifactorial Model of Disease Transmission and the Tau Path Analytic Model. Using the non-parametric approach, only the sibs birth cohort, sex and affectational status of the mother were significantly related to the time of onset of illness in siblings. Proband sex, age-of-onset, and the presence of illness in the father were not significant. The quantitative analysis confirmed that more recently born cohorts of individuals had an increased expected lifetime prevalence and a decreased age-of-onset of Primary Major Depressive Disorder. Assortative mating was present and environmental factors common to siblings did not make a significant contribution to the phenotypic variance. Sex specific transmissibilities were found and the transmissibility in females (t2 = 0.62) was significantly greater than that of males (t2 = 0.28). There was a trend for the transmissibility of Primary Major Disorder to be greater in more recently born cohorts.
We investigated the nosology of endogenous depression by numerical taxonomy. Five hundred and sixty-nine patients diagnosed as having unipolar major depressive disorder in the NIMH Clinical Research Branch Program on the Psychobiology of Depression-Clinical were studied. Thirty-six symptoms which might distinguish endogenous from non-endogenous depressions were chosen from the literature. Patients' symptom profiles assessed by structured interview were grouped by two methods: a K-means improvement of Ward's method of cluster analysis, and a latent class algorithm. The methods produced very similar groups and several internal validity criteria suggested that the groups were not spurious. Cluster 1, 'nuclear depression,' included a nucleus of patients common to multiple definitions of endogenous depression. The non-nuclear group scored as less neurotic than the nuclear group on personality tests administered during the index episode. The groups do not differ in frequency, number or severity of reported life events prior to onset of the index episode. The nuclear group shows a poor prognosis on two-year prospective follow-up, greater disturbance on personality inventories, and increased heritability of depression in siblings.