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Biomedical subjects

J Endicott

Publications and source records attributed to J Endicott.

At least 19 recordsLinked to original sources

Characterization of the hemolysin transporter, HlyB, using an epitope insertion.

The prokaryotic hlyB gene product is a member of a superfamily of ATP-binding transport proteins that include the eukaryotic multidrug-resistance P-glycoprotein, the yeast STE6, and the cystic fibrosis CFTR gene products (Juranka, P. F., Zastawny, R. L., and Ling, V. (1989) FASEB J. 3, 2583-2592). Previous genetic studies have indicated that HlyB is involved in the transport of the 107-kDa HlyA protein from Escherichia coli; however, the HlyB protein has not been purified for biochemical studies due to its low abundance. In this study, we have engineered a monoclonal antibody epitope into the C-terminal end of HlyB that did not destroy its function. This has allowed us to use immunological methods to identify and localize various molecular forms of the HlyB protein present in vivo.

Amino Acid Sequence

Major depression in a nonclinical sample. Demographic and clinical risk factors for first onset.

The relatives, controls, and spouses of affectively ill probands underwent diagnostic examinations on two occasions, 6 years apart. Of 965 subjects who had never been mentally ill when first examined, 11.8% had development of at least one episode of major depression as defined by the Research Diagnostic Criteria during the ensuing 6 years. Subjects younger than 40 years were three times more likely than older subjects to develop depression and women were approximately twice as likely as men to develop depression regardless of age. Marital disruption, a farm setting, and high educational achievement substantially increased the risk of depression among female subjects. Of 214 never-depressed subjects with a history of nonaffective mental disorder, 62 (29.0%) developed major depression. Age and sex were again powerful determinants. The course of prospectively observed secondary depression was more severe than that for primary depression.

Adult

Rapidly cycling affective disorder. Demographics, diagnosis, family history, and course.

Of 919 patients with major affective disorders who completed at least 1 year of a 5-year, semiannual follow-up, 45 developed a rapidly cycling bipolar course during the first year, but only one developed a rapidly cycling unipolar course. In comparison with patients who showed a non-rapidly cycling bipolar course, those who became rapid cyclers were more likely to be female and to have exhibited depression, hypomania, or cycling between depression and hypomania within the index episode. Family study data revealed no evidence that high cycle frequencies breed true. Rapid cycling was associated with a significantly lower likelihood of recovery in the second year of follow-up but not in the third, fourth, or fifth. These data suggest that rapid cycling is, in the large majority of cases, a transient, nonfamilial manifestation of bipolar affective disorder.

Adult

Time to recovery, chronicity, and levels of psychopathology in major depression. A 5-year prospective follow-up of 431 subjects.

The course of illness of 431 subjects with major depression participating in the National Institute of Mental Health Collaborative Depression Study was prospectively observed for 5 years. Twelve percent of the subjects still had not recovered by 5 years. There were decreasing rates of recovery over time. For example, 50% of the subjects recovered within the first 6 months, and then the rate of recovery declined markedly. Instantaneous probabilities of recovery reflect that the longer a patient was ill, the lower his or her chances were of recovering. For patients still depressed, the likelihood of recovery within the next month declined from 15% during the first 3 months of follow-up to 1% to 2% per month during years 3, 4, and 5 of this follow-up. The severity of current psychopathology predicted the probability of subsequent recovery. Subjects with moderately severe depressive symptoms, minor depression, or dysthymia had an 18-fold greater likelihood of beginning recovery within the next week than did subjects who were at full criteria for major depressive disorder. Many subjects who did not recover continued in an episode that looked more like dysthymia than major depressive disorder.

Adolescent

Stability of psychiatric diagnoses. An application to the affective disorders.

In the National Institute of Mental Health Collaborative Program on the Psychobiology of Depression study, data were collected on 2226 first-degree relatives of 612 probands. A second, "blind" reassessment of all relatives was attempted 6 years after the initial evaluation. We report on a final sample of 1629 relatives assessed twice using the Schedule for Affective Disorders and Schizophrenia-Lifetime version. We summarize methods for using stability of diagnosis to model the relationship between clinical covariates and the probability of being a true case. Moreover, we define an index of caseness that can be used to narrow the criteria for who is a case. Of those positive for major depressive disorder at initial evaluation, 74% were positive (on a lifetime basis) at follow-up (ie, were stable). There is a gradient: 48% of those who had three symptoms and no treatment were stable, compared with 96% of those with eight symptoms and treatment. For major depressive disorder, we found the caseness index for those with lifetime mania more severe than that of nonbipolar patients, with those who had hypomania being intermediate. A hierarchical analysis indicated that bipolar I tends to be diagnosed as schizoaffective-manic across occasions, and vice versa. This is consistent with the prior familial analyses that suggest these two diagnoses be combined into a single bipolar phenotype. The analysis for major depressive disorder indicates that caseness appears to represent quantitative, rather than qualitative, differences, with no natural cutoff to identify distinct subgroups. Finally, we discuss implications including utility in genetic analyses, estimation of incidence or prevalence allowing for diagnostic error, and examination of cohort effects.

Adolescent

An extension of the acquaintanceship procedure in family studies of mental disorder.

The acquaintanceship procedure is a method for obtaining a control group matched to relatives of probands on demographic variables. Relatives are asked to name six acquaintances who are the same gender, and who are about the same age and social class as themselves. An acquaintance is randomly selected from this list and contacted for recruitment. Rates of mental disorder in this group are assumed to approximate general population rates in a group with these demographic characteristics. This report focuses on an extension of the acquaintanceship procedure in which "super-normal" controls are used in a family study design. Two questions were addressed: (1) Does the acquaintance group (n = 166), as a whole, show a higher rate of illness than the relatives of acquaintances with no mental disorder (n = 129)? (2) Is there a relationship between mental disorder in acquaintances and in providers of acquaintance names? The prevalence of mental illness was significantly greater among acquaintances compared to relatives of "never ill" acquaintances. There was no evidence of assortative selection. We concluded that using the relatives of well acquaintances is a cost-effective control selection methodology which maximizes the detection of intergenerational transmission in family studies of mental disorder.

Adult

Alcoholism and primary major depression: a family study approach to co-existing disorders.

Alcoholism and major depression appear together at much higher than chance rates, but reasons for this are obscure. We used the direct diagnostic assessment of 177 probands with primary, unipolar depression and 619 of their first degree relatives to explore the significance of concomitant alcoholism. The male relatives of alcoholic probands of both sexes had substantially higher rates of alcoholism than did the male relatives of non-alcoholic probands. Among female probands, but not among male probands, alcoholism was associated with markedly higher familial rates of primary depression, particularly among female relatives. These data contained no evidence that comorbidity itself was familial. The appearance of alcoholism in depressed women may indicate depression spectrum disease, a disorder which manifests as depression in women and alcoholism in men. In contrast, men with both primary depression and alcoholism may be exhibiting two distinct illnesses.

Adolescent

Anxiety syndromes as epiphenomena of primary major depression: outcome and familial psychopathology.

OBJECTIVE: Anxiety symptoms often appear within depressive episodes, but their significance is uncertain. This study sought to determine whether they indicate the coexistence of a separate disease process and whether they have prognostic significance. METHOD: A series of patients with primary depression who entered a follow-up and family study included 37 who also had obsessions or compulsions, 93 who had panic attacks, 101 who had phobias, and 196 who had none of these anxiety syndromes. Each of the overlapping groups defined by the presence of a specific anxiety syndrome was compared to the group that had none of these syndromes with respect to baseline demographic, phenomenological, and historical features, illness rates among directly interviewed relatives, and diagnostic stability and clinical outcome at semiannual follow-ups over a period of 5 years. RESULTS: Depressive symptoms at intake were more longstanding and severe among patients with specific anxiety symptoms, and these patients went on to experience more depressive morbidity during the ensuing 5 years. The development of autonomous anxiety disorders was rare, however, and specific anxiety syndromes in the probands did not increase risks for the corresponding disorders among relatives. CONCLUSIONS: When restricted to episodes of major depression, anxiety syndromes appear to be prognostically significant epiphenomena rather than indicators of an additional disorder.

Adolescent

Behavioral syndromes in Alzheimer's disease.

The Behavioral Syndromes Scale for Dementia (BSSD) is a new instrument that showed strong internal consistency and interrater reliability in an outpatient sample of 106 patients with probable Alzheimer's disease. Factor analysis provided support for a priori symptom groupings, particularly the syndromes of disinhibition and apathy-indifference. Dependency (87%), denial of illness (63%), and motor agitation (55%) were common, while sexual disinhibition (2.9%) and self-destructive behaviors (2.9%) were rare. Virtually all symptoms were predominantly minimal to mild in severity. Patients with longer illness duration were more apathetic. Disinhibited behaviors and apathy-indifference increased with greater severity of dementia. Catastrophic reactions, aggression, and agitation were associated with greater functional impairment. There was great heterogeneity in symptom presentation. In Alzheimer's disease, several behavioral changes might be direct manifestations of underlying brain pathology, rather than being solely secondary to cognitive impairment.

Activities of Daily Living

Predictors of relapse into major depressive disorder in a nonclinical population.

OBJECTIVE: This study sought to describe, the natural history of major depressive disorder in a large group of nonclinical subjects. In particular, the analysis determined demographic and clinical risk factors for the recurrence of major depressive disorder. METHOD: Relatives, comparison subjects (matched to relatives for age and sex), and spouses of affectively ill probands underwent structured clinical assessments before and after a 6-year interval. RESULTS: Of 396 individuals who had had only major depressive disorder that ended before the initial evaluation, 33.8% (N = 134) developed a new episode during the 6-year follow-up period. Youth, but not sex, was an important demographic risk factor. The presence of minor depression at the time of initial evaluation and the number of symptoms recalled from the worst previous episode were additional clinical risk factors. At the initial evaluation, 200 other subjects had described a previous history of both major depressive disorder and a nonaffective mental disorder. When compared to the subjects who recalled only a history of major depressive disorder, these subjects were more likely to have been in an episode of chronic intermittent depression at the initial evaluation and to recall a greater number of episodes as well as a greater number of symptoms in the worst episode. A history of a nonaffective mental disorder significantly increased the risk of relapse into major depressive disorder. CONCLUSIONS: These findings agree well with a recent review of clinically based follow-up studies. Thus, youth and a history of nonaffective illness are important risk factors for the recurrence of major affective disorder in a broad variety of settings.

Adult

Treatment of premenstrual dysphoria with alprazolam. A controlled study.

Thirty women who met DSM-III-R criteria for late luteal phase dysphoric disorder completed a double-blind, randomly assigned crossover treatment study comparing alprazolam with placebo. Alprazolam was found to be superior to placebo. The outcome measures included physicians' global ratings as well as patients' prospective (daily) ratings and retrospective assessments. Improved study design, which addressed methodologic flaws of most previous studies of treatment outcome of "premenstrual syndrome" may account, in part, for our ability to demonstrate significant drug/placebo differences. This includes extensive screening to eliminate women who had premenstrual exacerbations of a more persistent mental illness rather than a discrete premenstrual disorder, use of prospective ratings to confirm retrospective reports of symptom patterns, placebo washout before randomization, and use of patients as their own controls.

Adolescent

Affective syndromes, psychotic features, and prognosis. I. Depression.

Prognosis is an important issue among patients who have psychotic features and a depressive syndrome; some have outcomes that suggest diagnostic revisions to schizophrenia, and this has far-reaching implications for treatment. To explore this issue, we used biannual evaluations to follow up 103 such individuals for 5 years. Patients with Research Diagnostic Criteria schizoaffective disorder experienced substantially more morbidity of various sorts than did patients with Research Diagnostic Criteria psychotic major depression. Within the group with schizoaffective disorder, patients with the chronic subtype experienced more morbidity than did those with nonchronic schizoaffective disorder; the mainly affective--mainly schizophrenic distinction had less prognostic significance. Factors that predicted sustained delusions at the end of follow-up were exclusively historical and suggested a poor-outcome prototype patient who is single, was socially impaired as an adolescent, and has a history of schizophrenialike psychotic features temporarily dissociated from affective symptoms.

Adult

Affective syndromes, psychotic features, and prognosis. II. Mania.

Fifty-six patients with mania and psychotic features and 14 with schizoaffective disorder, manic type, were followed up with biannual assessments during a 5-year period. Results were treated as they were in an analogous follow-up of patients with psychotic major depression or schizoaffective disorder, depressed type. Patients with schizoaffective mania experienced more morbidity during follow-up than did patients with psychotic mania. Among patients with schizoaffective mania, those with a chronic subtype did far worse than did the others, while the mainly schizophrenic--mainly affective distinction was not predictive. When depressed and manic groups were combined (n = 173), the following baseline variables were significant independent predictors of a sustained delusional outcome: longer duration of the index episode, temporal dissociation between psychotic features and affective symptoms, and impaired adolescent friendship pattern.

Adult

Relationship between premenstrual symptoms and general well-being.

Data on the general well-being and premenstrual symptoms of military wives were collected on two occasions one year apart. The women's general well-being and premenstrual symptoms were highly correlated on both occasions, but an even higher correlation was found between the presence of premenstrual symptoms at time 1 and the presence of premenstrual symptoms at time 2. Further analyses revealed that women with higher scores on general well-being and premenstrual symptoms were older and reported fewer cognitive depressive symptoms than women with lower scores on general well-being and premenstrual symptoms. At the one-year follow-up, the women with lower scores on general well-being who complained of premenstrual symptoms were more depressed than those who did not.

Adolescent

The impact of phenotypic variation on genetic analysis: application to X-linkage in manic-depressive illness.

Genetic linkage studies have opened new vistas for behavioral and psychiatric genetics. However, phenotypic diversity and diagnostic uncertainties can lead to spurious linkage findings. A method of analysis is proposed that takes these factors into account. When applied to manic-depressive disease, the results indicate that previous evidence for a major gene localized on the distal long arm of the X-chromosome cannot be ascribed to phenotypic uncertainties and misclassifications, i.e., a type I error. Although the lod score (the logarithm of odds) favoring linkage is reduced with the more restrictive clinical definitions of the phenotype, it remains significant nonetheless. Thus, the linkage finding is robust over a range of phenotypic patterns and presumed phenocopy frequencies. The results also suggest that the X-linked phenotype is a particularly severe form of manic depression characterized by early onset, high familial prevalence of the bipolar form, and high recurrence rate of major depression. These findings may have important implications for the design and interpretation of genetic linkage studies and for refining diagnostic techniques in mental disorders.

Adolescent

Premenstrual depression predicts future major depressive disorder.

To assess the power of premenstrual changes as a risk factor for future major depressive disorder (MDD), we conducted a follow-up study of 36 women who had volunteered for menstrual cycle studies. Scores on the depressive subscale of the Premenstrual Assessment Form (PAF) at initial evaluation were found to be significantly correlated (r = 0.35) with the occurrence of MDD during the follow-up period. Moreover, multiple regression analysis indicated that the PAF scores had predictive value above and beyond 2 known risk factors for MDD, family history of depression and prior personal history of depression. The Premenstrual Change Index, a score derived from prospective daily self-ratings of severity of dysphoric symptoms, was also correlated with interval MDD, but did not enhance the predictive power of the PAF score. We conclude that the assessment of premenstrual depression has validity in identifying women at risk for future MDD, even when a retrospective instrument, PAF, is utilized for such assessment.

Adult

The natural history of alcohol abuse: implications for definitions of alcohol use disorders.

Is the DSM-III-R category of alcohol abuse validly differentiated from the DSM-III-R category of alcohol dependence, or is abuse primarily a mild, prodromal condition that typically deteriorates into dependence? A 4-year longitudinal epidemiologic study of male drinkers provided data to answer this question. The study used identical questions at baseline and follow-up. At follow-up, 70% of the subjects who were initially classified as alcohol abusers were still abusers or were classified as remitted. This contrasted significantly with outcome in the subjects who initially reported alcohol dependence. Although additional research is needed, these results indicate that alcohol abuse often has a course distinct from that of alcohol dependence.

Adult

Outcome of patients with chronic affective disorder: a five-year follow-up.

Patients with major depression, mania, or schizo-affective disorder that had been present without remission for 2 years or more at intake (N = 129) were followed prospectively for 5 years, as were 580 patients who had been ill for shorter periods at intake. Despite very substantial durations of episode, three-quarters of the chronic patients recovered, although recovery occurred much later in the follow-up period than it did among the nonchronic patients. Factors associated with recovery were less severe illness at intake, lack of psychotic features, good friendship patterns in adolescence, and, most important, a relatively high maximum level of functioning in the 5 years preceding intake.

Adolescent