The association between early parental loss and diagnosis in the Iowa 500.

While a number of studies have found an association between the experience of death of a parent during childhood and the later development of depression as an adult, few of these studies have controlled for possible confounders such as social class, sibship size, parental age at birth, and the patient's age at admission. The results of several studies that do control for such confounders have been negative. The authors investigated the frequency of parental loss and parental death among 129 depressives, 155 schizophrenics, and 63 manics from the Iowa 500 data base. Using a logistic regression to control for confounders, depressives are found to experience early maternal death 3.4 times more frequently than the schizophrenics and 2.1 times more frequently than the bipolars. The failure to confirm other hypotheses and possible implications are discussed.

The reliability of the family history method for psychiatric diagnoses.

We evaluated the test-retest interrater reliability of the Family History Research Diagnostic Criteria (FH-RDC) in 58 depressed patients who described 341 first-degree relatives. Reliability was examined as a function of the threshold to determine caseness. In general, diagnostic reliability was good-excellent for specific FH-RDC disorders, but not for the residual category of other psychiatric disorder. A higher diagnostic threshold was associated with greater reliability, especially for the diagnosis of depression. Patient variance accounted for a greater percentage of the disagreements between the interviewers than did rater variance.

The validity of four definitions of endogenous depression. II. Clinical, demographic, familial, and psychosocial correlates.

Based on a survey of the classic literature and studies examining the correlates of a clinical diagnosis of endogenous or nonendogenous depression, we found 14 variables that should discriminate endogenous and nonendogenous depressives. We applied four definitions of endogenous depression (Feinberg and Carroll, DSM-III, Research Diagnostic Criteria, and Newcastle) to a consecutive series of 152 unipolar major depressive inpatients. We examined the concordance between the definitions and the relationship between each definition and clinical, demographic, family history, and psychosocial factors. The DSM-III and Newcastle definitions were less inclusive than the other two definitions. We found some support for the validity of each of the four definitions. The validity of the Newcastle scale was the most frequently supported, with the endogenous depressives having a lower rate of personality disorder, marital separations and divorces, familial alcoholism, life events, and nonserious suicide attempts.

A structured interview for the DSM-III personality disorders. A preliminary report.

With few exceptions, published studies fail to indicate that the DSM-III personality disorders can be distinguished from each other with respect to etiology, prognosis, treatment response, or family history. The Structured Interview for the DSM-III Personality Disorders (SIDP) was developed to improve axis II diagnostic reliability, and hence allow validity testing of axis II. Sixty-three subjects were independently rated by two interviewers using the SIDP. The kappa coefficients for interrater agreement reached .70 or higher for histrionic, borderline, and dependent personalities. While it is impossible to separate the validity testing of the SIDP from validity testing of the DSM-III personality criteria themselves, preliminary results from 102 inpatient SIDP interviews suggest some criterion-based validity with respect to standard personality rating scales and some construct validity with respect to the dexamethasone suppression test.

Methodologic issues in maintenance therapy clinical trials.

In the early 1980s, the National Institute of Mental Health supported a multicenter, randomized, controlled, clinical trial on unipolar and bipolar disorder to evaluate the comparative efficacies of lithium carbonate, imipramine hydrochloride, a lithium-imipramine combination, and placebo in preventing the recurrence of affective disorders. The objective of this report is to present a reanalysis of the relative efficacies of these treatments in patients with unipolar disorder to focus attention on general issues related to the design and conduct of maintenance therapy trials. We show that the earlier conclusions of that study that imipramine and the combination therapy are more effective than lithium and placebo in preventing the recurrence of depression in unipolar patients can be accounted for by alternative explanations that are a consequence of the design of the study. Our findings have important implications for the design, conduct, and interpretation of results of maintenance therapy clinical trials in general.

Diagnosing personality disorder in depressed patients. A comparison of patient and informant interviews.

Personality disorder (PD) diagnosis were made in 66 depressed patients based on independent interviews of the patient and a close informant. The patients and informants markedly differed in their descriptions of the patients' normal personality. The kappa coefficient of agreement for the diagnosis of any PD was .13, and all kappa values for the individual PD diagnoses were below .35. Informants reported more pathologic conditions than the patients, such that PDs were diagnosed in 57.6% (38/66) of the patients, based on the informant interview, and in 36.4% (24/66), based on the patient interview. We also examined dimensional scores. In general, we found only modest correlations between the patient and informant dimensional scores and that the ratings based on the informant interviews were higher. These results varied by specific PD diagnoses. Consensus ratings, which were based on both sources of information, were sometimes more strongly associated with patient information and sometimes with informant information, and this, too, varied among the different PDs.

The Great Smoky Mountains Study of Youth. Functional impairment and serious emotional disturbance.

BACKGROUND: Federal regulations require states to estimate the prevalence and incidence of serious emotional disturbance (SED) in children, defined as a DSM-III-R diagnosis in the presence of impaired functioning in 1 or more areas. We reviewed the published data on SED and examined rates and correlates of SED in an ongoing epidemiologic study of children. METHODS: Rates of DSM-III-R disorders, functional impairment, and their co-occurrence (SED) were examined in a representative population sample of 9-, 11-, and 13-year-olds from a predominantly rural area of North Carolina. Three measures of functional impairment were used, and their interrelationship and impact on rates of SED were examined. RESULTS: Serious emotional disturbance was identified in 4% to 8% of the study population, depending on the measure of impairment; the rate of DSM-III-R disorder ignoring impairment was 20.3%. One quarter of children identified as having SED on any measure were identified by all 3, and one half by 2 or more. Behavioral disorders, emotional disorders, and comorbidity were associated with a significant increase in the likelihood of SED; enuresis and tic disorders in the absence of comorbidity were not. Diagnosis and impairment made independent contributions to the increase in service use seen in children with SED. Poverty greatly increased the likelihood of SED. CONCLUSIONS: Specific areas of functional impairment should be examined when SED is assessed and treatment is planned. Plans to target mental health care resources to children with SED need to be accompanied by efforts to ensure access to those resources.

The Great Smoky Mountains Study of Youth. Goals, design, methods, and the prevalence of DSM-III-R disorders.

BACKGROUND: The Great Smoky Mountains Study of youth focuses on the relationship between the development of psychiatric disorder and the need for and use of mental health services. METHODS: A multistage, overlapping cohorts design was used, in which 4500 of the 11758 children aged 9, 11, and 13 years in an 11-county area of the southeastern United States were randomly selected for screening for psychiatric symptoms. Children who scored in the top 25% on the screening questionnaire, together with a 1 in 10 random sample of the rest, were recruited for 4 waves of intensive, annual interviews (n = 1015 at wave 1). In a parallel study, all American Indian children aged 9, 11, and 13 years were recruited (N = 323 at wave 1). RESULTS: The 3-month prevalence (+/-SE) of any DSM-III-R axis I disorder in the main sample, weighted to reflect population prevalence rates, was 20.3% +/- 1.7%. The most common diagnoses were anxiety disorders (5.7% +/- 1.0%), enuresis (5.1% +/- 1.0%), tic disorders (4.2% +/- 0.9%), conduct disorder (3.3% +/- 0.6%), oppositional defiant disorder (2.7% +/- 0.4%), and hyperactivity (1.9% +/- 0.4%). CONCLUSIONS: The prevalence of psychiatric disorder in this rural sample was similar to rates reported in other recent studies. Poverty was the strongest demographic correlate of diagnosis, in both urban and rural children.

Photoaffinity labeling of rat calcitonin gene-related peptide receptors and adenylate cyclase activation: identification of receptor subtypes.

Different biological effects of calcitonin gene-related peptide (CGRP) analogs have suggested receptor subtypes. Here we have investigated molecular forms of rat CGRP receptors, ligand binding, and activation of adenylate cyclase. A single class of [125I]alpha-human (h)CGRP binding sites was identified in rat cerebellum, liver, and spleen, with dissociation constants of 206 +/- 70 pM, 128 +/- 23 pM, and 229 +/- 64 pM (mean +/- SEM), respectively. Competition experiments showed the same rank order of displacement of [125I]alpha-hCGRP binding in all the tissues examined with rat alpha-CGRP approximately alpha-hCGRP approximately beta-hCGRP > alpha-hCGRP(8-37) > [acetamidomethyl-Cys2,7]alpha-hCGRP > human amylin > salmon calcitonin. Photoaffinity labeling of CGRP receptors using [125I][C gamma-(4-azidoanilino)Asp3]alpha-hCGRP revealed specifically labeled 71-kilodalton (kDa) binding proteins in the cerebellum, brainstem, and spinal cord, of 74 kDa and 68 kDa in the liver, and of 75-90 kDa in the spleen. Enzymatic N-deglycosylation converted the labeled binding proteins into a common 48-kDa form (44 kDa with the molecular mass of the photoligand subtracted). In the presence of 100 microM guanosine-5'-O-(3-thiotriphosphate), the dissociation constant of [125I]alpha-hCGRP binding remained unchanged in the cerebellum but was increased 3-fold in the liver and spleen, suggesting interaction with GTP-binding proteins. In accordance with these results, adenylate cyclase was stimulated by CGRP in the liver and spleen, but not in the cerebellum and brainstem. Furthermore, the linear analog [acetamidomethyl-Cys2,7]alpha-hCGRP enhanced cAMP formation in the liver but not in the spleen. In conclusion, rat CGRP receptors with tissue-specific N-glycosylation but indistinguishable protein molecular mass have been identified in the cerebellum, brainstem, spinal cord, liver, and spleen. Activation of adenylate cyclase by CGRP in the liver and spleen, but not in the central nervous system, and by the linear analog [acetamidomethyl-Cys2,7]alpha-hCGRP in the liver alone provide evidence for CGRP receptor subtypes.

Body weight and reported versus measured weight loss as confounders of the dexamethasone suppression test.

We examined the association between post-dexamethasone suppression test (DST) serum cortisol and body weight, self-report of weight loss during the episode, and measured weight loss during the first week of admission in a series of 245 depressed inpatients. Data on measured weight loss between two successive admissions was available in a group of 57 depressed inpatients. Reported weight loss during the episode and measured weight loss during the first week of admission were not related to DST nonsuppression. In contrast, DST nonsuppression was significantly more frequent in patients with measured weight loss between two successive admissions. This association was particularly strong in patients with below-average body weight and was practically nonexistent in patients with above-average body weight. Multivariate analysis indicates that a significant association between DST results and weight loss may be missed if self-report is substituted for direct measurement of weight loss and if potential confounders, such as total body weight, age, and sex, are ignored.

The validity of DSM-III axis IV (severity of psychosocial stressors).

One hundred thirty depressed inpatients were rated on DSM-III axis IV on the basis of information collected from a comprehensive life events interview. Axis IV scores were more highly correlated with undesirable than desirable events, with exits than entrances, and with time-limited than chronic events. Higher axis IV scores were associated with a lower rate of abnormal dexamethasone suppression test results, a higher morbid risk for alcoholism, a greater frequency of personality disorders, and a greater likelihood of attempted suicide during the index episode.

The prognostic validity of DSM-III axis IV in depressed inpatients.

DSM-III suggests that axis IV should have prognostic value--that patients with higher scores will have a better outcome than patients with low ratings. The authors used axis IV to assign scores to 130 depressed inpatients and examined these scores in association with the patients' course during the index hospitalization and at 6-month prospective follow-up. Higher axis IV scores were associated with more depressive symptoms on hospital discharge, but they did not predict follow-up outcome. These results are consistent with other studies of the prognostic value of ratings of psychosocial stress and indicate that, at least for depression, there is little empirical support for DSM-III's suggestion that stress is a favorable prognostic sign.

ECT response in depressed patients with and without a DSM-III personality disorder.

Twenty-five inpatients with DSM-III major depressive disorder received ECT and were interviewed with the Structured Interview for DSM-III Personality Disorders. Patients with and patients without a personality disorder had similar short-term responses to ECT. The results of a 6-month prospective follow-up showed that depressed patients with a personality disorder were significantly more symptomatic and eight times more likely to be rehospitalized.

Prognostic validity of self-report and interview measures of personality disorder in depressed inpatients.

Presence of personality disorders was assessed with the Structured Interview for the DSM-III Personality Disorders (SIDP) in a series of 78 nonpsychotic inpatients with major depression. Measures of severity of depression were administered at admission, at discharge, and 6 months after admission. Outcome for the depression was especially poor in patients meeting criteria for multiple personality disorders from multiple DSM-III clusters. A subgroup of 38 patients received both the SIDP interview and a self-report measure of personality disorder, the Personality Diagnostic Questionnaire. Depressed inpatients who met more than the median number of personality disorder criteria by either measure were approximately half as likely to show improvement at discharge and at 6-month follow-up than were patients with less than the median number of criteria.

Assessment of DSM-III personality disorders: the importance of interviewing an informant.

The Structured Interview for DSM-III Personality Disorders was used to interview 82 patients. In addition, a close relative or friend of the patient was interviewed regarding each patient's normal personality. After the informant interview, the diagnosis of the presence or absence of any personality disorder was changed in almost 20% of the sample. In general, the information given by the informants revealed additional pathology in the patients and was less frequently used to retract a diagnosis. Despite conflicting information from the patients and informants, the reliability of personality disorder assessment remained high.

Comparison of a calcitonin gene-related peptide receptor in a human neuroblastoma cell line (SK-N-MC) and a calcitonin receptor in a human breast carcinoma cell line (T47D).

A specific CGRP-binding protein of M(r) 60,000 has been identified in the human neuroblastoma cell line SK-N-MC. After N-deglycosylation a M(r) of 48,000 was found. The M(r) were indistinguishable from those determined in the human cerebellum. Receptor binding of CGRP is coupled to cyclic AMP formation. The latter is antagonized by hCGRP-I8-37. CT and DAPamide interact only minimally with the CGRP receptor, whereas CGRP and DAPamide are full agonists in T47D cells. The CT receptor on human breast cancer cell line T47D is clearly different from the human CGRP receptor.

Children's mental health service use across service sectors.

This DataWatch explores the roles of human service sectors (mental health, education, health, child welfare, and juvenile justice) in providing mental health services for children. The data are from the first wave of the Great Smoky Mountains Study of Youth, a population-based study of psychopathology and mental health service use among children. The results show somewhat higher rates of mental health service use than has been reported previously, while continuing to show a substantial amount of unmet need, even among children with both a psychiatric diagnosis and functional impairment. The findings point to a significant role for the education sector, suggesting that schools may function as the de facto mental health system for children and adolescents.

An introduction to survival analysis: statistical methods for analysis of clinical trial data.

The randomized controlled clinical trial (RCT) is a prospective study using random assignment of subjects to treatment groups to compare the effect and value of a therapeutic intervention against a control. The RCT is the most definitive clinical research tool for evaluating the efficacy of a new therapy in human subjects. Often the outcome of interest in an RCT is the length of time until an event occurs after treatment or intervention. In this article we introduce statistical methods for evaluating differences in the patterns of time to response between two groups of subjects to determine whether one therapy is better than another. The collection of methods for analyzing such data, known as survival data, is called survival analysis. Using data from a hypothetical clinical trial for the prevention of the recurrence of depression, we illustrate two elementary methods for analyzing survival data. We also discuss generalizations of these methods to incorporate covariates and conclude with a general discussion of clinical trials of psychiatric therapies.

The implications of DSM-III personality disorders for patients with major depression.

We studied 78 inpatients with DSM-III major depression. Forty-one (53%) had a concurrent personality disorder (PD) according to a detailed structured interview for DSM-III personality disorders. The patients with depression plus PD differed from patients with depression alone on numerous measures. The PD patients had earlier onset; higher HRS scores; poorer social support; more life stressors; more frequent separation and divorce; more frequent nonserious suicide attempts, less frequent dexamethasone nonsuppression; poorer response to antidepressant medication; and higher risk for depression, alcoholism and antisocial personality among first-degree relatives. The PD subgroup shares many attributes with Winokur's subtype of depression spectrum disorder and Akiskal's character spectrum disorder. An attempt to identify a subgroup of personality disorders which might be an atypical affective disorder was inconclusive. However, patients in DSM-III cluster III were similar to the patients with no-PD on the dexamethasone suppression test, response to treatment, and familial risk for depression and antisocial personality.

Four definitions of endogenous depression and the dexamethasone suppression test.

We examined the relationship between the DST and 4 definitions of endogenous depression: DSM-III, Feinberg and Carroll, Newcastle and RDC. Endogenous patients had a significantly higher rate of nonsuppression than nonendogenous patients according to the DSM-III and Newcastle definitions but not according to the RDC and Feinberg and Carroll criteria. Moreover, the relationship between the DST and the DSM-III and Newcastle definitions was significant even after individually controlling for age, psychosis and weight loss. We review the literature on the relationship between the DST and the RDC definition of endogenous depression and suggest that interstudy differences in criteria application may be partially responsible for the inconsistent results across studies.