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Biomedical subjects

W H Coryell

Publications and source records attributed to W H Coryell.

17 recordsLinked to original sources

Major depression and personality disorder.

The authors examined an interview and paper-and-pencil assessment of the DSM-III personality disorders (PDs) in depressed inpatients, and depressed relatives of psychiatric patients and never-ill controls who had a lifetime history of major depression. The rates of PDs according to the Structured Interview for DSM-III Personality Disorders (SIDP) were similar in the two groups, except for borderline PD which was more frequent in the inpatients. Of the individuals with a PD, the patients were more likely than the relatives to have two or more PDs, and the borderline and histrionic patients were more prototypic of these disorders than were the borderline and histrionic relatives. In contrast to the SIDP results, the rates of PDs according to the Personality Disorders Questionnaire (PDQ) were higher in the patient sample. These results thus extend the previously described high rates of PDs in depressed patients to a sample of individuals with a lifetime history of treated or untreated depression, and they suggest that interview assessments of personality may be less sensitive to the state effects of depression than are questionnaires.

Adult

Diagnosing personality disorders in the community. A comparison of self-report and interview measures.

The rapidly expanding empirical study of personality disorders is the result of the publication of operational diagnostic criteria in DSM-III and the development of instruments to assess these criteria. Few researchers have examined the comparability of measures of personality disorders, and to our knowledge there are no studies of the factors associated with discordance between measures. In the present study, 697 relatives of psychiatric patients and healthy controls were interviewed with the Structured Interview for Personality Disorders (SIDP) and completed the Personality Disorders Questionnaire (PDQ). Significantly more individuals had a personality disorder according to the SIDP; however, multiple personality disorders were more frequently diagnosed on the PDQ. Schizotypal, compulsive, dependent, and borderline personality disorders were significantly more frequently diagnosed by the PDQ, whereas the SIDP more frequently diagnosed antisocial and passive-aggressive personality disorder. The corresponding dimensional scores of the two measures were all significantly correlated; however, the concordance for categorical diagnoses was poor. Discrepancies between the PDQ and the SIPD dimensional scores were significantly associated with current level of depressive symptoms and PDQ lie scale scores.

Adult

Reduced haloperidol plasma concentration and clinical response in acute exacerbations of schizophrenia.

Twenty-nine hospitalized patients suffering acute exacerbations of schizophrenia were treated for 2 weeks with fixed daily oral doses of haloperidol prospectively calculated to achieve a haloperidol plasma concentration of either 8-18 ng/ml or 25-35 ng/ml. Reduced haloperidol as well as haloperidol concentrations were assayed to determine if the former enhanced the predictability of response. Wee 2 haloperidol plasma concentrations were negatively correlated to clinical response as measured by the percentage change in the BPRS score from baseline (r = -0.43, P less than 0.05). In contrast, week 2 plasma concentrations of reduced haloperidol, total haloperidol (haloperidol + reduced haloperidol), and reduced haloperidol/haloperidol ratio did not correlate with the change in the BPRS score. Chi-square analysis concluded that patients with ratios greater than one were no less likely to be treatment responders (less than 25% improvement in BPRS from baseline and week 2 BPRS less than 55) than those with ratios less than one. Although these data lend additional support to reports of a curvilinear relationship between haloperidol plasma concentration and clinical response, they also suggest that reduced haloperidol plasma concentrations are of no value in predicting treatment response.

Acute Disease

DSM-III personality disorder dimensions.

Dimensional scores were computed for the 11 DSM-III personality disorders (PDs) in 797 relatives of psychiatric patients and never ill control subjects interviewed with the Structured Interview for DSM-III Personality Disorders. The distribution of scores for all 11 PD dimensions was skewed to the right. A principal components analysis with varimax rotation produced three factors that closely corresponded to DSM-III's suggested clustering of the PDs into eccentric, dramatic, and anxious types. Men scored significantly higher on the paranoid, schizoid, compulsive, antisocial, and narcissistic dimensions, whereas women had significantly higher histrionic, dependent, and avoidant scores. Age was negatively correlated with most of the PD dimensions, and the correlations were strongest with the four PDs in cluster 2 (histrionic, antisocial, narcissistic, and borderline). Each of the eight axis I disorders examined was associated with increased axis II pathology.

Adult

Variability in the application of contemporary diagnostic criteria: endogenous depression as an example.

Specified diagnostic criteria have been credited, in part, with improving diagnostic reliability. The authors hypothesize that nonuniform application of these criteria across different research centers has been one factor responsible for the failure to replicate research findings. For example, researchers using a narrow interpretation of the Research Diagnostic Criteria (RDC) have found a highly significant association between endogenous depression and a positive dexamethasone suppression test result, whereas researchers using a broad interpretation have failed to find the predicted relationship. The authors used two interpretations of the RDC and DSM-III endogenous/melancholia criteria to diagnose 60 depressed patients and found significant difference in rates of diagnoses and symptoms.

Adult

Pharmacokinetic protocol for predicting plasma haloperidol concentrations.

The accurate prediction of steady-state plasma haloperidol concentrations was successfully accomplished by obtaining two blood samples following a 20 mg test dose (kinetic method). Prediction of steady-state concentrations on the basis of a mg/kg/day dosage (dose method), although equally precise, generated significantly less information concerning the variance between observed and predicted haloperidol plasma concentrations. Both predictive methods were less precise when the daily doses exceeded 0.47 mg/kg/day. Fifty percent (6/12 patients) of the haloperidol plasma concentrations were underpredicted if this threshold was exceeded. This finding may suggest the possibility of dose-dependent pharmacokinetics with haloperidol in some patients.

Dose-Response Relationship, Drug

HPA axis disturbance in obsessive-compulsive disorder.

Twenty nondepressed outpatients with DSM-III obsessive-compulsive disorder entered a 10-week placebo-controlled study of clomipramine and underwent a 1-mg dexamethasone suppression test (DST) at baseline; 11 had a repeat DST at the end of treatment: Nonsuppression was rare. When compared to 82 previously described outpatients with panic disorder studied in a similar fashion, OCD patients had postdexamethasone cortisol values that were substantially lower and more stable over time. Results within the OCD group closely resembled those from a group of never-ill controls.

Clinical Trials as Topic

HPA axis hyperactivity and recovery from functional psychoses.

Some patients with functional psychoses follow a chronic, deteriorating course and others recover; at present clinicians have essentially no established factors beyond diagnosis and chronicity to predict which course a psychotic patient might follow. Because data on diagnostic specificity suggested that the dexamethasone suppression test might provide another, much needed prognostic factor, the authors administered these tests to 98 consecutively admitted patients with nonmanic psychoses. High postdexamethasone cortisol levels (6 micrograms/dl or higher) at baseline predicted recovery from psychosis at 1 year, independent of episode chronicity and diagnosis. Diagnosis did not correspond well to test results but was itself an important predictor.

Adult

Personality disorder in the families of depressed, schizophrenic, and never-ill probands.

In a blind family study of 176 probands with nonpsychotic major depression, psychotic major depression, schizophrenia, or no history of DSM-III disorders, only the relatives of depressed probands with mood-incongruent psychotic features had a risk for personality disorders higher than that for the relatives of never-ill probands. The authors did not find a high rate of borderline personality in relatives of depressed probands or of schizotypal personality disorder in relatives of probands with schizophrenia or any psychosis. However, depressed probands with normal dexamethasone test results had a significantly higher familial loading for the DSM-III cluster of histrionic, antisocial, borderline, and narcissistic personality disorders.

Adult

Seizures following the withdrawal of alprazolam.

Seizures were observed following the withdrawal of alprazolam administered in therapeutic dose for 10 weeks. A review of available case reports suggests that seizures, like other withdrawal phenomena, are more apt to occur with short-acting benzodiazepines. To prevent their occurrence these drugs should be discontinued gradually and consideration given to substituting long-acting drugs during the withdrawal period. Physicians should remain alert to the fact that seizures may occur as early as 24 hours after the abrupt withdrawal of short-acting benzodiazepines.

Adult

A withdrawal syndrome after abrupt discontinuation of alprazolam.

A patient who received therapeutic doses of alprazolam for 8 weeks experienced a withdrawal syndrome beginning 18 hours after its abrupt discontinuation. Short-acting and minimally sedating benzodiazepines may have increased potential for withdrawal reactions.

Adult

Doxepin kinetics.

The kinetics of doxepin (DOX) hydrochloride were studied in 7 volunteers after the oral administration of 75 mg. Peak plasma concentrations of DOX ranged from 8.8 to 45.8 ng/ml and were reached within 4 hr. The disappearance of DOX was biphasic and followed first-order kinetics. The mean DOX half life (t1/2) was 16.8 hr and in individuals ranged from 8.2 to 24.5 hr. The mean apparent volume of distribution was 20.2 L/kg and ranged from 9.1 to 33.3 L/kg. The estimated first-pass metabolism of DOX ranged from 55% to 87% of the oral dose assuming complete absorption. Significant quantities of the metabolite desmethyldoxepin (DMD) were produced. Peak levels of DMD ranged from 4.8 to 14.5 ng/ml and were reached between 2 and 10 hr after administration. The mean t1/2 of DMD was 51.3 hr and in individuals ranged from 33.2 to 80.7 hr. There was no correlation between the DOX and DMD t1/2s. The amount of DMD produced correlated with the plasma concentration of DOX and appears to explain the correlation between the steady-state concentrations of DOX and DMD in patients given DOX.

Adult

Protriptyline kinetics.

The kinetics of protriptyline were examined in 8 subjects after a single oral dose of 30 mg protriptyline hydrochloride. Peak protriptyline levels ranged from 10.4 to 22.3 ng/ml and were reached 6 to 12 hr after the oral dose. The mean protriptyline half-life (t1/2) was 74.3 hr and ranged from 53.6 to 91.7 hr in individual subjects, confirming the long t1/2 of protriptyline reported by Moody and associates. The estimated first-pass metabolism of protriptyline was relatively small, ranging from 10% to 25% of the oral dose, assuming complete absorption. The mean volume of distribution was 22.5 L/kg and ranged from 15.0 to 31.2 L/kg. No relationship was found between the kinetics of protriptyline and those of doxepin studied previously in 7 of the 8 subjects.

Adult

Primary and secondary affective disorders: baseline characteristics of unipolar patients.

We studied 569 patients with RDC non-bipolar major depressive disorder from the clinical portion of the NIMH Program on the Psychobiology of Depression. Primary (n = 327; never had a non-affective disorder), secondary (n = 191; had a non-affective disorder before ever having a major depressive episode), and "complicated' (n = 51; had at least one depressive episode before and another since developing a non-affective condition) patients were compared on demographic variables, past episodes of depression, past treatments received, and symptoms seen in the index episode. For most characteristics, the groups fell in the order primary, secondary, complicated, such that complicated cases had the earliest onset, the longest duration and the greatest severity in the index episode. These data do not discriminate between two hypotheses: that secondary and complicated depressions are basically depressions which happen to occur in a non-affectively ill person, or that they are different disorders which are distinguished clinically by characteristics related to severity.

Adult

Bipolar versus unipolar and primary versus secondary affective disorder: which diagnosis takes precedence?

The primary versus secondary distinction is often used as a way of subtyping depression. Its applicability to bipolar disorders has been unclear. This report examines the relative primacy of the bipolar versus unipolar distinction as compared to the primary versus secondary distinction in a sample of 955 patients in the NIMH Collaborative Study of the Psychobiology of Depression. These patients are divided into nine groups of the basis of whether they are bipolar I, bipolar II, or unipolar, and whether they are primary, 'pure' secondary, or 'complicated' secondary (i.e. bipolar I primary, bipolar I pure secondary, bipolar I complicated, etc.). Three sets of variables are used to determine the predictive validity of these various subtypes: data concerning age of onset and phenomenology of current episode, outcome, and familial prevalence. In general, data from these three sets of validators suggest that the bipolar distinction takes precedence over the primary versus secondary distinction. Within bipolars, there is little value in further subtyping into primary versus secondary.

Adult