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Biomedical subjects

W Coryell

Publications and source records attributed to W Coryell.

At least 37 records · Page 2Linked to original sources
PubMed1998

Haloperidol plasma levels and dose optimization.

OBJECTIVE: This study was designed to test the practical utility of haloperidol plasma level determinations in the management of schizophrenic patients who show poor initial responses to haloperidol. METHOD: Inpatients with acute exacerbations of DSM-III schizophrenia (N = 66) were randomly assigned to receive fixed haloperidol doses intended to achieve plasma levels of 8-18 ng/ml or of 25-35 ng/ml. Patients whose scores on the Brief Psychiatric Rating Scale (BPRS) failed to improve by at least 30% at the end of 3 weeks were then subject to dose reassignment. RESULTS: Among the patients who completed the first phase of the protocol, 30 had steady-state haloperidol plasma levels of less than 18 ng/ml, and 22 had levels that exceeded 25 ng/ml; 14 had intermediate plasma levels of 18-25 ng/ml. A survival analysis of time to 30% improvement significantly favored the two lower plasma level groups, although side effect ratings did not differ. Of the 30 patients whose BPRS scores failed to improve by 30% after 3 weeks, 11 and five were randomly assigned to receive lower and higher doses, respectively. Those whose dose was lowered experienced significantly more improvement in the subsequent weeks than did those whose dose was increased. CONCLUSIONS: Haloperidol plasma levels that substantially exceed 18 ng/ml may be countertherapeutic. In particular, increases in dose beyond this level are not efficacious for patients who have not responded to lower doses.

Adolescent↗
PubMed1998

Lithium discontinuation and subsequent effectiveness.

OBJECTIVE: Several reports have raised concern that the discontinuation of lithium may result in treatment resistance following recurrence of affective disorder. This report explores this possibility. METHOD: The data derive from a large, naturalistic follow-up of patients with major depressive disorder or mania. Twenty-eight of the patients in the study were free of lithium and experiencing an episode of mania or schizoaffective mania diagnosed according to Research Diagnostic Criteria when they entered the study, recovered while taking lithium, later experienced a recurrence while not taking lithium, and then resumed lithium treatment. Survival analyses of time to recovery and, subsequently, time to recurrence, used continued lithium treatment as an additional censoring variable. RESULTS: Patients given lithium recovered no more quickly from their index episode than they did from their first prospectively observed episode. Moreover, lithium prophylaxis appeared no less effective after the first prospectively observed episode than after the index episode. CONCLUSIONS: These findings provide no evidence that lithium discontinuation results in treatment resistance when lithium is resumed.

Adult↗
PubMed1998

The treatment of psychotic depression.

Psychotic depression is marked by increased severity, longer episodes, greater incapacity, and a lower likelihood of placebo response. Psychotic features often recur in subsequent episodes and interepisode intervals are shorter when psychotic features have been previously present. Among the treatment options for psychotic depression, electroconvulsive therapy is particularly effective. Conventional pharmacotherapy consists of tricyclic antidepressants combined with antipsychotics; recovery with tricyclic antidepressant monotherapy is less likely. Serotonin selective reuptake inhibitors may prove useful but the relevant literature is scant. Pharmacokinetic interactions are likely in combination treatment, as are side effects that may mimic the underlying condition. Little is known regarding the importance of antipsychotics to maintenance therapy.

Antidepressive Agents, Tricyclic↗
PubMed1997

Hypersensitivity to carbon dioxide as a disease-specific trait marker.

There is now substantial evidence that an abnormal threshold for suffocation alarm underlies panic disorder. Because this disorder is highly familial, evidence of an abnormal suffocation threshold may be apparent in high-risk individuals before they develop clinical illness. To explore this possibility, we used a single inhalation of 35% CO2 vs. air to evaluate 11 subjects who had at least one first-degree relative with DSM-III-R panic disorder, 13 who had at least two relatives treated for mania or for depression (HR-AD), and 15 low-risk controls who had no family history of panic disorder, affective disorder, or alcoholism (LR-C). All were aged 18-34 and had no history of panics or of any Research Diagnostic Criteria disorder. Five (45.5%) of the subjects at high risk for panic disorder, but none of the LR-C subjects (p = .007), nor any of the HR-AD subjects (p = .011), developed a panic attack following inhalation of the CO2 mixture.

Adolescent↗
PubMed1997

Recovery from major depression. A 10-year prospective follow-up across multiple episodes.

BACKGROUND: Major depressive disorder is often marked by repeated episodes of depression. We describe recovery from major depression across multiple mood episodes in patients with unipolar major depression at intake and examine the association of sociodemographic and clinical variables with duration of illness. METHODS: A cohort of 258 subjects treated for unipolar major depressive disorder was followed up prospectively for 10 years as part of the Collaborative Depression Study, a multicenter naturalistic study of the mood disorders. Diagnoses were made according to the Research Diagnostic Criteria, and the course of illness was assessed with the Longitudinal Interval Follow-up Evaluation. Survival analyses were used to calculate the duration of illness for the first 5 recurrent mood episodes after recovery from the index episode. RESULTS: Diagnosis remained unipolar major depressive disorder for 235 subjects (91%). The median duration of illness was 22 weeks for the first recurrent mood episode, 20 weeks for the second, 21 weeks for the third, and 19 weeks for the fourth and fifth recurrent mood episodes; the 95% confidence intervals were highly consistent. From one episode to the next, the proportion of subjects who recovered by any one time point was similar. For subjects with 2 or more recoveries, the consistency of duration of illness from one recovery to the next was low to moderate. None of the sociodemographic or clinical variables consistently predicted duration of illness. CONCLUSION: In this sample of patients treated at tertiary care centers for major depressive disorder, the duration of recurrent mood episodes was relatively uniform and averaged approximately 20 weeks.

Adult↗
PubMed1997

Do psychotic, minor and intermittent depressive disorders exist on a continuum?

The following paper uses information from a family study and 10-year follow-up of probands with unipolar depression to describe relationships between psychotic and non-psychotic major depressive disorder (MDD) and, in turn, between psychotic MDD and minor or intermittent depressive disorders. Probands began follow-up as they sought treatment for MDD at any of five participating academic centers. Follow-up evaluations then occurred at 6-month intervals for 5 years and then annually for an additional 5 years. Two-thirds of the probands also entered a family study in which raters attempted direct interviews of all available adult first-degree relatives. Findings that individual symptoms comprising the endogenous MDD subtype had higher severity ratings, that the full MDD syndrome was present for a greater number of weeks in each year of follow-up, and that time to new episodes of MDD were shorter, all indicated that patients with psychotic features had a severe variant of MDD. An increased familial risk for psychotic MDD per se, and a sustained tendency for psychotic features to recur, indicated an important discontinuity, however. The increase in morbidity over time which characterized psychotic patients manifested in the full MDD syndrome, but not in mild MDD, minor or intermittent depressive syndromes. These milder syndromes tended to be more prominent over time among patients who began with non-psychotic MDD. This fails to support a continuum spanning both psychotic MDD and the mild, subsyndromal forms of unipolar depression.

Adult↗
PubMed1997

Lithium and recurrence in a long-term follow-up of bipolar affective disorder.

BACKGROUND: Though previous studies have clearly shown that lithium affords prophylaxis in bipolar affective disorder, these studies have not demonstrated the persistence of this prophylactic effect beyond the first year of recovery. METHODS: One hundred and eighty-one patients with bipolar affective disorder recovered during 5 years of semi-annual follow-up. After 8 weeks of recovery, 139 were taking lithium prophylaxis and 42 were not. Analyses used drug status (lithium v. no-lithium) as a censoring variable to compare these two groups by interval-specific probabilities of recurrence. RESULTS: Recurrence was initially less likely in the lithium group but interval-specific probabilities of recurrence did not consistently favour either group after the first 32 weeks of recovery. CONCLUSIONS: Biases in treatment decisions may have both reduced the size and altered the specificity of the lithium effects seen here. Nevertheless, the apparent transience of lithium prophylactic effects is unexplained and may reflect important, physiological differences between relapse and recurrence. This possibility invites a controlled lithium discontinuation study, with gradual taper, of patients who have had at least 8 months of sustained euthymia.

Adult↗
PubMed1996

Parent-of-origin effect in transmission of bipolar disorder.

Recently, possible involvement of a parent-of-origin effect in the transmission of bipolar disorder has been suggested. We examined the possible contribution of parent-of-origin effect by using data from a large family and family history study of bipolar patients in the Collaborative Depression Study. In 276 probands with bipolar I disorder, family histories were examined using three diagnostic criteria: 1) bipolar I disorder, 2) bipolar I or bipolar II disorder, and 3) bipolar disorders or recurrent unipolar depression for parents and siblings. An excess of affected mothers was not observed when unipolar depression was excluded. Age-at-onset was significantly lower in probands having a father with bipolar disorders or recurrent unipolar depression than in probands with an affected mother. This difference was not observed when unipolar depression was excluded. There was no significant difference of prevalence rate in children of affected mothers and those with affected fathers. These data do not support the contribution of parent-of-origin effect in the transmission of bipolar disorder.

Adult↗
PubMed1996

Five-year course of major depression: effects of comorbid alcoholism.

Some patients enter psychiatric treatment with clear cases of both major depression and alcoholism. While assumptions are often made about the relationships of these two conditions, little empirical evidence exists on the effects of sustained remissions in alcoholism on sustained remissions in depression. 127 patients with both disorders at treatment entry were studied over a 5-year period. Survival analyses with time-dependent covariates indicating alcoholism status were used to investigate remissions and relapses in major depression. Remission in alcoholism strongly and significantly increased the chances of remission in depression and were also related to reduced chances of depression relapse, although at a weaker level.

Adult↗
PubMed1996

Personality traits in subjects with bipolar I disorder in remission.

This study compared the personality traits of subjects with bipolar I disorder in remission to the personality traits of subjects with no history of any mental illness. Subjects were assessed as part of a prospective, multicenter, naturalistic study of mood disorders. Diagnoses were rendered according to Research Diagnostic Criteria, through use of the Schedule for Affective Disorders and Schizophrenia - Lifetime Version. A total of 30 euthymic bipolar I subjects were compared to 974 never-ill subjects on 17 personality scales selected for their relevance to mood disorders. The subjects with bipolar I disorder in remission had more aberrant scores on 6 of the 17 personality measures, including Emotional Stability, Objectivity, Neuroticism, Ego Resiliency, Ego Control, and Hysterical Factor. These findings indicate that patients with bipolar I disorder in remission have personality traits that differ from those of normal controls.

Adult↗
PubMed1996

Familial alcoholism in manic-depressive (bipolar) disease.

A previous analysis found a relatively high rate of alcoholism in a cohort of bipolar I subjects, and a trend for increased rates of alcoholism in relatives of subjects with both bipolar I disorder and alcoholism, compared to relatives of subjects with bipolar I disorder and no alcoholism. The sample of subjects with bipolar I disorder has been enlarged through continued follow-up, permitting new analyses to address the association and heritability of bipolar I disorder with alcoholism. Probands with bipolar I disorder were followed for 10 years as part of the NIMH Collaborative Depression Study. The rate of alcoholism in relatives of probands with both bipolar I disorder and alcoholism was compared to the rate of alcoholism in relatives of probands with bipolar disorder and no alcoholism. The prevalence of alcoholism in relatives of subjects with bipolar I disorder was compared to the rate of alcoholism in relatives of control subjects. Relatives of probands with bipolar I disorder showed a higher rate of alcoholism than relatives of controls. Relatives of probands with bipolar I disorder and alcoholism showed a higher rate of alcoholism than relatives of probands with bipolar I disorder without alcoholism. These data suggest that familial alcoholism may contribute to a vulnerability to bipolar I disorder, and that there is a shared heritability for the two disorders.

Adult↗
PubMed1996

Recovery after 5 years of unremitting major depressive disorder.

BACKGROUND: The long-term course of depression in patients who present for treatment carries prognostic and therapeutic implications. This study presents prospective data on the time to recovery from an episode of major depressive disorder of 5 years' duration among patients followed up since 1978 in the National Institutes of Mental Health Collaborative Program on the Psychobiology of Depression. METHODS: Survival analysis was used to examine the 10-year course of the 431 probands with major depressive disorder with a specific focus on the 35 probands who were observed to be continuously ill for the first 5 years. Univariate analytic techniques were used to describe the demographic and clinical variables in the group that recovered and the group that did not. By study design, somatic treatment was assessed but not controlled by the investigators. RESULTS: By year 10, 93% (Kaplan-Meier estimate) of probands had recovered from their intake episode of major depressive disorder. In those ill for the first 5 years, 38% had recovered within the next 5 years. Shorter duration of illness prior to intake and being married were associated with the group that recovered. Pharmacological treatment dosages averaged 100 mg of imipramine hydrochloride equivalent in the chronically ill group. CONCLUSIONS: Despite lengthy periods of illness, people continued to recover from major depressive disorder for up to 10 years of prospective follow-up. Few demographic and clinical variables distinguished those who recovered from those who did not. Treatment, as observed in this naturalistic study, was at a low level despite lengthy illness.

Adult↗
PubMed1996

Importance of psychotic features to long-term course in major depressive disorder.

OBJECTIVE: Most efforts to describe the prognostic significance of psychotic features in depression have been limited to single assessments 1 year or less after the initial evaluation. However, the various biological and treatment response differences between patients with psychotic and nonpsychotic depression suggest that prognostic differences may be very long-term. METHOD: The 787 patients described here entered the study as they sought treatment at one of five academic medical centers; they had either RDC major depressive disorder or schizo-affective depression (other than the mainly schizophrenic subtype) and completed at least 6 months of follow-up. Of these, 144 (18.3%) had psychotic depression as defined here. Patients provided follow-up interviews at 6-month intervals for 5 years and annually thereafter; 98 of those with psychotic depression and 434 of those with non-psychotic depression were followed for 10 years. RESULTS: Those who began follow-up with psychotic depression had fewer weeks with minimal symptoms in each of the 10 years of follow-up and reported more psychosocial impairment at both 5 and 10 years. Both the index episode and the first recurrence of psychotic depression lasted longer than nonpsychotic episodes, but nonpsychotic episodes among previously psychotic individuals were relatively brief. Intervals between episodes were significantly shorter for patients who had ever been psychotic. CONCLUSIONS: Together with evidence that psychotic features are highly recurrent, these data show 1) that psychotic features denote a lifetime illness of greater severity and 2) that within individuals, psychotic features may emerge in only the more severe episodes.

Adult↗
PubMed1996

Psychotic depression.

The presence of delusions or hallucinations in major depressive disorder indicates a severe form of that disorder. Compared with patients with nonpsychotic depression, those with psychotic depression have depressive symptoms that are individually more severe. They also are more likely to have hypothalamic-pituitary-adrenal axis hyperactivity and increased ventricular-to-brain ratios. The short- and long-term outcomes for such patients are poor. Findings that this prognostic disadvantage may be permanent and that psychotic features recur at high rates in subsequent episodes indicate that these symptoms in major depressive disorder have a lifelong significance. Although monotherapy with antidepressants may be effective, recovery is more rapid when antidepressants are combined with antipsychotics. Electroconvulsive therapy is particularly effective for psychotic depression. The importance of combination therapy for prophylaxis is unknown.

Antidepressive Agents↗
PubMed1995

The likelihood of recurrence in bipolar affective disorder: the importance of episode recency.

These analyses used a high-intensity follow-up of of patients with bipolar affective disorder to describe the immediate and long-term risks for recurrence and the importance of sustained recovery to those risks. At the baseline evaluation, all patients were in episodes of Research Diagnostic Criteria major depressive disorder, mania or schizoaffective disorder (excluding the mainly schizophrenic subtype); those who were depressed at intake had a history of mania or schizoaffective mania. Raters re-evaluated these patients at 6-month intervals for 5 years and annually for the remainder of a 10-year follow-up. The following report describes relapse risks for the 186 patients observed to recover from their index episodes. Survival analyses quantified the likelihood of relapse over time, beginning after symptom-free periods of 4 months and 1, 2 and 3 years. Further survival analyses used treatment status as a censoring variable to estimate the eventual likelihood of recurrence among those who reported sustained compliance with lithium prophylaxis; the prophylaxis group remained under observation until they relapsed, were lost to follow-up or ceased taking lithium. Progressively longer symptom-free periods were clearly associated with lower relapse risks over the subsequent 4 years. Thereafter, however, this effect dissipitated. 7 years after recovery, the cumulative likelihood of recurrence was four in five for all bipolar patients and two in three for those whose index episode had been followed by at least 3 years without symptoms. Even with sustained lithium prophylaxis, the likelihood of at least one recurrence exceeded 70% within 5 years of recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Switching from 'unipolar' to bipolar II. An 11-year prospective study of clinical and temperamental predictors in 559 patients.

BACKGROUND: Given the therapeutic and prognostic importance of the unipolar-bipolar dichotomy, predicting which patients will become bipolar subsequent to index diagnosis of major depressive disorder (MDD) is of paramount clinical significance. We sought to characterize the profile of patients with MDD who would convert to the more subtle bipolar subtype (known as BPII) on the basis of clinical and personality variables obtained during MDD episodes. METHODS: A total of 559 patients, comprehensively evaluated with the Schedule of Affective Disorders and Schizophrenia and "unipolar" MDD at entry, were administered 17 self-report personality measures. Hypomanic and manic episodes were systematically recorded over a prospective observation period of up to 11 years. We compared 48 converters to BPII (8.6%) with 22 converters to bipolar I (BPI) (3.9%) and the remaining larger group of unipolar patients. RESULTS: Except for greater acuteness, severity, and psychotic symptomatology, BPI converters were essentially similar to MDD nonconverters. By contrast, BPII converters were robustly distinguished from those with MDD who remained unipolar on the basis of self-report measures along the newly derived factors of Mood Lability, Energy-Activity, and Daydreaming. This profile was associated with early age at onset of MDD and pleomorphic psychopathology beyond the usual affective realm, high rates of substance abuse, as well as educational, marital, and occupational disruption and minor antisocial acts prior to discrete hypomanic episodes. Overall, BPII switchers had a more protracted and tempestuous course with shorter well intervals. "Habitual self" descriptions of temperamental instability during MDD episodes provided useful clinical information for predicting which depressed patients will switch to BPII, attaining a sensitivity of 91% for all three factors combined (23 items); Mood Lability alone (nine items) was the most specific predictor (86%), though of lower sensitivity (42%). CONCLUSIONS: The BPII subtype is best understood by such lability intruding into, and possibly its accentuation during, depressive episodes, thereby creating an intimate interweaving of trait and state. Clinicians must note that the foregoing temperamental profile appears more fundamental in defining the affective dysregulation of the BPII subtype than hypomanic episodes emphasized in DSM-IV.

Adult↗
PubMed1995

A family study of manic-depressive (bipolar I) disease. Is it a distinct illness separable from primary unipolar depression?

OBJECTIVE: To determine whether bipolar I illness is autonomous or part of a multifactorial continuum with unipolar depression. In this study, we compare familial bipolar I illness and depression among three groups: probands with bipolar I disorder; probands with primary unipolar disorder; and controls. We also examine a continuum of severity between psychotic and nonpsychotic patients with bipolar I disorder. Considerable data suggest that bipolar I illness is distinct from unipolar illness as regards epidemiology, familial psychiatric illness, course, response to treatment, and biologic findings. METHOD: Probands were separated into bipolar I and primary unipolar depressive groups. Personally interviewed family members of these patients were compared on variables of bipolar illness or schizoaffective mania and unipolar or schizoaffective depression. A personally examined control group was compared with the relatives of the two proband groups. Similar analyses were performed using data obtained by a systematic family history method. For the same familial variables, psychotic and nonpsychotic manic probands were compared. RESULTS: Familial mania is more frequent in families of patients with bipolar disease than in controls or in families of patients with primary unipolar disorder. The latter two groups did not differ in amount of mania. Unipolar depressive illness or schizoaffective depression was higher in families of probands with bipolar and unipolar disorder than in controls. Probands with bipolar disease separated into those who had psychotic symptoms (including schizoaffective mania) and no psychotic symptoms did not differ from each other in risk for familial mania or depression. CONCLUSIONS: Bipolar I illness is a separate illness from primary unipolar illness because of an increase in familial mania. Patients with primary unipolar disease and controls show the same amount of familial mania. Lack of an increase in familial illness according to the severity of bipolar disease is against an affective continuum.

Adolescent↗