PubMed Health⌕ Search

Biomedical subjects

D J Kupfer

Publications and source records attributed to D J Kupfer.

At least 55 records · Page 3Linked to original sources
PubMed2000

Social rhythm disruption and stressful life events in the onset of bipolar and unipolar episodes.

BACKGROUND: An association between social rhythm disruption (SRD) and onset of manic episodes has recently been observed. Whether other types of bipolar (depressive and cycling) or unipolar depressive episodes are similarly related to SRD is unclear, as is the association between severely threatening life events and onset of bipolar manic, depressed and cycling episodes. METHODS: Bipolar patients with purely manic (N= 21), purely depressed (N = 21) and cycling (N = 24) episodes, and 44 patients with recurrent unipolar depression, were interviewed with the Bedford College Life Events and Difficulties Schedule. The presence of severe and SRD events during the year prior to index episode onset was then determined. RESULTS: More manic than cycling and unipolar subjects experienced SRD events during 8- and 20-week pre-onset periods, and severe events during 20-week pre-onset periods. Controlling for age and prior number of episodes left most findings unchanged. An earlier finding of more manic subjects with SRD events in an 8-week pre-onset versus control period was also replicated. CONCLUSIONS: It appears that manic onsets are influenced by stressful life events, especially those involving SRD, in a unique manner compared to onsets of other types of bipolar and unipolar episodes. Onset of bipolar cycling episodes, in contrast, seems to be relatively unaffected by SRD or severe life events. These findings refine the hypothesis that SRD may precipitate onset of affective episodes to be specific to manic onsets.

Adult↗
PubMed2000

Inositol as an add-on treatment for bipolar depression.

OBJECTIVE: Inositol is a constituent of the intracellular phosphatidyl inositol (PI) second messenger system, which is linked to various neurotransmitter receptors. Inositol crosses the blood-brain barrier in pharmacological doses, and has shown efficacy in a small double-blind study of unipolar depression. This pilot study evaluated its potential efficacy and safety in bipolar depression. METHODS: Twenty-four consenting adult men and women with DSM-IV bipolar depression (bipolar I = 21; bipolar II = 3) were randomly assigned to receive either 12 g of inositol or D-glucose as placebo for 6 weeks. Efficacy and safety ratings were done weekly. Thymoleptic medications (lithium, valproate, carbamazepine) in stable doses and at therapeutic levels at study entry were continued unchanged. RESULTS: Two subjects receiving placebo dropped out early due to worsening or non-adherence to the protocol. Among the 22 subjects who completed the trial, six (50%) of the inositol-treated subjects responded with a 50% or greater decrease in the baseline Hamilton Depression Rating Scale (HAM-D) score and a Clinical Global Improvement (CGI) scale score change of 'much' or 'very much' improved, as compared to three (30%) subjects assigned to placebo, a statistically nonsignificant difference. On the Montgomery-Asberg Depression Rating Scale (MADRS), eight (67%) of twelve inositol-treated subjects had a 50% or greater decrease in the baseline MADRS scores compared to four (33%) of twelve subjects assigned to placebo (p = 0.10). Inositol was well tolerated with minimal side effects, and thymoleptic blood levels were unaltered. CONCLUSIONS: These pilot data suggest a controlled study with an adequate sample size, and the appropriate rating scale may demonstrate efficacy for inositol in bipolar depression. The tolerability and the 'natural substance' aspect of inositol may be particularly appealing to subjects with bipolar depression.

Adult↗
PubMed2000

Psychotropic drug prescription patterns among patients with bipolar I disorder.

INTRODUCTION: Combination treatment, rather than monotherapy, is prevalent in the treatment of subjects with bipolar disorder, probably due to the complex and phasic nature of the illness. In general, prescription patterns may be influenced by the demographic characteristics of patients as well. We evaluated prescription patterns and the influence of demographic variables on these patterns in a voluntary registry of subjects with bipolar disorder. METHODS: A subset of data from a larger voluntary registry was extracted for demographic variables and psychotropic medication use that had been reported in the month prior to registration by ambulatory, non-hospitalized subjects with bipolar I disorder in 1995/96 (n = 457). RESULTS: Among the thymoleptic agents, lithium was prescribed in over 50% of subjects, valproate in approximately 40%, and carbamazepine in 11% of subjects. Eighteen percent of subjects had no prescription for thymoleptic agents. Nearly one-third of all subjects were receiving antipsychotic agents, of whom two-thirds were receiving the traditional neuroleptic agents. More than half of all subjects were receiving concomitant antidepressants, of whom nearly 50% received the SSRI antidepressants and nearly 25% received buproprion. Approximately 40% of subjects received benzodiazepines. Only 18% of subjects received monotherapy, and nearly 50% received three or more psychotropic agents. In general, no associations were noted between demographic parameters including age, gender, marital or educational status, and psychotropic prescriptions. CONCLUSION: Consistent with the anecdotal reports, these data confirm that combination treatment is far more common than monotherapy. Demography appears to have a minimal impact on cross-sectional prescription patterns in subjects with bipolar disorder. Given that combination treatments are the rule rather than the exception, we should strive to achieve rational, yet pragmatic, treatment guidelines and algorithms to minimize the risks while maximizing the benefits of these combination treatments for patients with bipolar disorder.

Adult↗
PubMed2000

Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry.

OBJECTIVE: To evaluate the prevalence of substance abuse dependence and/or alcohol abuse dependence among subjects with bipolar I versus bipolar II disorder in a voluntary registry. METHOD: One hundred randomly selected registrants in a voluntary case registry for bipolar disorder were interviewed, using the Structured Clinical Interview for DSM-IV Axis I Disorders, to validate the diagnosis of this registry. Corroborative information was obtained from medical records, family members and the treating psychiatrist. Eighty-nine adults (18-65 years) met criteria for bipolar disorder (bipolar I = 71, bipolar II = 18) and were included in this analysis. RESULTS: Forty-one (57.8%) subjects with bipolar I disorder abused, or were dependent on one or more substances or alcohol, 28.2% abused, or were dependent on, two substances or alcohol, and 11.3% abused or were dependent on three or more substances or alcohol. Nearly 39% of bipolar II subjects abused or were dependent on one or more substances, nearly 17% were dependent on two or more substances or alcohol, and 11% were dependent on three or more substances or alcohol. Alcohol was the most commonly abused drug among either bipolar I or II subjects. CONCLUSIONS: Consistent with other epidemiologic and hospital population studies, this voluntary bipolar disorder registry suggests a high prevalence of comorbidity with alcohol and/or substance abuse dependence. Bipolar I subjects appear to have higher rates of these comorbid conditions than bipolar II subjects; however, as the number of bipolar II subjects was rather small, this suggestion needs confirmation.

Adolescent↗
PubMed2000

Response to placebo among bipolar I disorder patients experiencing their first manic episode.

BACKGROUND: The first episode of an illness may respond differently to any treatment compared to multiple episodes of the same illness. This study details the treatment response of six first-episode manic patients who participated in a previously reported study of 139 subjects comparing olanzapine to placebo in bipolar I mania (Tohen M, Sanger TM, McElroy SL, Tollefson GD, Chengappa KNR, Daniel DG. Olanzapine versus placebo in the treatment of acute mania. Am J Psychiatry 1999; 156: 702-709). METHODS: Six first-episode subjects participated in a 3-week double-blind, random assignment, parallel group, placebo-controlled study of olanzapine for bipolar mania. The Young Mania Rating Scale (Y-MRS), Clinical Global Impression, and Hamilton Depression ratings were administered weekly. Lorazepam as rescue medication was permitted for the first 10 days. RESULTS: Five subjects were randomized to placebo and one to olanzapine. Two subjects (40%) with psychotic mania (who also had their first-illness episode) were assigned to placebo and responded with greater than 50% reduction in the Y-MRS score and also remitted in 3 weeks. Another placebo-assigned subject had a 46% reduction in the Y-MRS scores, and two placebo-assigned subjects worsened. The olanzapine-assigned subject had a 44% reduction in the Y-MRS score. In contrast, 34 of 69 (48.6%) multiple-episode olanzapine subjects responded and 14 of 61 (23.0%) of placebo-treated subjects did. CONCLUSIONS: This preliminary data set suggest there may be differences in treatment response between first-illness episode versus multi-episode bipolar manic subjects. Larger numbers of subjects with these illness characteristics are needed to either confirm or refute this suggestion.

Acute Disease↗
PubMed2000

Stressful life events, bipolar disorder, and the "kindling model".

A common misconception is that bipolar disorder is an endogenous process. However, previous research suggests a role for life events in the onset of and recovery from bipolar episodes. Yet, there remains some question as to whether the relationship between life events and onset changes over the course of the disorder as a result of the number of episodes an individual has experienced. Using a rigorous interview measure of stressful life events, the current study tested the kindling model (R. M. Post, 1992), which theorizes that major life events play a diminishing role over the course of illness in bipolar patients. Analyses revealed that the number of episodes experienced does not appear to have a significant effect on bipolar 1 patients' reactivity to external stressors. In addition, the results suggest that a more complex relationship exists among age, stress, and onset of new episodes than can be adequately explained by the kindling model.

Adult↗
PubMed2000

A comparison of two life stress assessment approaches: prospective prediction of treatment outcome in recurrent depression.

Research on life stress has been characterized by inconsistent results, which some researchers attribute to different assessment methodologies. Generally, studies have used either self-report checklists or investigator-based interviews. To test whether different results are derived from these approaches, the authors compared information from a self-report measure of life stress with the additional data available from a follow-up investigator-based measure in prospectively predicting the outcome of treatment for recurrent major depression. The 2 approaches produced different results, with investigator-based life events predicting lower probability of remission and self-report life events either predicting increased likelihood of remission or not predicting at all. The results demonstrated that methodology may account for some of the inconsistencies in the life stress literature.

Adult↗
PubMed2000

Inducing jet-lag in older people: directional asymmetry.

Twenty healthy elderly subjects (12 female, 8 male; mean age 81 years, range 67-87 years) each experienced a 15-day time isolation protocol in which they lived individually in a special laboratory apartment in which sleep and circadian rhythm measures could be taken. There were two experiments: one (6 females, 4 males) involved a 6-h phase advance of the sleep/wake cycle, and the other (6 females, 4 males) a 6-h phase delay. Each started with 5 baseline days, immediately followed by the phase shift. The subject was then held to the phase shifted routine for the remainder of the study. Rectal temperatures were recorded minute-by-minute throughout the entire experiment and each night of sleep was recorded using polysomnography. A directional asymmetry in phase-shift effects was apparent, with significantly more sleep disruption and circadian rhythm amplitude disruption after the phase advance than after the phase delay. Sleep disruption was reflected in reduced time spent asleep, and in changed REM latency, which increased in the phase advance direction but decreased in the phase delay direction. Although the phase advance led to a significant increase in wakefulness in the first half of the night, the phase delay did not lead to an equivalent increase in wakefulness during the second half of the night. Examination of both raw and 'demasked' circadian rectal temperature rhythms confirmed that phase adjustment was slow in both directions, but was less slow (and more monotonic) after the phase delay than after the phase advance. Subjective alertness suffered more disruption after the phase advance than after the phase delay.

Aged↗
PubMed2000

The sleep of healthy people--a diary study.

To provide baseline data for various research studies at the University of Pittsburgh over a 10-year period, 266 healthy subjects (144 male, 122 female, aged 20-50 years) meeting certain criteria each completed a 14-night sleep diary. For each night, the diary allowed the subjective measurement of bedtime, wake time, time in bed (TIB), sleep efficiency, number of minutes of wake after sleep onset (WASO), alertness on awakening, and percentage of morning needing an alarm (or a person functioning as one). Weeknight versus weekend night differences in TIB (TIBdiff), weekday altertness, and reliance on alarms were examined as possible indicators of sleep debt. In addition, general descriptive data were tabulated. On average, bedtimes were at 23:48 and wake times at 07:23, yielding a mean TIB of 7 hours 35 minutes. As expected, bedtimes and wake times were later on weekend nights than on weeknights. Bedtimes were 26 minutes later, wake times 53 minutes later, yielding a mean weekend TIB increase of 27 minutes. Overall, subjects perceived their sleep latency to be 10.5 minutes, reported an average of one awakening during the night (with an average of 6.4 minutes of WASO), had a diary sleep efficiency of 96.3%, and awoke with an alterness rating of 69.5%. These variables differed little between weeknight and weekend nights. Subjects used an alarm (or a person functioning as an alarm) on 60.9% nights overall, 68.3% on weeknights, 42.5% on weekends. When TIBdiff was used as an estimate of sleep debt (comparing subjects with TIBdiff > 75 minutes with those with a TIBdiff < 30 minutes), the group with more "catch-up sleep" on weekends had shorter weeknight TIB durations (by about 24 minutes) and relied more on an alarm for weekday waking (by about 22%), indicating the possible utility of these variables as sleep debt indices.

Adult↗
PubMed2000

Circadian rhythms in healthy aging--effects downstream from the pacemaker.

Using both previously published findings and entirely new data, we present evidence in support of the argument that the circadian dysfunction of advancing age in the healthy human is primarily one of failing to transduce the circadian signal from the circadian timing system (CTS) to rhythms "downstream" from the pacemaker rather than one of failing to generate the circadian signal itself. Two downstream rhythms are considered: subjective alertness and objective performance. For subjective alertness, we show that in both normal nychthemeral (24 h routine, sleeping at night) and unmasking (36 h of constant wakeful bed rest) conditions, advancing age, especially in men, leads to flattening of subjective alertness rhythms, even when circadian temperature rhythms are relatively robust. For objective performance, an unmasking experiment involving manual dexterity, visual search, and visual vigilance tasks was used to demonstrate that the relationship between temperature and performance is strong in the young, but not in older subjects (and especially not in older men).

Adult↗
PubMed2000

Anxiety as a correlate of response to the acute treatment of bipolar I disorder.

OBJECTIVE: Given the adverse impact of anxiety on treatment outcome in unipolar depression and the paucity of data on the role of anxiety in bipolar disorder, the authors sought to determine the effect of anxiety on the acute treatment response of patients with bipolar I disorder. METHOD: The authors examined the correlates of response to the acute treatment of 124 consecutively treated patients with bipolar I disorder. Measures of anxiety included history of panic attacks and a composite variable reflecting current or past anxiety symptoms. RESULTS: History of panic attacks proved to be a significant correlate of nonremission. Anxiety, as assessed with the composite variable, was associated with longer time to remission, as was the treatment of depressive versus manic symptoms and mixed versus manic symptoms. Patients with anxiety as assessed with the composite variable and patients with a history of panic attacks reported more severe medication side effects. They also required a greater number of medications, either sequentially or in combination, in order to achieve remission. CONCLUSIONS: The findings suggest that anxiety is a clinically meaningful correlate of poor outcome in the acute treatment of bipolar I disorder.

Adult↗
PubMed2000

Influence of panic-agoraphobic spectrum symptoms on treatment response in patients with recurrent major depression.

OBJECTIVE: The authors tested the hypothesis that a lifetime history of panic-agoraphobic spectrum symptoms predicts a poorer response to depression treatment. METHOD: A threshold for clinically meaningful panic-agoraphobic spectrum symptoms was defined by means of receiver operating characteristic curve analysis of total scores on the Structured Clinical Interview for Panic-Agoraphobic Spectrum in a group of 88 outpatients with and without panic disorder. This threshold was then applied to a group of 61 women with recurrent major depression, who completed a self-report version of the same instrument, in order to compare treatment outcomes for patients above and below this clinical threshold. RESULTS: Women with high scores (> or =35) on the Panic-Agoraphobic Spectrum Self-Report were less likely than women with low scores (<35) to respond to interpersonal psychotherapy alone (43.5% versus 68.4%, respectively). Women with high scores also took longer (18.1 versus 10.3 weeks) to respond to a sequential treatment paradigm (adding a selective serotonin reuptake inhibitor when depression did not remit with interpersonal psychotherapy alone). This effect was only partially accounted for by the higher likelihood that patients with high scores required the addition of antidepressants. Although four domains from the Panic-Agoraphobic Spectrum Self-Report were individually associated with a longer time to remission, only stress sensitivity emerged as significant in multivariate regression analyses. CONCLUSIONS: A lifetime burden of panic-agoraphobic spectrum symptoms predicted a poorer response to interpersonal psychotherapy and an 8-week delay in sequential treatment response among women with recurrent depression. These results lend clinical validity to the spectrum construct and highlight the need for alternate psychotherapeutic and pharmacologic strategies to treat depressed patients with panic spectrum features.

Adult↗
PubMed2000

Interpersonal psychotherapy and antidepressant medication: evaluation of a sequential treatment strategy in women with recurrent major depression.

BACKGROUND: Few data are available to guide treatment selection in major depression. With increasing pressure to maximize the efficiency and minimize the costs of treatment, it is important to have information that could guide treatment selection or point to treatment strategies that have a high probability of success. METHOD: We used a successive cohort approach to compare 2 highly similar groups of women with recurrent unipolar disorder (DSM-III-R or DSM-IV): one in which the combination of interpersonal psychotherapy (IPT) and pharmacotherapy was initiated at the outset of treatment and a second in which IPT alone was provided first and only those who did not remit with IPT alone were offered the combination treatment. RESULTS: In the group in which the combination was initiated at the outset of treatment (N = 180), the remission rate was 66%, comparable to the remission rate observed in most outpatient treatment studies of major depression. In contrast, among the women in the second cohort who were first treated with IPT alone and only those who did not remit were given combination therapy (N = 159), the remission rate was 79%, significantly greater than that observed in the group that received combination treatment from the outset (chi2 = 6.55, p = .02). CONCLUSION: These results suggest that the strategy of offering IPT to women with recurrent unipolar disorder and, in the absence of remission, adding antidepressant pharmacotherapy can be a highly effective treatment, one that may be particularly attractive to women in the childbearing years. Although slower in its onset of action, this sequential strategy is likely to enable the clear majority of such women to achieve a full remission of depressive symptoms.

Adult↗
PubMed1999

PET imaging of serotonin 1A receptor binding in depression.

BACKGROUND: The serotonin-1A (5HT1A) receptor system has been implicated in the pathophysiology of major depression by postmortem studies of suicide victims and depressed subjects dying of natural causes. This literature is in disagreement, however, regarding the brain regions where 5HT1A receptor binding differs between depressives and controls and the direction of such differences relative to the normal baseline, possibly reflecting the diagnostic heterogeneity inherent within suicide samples. PET imaging using the 5HT1A receptor radioligand, [11C]WAY-100635, may clarify the clinical conditions under which 5HT1A receptor binding potential (BP) is abnormal in depression. METHODS: Regional 5HT1A receptor BP values were compared between 12 unmedicated depressives with primary, recurrent, familial mood disorders and 8 healthy controls using PET and [carbonyl-11C]WAY-100635. Regions-of-interest (ROI) assessed were the mesiotemporal cortex (hippocampus-amygdala) and midbrain raphe, where previous postmortem studies suggested 5HT1A receptor binding is abnormal in depression. RESULTS: The mean 5HT1A receptor BP was reduced 41.5% in the raphe (p < .02) and 26.8% in the mesiotemporal cortex (p < .025) in the depressives relative to the controls. Post hoc comparisons showed the abnormal reduction in 5HT1A receptor BP was not limited to these regions, but extended to control ROI in the occipital cortex and postcentral gyrus as well. The magnitude of these abnormalities was most prominent in bipolar depressives (n = 4) and unipolar depressives with bipolar relatives (n = 4). CONCLUSIONS: Serotonin-1A receptor BP is abnormally decreased in the depressed phase of familial mood disorders in multiple brain regions. Of the regions tested, the magnitude of this reduction was most prominent in the midbrain raphe. Converging evidence from postmortem studies of mood disorders suggests these reductions of 5HT1A receptor BP may be associated with histopathological changes involving the raphe.

Adult↗
PubMed1999

Changes in forebrain function from waking to REM sleep in depression: preliminary analyses of [18F]FDG PET studies.

Based on recent functional brain imaging studies of healthy human REM sleep, we hypothesized that alterations in REM sleep in mood disorder patients reflect a functional dysregulation within limbic and paralimbic forebrain structures during that sleep state. Six unipolar depressed subjects and eight healthy subjects underwent separate [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) PET scans during waking and during their first REM period of sleep. Statistical parametric mapping contrasts were performed to detect changes in relative regional cerebral glucose metabolism (rCMRglu) from waking to REM sleep in each group as well as interactions in patterns of change between groups. Clinical and EEG sleep comparisons from an undisturbed night of sleep were also performed. In contrast to healthy control subjects, depressed patients did not show increases in rCMRglu in anterior paralimbic structures in REM sleep compared to waking. Depressed subjects showed greater increases from waking to REM sleep in rCMRglu in the tectal area and a series of left hemispheric areas including sensorimotor cortex, inferior temporal cortex, uncal gyrus-amygdala, and subicular complex than did the control subjects. These observations indicate that changes in limbic and paralimbic function from waking to REM sleep differ significantly from normal in depressed patients.

Adult↗
PubMed1999

Relationship between social rhythms and mood in patients with rapid cycling bipolar disorder.

Disruptions in the sleep-wake cycle frequently characterize affective illness and have led to a number of theories linking sleep-wake and/or circadian rhythm disturbance to affective illness. Recently, researchers have expanded these chronobiological theories to include the role of lifestyle regularity, or daily social rhythms. In this study, the Social Rhythm Metric (SRM) was used to explore the relationship between social rhythms and mood in patients with rapid cycling bipolar disorder and to compare the social rhythms of patients with those of healthy control subjects. Patients' SRM scores and activity level indices were significantly lower than those of control subjects. In addition, the timing of five, mostly morning, activities was phase delayed in patients compared to control subjects. Patients also demonstrated a phase delay in the timing of morning activities during depression compared to hypomania or euthymia. The phase changes in the timing of morning activities are consistent with other data implicating morning zeitgebers in the pathophysiology of rapid cycling bipolar disorder.

Adult↗
PubMed1999

Platelet membrane phospholipids in euthymic bipolar disorder patients: are they affected by lithium treatment?

BACKGROUND: Abnormalities in cell membrane processes and intracellular signal transduction pathways may be implicated in the pathophysiology of bipolar disorder. In this study, we attempted to investigate, in euthymic bipolar patients: 1) in vivo signal transduction abnormalities of the phosphatidylinositol pathway in platelets; and 2) possible in vivo effects of lithium treatment on platelet membrane phospholipids. METHODS: We determined the relative absorbances of eight individual classes of platelet membrane phospholipids, using two-dimensional thin-layer chromatography in high-performance plates, followed by scanning laser densitometry, in a group of 10 lithium-treated euthymic bipolar patients and 11 normal controls. RESULTS: The mean relative absorbance of phosphatidyl-inositol-4,5-bisphosphate (PIP2) was lower in the patient group (0.29 +/- 0.08% vs. 0.39 +/- 0.12%; t = 2.35, df = 19, p = .03); no significant differences between patients and controls were found for the other phospholipids. CONCLUSIONS: This study provides in vivo evidence that bipolar patients on lithium treatment exhibit a decreased relative amount of PIP2 in the platelet cell membranes compared to normal controls.

Adult↗