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Biomedical subjects

D J Kupfer

Publications and source records attributed to D J Kupfer.

At least 145 records · Page 8Linked to original sources

Is life stress more likely to provoke depressive episodes in women than in men?

One of the most consistent findings in psychiatric research is that rates of major depression are at least twofold higher among women than among men. Although there is considerable agreement in the literature that life events play a role in producing, triggering, or maintaining episodes of depression, less is known about the relationship among gender, life events, and depression. In the present study, we compared the rates, focus ("interpersonal" vs. "non-interpersonal"), and timing of stressful life experiences reported in rigorous interviews of male and female patients with unipolar recurrent depression and nondepressed contrast subjects. Consistent with hypotheses, female patients were more likely to experience stressful life experiences than their male counterparts; rates of stressful life experiences did not differ between female and male controls. Unexpectedly, rates of interpersonal stress did not differ among males and females regardless of patient or control status. We also found no significant differences in the timing of pre-onset events: stressful events were generally concentrated in the period immediately preceding onset for both men and women. Thus, although these data suggest that life stress may play a larger role in the provocation of recurrent episodes of depression for women than for men, there do not seem to be sex differences in the extent to which interpersonal vs. noninterpersonal events and difficulties are associated with depression onset or in the temporal distribution of events. Implications of these results are discussed in the context of research on other putative factors contributing to gender differences in rates of depression.

Adult↗

Intrusive thoughts and avoidance behaviors are associated with sleep disturbances in bereavement-related depression.

Cognitive arousal has been associated with disrupted sleep in individuals with insomnia and may be one mechanism underlying sleep disturbances in depression. We evaluated the relationship of sleep to bereavement-related intrusive thoughts and avoidance behaviors in 40 men and women with major depression consequent to bereavement. Mean subject age was 65 years, 25% of the same was male, and median time since loss was 7.4 months. Levels of intrusive thoughts and avoidance behaviors were similar to samples seeking treatment for stress response syndromes, including post-traumatic stress disorder. After controlling for the effects of age, time since loss, and depression severity, greater frequency of bereavement-related intrusive thoughts and avoidance behaviors was associated with longer sleep latency and lower delta sleep ratio (P values < .01). Intrusive thoughts and avoidance behaviors were not strongly related to gender, time since loss, depression severity, or subjective sleep quality. These results suggest that intrusive thoughts and avoidance behaviors affect sleep in bereavement-related depression and may therefore be related to the clinical course of depression.

Aged↗

Accelerating response in geriatric depression: a pilot study combining sleep deprivation and paroxetine.

Elderly depressed patients often require an average of 12 weeks of pharmacotherapy before attaining remission. The delay between treatment initiation and remission may decrease compliance and prolongs suffering; hence, interventions that decrease the time to onset of antidepressant activity are needed. Our objective was to evaluate, in an open trial, the use of one night of total sleep deprivation combined with paroxetine to accelerate antidepressant response in elderly patients. Thirteen elderly patients with major depression were sleep-deprived for one night and started paroxetine on the night of recovery sleep. Patients were followed for twelve weeks, and clinical improvement was rated using the 17-item Hamilton Depression Rating Scale and a version of the Hamilton modified for sleep deprivation studies. 8/13 (62%) patients experienced significant improvement of depressive symptoms by 2 weeks. Within 12 weeks 11/13 (85%) patients responded to the combination of sleep deprivation and paroxetine. Median response time was 2 weeks. Clinical response at 12 weeks was correlated with changes in Sleep Deprivation Depression Rating Scale Scores between baseline and recovery sleep. In an open trial, the combined use of total sleep deprivation and paroxetine appears to be an effective method for speeding the onset of clinical antidepressant activity in geriatric depression and for improving early recognition of non-response.

Aged↗

Quality of life in elderly patients with recurrent major depression: a factor analysis of the General Life Functioning Scale.

Quality of life profiles measured by the General Life Functioning (GLF) Scale were examined in elderly patients with recurrent major depression, before and during combined treatment with nortriptyline and interpersonal psychotherapy. The study group included 110 patients, 91 recovered and 19 nonrecovered, aged 60 to 80 years, suffering from at least their second lifetime episode of major depression. Repeated measures analysis of covariance (with Hamilton and Beck depression scores as time-dependent covariates) was used to compare the temporal course of overall GLF scores for the recovered and the nonrecovered groups. Factor analysis was used to examine whether the GLF Scale yielded an overall score and measured specific aspects of well-being and coping. There were significant differences in the overall GLF scores between recovered and nonrecovered patients, with the differences increasing from week 8 of treatment onward. Analysis revealed significant improvements in quality of life, as measured by overall GLF scores, over the course of treatment in both recovered and nonrecovered patients. Even when changes in Hamilton and Beck depression ratings were controlled for in the statistical analysis, improvements in GLF scores were found to be greater in recovered than in nonrecovered patients. Thus, the GLF measures more than change in level of depression. Its overall score also has high internal reliability.

Adaptation, Psychological↗

Social rhythm stability following late-life spousal bereavement: associations with depression and sleep impairment.

The aim of this study was to investigate changes in social rhythm stability and sleep in spousally bereaved subjects (n = 94) and in nonbereaved elderly control subjects (n = 45). Social rhythm stability and activity level were measured with a diary-like instrument, the Social Rhythm Metric (SRM). We observed that spousal bereavement, per se, was not associated with a lower social rhythm stability or activity level except in the presence of a major depressive episode. We also observed an inverse correlation between severity of depression and social rhythm stability, and a positive correlation between depression and both subjective and objective measures of sleep impairment. Higher social rhythm stability was correlated with better sleep in subjects with high activity levels, but not in subjects with low activity levels. Longitudinal data, including pre-bereavement assessment of social rhythm stability, are necessary to ascertain directional effects, i.e., whether loss of spouse occasions disruption of social rhythms or whether such disruption precedes sleep impairment and depression.

Adjustment Disorders↗

Sleep onset abnormalities in depressed adolescents.

Sleep measures were obtained in 16 depressed and 21 control adolescents following 1 week of adherence to a uniformly imposed and strictly enforced sleep/wake schedule. Three nights of baseline electroencephalographic (EEG) sleep on the same 10:00 PM to 7:00 AM schedule revealed prolonged sleep latency and reduced rapid eye movement (REM) latency in the depressed adolescents. Following baseline measures, sleep was restricted for 2 nights (10:00 PM-4:00 AM) and measures of recovery sleep were obtained showing further sleep latency differences. There was no evidence for delta sleep changes or sleep continuity differences in depressed adolescents. These results suggest that control over sleep/wake schedules is an important methodological issue in adolescent sleep studies. Furthermore, the findings are consistent with a larger body of evidence indicating that dysregulation near sleep onset represents a primary psychobiological change in early-onset depression.

Adolescent↗

Estimation of the time course of slow-wave sleep over the night in depressed patients: effects of clomipramine and clinical response.

The distribution of slow-wave activity during sleep has been analyzed using a method related to the two-process model of sleep regulation. This method is applied to the analyses of data collected from 21 inpatients with unipolar depression who received the antidepressant clomipramine (CMI) in a pulse-loading protocol. CMI infusion was found to redistribute slow-wave activity, producing more concentration in the early part of the night, and also significantly reduced the fluctuation in slow-wave power as a function of time. These measures also distinguished clinical responders from the nonresponders. Drug responders had a significant redistribution of slow-wave activity to the earlier part of the night as compared to nonresponders. This suggests that measures of the distribution of slow-wave activity over the night may represent a good measure of clinical response to antidepressant therapy and have implications for the interpretation of the two-process model and sleep in depression.

Administration, Oral↗

Electroencephalographic sleep profiles during depression. Effects of episode duration and other clinical and psychosocial factors in older adults.

BACKGROUND: Limited evidence suggests that polysomnographic alterations may be more prominent early in a depressive episode. Whether the effects of episode duration extend beyond middle age and appear in late-life depression as well has important implications for treatment decisions and for understanding depressive illness across the life span. Furthermore, the impact of episode duration on sleep has not been examined in the context of other factors related to clinical history and psychosocial status. METHODS: Eighty-three persons aged 60 years or older with recurrent depression were studied: 34 had been depressed for 2 to 16 weeks and 49 for longer periods. An age- and gender-matched group of 48 persons with no history of major depression served as controls. Initial univariate analyses examined duration effects on electroencephalographic (EEG) sleep measurements. Multivariate analyses considered the combined effects of episode duration, clinical variables, and psychosocial variables on EEG sleep profile. RESULTS: Episode duration was strongly associated with sleep continuity, architecture, and rapid eye movement: subjects who were earlier in their depressive episodes had their sleep impaired more than those later in their episodes, who, in turn, were more impaired than controls. Moreover, clinical characteristics of subjects' depressive illness, demographic variables, and psychosocial stressors and supports had unique effects on the EEG sleep profile. CONCLUSION: Episode duration appears to be a potent factor to consider when evaluating sleep during depression. The additional contribution of clinical and psychosocial characteristics to the prediction of the EEG sleep profile demonstrates the importance of incorporating these variables into models of the psychobiologic characteristics of depression. The results are relevant to the timing and focus of therapeutic interventions.

Age Factors↗

Anxiety among widowed elders: is it distinct from depression and grief?

The purpose of this study was to test the validity and utility of distinguishing symptoms of anxiety from those of depression and grief in recently spousally bereaved elders. We also examined pathways from baseline (six months or less post-spousal death) to follow-up (12 and 18 months post-death) levels of anxiety, depression and grief-related symptoms. Baseline and follow-up data were available from 56 recently widowed elderly subjects recruited for an investigation of physiological changes in bereavement. Confirmatory factor analyses indicated that a model in which anxiety was specified as a third factor, apart from depression and grief factors, fit the data well and significantly better than either the one or two factor models. Path analyses revealed that both baseline severity of grief and anxiety had significant lagged effects and predicted follow-up severity of depression. Symptoms of anxiety appeared distinct from those of depression and grief, and the anxiety, depression and grief factors differentially predicted subsequent symptomatology. These findings suggest a need for more specific identification and treatment of anxiety, depression and grief symptoms within the context of late-life spousal bereavement.

Aged↗

Longitudinal effects of nortriptyline on EEG sleep and the likelihood of recurrence in elderly depressed patients.

Our objectives were to determine the effects of nortriptyline and placebo on subjective and EEG sleep measures over 1 year of maintenance therapy in elderly depressed patients and to determine the relationship of such effects to recurrence in nortriptyline or placebo-treated patients during maintenance therapy. EEG and subjective sleep assessments were conducted before and during a maintenance therapy study of patients suffering from major depression. During acute treatment all patients received nortriptyline plus interpersonal psychotherapy (IPT). During maintenance treatment patients were randomly assigned to double-blind treatment in one of four cells: nortriptyline with IPT; nortriptyline with medication clinic (no IPT); placebo with IPT; or placebo with medication clinic. Sleep evaluations were conducted at one point before treatment, one point following remission during continuation nortriptyline/IPT treatment, and at three time points after random assignment to maintenance treatment. The setting was the sleep laboratory of the outpatient depression treatment clinic, and subjects were a convenience sample of media-recruited and clinically referred elderly outpatient depressed patients (n = 72). Complete sleep analyses were conducted for 21 nortriptyline- and 10 placebo-treated patients throughout 1 year of maintenance treatment. The main outcome measures were subjective and EEG sleep measures and the recurrence of major depression. Our results show that nortriptyline acutely and persistently decreased REM sleep, increased phasic REM activity, decreased sleep apnea, and had no effect on periodic limb movements during sleep. Recurrence on maintenance nortriptyline was associated with lower phasic REM activity during early continuation therapy, but EEG sleep measures did not predict recurrence during placebo maintenance therapy. Patients treated with nortriptyline had a lower recurrence rate than those treated with placebo. Better subjective sleep quality and maintenance IPT were associated with a lower rate of recurrence regardless of nortriptyline treatment. It seems that nortriptyline has persistent effects on REM sleep and sleep apnea in elderly depressed patients. Maintenance nortriptyline, maintenance IPT, good subjective sleep quality, and high-phasic REM activity are associated with a reduced likelihood of the recurrence of depression during maintenance therapy.

Aged↗

The prophylaxis of depressive episodes in recurrent depression following discontinuation of drug therapy: integrating psychological and biological factors.

Models of long-term treatment in recurrent unipolar illness ideally should integrate both psychological and biological factors. In earlier reports we noted that high treatment specificity (i.e. good-quality maintenance interpersonal psychotherapy) and high delta sleep ratio were each associated with significantly increased wellness intervals in the absence of pharmacotherapy among patients with recurrent unipolar depression. To determine how these specific factors when taken together are related to length of survival time, we examined the concurrent effects of treatment specificity and delta sleep ratio on wellness intervals using survival analysis. We found significant effects of both treatment specificity and delta ratio on survival time. Seventy-three per cent of the patients in the high treatment specificity/high delta ratio group survived the 3-year trial, while 44% of the patients in the low delta ratio but high treatment specificity group survived. None of those rated low on both variables survived. We also found an effect for individual clinicians on treatment specificity and survival time and noted that the prophylactic effect of treatment specificity was maintained even within subsets of therapists grouped by their patients' survival times. Secondary analyses revealed an effect of patient attitudes on treatment specificity and survival time, although, when taken together, treatment specificity was the only variable remaining significantly associated with outcome. We conclude that patients remain well the longest when pre-treatment delta sleep parameters more closely approximate those of non-depressed individuals and when monthly psychotherapy is of higher quality. The key finding is that high specificity is of significant prophylactic benefit even for patients with a biological vulnerability for recurrence. We also conclude that in addition to therapists, patient expectancies contribute to treatment specificity, and high treatment specificity is, in turn, reflected in longer times to recurrence.

Adult↗

Effects of positive and negative life events on time to depression onset: an analysis of additivity and timing.

While the relationship of life events to depression onset has occupied researchers for almost a quarter of a century, few studies have attempted to account for either the temporal patterning of events relative to episode onset, or, the effect of multiple events in a study period. In this report, we attempt to address the issues of timing of events, multiple events (both positive and negative) and multiple aspects (both positivity and negativity) of single events on latency time to depression onset, while simultaneously accounting for possible decay in the effects of events over time. We use the proportional hazards approach to model the effects of life events and consider modelling the change in impact of events with the passage of time. After interviewing 142 recurrent unipolar patients using the Life Events and Difficulties Schedule, we rated severity and positivity of life events reported during the 6-month period prior to onset. As we hypothesized, additional life events occurring after an initial provoking agent level event significantly alter the risk of illness onset. Additional severely threatening events decrease the time to onset, but positive events do not appear to delay onset. Interestingly, seemingly neutral events had a highly significant effect in shortening the time to onset. We note the many limitations imposed on the interpretation of these findings related to the selected group of subjects studied and encourage those who have more generalizable data to apply these methods of analysis.

Adult↗

Life stress and treatment course of recurrent depression: II. Postrecovery associations with attrition, symptom course, and recurrence over 3 years.

Life stress was studied in relation to postrecovery attrition, symptom course, and recurrence of depression over 3 years. Participants were 67 individuals with recurrent depression who had responded to treatment. Life stress was assessed for the prior 12 weeks at acute treatment entry (T1), initial recovery (T2), and after 17 weeks of sustained recovery (T3). Severe life events at T1 predicted greater attrition, a more favorable postrecovery symptom course, and a lower likelihood of recurrence over 3 years. Life stress at T2 was not predictive of outcomes. Finally, undesirable life events at T3 tended to predict a worse symptom course and a higher likelihood of recurrence, particularly for individuals on medication. The findings are discussed in terms of (a) different processes influenced by life stress over time and (b) limitations of existing longitudinal research for studying the effects of life stress over prolonged intervals.

Adult↗

Recent developments in the pharmacotherapy of mood disorders.

This article reviews recent developments in the pharmacotherapy of mood disorders. Pharmacotherapy is the best studied and most widely validated approach for acute phase treatment and prevention of relapse-recurrence for patients with major depression, dysthymia, and bipolar affective disorder. Antidepressants are also the mainstay of inpatient treatment and, when considered together with electroconvulsive therapy, represent the first line of treatment for the most severe and incapacitating forms of depression. Similarly, pharmacotherapy with mood stabilizers is the first line of treatment for bipolar depression and mania. Despite such efficacy, problems associated with pharmacotherapy include acceptability, tolerability, adherence, incomplete remission, and high rates of recurrence after drug discontinuation. Moreover, a small subset of patients do not respond to multiple medication trials.

Antidepressive Agents↗

Muscle artifacts in the sleep EEG: automated detection and effect on all-night EEG power spectra.

Owing to the use of scalp electrodes in human sleep recordings, cortical EEG signals are inevitably intermingled with the electrical activity of the muscle tissue on the skull. Muscle artifacts are characterized by surges in high frequency activity and are readily identified because of their outlying high values relative to the local background activity. To detect bursts of myogenic activity a simple algorithm is introduced that compares high frequency activity (26.25-32.0 Hz) in each 4-s epoch with the activity level in a local 3-min window. A 4-s value was considered artifactual if it exceeded the local background activity by a certain factor. Sensitivity and specificity of the artifact detection algorithm were empirically adjusted by applying different factors as artifact thresholds. In an analysis of sleep EEG signals recorded from 25 healthy young adults 2.3% (SEM: 0.16) of all 4-s epochs during sleep were identified as artifacts when a threshold factor of four was applied. Contamination of the EEG by muscle activity was more frequent towards the end of non-REM sleep episodes when EEG slow wave activity declined. Within and across REM sleep episodes muscle artifacts were evenly distributed. When the EEG signal was cleared of muscle artifacts, the all-night EEG power spectrum showed significant reductions in power density for all frequencies from 0.25-32.0 Hz. Between 15 and 32 Hz, muscle artifacts made up a substantial part (20-70%) of all-night EEG power density. It is concluded that elimination of short-lasting muscle artifacts reduces the confound between cortical and myogenic activity and is important in interpreting quantitative EEG data. Quantitative approaches in defining and detecting transient events in the EEG signal may help to determine which EEG phenomena constitute clinically significant arousals.

Adolescent↗

Inducing a 6-hour phase advance in the elderly: effects on sleep and temperature rhythms.

The aim of this experiment was to study the effects on sleep and temperature rhythms of a 6-hour (h) phase advance of the sleep/wake cycle in healthy elderly subjects. Twenty-five subjects (77-91 y.o.) lived in a time-isolation apartment on an experimenter-controlled routine for 15 days. The experiment started with five baseline days. The wake time on the 6th night was phase advanced by 6-h and the routine for the remaining nine days was held constant to the new phase position. After the phase shift, temperature circadian rhythms showed rapid phase adjustment leading to a small (1.1 h) phase angle disturbance. Sleep efficiency decreased and showed little evidence of recovery back to baseline following the phase shift. The amount of wakefulness in the first two hours of sleep increased after the phase shift while no effect was found for the amount of wakefulness in the last two hours of sleep. The 6-h phase shift did not change the percentages of REM and SWS. Early night sleep propensity appeared to be very sensitive to a small phase angle disturbance of the circadian oscillator in this healthy elderly sample. The phase angle disturbance induced in this study did not seem to be large enough to have a systematic effect on sleep propensity at the end of the night or on REM sleep parameters, suggesting that these variables are less sensitive to an altered phase relationship with the circadian oscillator than early night sleep propensity. These results indicate that there might be a variable phase tolerance for different sleep parameters in older subjects.

Aged↗

Recovery from depression: risk or reality?

Depression is a serious condition associated with a high rate of recurrence in all populations of depressed patients. Research studies in the past have focused more on the criteria for onset of depressive disorder than on consistent criteria for outcome. However, the issue of concern to the patient is whether their depression is a lifelong condition or a condition from which they can reasonably expect to make a complete recovery. The issues surrounding recovery from depression are reviewed in the following article. The lifetime prognosis of depression is examined with reference to the Zürich follow-up study, and outcome criteria and the importance of assessing recovery in terms of quality of life as well as symptomatic improvement are considered. The relevance of clinical trial results to the clinical management of depression is also addressed.

Depressive Disorder↗

Treatment outcome in recurrent major depression: a post hoc comparison of elderly ("young old") and midlife patients.

OBJECTIVE: The authors compared response rates, the temporal course of response to acute treatment, and relapse rates during continuation treatment of elderly and midlife patients with recurrent major depression. METHOD: They analyzed results from two separate controlled studies of maintenance therapies for recurrent major depression, in which 148 elderly patients (mean age = 67.9 years) and 214 midlife patients (mean age = 38.5 years) were treated in open acute and continuation therapy with a combination of interpersonal psychotherapy and a tricyclic antidepressant (nortriptyline for the elderly, imipramine for the midlife patients). In an intent-to-treat analysis, remission rates during acute treatment and relapse rates during continuation treatment were examined. Random regression analysis of weekly Hamilton depression scale ratings was used to compare the temporal course of response. RESULTS: During acute-phase therapy, 78.4% (N = 116) of the elderly patients and 69.6% (N = 149) of the midlife patients had remissions. The midlife patients had a faster reduction of Hamilton depression ratings. Following stabilization, 15.5% of the elderly patients and 6.7% of the midlife patients relapsed. Ultimately, 66.2% of the late-life patients and 57.0% of the midlife patients recovered fully. CONCLUSIONS: Older patients appear to benefit as much as, but perhaps more slowly then, midlife patients from treatment of major depression. Continuation treatment should be vigorous and closely monitored, given the apparently higher relapse rates among the elderly. These conclusions should be viewed as preliminary because of the post hoc nature of the analysis reported here.

Adult↗