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Biomedical subjects

D J Kupfer

Publications and source records attributed to D J Kupfer.

At least 163 records · Page 9Linked to original sources
PubMed1996

High relapse rate after discontinuation of adjunctive medication for elderly patients with recurrent major depression.

OBJECTIVE: The authors documented outcomes of elderly depressed patients requiring adjunctive medication during acute-phase pharmacotherapy because of slow or partial response to nortriptyline. Twenty-eight patients (17.7%) received inpatient care at some point during acute-phase treatment. METHOD: Rates of response, relapse, and sustained remission were examined in 158 elderly patients with recurrent major depression, grouped by whether they received brief treatment with adjunctive medication (lithium, perphenazine, or paroxetine) (N = 39) or did not (N = 119). RESULTS: The group receiving adjunctive medication had a lower rate of response to acute therapy (64.1% versus 83.2%), a higher relapse rate during continuation therapy (52.0% versus 6.1%), and a lower rate of sustained remission (recovery) (48.7% versus 76.5%) than did the group without augmentation. CONCLUSIONS: Elderly depressed patients requiring augmented pharmacotherapy to achieve remission may need continuation of adjunctive medication to remain well and to avoid early relapse. Alternatively, factors that lead to augmentation in the first place (e.g., heightened anxiety) may also increase the risk of relapse.

Age Factors↗
PubMed1996

Subjective alertness rhythms in elderly people.

The aim of this study was to evaluate age-related changes in the circadian rhythm of subjective alertness and to explore the circadian mechanisms underlying such changes. Using a visual analogue scale (VAS) instrument, 25 older men and women (71 y and older; 15 female, 10 male) rated their subjective alertness about 7 times per day during 5 baseline days of temporal isolation during which habitual bedtimes and waketimes were enforced. Comparisons were made with 13 middle-aged men (37-52 y) experiencing the same protocol. Advancing age (particularly in the men) resulted in less rhythmic alertness patterns, as indicated by lower amplitudes and less reliability of fitted 24-h sinusoids. This appeared in spite of the absence of any reliable age-related diminution in circadian temperature rhythm amplitude, thus suggesting the effect was not due to SCN weakness per se, but to weakened transduction of SCN output. In a further experiment, involving 36 h of constant wakeful bedrest, differences in the amplitude of the alertness rhythm were observed between 9 older men (79 y+), 7 older women (79 y+), and 17 young controls (9 males, 8 females, 19-28 y) suggesting that with advancing age (particularly in men) there is less rhythmic input into subjective alertness from the endogenous circadian pacemaker. These results may explain some of the nocturnal insomnia and daytime hypersomnia that afflict many elderly people.

Adult↗
PubMed1996

Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol.

Data from rodent studies indicate that cumulative stress exposure may accelerate senescence and offer a theory to explain differences in the rate of aging. Cumulative exposure to glucocorticoids causes hippocampal defects, resulting in an impairment of the ability to terminate glucocorticoid secretion at the end of stress and, therefore, in increased exposure to glucocorticoids which, in turn, further decreases the ability of the hypothalamo-pituitary-adrenal axis to recover from a challenge. However, the consensus emerging from reviews of human studies is that basal corticotropic function is unaffected by aging, suggesting that the negative interaction of stress and aging does not occur in man. In the present study, a total of 177 temporal profiles of plasma cortisol from 90 normal men and 87 women, aged 18-83 yr, were collected from 7 laboratories and reanalyzed. Twelve parameters quantifying mean levels, value and timing of morning maximum and nocturnal nadir, circadian rhythm amplitude, and start and end of quiescent period were calculated for each individual profile. In both men and women, mean cortisol levels increased by 20-50% between 20-80 yr of age. Premenopausal women had slightly lower mean levels than men in the same age range, primarily because of lower morning maxima. The level of the nocturnal nadir increased progressively with aging in both sexes. An age-related elevation in the morning acrophase occurred in women, but not in men. The diurnal rhythmicity of cortisol secretion was preserved in old age, but the relative amplitude was dampened, and the timing of the circadian elevation was advanced. We conclude that there are marked gender-specific effects of aging on the levels and diurnal variation of human adrenocorticotropic activity, consistent with the hypothesis of the "wear and tear" of lifelong exposure to stress. The alterations in circadian amplitude and phase could be involved in the etiology of sleep disorders in the elderly.

Adult↗
PubMed1996

Amplitude reduction of the circadian temperature and sleep rhythms in the elderly.

This study examined the relationship between circadian temperature rhythm amplitude reduction and sleep consolidation parameters in a group of healthy elders experiencing a 6-h phase advance in routine. Twenty-five healthy old people (15 women, 10 men, 77-91 years old) lived in a time-isolation apartment. Throughout the study, subjects were instructed when to go to bed, get up, and take meals. The experiment started with 5 baseline days during which subjects were kept to a daily routine corresponding to their habitual sleep-wake cycle. The wake time of the 6th night was phase-advanced by 6 h and the routine for the remainder of the experiment was held constant at the new earlier phase position. Rectal temperature was recorded continuously and all sleep episodes recorded polygraphically. Time series of temperature data for each subject were analyzed by complex demodulation (CD). Five of the subjects were excluded from analysis because the percentage of variance accounted for by the remodulate was less than 55% for the postshift days and one subject was excluded because he showed an average sleep efficiency of less than 55% during baseline. In the remaining 19 subjects, the phase shift produced a large decrease of the mean amplitude of the temperature circadian rhythm (from 0.45 degree C to 0.25 degree C). During the first 3 nights following the phase shift, sleep efficiency was decreased and amount of wakefulness in the first half of the night (WFirst) was increased. No effect was found for the amount of wake in the second half of the night (WSecond). The change in amplitude of the temperature rhythm was significantly correlated with change in sleep efficiency (r = 0.5; p = 0.03) and with change in WFirst (r = -0.7; p < 0.001). There was no correlation between change in the amplitude of the temperature rhythm and WSecond. These results suggest that in older subjects, amplitude of the output of the circadian oscillator might indeed be involved in the sleep consolidation process but, in the first, rather than the second half of the night.

Aged↗
PubMed1996

Circadian determinants of the postlunch dip in performance.

This study compared rectal temperature rhythms in groups of subjects who either did (n = 5) or did not (n = 7) show a clear postlunch dip in performance at a monotonous (25-30 min) vigilance task. Performance was tested every 2h in a standardized routine with lunch replaced by hourly liquid food supplements. Those showing the postlunch performance dip had a higher amplitude and later peaking 12h component to their rectal temperature rhythm that those who did not, resulting in flat, rather than rising, temperatures over the 10:00-15:00 time interval. The effect could not be explained by intergroup differences in prior sleep, morningness, or gender, although there was a trend (p = 0.09) for the "dip" group to be slightly younger (21.8y vs. 24.2y). The postlunch dip appears to be an endogenous phenomenon individually determined, but related to the strength of the (12h) harmonic of the circadian system.

Adult↗
PubMed1996

Comorbidity and boundaries of affective disorders with anxiety disorders and substance misuse: results of an international task force.

Associations between affective disorders, anxiety disorders, and substance use disorders were examined in epidemiological studies conducted in Germany, Switzerland, Puerto Rico, and the mainland US. There was a remarkable degree of similarity across studies in the magnitude and type of specific disorders associated with the affective disorders. Comorbidity with affective disorders was greater for the anxiety disorders than for substance misuse. Panic disorder was the subtype of anxiety that was most highly comorbid with depression. Social phobia was the specific phobic type with the strongest association with the affective disorders. The magnitude of associations between substance misuse and affective disorders generally was quite low and less consistent across sites. No major differences were found in the patterns of comorbidity by gender or age group, affective subtype or prevalence period. The onset of anxiety disorders generally preceded that of depression, whereas alcohol misuse was equally likely to pre-or post-date the onset of affective disorders. Finally, comorbidity was associated with an elevation in treatment rates across all sites, confirming Berkson's paradox on an international level.

Adolescent↗
PubMed1995

Growth hormone secretion timing in depression: clinical outcome comparisons.

Growth hormone (GH) secretion in the 100 minutes preceding sleep onset (preSO), as well as in the first half of the night (1st HN), was examined for a group of 13 healthy women and 43 women with recurrent depression who participated in a 3-year maintenance therapy study. GH studies were obtained at several points during treatment and every 3 months during maintenance, during which patients were randomly assigned to active drug or drug-free maintenance treatment cells for 3 years, or until recurrence of depression. Depressed patients were divided into subgroups according to their maintenance treatment assignment (active drug or drug free) and treatment outcome (completing in remission or having a recurrence). Imipramine caused an increase in the GH ratio in all subgroups. Protocol completers had a significantly larger imipramine-induced increase in the GH ratio than did recurrers. The difference in time of GH secretion relative to sleep onset was found to correlate with treatment outcome and was independent of medication status during maintenance.

Adult↗
PubMed1995

Evidence for heritability of biogenic amine levels in the cerebrospinal fluid of rhesus monkeys.

Susceptibility to several human psychopathological disorders is under partial genetic influence, and many of these disorders have biological correlates that may form part of the basis of this vulnerability. In humans, alterations in cerebrospinal fluid (CSF) metabolite levels of the amine transmitters norepinephrine, dopamine, and serotonin have been associated with several forms of psychopathology, and altered levels of these metabolites have been found in healthy probands with a familial history of such illnesses. We report evidence for heritability of CSF levels of biogenic amine measures in rhesus monkeys, Macaca mulatta. In a pilot study of 54 monkeys with known pedigrees, significant differences among sire families were found for CSF levels of norepinephrine (p = 0.04), homovanillic acid (p = 0.02), and 5-hydroxyindoleacetic acid (p = 0.04). These data indicate that variation in bioaminergic measures is associated with pedigree, and that model systems incorporating both genetic and environmental factors can contribute to the understanding of the function of aminergic systems implicated in vulnerability to psychopathology.

Analysis of Variance↗
PubMed1995

Electroencephalographic sleep profiles in single-episode and recurrent unipolar forms of major depression: I. Comparison during acute depressive states.

The current study was conducted to examine if recurrent depression is associated with more severe disturbances of all-night EEG sleep profiles than single-episode depressions. Unmedicated sex- and age-matched groups of 22 single-episode (SE) and 44 recurrent unipolar (RU) outpatients with DSM-III-R/SADS/RDC major depression underwent 2 consecutive nights of EEG sleep recording. Multivariate analyses of covariance (MANCOVAs) and/or analyses of covariance (ANCOVAs) were performed on six sets of sleep measures. Recurrent unipolar depression was associated with significantly increased phasic REM sleep, as well as increased REM counts on the second night of study. Recurrent depression also was associated with significantly poorer sleep efficiency, although the groups did not show consistent differences in sleep architecture or slow-wave sleep. Our findings generally support the hypothesis that recurrent depression is associated with a more severe neurophysiologic substrate than phenotypically similar SE cases. Results are, for the most part, compatible with Post's (1992) model of illness progression, particularly with respect to greater disturbances of state-dependent sleep abnormalities in the RU cases. Longitudinal studies are needed to confirm the evolution of such changes prospectively.

Acute Disease↗
PubMed1995

Sleep research in depressive illness: clinical implications--a tasting menu.

It is well established that sleep patterns are altered in psychiatric disorders and represent a very common presenting complaint. Even though sleep disturbance is often a key feature of many psychiatric conditions, its most prominent role has been in mood disorders. The clinical implications of disordered sleep in mood disorders represent the focus for this paper. Specifically, the following questions will be discussed: (1) How sensitive and specific are the sleep findings in depressive disorders? (2) What are the characteristics of sleep in depression and subtypes of depression? (3) Are sleep changes in depression episodic (state-like) or persistent (trait-like)? As we point to specific characteristics of sleep in subtypes, it is important to note that more sophisticated analyses of sleep measures provide an opportunity to pinpoint changes between delusional/nondelusional depression or endogenous/nonendogenous depression. Furthermore, differences among subtypes will be best understood if we realize that both age and gender affect sleep measures in a consistent manner. Therefore, for example, there is a more robust separation between patients and controls in older individuals than in younger individuals.

Depressive Disorder↗
PubMed1995

Biological correlates of slow wave sleep deficits in functional psychoses: 31P-magnetic resonance spectroscopy.

Deficits in slow wave sleep (SWS) are consistently seen in schizophrenia and related psychotic disorders. However, the pathophysiological significance of this finding is uncertain. In 19 patients with psychotic illness, sleep and 31P-magnetic resonance spectroscopy (MRS) studies were carried out before the patients began medication treatment. Polysomnographic studies were carried out in 2-3 consecutive nights. MRS studies were performed with a surface coil and a depth-resolved pulse sequence focusing on the dorsal prefrontal cortex. Phosphomonoesters were correlated with visually scored delta and Stage 4 sleep, as well as with automated delta wave counts. An inverse relation was also seen between negative symptoms scores and SWS. The association between decreases brain anabolic processes (reflected by decreased PME) and decreased SWS may be related either to processes of accelerated aging or to developmentally mediated alterations in cortical synaptic pruning, postulated to underlie the pathophysiology of functional psychoses.

Adult↗
PubMed1995

Automating the sleep laboratory: implementation and validation of digital recording and analysis.

OBJECTIVES: We report on the implementation of digital processing in a large clinical and research sleep laboratory. The system includes the digital collection, display, analysis, and repository of physiological signals collected during sleep. METHODS: After describing the original analog system, the computer equipment and software necessary for the digital implementation are presented and we explain our algorithms for rapid eye movement (REM) and delta-wave detection. Finally, we describe an experiment validating the digital system of display and analyses. CONCLUSIONS: The digital processing of sleep signals saves computer operator, polysomnographic technologist, and computer time. It also saves resources such as polysomnographic paper and FM tape. The digital signals lend themselves to a large array of analysis techniques and result in improved signal quality. Automated REM and delta-wave detection via digital processing correlate highly with visual counts of rapid eye movements and delta waves.

Algorithms↗
PubMed1995

Maintenance therapies for late-life recurrent major depression: research and review circa 1995.

Major depression in the elderly is often a relapsing, chronic illness with high risk for chronic invalidism, poor treatment compliance, and suicide. In most cases, maintenance treatment to prevent recurrence and to enhance the quality of life is thought to be indicated. We review recent data from our ongoing studies that support both the efficacy and the safety of pharmacotherapeutic and psychotherapeutic maintenance treatments. However, the challenges of conducting maintenance therapy research (particularly with a placebo control) with the elderly are many, involving such areas as recruitment, retention, compliance, choice of outcome measures, and informed consent. We discuss each of these challenges and our responses to them. Finally, we suggest that maintenance therapy trials should be extended in several directions: (a) long-term treatment of bipolar and delusional subtypes in the elderly, as well as depression associated with progressive neurodegenerative disorders such as Alzheimer's dementia; (b) assessment of the benefits and risks of long-term therapy with other than tricyclic and monoamine oxidase inhibitor antidepressant agents, such as selective serotonin reuptake inhibitors; and (c) development of models of long-term course, including the interaction of treatments with medical and psychosocial variables that can have a profound impact on illness onset and offset. These issues are illustrated with a discussion of a new protocol designed to test the acute and maintenance efficacy of antidepressant therapy for depressed patients with Alzheimer's disease.

Alzheimer Disease↗
PubMed1995

Complicated grief and bereavement-related depression as distinct disorders: preliminary empirical validation in elderly bereaved spouses.

OBJECTIVE: This study sought to determine whether a set of symptoms interpreted as complicated grief could be identified and distinguished from bereavement-related depression and whether the presence of complicated grief would predict enduring functional impairments. METHOD: Data were derived from a study group of 82 recently widowed elderly individuals recruited for an investigation of physiological changes in bereaved persons. Baseline data were collected 3-6 months after the deaths of the subjects' spouses, and follow-up data were collected from 56 of the subjects 18 months after the baseline assessments. Candidate items for assessing complicated grief came from a variety of scales used to evaluate emotional functioning (e.g., the Hamilton Depression Rating Scale, the Brief Symptom Inventory). The outcome variables measured were global functioning, medical illness burden, sleep, mood, self-esteem, and anxiety. RESULTS: A principal-components analysis conducted on intake data (N = 82) revealed a complicated grief factor and a bereavement-depression factor. Seven symptoms constituted complicated grief: searching, yearning, preoccupation with thoughts of the deceased, crying, disbelief regarding the death, feeling stunned by the death, and lack of acceptance of the death. Baseline complicated grief scores were significantly associated with impairments in global functioning, mood, sleep, and self-esteem in the 56 subjects available for follow-up. CONCLUSIONS: The symptoms of complicated grief may be distinct from depressive symptoms and appear to be associated with enduring functional impairments. The symptoms of complicated grief, therefore, appear to define a unique disorder deserving of specialized treatment.

Age Factors↗
PubMed1995

REM sleep enhancement by bupropion in depressed men.

OBJECTIVE: The authors compared the effects of bupropion, fluoxetine, and cognitive behavior therapy on EEG sleep in depressed subjects. METHOD: All-night sleep EEG studies were performed before treatment and after partial or full remission on 18 men with depression diagnosed according to Research Diagnostic Criteria and randomly assigned to treatment with either bupropion (N = 7) or fluoxetine (N = 11). Response to these drugs was measured by changes in Hamilton Depression Rating Scale scores. Pre- and posttreatment EEG sleep study results before and after treatment with cognitive behavior therapy were also available for 18 men matched in age and severity of Hamilton depression scale score, and one-time EEG sleep measures were available for 36 men who were not depressed. RESULTS: REM latency was reduced and REM sleep percent and REM time increased after treatment in the depressed men given bupropion. These effects contrasted with the effects of fluoxetine and cognitive behavior therapy. CONCLUSIONS: This study represents the first report of an antidepressant medication that shortens REM latency and increases REM sleep. If confirmed, this finding may require a revision of our current understanding of the relation among depression, REM sleep, and anti-depressant mechanisms.

Adult↗
PubMed1995

Alliance not compliance: a philosophy of outpatient care.

Over the last decade, our clinical research team has evolved effective methods for forming a strong treatment alliance with mood disorder patients. These methods, in turn, have been associated with very low rates of patient dropout (< 10%) and high rates of objectively measured medication compliance (> 85%) over multiyear treatment trials. We have every reason to believe that our technique for alliance building would be equally effective in general clinical practice. The cornerstones of our methods are education of, information for, and active participation by the patient in the treatment process. We begin by educating the patient about his or her disorder and its treatment, giving patients as much information as their clinical condition will allow them to absorb. As patients begin to improve, we provide additional information. We continuously inform patients about what to expect in treatment and when, both with respect to amelioration of symptoms and with respect to the medication side effects they may experience. We present the treatment experience as an experiment in which clinician and patient are coinvestigators, each with his or her own expertise. The clinician is the expert on the disorder and its treatment in general; the patient is the expert on his or her own disorder and his or her own experience of the treatment. We try to keep the experiment interesting and, whenever possible, to inject some humor into it. We work to engage family members as adjunct members of the experimental team by educating them as well and keeping them informed throughout the treatment process.(ABSTRACT TRUNCATED AT 250 WORDS)

Ambulatory Care↗