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Biomedical subjects

D J Kupfer

Publications and source records attributed to D J Kupfer.

At least 109 records · Page 6Linked to original sources
PubMed1998

Nature of life events and difficulties in depressed adolescents.

OBJECTIVE: To examine the significance of acute life events and ongoing difficulties in adolescents with a recent major depressive disorder. METHOD: Adolescents (aged 13-18 years) with a recent episode of major depressive disorder based on DSM-III-R (n = 26) and normal controls free of any Axis I lifetime psychiatric disorder (n = 15) were assessed using the investigator-based Life Events and Difficulties Schedule (LEDS). RESULTS: Traditionally defined severe events were more likely to occur in the year prior to onset among depressed adolescents (46%) than in a comparable period among normal controls (20%), but these differences did not reach statistical significance. Expanding the definition of severe events to include those events focused on others important to the adolescent resulted in a significantly higher percentage of depressed adolescents having one or more refined "severe" events in the year prior to onset (62%) compared with normal controls (27%) (p < or = .02). It is interesting that one half of the depressed adolescents had two or more refined severe events occur during the year prior to onset compared with none of the normal controls (p < or = .01). Further analyses showed that depressed adolescents were significantly more likely to have a major difficulty precede the onset of their depression (27%) compared with normal controls (0%) (p < or = .04). CONCLUSIONS: The results suggest that depressed adolescents are exposed to high levels of stress prior to becoming depressed. Future investigations might benefit from using the LEDS with adolescents to assess acute and ongoing stressors.

Adaptation, Psychological↗
PubMed1998

Controlled comparison of electrophysiological sleep in families of probands with unipolar depression.

OBJECTIVE: This study presents polysomnographic data and psychiatric history for parents and siblings of probands with unipolar depression and short REM latency, probands with unipolar depression and normal REM latency, and normal comparison probands. METHOD: Parents and adult siblings (N = 252) of probands (N = 64) were evaluated for lifetime history of psychiatric disorders and were studied in the sleep laboratory for 3 nights. RESULTS: REM latency predicted lifetime history of major depression. Short REM latency was also associated with slow wave sleep deficits. Rate of short REM latency in relatives of depressed probands with short REM latency quadrupled the rate in relatives of both depressed probands with normal REM latency and normal probands. Lifetime risk of depression was almost twice as high in relatives of depressed probands with short REM latency as in relatives of depressed probands with normal REM latency. CONCLUSIONS: Short REM latency and slow wave sleep deficits are familial. Short REM latency is associated with increased risk of major depression beyond the familial risk associated with a depressed proband. Polysomnographic abnormalities also occurred in unaffected relatives. Although the data can be considered only suggestive, these findings indicate that polysomnographic abnormalities may precede the clinical expression of depression and may be useful in identifying those at highest risk for the illness.

Adult↗
PubMed1998

Effects of age at onset of first lifetime episode of recurrent major depression on treatment response and illness course in elderly patients.

OBJECTIVE: The goal of this study was to examine treatment outcome differences in relation to age at onset of first lifetime episode of recurrent major depression in elderly patients. METHOD: Patients were grouped as having early-onset (N = 129) or late-onset (N = 58) depression. Early onset was defined as having a first lifetime episode of major depression at age 59 or earlier; late onset was defined as age 60 or later. The two groups of patients were compared with respect to demographic and clinical characteristics, types of treatment given (nortriptyline and interpersonal psychotherapy), and treatment outcomes. RESULTS: The groups did not differ in the percentage of patients who remitted, recovered, or relapsed during continuation treatment or in the percentage who experienced a recurrence of major depression during the first year of maintenance treatment. However, early-onset patients took 5-6 weeks longer to achieve remission than did late-onset patients, and a higher proportion had a history of suicide attempts. CONCLUSIONS: These data suggest that age at lifetime onset of recurrent major depression does not influence short- or long-term treatment response in elderly patients treated with combined interpersonal psychotherapy and nortriptyline, with the exception of slowing the speed of remission in early-onset cases. Difference in remission speed may reflect the greater number of previous episodes in the early-onset patients. Nevertheless, the likelihood of a longer time to remission, together with a higher rate of past suicide attempts, suggests that elderly depressed patients with a history of early-onset illness need particularly careful management.

Age Factors↗
PubMed1998

How common is resistance to treatment in recurrent, nonpsychotic geriatric depression?

OBJECTIVE: Effective treatments are available for major depressive disorder in later life. The purpose of this study was to elucidate the frequency of treatment resistance among the elderly. METHOD: Treatment resistance, defined as lack of recovery despite combined pharmacotherapy and psychotherapy, was prospectively examined in 180 elderly patients in an episode of recurrent, nonpsychotic major depression who were referred to a university medical center for treatment. They received open acute and continuation treatment with nortriptyline and interpersonal psychotherapy. RESULTS: Among the 159 patients who completed acute treatment, 19 (11.9%) did not experience a remission of depression. In addition, nine patients who had achieved remission relapsed during continuation therapy and did not recover despite vigorous treatment. Hence, excluding dropouts, 18.4% of the patients met the criteria for treatment resistance by their lack of response to acute treatment or by relapsing during continuation therapy and not recovering subsequently despite further vigorous treatment. CONCLUSIONS: The study suggests a relatively low rate of resistance to treatment among depressed geriatric patients referred to a university tertiary care setting.

Academic Medical Centers↗
PubMed1998

EEG sleep in African-American patients with major depression: a historical case control study.

This study was designed to evaluate the effect of race, specifically African-American, on electroencephalographic (EEG) sleep and clinical symptom profile in unipolar major depression. A clinical research database was used to identify appropriate subjects and a double-matched historical case-control design was implemented. African-American depression patients were double matched within protocol to Euro-American depressed patients. Age, sex, and protocol of origin were matching variables. African-American depressed patients had less total sleep, less slow wave sleep, more stage 2 sleep, longer rapid eye movement (REM) sleep latency, less REM sleep, and lower REM density than Euro-American depressed patients. African-American depressed patients did not differ from Euro-American patients in symptom severity, age of onset, number of episodes, socio-economic status, and, as planned, did not differ in age and sex distribution. Depressive symptom constellation also did not distinguish the two groups. African-American depressed patients demonstrated differences in EEG sleep profile, with less total sleep, overall lighter nonREM sleep, and relatively preserved REM sleep, despite a clinical symptom profile that did not differ from Euro-American depressed patients. The sleep profile appeared to be consonant with the sleep findings in chronic insomnia. The pathological implications of these differences remained to be explored in careful prospective studies of African-American depressed patients and in well-characterized, racially matched normal control comparisons.

Adult↗
PubMed1998

Anxiety as a predictor of response to interpersonal psychotherapy for recurrent major depression: an exploratory investigation.

Major depression and anxiety frequently co-occur, but the implications for psychological treatments have rarely been studied. We examined predictors of acute response to interpersonal psychotherapy in 134 consecutively treated female outpatients with recurrent unipolar depression. Women who failed to remit with interpersonal psychotherapy alone experienced higher levels of somatic anxiety, were more likely to meet criteria for lifetime panic disorder, were more likely to meet criteria for nonendogenous or nonmelancholic depression, and reported greater vocational impairment, higher levels of global severity, a longer duration of the index episode, and, somewhat surprisingly, lower levels of social impairment at pretreatment evaluation. A series of backwards stepping logistic regression analyses showed higher levels of baseline somatic anxiety and social functioning to be the most consistent predictors of nonresponse. Our findings strengthen existing evidence that concomitant anxiety can adversely affect the outcome of interpersonal therapy for depression.

Adult↗
PubMed1997

Which depressive symptoms are related to which sleep electroencephalographic variables?

Sleep complaints and electroencephalographic (EEG) sleep abnormalities are associated with risk for new onset depression, illness severity, treatment outcome, and vulnerability for recurrence of depression. The aim of this study was to evaluate the strength of association between EEG sleep measures and depression symptoms, and to identify the variables that account for the majority of the association. Depression ratings from the Hamilton Rating Scale for Depression and the Beck Depression Inventory and polysomnographic measures were examined in 361 adult outpatients with major depressive disorder. Canonical correlation and serial multiple regression analyses were used to determine the associations between depressive symptoms and sleep measures. Canonical correlation showed a unidimensional relationship between depressive symptoms and sleep measures (R = .55, p < .05). Fifteen depression items and nine sleep measures accounted for 95% of the correlation. Depression variables encompassed a core set of mood, neurovegetative, and cognitive symptoms. Sleep variables were primarily related to delta EEG activity, and this may be reflective of impaired sleep "drive" or heightened arousal during sleep.

Adult↗
PubMed1997

Forebrain activation in REM sleep: an FDG PET study.

Rapid eye movement (REM) sleep is a behavioral state characterized by cerebral cortical activation with dreaming as an associated behavior. The brainstem mechanisms involved in the generation of REM sleep are well-known, but the forebrain mechanisms that might distinguish it from waking are not well understood. We report here a positron emission tomography (PET) study of regional cerebral glucose utilization in the human forebrain during REM sleep in comparison to waking in six healthy adult females using the 18F-deoxyglucose method. In REM sleep, there is relative activation, shown by increased glucose utilization, in phylogenetically old limbic and paralimbic regions which include the lateral hypothalamic area, amygdaloid complex, septal-ventral striatal areas, and infralimbic, prelimbic, orbitofrontal, cingulate, entorhinal and insular cortices. The largest area of activation is a bilateral, confluent paramedian zone which extends from the septal area into ventral striatum, infralimbic, prelimbic, orbitofrontal and anterior cingulate cortex. There are only small and scattered areas of apparent deactivation. These data suggest that an important function of REM sleep is the integration of neocortical function with basal forebrain-hypothalamic motivational and reward mechanisms. This is in accordance with views that alterations in REM sleep in psychiatric disorders, such as depression, may reflect dysregulation in limbic and paralimbic structures.

Adult↗
PubMed1997

Maintenance nortriptyline effects on electroencephalographic sleep in elderly patients with recurrent major depression: double-blind, placebo- and plasma-level-controlled evaluation.

Our aim was to contrast the effects of maintenance nortriptyline and placebo on electroencephalographic sleep measures in elderly recurrent depressives who survived 1-year without recurrence of depression. Patients on nortriptyline took longer to fall asleep and did not maintain sleep better than patients on placebo; however, maintenance nortriptyline was associated with more delta-wave production and higher delta-wave density in the first non-REM (NREM) period relative to the second. Nortriptyline levels were positively but weakly related to all-night delta-wave production during maintenance (accounting for 6.6% of the variance in delta-wave counts). Total phasic REM activity increased 100% under chronic nortriptyline relative to placebo, with a robust increase in the rate of REM activity generation across the night. Effective long-term pharmacotherapy of recurrent major depression is associated with enhancement in the rate of delta-wave production in the first NREM period (i.e., delta sleep ratio) and of REM activity throughout the night.

Aged↗
PubMed1997

Inducing lifestyle regularity in recovering bipolar disorder patients: results from the maintenance therapies in bipolar disorder protocol.

On the basis of theories we articulated in earlier papers (Ehlers et al 1988: Arch Gen Psychiatry 45:948-952, 1993: Depression 1:285-293), we have developed an adjunctive psychosocial intervention for patients with bipolar 1 disorder. Central to this intervention is the establishment of regularity in daily routines. In this report, we present data from a controlled investigation comparing this new treatment, interpersonal and social rhythm therapy (IPSRT), with a conventional medication clinic approach. Despite comparable changes in symptomatology over a treatment period lasting up to 52 weeks, subjects assigned to IPSRT (n = 18) show significantly greater stability (p = .047) of daily routines with increasing time in treatment, while subjects assigned to the medication clinic condition (n = 20) show essentially no change in their social routines as measured by Social Rhythm Metric (SRM-Monk et al 1990: J Nerv Ment Dis 178(2):120-126) score. We conclude that IPSRT is capable of influencing lifestyle regularity in patients with bipolar 1 disorder, with the possible benefit of protection against future affective episodes.

Adult↗
PubMed1997

Identifying an abnormal electroencephalographic sleep profile to characterize major depressive disorder.

There is little agreement as to the best definition of a categorically abnormal electroencephalographic (EEG) sleep profile to characterize major depressive disorder. Therefore, a series of classification, replication, and validation analyses were conducted to identify such a profile. The EEG sleep studies of healthy controls (n = 44), depressed inpatients (n = 44), and depressed outpatients (n = 181) were utilized, including subgroups of patients studied both before and after nonpharmacologic treatment with either cognitive behavior therapy (CBT) or interpersonal psychotherapy (IPT). A discriminant index score (based on reduced REM latency, increased REM density, and decreased sleep efficiency) was found to: 1) reliably discriminate between depressed inpatients, depressed outpatients, and controls; 2) show good test-retest reliability; and 3) identify a subset of depressed outpatients who were older, manifested a broader array of EEG sleep disturbances, and were less responsive to CBT or IPT. Posttreatment studies of patients indicated that normal sleep profiles were relatively stable, whereas abnormal profiles tended to normalize. These findings provide an empirically validated method that may improve the applicability, efficiency, and prognostic utility of EEG sleep studies of depressed patients.

Adult↗
PubMed1997

Sleep in the wake of complicated grief symptoms: an exploratory study.

Our aim was to explore the concept that the symptoms of complicated grief may be a form of posttraumatic distress, rather than depression, and thus may have different effects on sleep. Sixty-five recently bereaved elders with varying levels of symptoms of complicated grief and depression were stratified by high versus low levels of symptoms; a two-way analysis of variance examined main effects of level of complicated grief symptoms and depressive symptoms on selected sleep measures, as well as interactions. Complicated grief symptoms were independently associated with mild subjective sleep impairment but showed no main effects on electroencephalographic (EEG) sleep measures. In a multiple regression analysis, complicated grief symptoms interacted with depressive symptoms to increase REM sleep percent. Thus, it appears that complicated grief symptoms do not entail the changes of EEG sleep physiology seen in depression, with the possible exception of an interaction with coexisting depression to enhance REM sleep percent.

Aged↗
PubMed1997

Electroencephalographic sleep correlates of episode and vulnerability to recurrence in depression.

The study of electroencephalogram (EEG) sleep in depressed patients before and after treatment with psychotherapy can distinguish episode-related and persistent biological features. With longitudinal follow-up, we can also assess whether EEG sleep measures are associated with recurrence of depression. In the current study, we examined EEG sleep during the depressed state and during symptomatic remission after treatment with interpersonal psychotherapy in 42 outpatients with major depression. Analyses included both visually-scored and computer-analyzed measures. Patients showed significant increases in sleep latency (p = .01) and rapid eye movement (REM) latency (p = .04) from baseline to remission, as well as a decrease in REM sleep percent (p = .03). Total delta EEG counts decreased from baseline to remission (p = .03), specifically in the second nonrapid eye movement (NREM) period (p = .03); as a result, the relative distribution of delta activity shifted toward sleep onset (i.e., increased delta sleep ratio; p = .03). Automated REM counts also decreased from depression to remission (p = .006). Compared to patients who remained well through one year of follow-up, those who suffered a recurrence of depression had less delta EEG activity at baseline and remission (p = .01), particularly in the lowest delta frequency band of 0.5-1.0 Hz. Specific components of sleep (total delta activity, delta ratio, REM activity) constitute episode-related biological features. Other components (slowest delta activity) may represent vulnerability factors for recurrence.

Adult↗
PubMed1997

Role of psychosocial factors in the onset of major depression.

Although the role of psychosocial factors in the onset of major depression has been well recognized for several decades, we argue that an integrated theory embracing psychosocial and biological domains will most likely provide a full understanding of the pathogenesis of depression. Advances in biology and psychopharmacology for depression provide the stimuli to examine the potency of different sets of variables to "predict" onset of depression. Recent attempts to develop new strategies for assessing both psychosocial and biological risk factors and examples of how such strategies might apply to depression are discussed.

Adolescent↗
PubMed1997

Coming to terms with the terms of risk.

Terms such as risk, risk factors, and especially the term cause are inconsistently and imprecisely used, fostering scientific miscommunication and misleading research and policy. Clarifying such terms is the essential first step. We define risk and a risk factor (protective factor) and their potency, set out the conceptual basis of the methods by which risk factors are identified and potency demonstrated, and propose criteria for establishing the status of a risk factor as a fixed or variable marker or a causal risk factor. All definitions are based on the state of scientific knowledge (empirical documentation), rather than on hypotheses, speculations, or beliefs. We discuss common approaches and pitfalls and give a psychiatric research example. Imprecise reports can impede the search for understanding the cause and course of any disease and also may be a basis of inadequate clinical or policy decision-making. The issues in risk research are much too important to tolerate less than precise terminology or the less than rigorous research reporting that results from imprecise and inconsistent terminology.

Causality↗
PubMed1997

Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy combinations.

BACKGROUND: Few reliable correlates of treatment response in depression have emerged despite nearly 40 years of research. We examined the correlates of recovery in a "mega-analysis," or meta-analysis of original data, of 595 patients with major depressive disorder enrolled in 6 standardized treatment protocols. METHODS: All patients (mean age, 44 years; 31% male and 69% female) met criteria for nonbipolar, nonpsychotic primary major depressive disorder and were treated for 16 weeks with either cognitive behavior therapy or interpersonal psychotherapy alone (psychotherapy alone; n = 243) or interpersonal psychotherapy plus antidepressant pharmacotherapy (combined therapy; n = 352). The impact of treatment type, severity, study, and other covariates on recovery rates or time to recovery were examined by means of chi 2, log-rank tests, the Cox proportional hazards model, and sensitivity analyses. RESULTS: Whereas combined therapy was not significantly more effective than psychotherapy alone in milder depressions, a highly significant advantage was observed in more severe recurrent depressions. Poorer outcomes were also observed in women and older patients, although these effects were dependent on inclusion of particular studies. CONCLUSIONS: Mega-analysis is a powerful method for comparing the efficacy of treatments and examining correlates of response. Using this method, we found new evidence in support of the widespread clinical impression that combined therapy is superior to psychotherapy alone for treatment of more severe, recurrent depressions.

Adult↗
PubMed1997

Temporal profiles of the course of depression during treatment. Predictors of pathways toward recovery in the elderly.

BACKGROUND: Predictors of treatment response and recovery from depression in late life remain poorly understood. Previous studies have focused on a narrow range of response and recovery variables; namely, whether patients achieve or do not achieve a defined outcome or time to achieve the outcome. Whether patients vary in their pathways toward those outcomes--and the extent to which such variation can be anticipated by patient characteristics prior to treatment--has not been empirically examined. METHODS: Depression symptom levels were monitored for 18 weeks in 95 persons aged 60 years or older who were experiencing a recurrence of major depression. Subjects received standardized combined nortriptyline treatment and interpersonal psychotherapy throughout the period. Cluster analysis was used to identify depression recovery patterns. Multivariate analyses considered whether recovery patterns were predicted by pretreatment psychosocial, clinical, and electroencephalographic sleep characteristics. RESULTS: Four subgroups of elders were identified who differed in rate, stability, and direction of recovery, ie, those showing (1) rapid sustained improvement, (2) delayed but sustained improvement, (3) partial or mixed response, or (4) no response. Pretreatment characteristics reliably predicted subjects' group membership. Higher levels of acute and chronic stressors, poorer social supports, younger age at first depressive episode, endogenous depression, higher current anxiety, older current age, and poorer subjective and objective (electroencephalographic) sleep predicted poorer response profiles. CONCLUSIONS: There are multiple pathways by which individuals begin to emerge from depression; these pathways can be identified empirically. Variables from diverse psychobiologic domains can be used to predict which persons are likely to advance along which trajectories toward recovery.

Age Factors↗