Search PubMed⌕ Search

Biomedical subjects

David J Kupfer

Publications and source records attributed to David J Kupfer.

At least 91 records · Page 5Linked to original sources
PubMed2003

A new approach to integrating data from multiple informants in psychiatric assessment and research: mixing and matching contexts and perspectives.

OBJECTIVE: When there exists no single source of information (informant) to validly measure a characteristic, it is typically recommended that data from multiple informants be used. In psychiatric assessment and research, however, multiple informants often provide discordant data, which further confuse the measurement. Strategies such as arbitrarily choosing one informant or using the data from all informants separately generate further problems. This report proposes a theory to explain observed patterns of interinformant discordance and suggests a new approach to using data from multiple informants to measure characteristics of interest. METHOD: Using the example of assessment of developmental psychopathology in children, the authors propose a model in which the choice of informants is based on conceptualizing the contexts and perspectives that influence expression of the characteristic of interest and then identifying informants who represent those contexts and perspectives in such a way as to have the weaknesses of one informant canceled by the strengths of another. RESULTS: Applications of this approach to several datasets indicate that when these principles are followed, a more reliable and valid consensus measure is obtained, and failure to obtain a reliable, valid measure is indicative of some deviation from the principles. CONCLUSIONS: In obtaining a consensus measure, the issue is not determining how many informants are needed but choosing the right set of informants.

Adult↗
PubMed2003

Relationship of birth cohort and early age at onset of illness in a bipolar disorder case registry.

OBJECTIVE: Utilizing data from a previously characterized registry of subjects with bipolar illness, the authors examined age at onset of the first illness episode in cohorts of subjects born from 1900 through 1939 and from 1940 through 1959. METHOD: Demographic and clinical characteristics at the first full episode of bipolar disorder of subjects in a diagnostically validated voluntary bipolar disorder registry (N=1,218) were reviewed and subjected to statistical analyses. RESULTS: The median age at onset of the first episode of bipolar illness was lower by 4.5 years in subjects born during or after 1940 (median age=19 years), compared with subjects born before 1940 (median age=23.5 years). The proportion of subjects with bipolar disorder presenting with a prepubertal onset was significantly higher in the later birth-year cohort than in the earlier birth-year cohort. More than 50% of male and female subjects in both cohorts had a depressive episode as the first episode of bipolar illness. Subjects in each cohort who had a parent with major depression, bipolar disorder, or schizophrenia experienced their first episode nearly 4 to 5 years earlier than the other subjects in the cohort. CONCLUSIONS: Prospective epidemiological studies conducted with bipolar disorder subjects are needed to either affirm or refute these data on age at illness onset. If the results are affirmed, the early recognition of prepubertal bipolar disorder will be important, so that the condition can be treated with appropriate medications and medications that could potentially worsen the illness course can be avoided. Similarly, early recognition of bipolar illness is important, especially in women, to minimize use of antidepressant monotherapy for patients with bipolar illness. Among young people presenting with major depression as the first illness episode, a parental history of major depression, bipolar disorder, or psychosis may be a useful pointer to future bipolar disorder. Early recognition and appropriate treatment of bipolar illness may prevent the development of chronicity and serious functional impairment.

Adolescent↗
PubMed2002

Increased gray matter volume in lithium-treated bipolar disorder patients.

Lithium's neurotrophic effects have been reported in several in vitro and ex vivo studies. Preliminary human studies with magnetic resonance imaging (MRI) and spectroscopy have recently provided evidence of lithium-induced increases in gray matter volumes and N-acetyl-aspartate levels. In order to further examine the hypothesis that lithium treatment would relate to detectable increases in gray matter brain content, we blindly measured gray and white matter volumes in MRI images of 12 untreated and 17 lithium-treated bipolar patients and 46 healthy controls. Using multivariate analysis of covariance with age and gender as covariates, we found that total gray matter volumes were significantly increased in lithium-treated (747.9 +/- 69.8 cm(3)) compared with untreated patients (639.2 +/- 91.2 cm(3); F = 10.6; d.f. = 1, 25; P = 0.003) and healthy individuals (675.8 +/- 61.8 cm(3); F = 17.4; d.f. = 1, 59; P < 0.001), suggesting in vivo effects of lithium on gray matter, which could possibly reflect lithium's neurotrophic effects.

Analysis of Variance↗
PubMed2002

Electroencephalographic sleep profiles in single-episode and recurrent unipolar forms of major depression: II. Comparison during remission.

BACKGROUND: Previous studies indicate that recurrent forms of depression are associated with greater biological disturbances as compared to single-episode cases. This study examines whether the observed differences in the sleep patterns during recurrent and single-episode depression persist into remission following nonpharmacologic treatment. METHODS: Two groups of patients (27 single episode [SE] and 53 recurrent unipolar [RU]) with major depression underwent sleep studies before and after nonpharmacologic treatment. Groups were equated for age, severity, and proportion of men and women. Groups were compared using multivariate analyses of covariance and/or analyses of covariance to examine six sets of sleep measures. RESULTS: The differences observed between the SE and RU groups during the index episode persisted into early remission. The findings of greater disturbances of sleep continuity, rapid eye movement sleep and diminished slow wave sleep in the RU group supports the hypothesis that recurrent depression is associated with a more severe neurophysiological substrate than clinically comparable SE cases. CONCLUSIONS: Although these observations are consistent with an illness progression model, the possibility that recurrent affective illness is associated with a more virulent, stable phenotype cannot be ruled out. Resolution of this issue requires longitudinal and family studies.

Adult↗
PubMed2002

Efficacy of olanzapine in combination with valproate or lithium in the treatment of mania in patients partially nonresponsive to valproate or lithium monotherapy.

BACKGROUND: A 6-week double-blind, randomized, placebo-controlled trial was conducted to determine the efficacy of combined therapy with olanzapine and either valproate or lithium compared with valproate or lithium alone in treating acute manic or mixed bipolar episodes. METHODS: The primary objective was to evaluate the efficacy of olanzapine (5-20 mg/d) vs placebo when added to ongoing mood-stabilizer therapy as measured by reductions in Young Mania Rating Scale (YMRS) scores. Patients with bipolar disorder (n = 344), manic or mixed episode, who were inadequately responsive to more than 2 weeks of lithium or valproate therapy, were randomized to receive cotherapy (olanzapine + mood-stabilizer) or monotherapy (placebo + mood-stabilizer). RESULTS: Olanzapine cotherapy improved patients' YMRS total scores significantly more than monotherapy (-13.11 vs -9.10; P = .003). Clinical response rates (> or = 50% improvement on YMRS) were significantly higher with cotherapy (67.7% vs 44.7%; P< .001). Olanzapine cotherapy improved 21-item Hamilton Depression Rating Scale (HAMD-21) total scores significantly more than monotherapy (4.98 vs 0.89 points; P< .001). In patients with mixed-episodes with moderate to severe depressive symptoms (DSM-IV mixed episode; HAMD-21 score of > or = 20 at baseline), olanzapine cotherapy improved HAMD-21 scores by 10.31 points compared with 1.57 for monotherapy (P< .001). Extrapyramidal symptoms (Simpson-Angus Scale, Barnes Akathisia Scale, Abnormal Involuntary Movement Scale) were not significantly changed from baseline to end point in either treatment group. Treatment-emergent symptoms that were significantly higher for the olanzapine cotherapy group included somnolence, dry mouth, weight gain, increased appetite, tremor, and slurred speech. CONCLUSION: Compared with the use of valproate or lithium alone, the addition of olanzapine provided superior efficacy in the treatment of manic and mixed bipolar episodes.

Acute Disease↗
PubMed2002

Clinical significance of lifetime panic spectrum symptoms in the treatment of patients with bipolar I disorder.

BACKGROUND: Given the observed association between panic disorder and bipolar disorder and the potential negative influence of panic symptoms on the course of bipolar illness, we were interested in the effects of what we have defined as "panic spectrum" conditions on the clinical course and treatment outcome in patients with bipolar I (BPI) disorder. We hypothesized that lifetime panic spectrum features would be associated with higher levels of suicidal ideation and a poorer response to acute treatment of the index mood episode in this patient population. METHODS: A sample of 66 patients with BPI disorder completed a self-report measure of lifetime panic-agoraphobic spectrum symptoms. Patients falling above and below a predefined clinical threshold for panic spectrum were compared for clinical characteristics, the presence of suicidal ideation during acute treatment, and acute treatment response. RESULTS: Half of this outpatient sample reported panic spectrum features above the predefined threshold. These lifetime features were associated with more prior depressive episodes, higher levels of depressive symptoms, and greater suicidal ideation during the acute-treatment phase. Patients with BPI disorder who reported high lifetime panic-agoraphobic spectrum symptom scores took 27 weeks longer than those who reported low scores to remit with acute treatment (44 vs 17 weeks, respectively). CONCLUSIONS: The presence of lifetime panic spectrum symptoms in this sample of patients with BPI disorder was associated with greater levels of depression, more suicidal ideation, and a marked (6-month) delay in time to remission with acute treatment. Alternate treatment strategies are needed for patients with BPI disorder who endorse lifetime panic spectrum features.

Adolescent↗
PubMed2002

National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders.

A consensus conference on the use of placebo in mood disorder studies consisted of expert presentations on bioethics, biostatistics, unipolar depression, and bipolar disorder. Work groups considered evidence and presented statements to the group. Although it was not possible to write a document for which there was complete agreement on all issues, the final document incorporated input from all authors. There was consensus that placebo has a definite role in mood disorder studies. Findings of equivalence between a new drug and standard treatment in active control studies is not evidence of efficacy unless the new drug is also significantly more effective than placebo. Add-on studies in which patients are randomized to standard therapy plus the investigational drug or standard therapy plus placebo are especially indicated for high-risk patients. Mood disorders in elderly and pediatric patients are understudied, and properly designed trials are urgently needed. Research is needed on the ethical conduct of studies to limit risks of medication-free intervals and facilitate poststudy treatment. Patients must fully understand the risks and lack of individualized treatment involved in research.

Bipolar Disorder↗
PubMed2002

Recruiting and retaining future generations of physician scientists in mental health.

The authors discuss 6 challenges facing the recruitment and retention of physician scientists as career mental health researchers. These challenges include (1) early identification and recruitment at the undergraduate and medical student level; (2) recruitment of a more diverse group of trainees; (3) safety nets for reducing attrition; (4) strategies to promote successful competition for K awards; (5) definition of appropriate roles and career development opportunities in multisite clinical trials; and (6) strategies for the mentoring "cost." A coalition of stakeholders--federal, academic, foundational, and in the pharmaceutical industry--is needed to meet these challenges.

Career Choice↗
PubMed2002

Course and rate of antidepressant response in the very old.

OBJECTIVE: The authors examined elderly patients with major depression to determine the relationship of current age to treatment response course and success rate. METHODS: Three studies of elderly depressed patients provided data on antidepressant treatment response in 323 subjects, treated in protocols using either nortriptyline or paroxetine. We grouped the subjects by current age: 'young-old' (59-69, N=163), 'middle-old' (70-75, N=80), and 'older-old' (76-99, N=80). We employed mixed-effect random regression analyses to examine Hamilton Rating Scale for Depression scores over 12 weeks of acute treatment. RESULTS: Older-old patients responded as quickly and successfully as the young- and middle-old. CONCLUSIONS: Major depression in the very old can be treated as successfully as in early old age.

Age Factors↗
PubMed2002

Anatomical MRI study of subgenual prefrontal cortex in bipolar and unipolar subjects.

This study attempted to replicate previous findings of decreased gray matter content in the subgenual prefrontal cortex (SGPFC) in mood disorder patients. Eighteen DSM-IV unipolar patients, 27 DSM-IV bipolar patients, and 38 healthy controls were studied. A 1.5T GE Signa Imaging System with Signa 5.4.3 software was used. The semi-automated software MedX (Sensor Systems, Sterling, VA) was utilized for the anatomical measures of SGPFC volumes. There were no significant differences in SGPFC volumes in familial and non-familial unipolar and bipolar patients compared with healthy controls, nor between drug-free and lithium-treated bipolar patients (ANOVA, p >.05). In vivo abnormalities in the volumes of SGPFC were not identified in mildly depressed or euthymic unipolar or bipolar mood disorder outpatients, either familial or non-familial.

Adult↗
PubMed2002

Does interpersonal psychotherapy protect women from depression in the face of stressful life events?

The present study compared the role of life events in predicting time to index episode onset under conditions of no or variable treatment versus the role of life events in predicting time to recurrence during maintenance interpersonal psychotherapy (IPT). Eighty-three women with recurrent major depression participated in acute IPT treatment followed by 2 years of maintenance IPT. Life events were assessed using contextual interview and rating methods. Cox regression survival analyses indicated that, although severe life events were significantly associated with time to index episode onset, there was little evidence of an association between events experienced during maintenance treatment and time to recurrence. These results provide evidence that IPT may decrease the potency of life events in provoking recurrence.

Adult↗
PubMed2002

A simple way to measure daily lifestyle regularity.

A brief diary instrument to quantify daily lifestyle regularity (SRM-5) is developed and compared with a much longer version of the instrument (SRM-17) described and used previously. Three studies are described. In Study 1, SRM-17 scores (2 weeks) were collected from a total of 293 healthy control subjects (both genders) aged between 19 and 92 years. Five items (1) Get out of bed, (2) First contact with another person, (3) Start work, housework or volunteer activities, (4) Have dinner, and (5) Go to bed were then selected from the 17 items and SRM-5 scores calculated as if these five items were the only ones collected. Comparisons were made with SRM-17 scores from the same subject-weeks, looking at correlations between the two SRM measures, and the effects of age and gender on lifestyle regularity as measured by the two instruments. In Study 2 this process was repeated in a group of 27 subjects who were in remission from unipolar depression after treatment with psychotherapy and who completed SRM-17 for at least 20 successive weeks. SRM-5 and SRM-17 scores were then correlated within an individual using time as the random variable, allowing an indication of how successful SRM-5 was in tracking changes in lifestyle regularity (within an individual) over time. In Study 3 an SRM-5 diary instrument was administered to 101 healthy control subjects (both genders, aged 20-59 years) for two successive weeks to obtain normative measures and to test for correlations with age and morningness. Measures of lifestyle regularity from SRM-5 correlated quite well (about 0.8) with those from SRM-17 both between subjects, and within-subjects over time. As a detector of irregularity as defined by SRM-17, the SRM-5 instrument showed acceptable values of kappa (0.69), sensitivity (74%) and specificity (95%). There were, however, differences in mean level, with SRM-5 scores being about 0.9 units [about one standard deviation (SD)] above SRM-17 scores from the same subject-weeks. SRM-5 scores also deviated more from a Gaussian distribution than did SRM-17 ones. In a study with a sample size of 101, the new SRM-5 instrument yielded scores with a mean of 4.11 and an SD of 1.13. Correlations between lifestyle regularity and age, and between lifestyle regularity and morningness appeared similar whether 5-item or 17-item SRM measures were used. When a gender difference in lifestyle regularity appeared, it was detected by both SRM-5 and SRM-17 measures.

Adult↗
PubMed2002

Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking.

Sleep is an essential human function. Although the function of sleep has generally been regarded to be restorative, recent data indicate that it also plays an important role in cognition. The neurobiology of human sleep is most effectively analysed with functional imaging, and PET studies have contributed substantially to our understanding of both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. In this study, PET was used to determine patterns of regional glucose metabolism in NREM sleep compared with waking. We hypothesized that brain structures related to waking cognitive function would show a persistence of function into the NREM sleep state. Fourteen healthy subjects (age range 21-49 years; 10 women, 4 men) underwent concurrent EEG sleep studies and [(18)F]fluoro-2-deoxy-D-glucose PET scans during waking and NREM sleep. Whole-brain glucose metabolism declined significantly from waking to NREM sleep. Relative decreases in regional metabolism from waking to NREM sleep occurred in wide areas of frontal, parietal, temporal and occipital association cortex, primary visual cortex, and in anterior/dorsomedial thalamus. After controlling for the whole-brain declines in absolute metabolism, relative increases in regional metabolism from waking to NREM were found bilaterally in the dorsal pontine tegmentum, hypothalamus, basal forebrain, ventral striatum, anterior cingulate cortex and extensive regions of the mesial temporal lobe, including the amygdala and hippocampus, and in the right dorsal parietal association cortex and primary somatosensory and motor cortices. The reductions in relative metabolism in NREM sleep compared with waking are consistent with prior findings from blood flow studies. The relative increases in glucose utilization in the basal forebrain, hypothalamus, ventral striatum, amygdala, hippocampus and pontine reticular formation are new observations that are in accordance with the view that NREM sleep is important to brain plasticity in homeostatic regulation and mnemonic processing.

Adult↗
PubMed2002

Differential performance of the macarthur HBQ and DISC-IV in identifying DSM-IV internalizing psychopathology in young children.

OBJECTIVE: Three sites collaborated to evaluate the differential performance of the MacArthur Health and Behavior Questionnaire (HBQ) and the Diagnostic Interview Schedule for Children Version IV (DISC-IV) in identifying DSM-IV psychopathology in young children. METHOD: A sample of 120 four- to eight-year-old nonreferred (community) (n = 67) and referred (clinical) (n = 53) children was examined. Mothers reported on their child's mental health symptoms using the HBQ (a dimensional measure with a clinical cutoff score) and the DISC-IV. Teachers independently reported on the child's symptoms and impairment in school using the teacher HBQ. Children self-reported on their symptoms using the companion Berkeley Puppet Interview. RESULTS: On the basis of its derived clinical cutoff scores, the HBQ identified significantly more children with clinical symptoms of DSM-IVinternalizing psychopathology than the DISC-IV in both referred and nonreferred groups. There was a high level of agreement between the two measures in the identification of externalizing psychopathology. Children identified as having internalizing psychopathology by the HBQ were also rated as highly symptomatic and impaired by teachers. CONCLUSION: The findings support the general validity of the parent HBQ for the assessment of young child psychopathology and the hypothesis that it captures more internalizing psychopathology than the DISC-IV in this population.

Child↗
PubMed2002

The confluence of mental, physical, social, and academic difficulties in middle childhood. I: exploring the "head waters" of early life morbidities.

OBJECTIVE: To present the conceptual and methodological backgrounds for development of the MacArthur Assessment Battery for Middle Childhood and one of its constituent instruments, the MacArthur Health and Behavior Questionnaire (HBQ). METHOD: As a component of HBQ development, research addressing "developmental psychopathology" as a nosological category of human disorder was reviewed. Such research bears, as its conceptual legacy, the strengths and frailties of the nosology from which the category was derived. RESULTS: Defining developmental psychopathology has done much to foster psychiatric and medical awareness of the particular dilemmas and problems intrinsic to childhood psychopathology. On the other hand, its delineation has obscured the tendency for psychiatric morbidities to emerge gradually along trajectories of development, to involve interactions among organismic and contextual factors, and to represent "confluences" of childhood difficulties suggesting common, less distinctive origins among psychiatric and biomedical disorders. The recognizable psychopathology of adolescence is most often preceded by protean manifestations of early difficulties resulting from the conjoint operation of child-specific vulnerabilities and context-derived risk factors. Co-occurrences of mental, physical, social, and academic difficulties in children's lives are more frequently the rule than the exception, and isolated, singular psychopathology is less common in childhood than the prevailing diagnostic nosology may imply. CONCLUSIONS: The MacArthur Assessment Battery represents an effort to assemble, in a single set of instruments, measures of child, context, and health risk factors for the prevalent morbidities of middle childhood. The HBQ, a component of the Battery, is a parent- and teacher-report instrument that assesses mental health, physical health, social, and school adaptation in 4- to 8-year-old children.

Child↗
PubMed2002

The confluence of mental, physical, social, and academic difficulties in middle childhood. II: developing the Macarthur health and Behavior Questionnaire.

OBJECTIVES: (1) To evaluate the psychometric properties of the MacArthur Health and Behavior Questionnaire (HBQ) in two studies of 4- to 8-year-old children and (2) to explore the empirical and theoretical implications of HBQ-based study findings. METHOD: Samples of children were recruited from (1) mental health clinics (n = 53) and community schools (n = 67) for a case-control study in three research sites and (2) a Wisconsin-based community cohort study of families and work, comprising children with high levels of internalizing and/or externalizing behavior problems and asymptomatic children (N = 122). Combinations of mothers, fathers, and teachers completed the HBQ at one or two time points in four geographically and culturally distinctive settings. RESULTS: Assessment of HBQ reliability showed high test-retest stability and cross-informant agreement. The instrument discriminated strongly and significantly among symptom groups (i.e., high internalizing, high externalizing, high both, and low both) and showed moderate to large effect sizes for between-group differences. Substantial covariance was also found among the HBQ mental, physical, social, and academic problem subscales. CONCLUSIONS: The HBQ is a reliable and valid parent- and teacher-report instrument for assessing multiple dimensions of health and dysfunction in middle childhood and for identifying children on whom more intensive diagnostic procedures may be warranted. Confluences among the four health dimensions suggest phenomenological and perhaps etiological commonalities among traditionally partitioned childhood difficulties and suggest possible artificiality in the conventional distinction between pediatric and child psychiatric morbidities.

Child↗
PubMed2002

Slower treatment response in bipolar depression predicted by lower pretreatment thyroid function.

OBJECTIVE: Because treatment of the depressed phase of bipolar disorder is a clinical challenge and hypothyroidism is known to be associated with depression, the authors examined the relationship between pretreatment thyroid values and response to antidepressant treatment. It was hypothesized that subjects with lower thyroid function, even within the normal range, would have a poorer response to initial treatment. METHOD: The subjects were 65 patients in the depressed phase of bipolar I disorder who were enrolled in a larger ongoing study. A panel of thyroid measures, including thyroid-stimulating hormone (TSH), thyroxine, triiodothyronine resin uptake, and free thyroxine index (FTI), were determined before initiation of algorithm-guided treatment. The effect of each thyroid measurement on time to remission was estimated by using the Cox proportional hazards model. RESULTS: Both lower values of FTI and higher values of TSH were significantly associated with longer times to remission, i.e., slower response to treatment. Outcomes were relatively poor unless patients had FTI values above the median and TSH values below the median. Patients with this optimal profile experienced remission 4 months faster than the remainder of the study group. CONCLUSIONS: This study provides further evidence that patients with bipolar disorder are particularly sensitive to variations in thyroid function within the normal range. Our results suggest that nearly three-quarters of patients with bipolar disorder have a thyroid profile that may be suboptimal for antidepressant response. It remains to be seen whether pharmacological enhancement of thyroid function will facilitate recovery from bipolar depression.

Adult↗