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Biomedical subjects

David J Kupfer

Publications and source records attributed to David J Kupfer.

At least 73 records · Page 4Linked to original sources
PubMed2004

Anger attacks in bipolar depression: predictors and response to citalopram added to mood stabilizers.

BACKGROUND: Of the 2 reports in the literature on anger attacks in bipolar depression, one found them to be uncommon (12%) compared with the rate in bipolar mixed states and unipolar depression (40%-60%), whereas the other found them to be common (62%). We examined anger attacks among participants in an 8-week trial of open-label citalopram added to mood stabilizer for the treatment of bipolar depression. We also examined trait anger, hypomanic symptoms, and depressive symptoms as predictors of anger attacks. We hypothesized that if anger attacks were related to hypomanic symptoms they would respond unfavorably to citalopram, whereas if they were related to trait anger or depressive symptoms they would respond favorably. METHOD: In 45 participants with a DSM-IV diagnosis of bipolar I or II depression, anger attacks, hypomanic symptoms, and depressive symptoms were assessed using a modified Anger Attacks Questionnaire, Young Mania Rating Scale, and Hamilton Rating Scale for Depression, respectively. Trait anger was measured using the State-Trait Anger Inventory. Posttreatment data were collected at the end of 8 weeks of treatment with citalopram or at dropout from the trial. The first participant study visit was in November 1998, and the final participant study visit was in December 2000. RESULTS: Before treatment with citalopram, 17 (38.6%) of 44 participants reported anger attacks (data on anger attacks were missing for 1 participant before treatment and 4 after treatment). Significantly fewer participants reported anger attacks after treatment (6 of 41, 14.6%; McNemar test, p <.05, 2-tailed). At pretreatment and post-treatment, trait anger was the only significant predictor of anger attacks (p <.05). CONCLUSIONS: These findings suggest that in bipolar depression anger attacks are common, may respond favorably to acute treatment with citalopram added to mood stabilizer, and are better predicted by trait anger than hypomanic or depressive symptoms. Further studies are needed to clarify the diagnostic and treatment implications of anger attacks in bipolar depression.

Adult↗
PubMed2003

Magnetic resonance imaging study of corpus callosum abnormalities in patients with bipolar disorder.

BACKGROUND: This study was conducted to further examine the hypothesis of abnormalities in size of corpus callosum in subjects with bipolar disorder. METHODS: Sixteen right-handed DSM-IV bipolar I patients and 27 right-handed healthy control subjects were studied. A 1.5-T GE Signa magnet was used, and three-dimensional gradient echo imaging (spoiled gradient recall acquisition) was conducted. Area measurements of corpus callosum were obtained blindly, with a semi-automated software, by a well-trained rater. RESULTS: Right-handed bipolar I patients had significantly smaller total corpus callosum, genu, posterior body, and isthmus areas compared with right-handed healthy control subjects (analysis of covariance with age, gender, and intracranial volume as covariates, p <.05). Partial correlation analyses, controlled for intracranial volumes, found a significant inverse relationship between age and total callosal, genu, anterior body, isthmus, and circularity in healthy control subjects (p <.05) but not in bipolar patients (p >.05). CONCLUSIONS: Smaller callosal areas may lead to altered inter-hemispheric communication and be involved in the pathophysiology and cognitive impairment found in bipolar disorder.

Adult↗
PubMed2003

Anatomical MRI study of basal ganglia in major depressive disorder.

The basal ganglia form a part of the brain neuroanatomic circuits that may be involved in mood regulation. Decreases in basal ganglia volumes have been previously reported in major depressive disorder patients in comparison to healthy controls. In this study, we measured caudate, putamen, and globus pallidus volumes in 25 patients with major depressive disorder (4 M; age+/-S.D.=41+/-11 years) and 48 healthy controls (29 M; age+/-S.D.=35+/-10 years), using high-resolution magnetic resonance imaging (MRI), in an attempt to replicate prior findings. Unlike most previous studies, we did not find significant differences between patient and control groups in basal ganglia volumetric measures. Nonetheless, there was a significant interaction between diagnosis and cerebral hemisphere, with MDD patients showing decreased asymmetry in globus pallidus volumes in comparison with healthy controls. Furthermore, in the patient group, left putamen volumes correlated inversely with length of illness, and left globus pallidus volume correlated directly with number of prior depressive episodes. These findings suggest that abnormalities in lateralization and possibly neurodegenerative changes in basal ganglia structures participate in the pathophysiology of major depressive disorder.

Adolescent↗
PubMed2003

Linkage and association between serotonin 2A receptor gene polymorphisms and bipolar I disorder.

Several inconsistent associations between bipolar I disorder (BD1) and polymorphisms of the genes encoding the serotonin 2A receptor (HTR2A) have been published. We conducted the Transmission Disequilibrium Test (TDT) and case-control comparisons involving nine single nucleotide polymorphisms at the serotonin 2A receptor gene (four SNPs of HTR2A exons and five flanking SNPs). Comparison of BD1 cases (n = 93) with a group of unrelated population based controls (n = 92) revealed associations with SNPs on exons 2 and 3 (516C/T and 1354C/T, respectively), consistent with haplotype-based differences. Analysis of the cases and their available parents using the TDT suggested significant linkage and associations with 1354C/T, as well as haplotypes bearing this SNP. Our results support an etiological role for HTR2A in BD1. In view of the relatively small sample, replicate studies using large samples are needed.

Adolescent↗
PubMed2003

Beyond the question of placebo controls: ethical issues in psychopharmacological drug studies.

RATIONALE: There is a broad range of complex ethical issues in the conduct of psychopharmacological drug studies that go beyond the question of the ethics of placebo controls. However, our empirical knowledge with respect to these issues is very limited. This review, although not exhaustive, highlights an array of ethical issues that arose from discussions within the NIMH Human Subjects Research Council Workgroup. OBJECTIVES: To delineate issues in psychopharmacological drug studies that require debate and would benefit from research leading to the development of empirically-supported guidelines. METHODS: Information included in this report was drawn from the first author's participation as chair of the NIMH Human Subjects Research Council Workgroup, guidelines for the ethical conduct of research proposed by professional organizations to which the first and third author belong, and relevant research literature. RESULTS: We have focused on general issues relating to informed consent, research with special populations, and long-term treatment studies. Additionally, we raise issues relevant to large research-oriented institutions. CONCLUSIONS: The essential ethical challenge in psychopharmacological trials is to balance risks and benefits in the context of the needs and capacities of individual research subjects. The IRB system must become evidence-based and not rely on unproven assumptions. Specific research studies should be undertaken to address many of the issues of informed consent and research ethics postulated in this paper.

Adolescent↗
PubMed2003

Is treatment-resistant depression a unique subtype of depression?

Treatment-resistant depression (TRD) continues to represent a major challenge for treating clinicians. This report reviews the relevant literature to evaluate whether TRD can be considered a specific subtype of depression based on 1) clinical characteristics and course (behavioral phenotype), 2) neurobiological profile, and 3) context and environment in which TRD develops. Although patients with TRD share a number of clinical, neurobiological, and context and environment characteristics, the lack of available data and the clinical heterogeneity of this condition do not currently permit the classification of TRD as a unique subtype of depression; however, this topic is worthy of further evaluation and research. Performing genetics and neuroimaging studies on patients enrolled in large, prospective and controlled studies may provide enough data for classifying TRD (or at least a part of what is currently described as TRD) as a specific subtype of depression. This in turn may facilitate the identification of more effective treatment strategies.

Clinical Laboratory Techniques↗
PubMed2003

Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review.

BACKGROUND: Antidepressant drugs can promote remission from acute depressive episodes. Our aim was to establish how long such treatments should be continued to prevent relapse. METHOD: We did a systematic overview of evidence from randomised trials of continuing treatment with antidepressants in patients with depressive disorders who have responded to acute treatment. Medline, Embase, Cinahl, PsycLIT, Psyndex, and Lilacs were searched. FINDINGS: Data were pooled from 31 randomised trials (4410 participants). Continuing treatment with antidepressants reduced the odds of relapse by 70% (95% CI 62-78; 2p<0.00001) compared with treatment discontinuation. The average rate of relapse on placebo was 41% compared with 18% on active treatment. The treatment effect seemed to persist for up to 36 months, although most trials were of 12 months' duration, and so the evidence on longer-term treatment requires confirmation. Significantly more participants allocated antidepressants withdrew from the trials than did those allocated to placebo (18% vs 15%, respectively; odds ratio 1.30, 95% CI 1.07-1.59): the treatment effect could be even greater in adherent patients. The two-thirds reduction in risk of depressive relapse seemed to be largely independent of the underlying risk of relapse, the duration of treatment before randomisation, or the duration of the randomly allocated therapy. INTERPRETATION: Antidepressants reduce the risk of relapse in depressive disorder, and continued treatment with antidepressants would benefit many patients with recurrent depressive disorder. The treatment benefit for an individual patient will depend on their absolute risk of relapse with greater absolute benefits in those at higher risk. Further trials are needed to establish the optimum length of therapy and should include patients who were not well represented in these trials, including those at low risk of relapse.

Antidepressive Agents↗
PubMed2003

Development and preliminary testing of the General 5-Spectrum Measure (GSM-V).

The Collaborative Spectrum Project has developed structured interviews and self-report instruments to assess the spectrum of symptomatology related to panic-agoraphobia, mood, social phobia, and obsessive-compulsive and eating disorders. In order to obtain a rapid pre-test on all five of these spectrum conditions, the authors sought to develop a brief instrument that would tap these conditions. This paper reports on 1) the procedures to derive this composite instrument, the General 5-Spectrum Measure (GSM-V), by selecting items from five existing spectrum instruments, and 2) preliminary testing of the internal consistency and test-retest reliability of the GSM-V. The GSM-V consists of 54 items grouped into scales that explore the five spectra described above. It was derived from existing data on five Structured Clinical Interviews that were designed to assess spectrum features by using multiple regression models. The GSM-V was administered as a stand-alone instrument along with the self-report versions of the spectrum interviews to a sample of 56 psychiatric patients in order to determine the internal consistency of its scales and the correlation with the parent spectrum measures. Moreover, to determine whether subjects would respond consistently to the same items on two different occasions (test-retest reliability), the GSM-V was re-administered within 1 month from the baseline. From each of the five spectrum interviews, items were selected that accounted for a significant proportion of variance of the total score of the parent instrument. The five sets of items so selected constitute separate scales. The scales of the GSM-V had a good to excellent internal consistency, excellent test-retest reliability, and proved to reproduce adequately the long-form measures. The GSM-V appears to provide a reliable alternative to the five longer spectrum interviews. It is envisaged that the instrument will be most useful as a pre-test to identify subjects with spectrum features that should be explored in greater detail. Additionally, it could provide a better characterization of patients with a syndromal level Axis-I disorder, who might require specific treatment strategies targeted to co-occurring subsyndromal conditions.

Adolescent↗
PubMed2003

Developmental and contextual influences on autonomic reactivity in young children.

Studies of cardiovascular reactivity in young children have generally employed integrated, physiologically complex measures, such as heart rate and blood pressure, which are subject to the multiple influences of factors such as blood volume, hematologic status, thermoregulation, and autonomic nervous system (ANS) tone. Reactivity studies in children have rarely employed more differentiated, proximal measures of autonomic function capable of discerning the independent effects of sympathetic and parasympathetic responses. We describe 1) the development, validity, and reliability of a psychobiology protocol assessing autonomic reactivity to challenge in 3- to 8-year-old children; 2) the influences of age, gender, and study context on autonomic measures; and 3) the distributions of reactivity measures in a normative sample of children and the prevalences of discrete autonomic profiles. Preejection period (PEP) and respiratory sinus arrythmia (RSA) were measured as indices of sympathetic and parasympathetic nervous system reactivity, respectively, and autonomic profiles were created to offer summative indices of PEP and RSA response. Results confirmed the protocol's validity and reliability, and showed differences in autonomic reactivity by age and study context, but not by gender. The studies' findings offer guidelines for future research on autonomic reactivity in middle childhood and support the feasibility of examining sympathetic and parasympathetic responses to challenge in 3- to 8-year-old children.

Arrhythmia, Sinus↗
PubMed2003

Microstructure of sleep in depressed patients according to the cyclic alternating pattern.

BACKGROUND: The aim of this study was to evaluate the microstructure of the EEG sleep of depressed subjects by cyclic alternating pattern (CAP) analysis. METHODS: 78 patients affected by major depression and 18 control subjects matched for age and sex underwent a full night polysomnographic study. RESULTS: A significant increase in CAP rate (60 versus 35%) was found in the patients group compared to controls while no significant difference was found with the traditional analysis. CONCLUSION: In depressed subjects CAP analysis is able to show a microstructural sleep impairment, which is not evident at the macrostructural level, providing an objective measure of sleep disturbance in those patients.

Adolescent↗
PubMed2003

White matter hyperintensities in bipolar and unipolar patients with relatively mild-to-moderate illness severity.

BACKGROUND: Increased rates of white matter hyperintense lesions have been reported in mood disorder patients. However, the potential effects of age and illness severity on reported findings are not fully established. We examined the rates of hyperintense lesions in adult, non-elderly bipolar and unipolar patients, with a relatively mild-to-moderate illness severity, and in matched healthy controls. METHOD: We examined brain MRI images in 24 bipolar (19-56 years, mean+/-S.D.=34.2+/-9.9 years) and 17 unipolar patients (24-59 years, 42.8+/-9.2 years), and 38 healthy controls (21-59 years, 36.8+/-9.7 years). T2-weighted and proton-density axial MRI images were obtained at 1.5 Tesla. The lesions were rated by two independent raters, using a semi-quantitative rating scale. RESULTS: There were no significant differences in the frequency of hyperintensities between bipolar or unipolar patients and healthy controls. Age was related to the presence of subcortical gray matter hyperintensities for the whole sample. Among the unipolar patients, length of illness and presence of mood disorder in a first-degree relative were related to deep and periventricular white matter lesions, respectively. LIMITATIONS: The methodology utilized for measurement of the white matter hyperintensities was semi-quantitative. CONCLUSIONS: Increased rates of white matter hyperintensities do not appear to be present in a group of relatively young mood disorder patients, with relatively mild to moderate illness severity. These brain lesions may be more directly related to late-life and more severe cases of these illnesses.

Adult↗
PubMed2003

Background and rationale for the sequenced treatment alternatives to relieve depression (STAR*D) study.

Sequenced Treatment Alternatives to Relieve Depression (STAR*D) attempts to fill in major clinical information gaps and to evaluate the theoretical principles and clinical beliefs that currently guide pharmacotherapy of major depressive disorder. The study is conducted in representative participant groups and settings using clinical management tools that easily can be applied in daily practice. Outcomes include clinical outcomes and health care utilization and cost estimates. Research findings should be immediately applicable to, and easily implemented in, the daily primary and specialty care practices. This article provides the overall rationale for STAR*D and details the rationale for key design, measurement, and analytic features of the study.

Antidepressive Agents↗
PubMed2003

Rates of response, euthymia and remission in two placebo-controlled olanzapine trials for bipolar mania.

OBJECTIVE: Clinically meaningful recovery from acute mania may not be captured by conventionally reported response categorizations. We defined new and stringent criteria for remission in bipolar mania. Using a cohort of patients with acute mania randomized to treatment with either olanzapine or placebo, we contrasted remission rates to findings using previously reported but more lenient categorical outcome measures of response and euthymia. METHODS: We pooled and reanalyzed results through 3 weeks from two published randomized double-blind trials of olanzapine versus placebo for treating acute bipolar mania (1, 2). Response was previously defined as > or = 50% decrease from baseline to endpoint total Young Mania Rating Scale (3) (Y-MRS) scores, and euthymia as an endpoint total Y-MRS score of < or = 12. In this report, remission required an endpoint total Y-MRS score of < or = 7, and an endpoint total Hamilton Depression Rating Scale, (HAM-D21) (4) score of < or = 7 and an endpoint Clinical Global Impression Scale - Bipolar version, CGI-BP (5), overall severity score of < or = 2. RESULTS: Olanzapine treated subjects achieved statistically significantly greater rates of clinical response, euthymia and remission than those assigned to placebo, 55% versus 29.5%, 50% versus 27%, and 18% versus 7%, respectively. CONCLUSIONS: Olanzapine monotherapy resulted in discernable clinical improvements in mania in over 50% of subjects and just under 20% of subjects achieved a near complete resolution of manic and accompanying depressive symptoms after 3 weeks of treatment. Full remission is an important but potentially elusive goal during short-term management of acute mania.

Adult↗
PubMed2003

The relationship between lifestyle regularity and subjective sleep quality.

In previous work we have developed a diary instrument-the Social Rhythm Metric (SRM), which allows the assessment of lifestyle regularity-and a questionnaire instrument--the Pittsburgh Sleep Quality Index (PSQI), which allows the assessment of subjective sleep quality. The aim of the present study was to explore the relationship between lifestyle regularity and subjective sleep quality. Lifestyle regularity was assessed by both standard (SRM-17) and shortened (SRM-5) metrics; subjective sleep quality was assessed by the PSQI. We hypothesized that high lifestyle regularity would be conducive to better sleep. Both instruments were given to a sample of 100 healthy subjects who were studied as part of a variety of different experiments spanning a 9-yr time frame. Ages ranged from 19 to 49 yr (mean age: 31.2 yr, s.d.: 7.8 yr); there were 48 women and 52 men. SRM scores were derived from a two-week diary. The hypothesis was confirmed. There was a significant (rho = -0.4, p < 0.001) correlation between SRM (both metrics) and PSQI, indicating that subjects with higher levels of lifestyle regularity reported fewer sleep problems. This relationship was also supported by a categorical analysis, where the proportion of "poor sleepers" was doubled in the "irregular types" group as compared with the "non-irregular types" group. Thus, there appears to be an association between lifestyle regularity and good sleep, though the direction of causality remains to be tested.

Adult↗
PubMed2003

Obesity as a correlate of outcome in patients with bipolar I disorder.

OBJECTIVE: This study sought to evaluate the relationship of obesity to demographic and clinical characteristics and treatment outcome in a group of 175 patients with bipolar I disorder who were treated for an acute affective episode and followed through a period of maintenance treatment. METHOD: Data were from participants entering the Maintenance Therapies for Bipolar Disorder protocol between 1991 and 2000. Analyses focused on differences in baseline demographic and clinical characteristics and in treatment outcomes between obese and nonobese patients. RESULTS: A total of 35.4% of the patients met criteria for obesity. Significant differences between the obese and nonobese patients were observed for years of education, numbers of previous depressive and manic episodes, baseline scores on the Hamilton Rating Scale for Depression, and durations of the acute episode. A Kaplan-Meier survival analysis indicated a significantly shorter time to recurrence during the maintenance phase among obese patients. The number of patients experiencing a depressive recurrence was significantly higher in the obese than in the nonobese group. CONCLUSIONS: Obesity is correlated with a poorer outcome in patients with bipolar I disorder. Preventing and treating obesity in bipolar disorder patients could decrease the morbidity and mortality related to physical illness, enhance psychological well-being, and possibly improve the course of bipolar illness. Weight-control interventions specifically designed for patients with bipolar illness should be developed, tested, and integrated into the routine care provided for these patients.

Adult↗
PubMed2003

Insurance expenditures on bipolar disorder: clinical and parity implications.

OBJECTIVE: This study assessed treatment rates and expenditures for behavioral health care by employers and behavioral health care patients in a large national database of employer-sponsored health insurance claims. METHOD: Insurance claims from 1996 from approximately 1.66 million individuals were examined. Average annual charges per person and payments for behavioral health care were calculated along with patient out-of-pocket expenses and inpatient hospital admission rates. Behavioral health care expenditures for bipolar disorder were compared to expenditures for other behavioral health care diagnoses in these same insurance plans. RESULTS: A total of 7.5% of all covered individuals filed a behavioral health care claim. Of those, 3.0% were identified as having bipolar disorder, but they accounted for 12.4% of total plan expenditures. Patients with bipolar disorder incurred annual out-of-pocket expenses of $568, more than double the $232 out-of-pocket expenses incurred by all claimants. The inpatient hospital admission rate for patients with bipolar disorder was also higher (39.1%) compared to 4.5% for all other behavioral health care claimants. Furthermore, annual insurance payments were higher for covered medical services for individuals with bipolar disorder than for patients with other behavioral health care diagnoses. CONCLUSIONS: Bipolar disorder is the most expensive behavioral health care diagnosis, both for patients with bipolar disorder and for their insurance plans. For every behavioral health care dollar spent on outpatient care for patients with bipolar disorder, $1.80 is spent on inpatient care, suggesting that better prevention management could decrease the financial burden of bipolar disorder.

Adult↗