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Biomedical subjects

D J Kupfer

Publications and source records attributed to D J Kupfer.

At least 37 records · Page 2Linked to original sources
PubMed2001

Illness characteristics and their association with prescription patterns for bipolar I disorder.

INTRODUCTION: The present study explores the relationships among psychotropic medications, illness-related parameters, patient demography, suicidality, and levels of functioning in a voluntary bipolar case registry. METHODS: Four hundred and fifty-seven subjects with bipolar I disorder were selected from a voluntary registry for subjects with bipolar illness. Demographic characteristics, psychotropic medications, age at onset of illness, duration of illness, number of hospitalizations, the ability to live independently, employment and driving status as well as the history of suicidal attempts were obtained through a structured phone interview. RESULTS: Subjects treated with antidepressants had a shorter duration of illness, while patients treated with antipsychotic drugs had an earlier onset of illness. The number of hospitalizations for mania was fewer among patients taking a combination of lithium and carbamazepine as compared to patients not receiving them, while subjects taking neuroleptics had more hospitalizations as compared to subjects not receiving them. The number of psychotropic agents prescribed correlated positively with the number of hospitalizations for depressive episodes. Curiously, no correlations were found between the types of psychotropic agents prescribed and the levels of functioning or a history of suicidal attempts. Interestingly, our results suggest that more than half of the subjects were unable to live independently or to work due to their illness. Also, more than 50% of the subjects had at least one suicidal attempt, the majority occurred during depressive episodes. CONCLUSIONS: Our results suggest that subjects with bipolar I disorder have high rate of suicidal attempts and may have serious functional impairments.

Adolescent↗
PubMed2001

Screening for anxiety and depression in early adolescence.

OBJECTIVE: To examine the level of diagnostic and discriminative accuracy of three dimensional rating scales for detecting anxiety and depressive disorders in a school-based survey of 9th grade youths. METHOD: Classroom screening instruments, the Center for Epidemiologic Studies-Depression Scale (CES-D), the Revised Children's Manifest Anxiety Scale (RCMAS), and the Multidimensional Anxiety Scale for Children (MASC) were administered to 632 youths from three sites in 1998. On the basis of rating scale results, samples of high-scoring and non-high-scoring youths were invited to participate in a diagnostic interview conducted within 2 months of the screening sessions. RESULTS: MASC scores were most strongly associated with individual anxiety disorders, particularly among females, whereas the CES-D composite score was associated with a diagnosis of major depression, after controlling for comorbid disorders. The RCMAS was least successful in discriminating anxiety and depression. When receiver operator characteristic curves were examined, diagnostic accuracy was moderate. CONCLUSIONS: The ability of the MASC and CES-D to discriminate within and between categorically defined diagnostic groups has important implications for the accurate identification of youths in need of services.

Adolescent↗
PubMed2001

Tolerability of combined treatment with lithium and paroxetine in patients with bipolar disorder and depression.

Patients with bipolar disorder are often prescribed lithium in combination with a selective serotonin reuptake inhibitor. Doubts still remain, however, about the safety of the combination, particularly with regard to the risk of developing a serotonin syndrome. The authors retrospectively evaluated the safety of the combination of lithium and paroxetine when the two medications were sequentially prescribed in patients with bipolar disorder. The authors examined a sample of 17 patients with bipolar disorder who were treated with lithium during a depressive episode and who required paroxetine as an adjunctive antidepressant to ongoing lithium treatment. Averaging across all subjects, no statistically significant increase was found for any of the somatic symptoms that were assessed before and after paroxetine was added to ongoing lithium therapy. Examining the clinical records of each patient in detail; however, four patients who developed significant adverse events, possibly related to an emerging serotonin syndrome were identified. Clinicians should be aware of the possible development of a serotonin syndrome among patients in whom paroxetine is added to ongoing lithium treatment.

Adult↗
PubMed2001

Differential effects of age on brain gray matter in bipolar patients and healthy individuals.

This study examined possible differences in total gray and white matter brain content in bipolar patients and healthy individuals, and their relationship with age. 22 DSM-IV bipolar patients and 22 healthy controls underwent a 1.5-tesla Spoiled Gradient Recalled Acquisition (SPGR) MRI. Evaluators blind to patients' identities measured total brain, gray and white matter volumes using a semi-automated software. No differences were found for total brain volume, gray matter or white matter volumes between bipolar patients and healthy controls (MANCOVA, age as covariate, p > 0.05). Age was inversely correlated with total gray matter volume in patients (r = -0.576, p = 0.005), but not in controls (r = -0.193, p = 0.388). Our findings suggest that any existing gray matter deficits in bipolar disorder are likely to be localized to specific brain regions, rather than generalized. The inverse correlation between age and brain gray matter volumes in bipolar patients, not present in healthy controls, in this sample of mostly middle-aged adults, could possibly indicate more pronounced age-related gray matter decline in bipolar patients, and may be of potential relevance for the pathophysiology of the disorder.

Adolescent↗
PubMed2001

Autonomic reactivity and psychopathology in middle childhood.

BACKGROUND: Better indicators are needed for identifying children with early signs of developmental psychopathology. AIMS: To identify measures of autonomic nervous system reactivity that discriminate children with internalising and externalising behavioural symptoms. METHOD: A cross-sectional study of 122 children aged 6--7 years examined sympathetic and parasympathetic reactivity to standardised field-laboratory stressors as predictors of parent- and teacher-reported mental health symptoms. RESULTS: Measures of autonomic reactivity discriminated between children with internalising behaviour problems, externalising behaviour problems and neither. Internalisers showed high reactivity relative to low-symptom children, principally in the parasympathetic branch, while externalisers showed low reactivity, in both autonomic branches. CONCLUSIONS: School-age children with mental health symptoms showed a pattern of autonomic dimorphism in their reactivity to standardised challenges. This observation may be of use in early identification of children with presyndromal psychopathology.

Arousal↗
PubMed2001

Narrowing the gap in treatment of depression.

OBJECTIVE: Although effective treatments for depression exist, under or non-treatment of depression is common. Efforts were made in the early 1990s to improve recognition and treatment of depression, with many of those efforts targeted at groups most vulnerable to under-treatment. The purpose of this study is to assess treatment rates in 1993-1994 and 1996-1997. METHOD: Using nationally representative surveys of office-based practice covering the years 1993, 1994, 1996, and 1997, we obtained estimates of visits by adults in which depression was diagnosed and a prescription for antidepressant medication and/or psychotherapy was provided or ordered. RESULTS: The proportion of physician office visits in which a depression diagnosis was recorded did not change from 1993-1994 (3.48 percent) to 1996-1997 (3.40 percent). However, the rate of antidepressant prescription or psychotherapy rose from 74.2 percent of visits with a depression diagnosis in 1993-1994 to 82.3 percent of these visits in 1996-1997. Significantly lower rates of treatment for depression during office visits made by African American patients, elderly patients, and patients on Medicaid occurred in 1993-1994, but were not evident in 1996-1997, reflecting improved rates of depression treatment in these populations. CONCLUSIONS: Although rates of diagnosis of depression during office visits have not increased, treatment rates for depression are improving among those who are diagnosed, including groups of people who historically were less likely to be offered treatment. Additional efforts to improve recognition and diagnosis of depression in ambulatory medical practice and to improve dissemination of treatment are needed.

Adolescent↗
PubMed2001

The development of study exit criteria for evaluating antimanic compounds.

BACKGROUND: There is increasing interest on the part of investigators and the public at large in finding ways to study and improve treatments for the seriously mentally ill without exposing such individuals to unnecessary risks. One group of particular interest in this regard are patients suffering from acute mania. We set out to define "exit" criteria or novel clinical endpoints that might help to assess the efficacy of antimanic compounds. We sought a method that would be safer, more economical, and less sensitive to nonspecific factors in the clinical environment while still allowing unambiguous assessment of efficacy. METHOD: From a pool of subjects being screened for or already participating in intervention studies, we retrospectively identified 76 admissions of patients with a manic or mixed episode according to DSM-IV. We fit a mixed-effects regression model to all available data obtained using the Bech-Rafaelsen Mania Scale from admission to day 28 of treatment. Using the estimated model coefficients, we obtained empirical Bayes (EB) estimates of each subject's trend coefficients based on (1) all available data and (2) data through day 11 of treatment for mania. RESULTS: We found a high correlation (r = .67) between EB estimates of final response at day 28 and actual day 28 scores on the Bech-Rafaelsen scale based on scores through day 11. When subjects were categorized as full, partial, or nonresponders according to their final Bech-Rafaelsen score, we were able to show that only 2 of the 23 predicted nonresponders became full responders, 27 of the 31 predicted full responders became full responders, and 16 of the 22 predicted partial responders became partial or full responders. CONCLUSION: We conclude on the basis of this chart review study that it should be possible to define exit criteria for trials assessing the efficacy of antimanic compounds on the basis of relatively short duration exposure to experimental treatment.

Acute Disease↗
PubMed2001

Citalopram as adjunctive therapy in bipolar depression.

BACKGROUND: The treatment of bipolar depression remains a major clinical challenge. The effectiveness and safety of adjunctive citalopram were evaluated in DSM-IV-diagnosed bipolar depressed patients in a 5-site study. METHOD: The treatment strategy consisted of an open-label add-on design in which patients received 8 weeks of acute treatment with citalopram adjunctive to their ongoing treatment with mood stabilizers. Ongoing treatment with 1 antipsychotic, 1 anxiolytic, and 1 hypnotic agent was permitted. Responders to the 8-week trial then received 16 weeks of additional treatment with citalopram. RESULTS: Forty-five subjects entered the trial; 12 dropped out before the end of the acute treatment phase. Of the 33 patients who completed the acute treatment phase, 64% (N = 21) were responders and 36% (N = 12) were nonresponders. In the continuation phase of the study, 14 patients achieved sustained remission, 3 patients did not achieve remission before completing 16 weeks of continuation treatment, 2 patients experienced a relapse, and 2 patients dropped out of the study and did not have a chance to remit. In spite of the extensive concomitant medication usage allowed in this study, citalopram treatment was well tolerated and the level of reported adverse events (including headache, nausea, diarrhea, and sexual dysfunction) relatively low. CONCLUSION: The high response rate, the high rate of sustained remission, and the low rate of adverse events strongly support the use of citalopram as a treatment for bipolar I or II depression. These findings should stimulate a controlled double-blind trial to demonstrate even more clearly the usefulness of this drug in the therapeutic regimen for bipolar disorder.

Adult↗
PubMed2001

The effects of age and gender on sleep EEG power spectral density in the middle years of life (ages 20-60 years old).

The effects of age and gender on sleep EEG power spectral density were assessed in a group of 100 subjects aged 20 to 60 years. We propose a new statistical strategy (mixed-model using fixed-knot regression splines) to analyze quantitative EEG measures. The effect of gender varied according to frequency, but no interactions emerged between age and gender, suggesting that the aging process does not differentially influence men and women. Women had higher power density than men in delta, theta, low alpha, and high spindle frequency range. The effect of age varied according to frequency and across the night. The decrease in power with age was not restricted to slow-wave activity, but also included theta and sigma activity. With increasing age, the attenuation over the night in power density between 1.25 and 8.00 Hz diminished, and the rise in power between 12.25 and 14.00 Hz across the night decreased. Increasing age was associated with higher power in the beta range. These results suggest that increasing age may be related to an attenuation of homeostatic sleep pressure and to an increase in cortical activation during sleep.

Adult↗
PubMed2000

Neuropsychologic impairments in bipolar and unipolar mood disorders on the CANTAB neurocognitive battery.

BACKGROUND: Cognitive deficits associated with mood disorders, especially bipolar disorder, have been the focus of limited systematic investigation. METHODS: We tested 35 bipolar (21 in depressed state and 14 in mixed or manic state) and 58 nonbipolar depressed consecutively admitted young adult inpatients and 51 matched healthy individuals on the Cambridge Neuropsychological Test Automated Battery, a computerized neurocognitive battery. RESULTS: The mixed/manic bipolar patients demonstrated robust deficits in episodic and working memory, spatial attention, and problem solving. In contrast, depressed bipolar and nonbipolar patients demonstrated impairments only in episodic memory. CONCLUSIONS: Neuropsychologic findings with the Cambridge Neuropsychological Test Automated Battery indicate widely distributed deficits in cognitive domains subserved by temporal, parietal, and frontostriatal systems in bipolar patients during mixed/manic states of illness. Significant deficits in bipolar and nonbipolar depressed patients were restricted to episodic memory, suggesting a more selective dysfunction in mesial temporal lobe function during episodes of depression. These findings highlight the different cognitive profiles of mania and depression, demonstrate similar patterns of neuropsychologic deficits in bipolar and nonbipolar depression, and point to a need for further research investigating the characteristics, causes, course, and treatment of severe cognitive deficits associated with mixed/manic phases of bipolar disorder.

Adult↗
PubMed2000

Interpersonal and social rhythm therapy: managing the chaos of bipolar disorder.

Interpersonal and social rhythm therapy is an individual psychotherapy designed specifically for the treatment for bipolar disorder. Interpersonal and social rhythm therapy grew from a chronobiological model of bipolar disorder postulating that individuals with bipolar disorder have a genetic predisposition to circadian rhythm and sleep-wake cycle abnormalities that may be responsible, in part, for the symptomatic manifestations of the illness. In our model, life events (both negative and positive) may cause disruptions in patients' social rhythms that, in turn, perturb circadian rhythms and sleep-wake cycles and lead to the development of bipolar symptoms. Administered in concert with medications, interpersonal and social rhythm therapy combines the basic principles of interpersonal psychotherapy with behavioral techniques to help patients regularize their daily routines, diminish interpersonal problems, and adhere to medication regimens. It modulates both biological and psychosocial factors to mitigate patients' circadian and sleep-wake cycle vulnerabilities, improve overall functioning, and better manage the potential chaos of bipolar disorder symptomatology.

Affect↗
PubMed2000

Concurrent measures of protein kinase C and phosphoinositides in lithium-treated bipolar patients and healthy individuals: a preliminary study.

This study examined the hypothesis that lithium inhibits the PI signaling pathway in humans during in vivo administration by concurrently measuring PKC isozymes and platelet membrane phosphoinositides in lithium-treated patients and healthy individuals. The platelet membrane and cytosolic levels of PKC alpha, beta I, beta II, delta, and epsilon were measured using Western blotting. The relative platelet membrane contents of phosphatidylinositol (PI), phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP(2)) were measured with two-dimensional thin-layer chromatography. Nine euthymic lithium-treated bipolar subjects and 11 healthy control subjects were studied. Compared to control subjects, lithium-treated bipolar patients had significantly lower levels of cytosolic PKC alpha isozyme (t-test=-3.24, d.f.=17, P=0.01) and PIP(2) platelet membrane levels (t-test=-2.51, d.f.=18, P=0.02), and a trend toward reduced levels of cytosolic PKC beta II isozyme (t=-2.17, d.f.=17, P=0.05). There was no significant correlation between PIP(2) and any of the PKC isozymes. These preliminary findings suggest that chronic lithium treatment may decrease the levels of both cytosolic PKC alpha isozyme and membrane PIP(2) in platelets of bipolar disorder patients.

Adult↗
PubMed2000

Towards a neurobiology of dysfunctional arousal in depression: the relationship between beta EEG power and regional cerebral glucose metabolism during NREM sleep.

This study sought to clarify the neurobiological basis of variations in one aspect of central nervous system 'arousal' in depression by characterizing the functional neuroanatomic correlates of beta electroencephalographic (EEG) power density during non-rapid eye movement (NREM) sleep. First, nine healthy (n=9) subjects underwent concurrent EEG sleep studies and [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) scans during their first NREM period of sleep in order to generate hypotheses about specific brain structures that show a relationship between increased beta power and increased relative glucose metabolism. Second, brain structures identified in the healthy subjects were then used as a priori regions of interest in similar analyses from identical studies in 12 depressed subjects. Statistical parametric mapping was used to identify the relationship between beta power and relative regional cerebral glucose metabolism (rCMRglu) during NREM sleep. Regions that demonstrated significant correlations between beta power and relative cerebral glucose metabolism in both the healthy and depressed subjects included the ventromedial prefrontal cortex and the right lateral inferior occipital cortex. During a baseline night of sleep, depressed patients demonstrated a trend toward greater beta power in relation to a separate age- and gender-matched healthy control group. In both healthy and depressed subjects, beta power negatively correlated with subjective sleep quality. Finally, in the depressed group, there was a trend for beta power to correlate with an indirect measure of absolute whole brain metabolism during NREM sleep. This study demonstrates a similar relationship between electrophysiological arousal and glucose metabolism in the ventromedial prefrontal cortex in depressed and healthy subjects. Given the increased electrophysiological arousal in some depressed patients and the known anatomical relations between the ventromedial prefrontal cortex and brain activating structures, this study raises the possibility that the ventromedial prefrontal cortex plays a significant role in mediating one aspect of dysfunctional arousal found in more severely aroused depressed patients.

Adult↗
PubMed2000

Effects of lithium on platelet membrane phosphoinositides in bipolar disorder patients: a pilot study.

RATIONALE: In vitro and in vivo animal studies suggest that the intracellular phosphatidylinositol (PI) pathway is an important target for the effects of lithium. OBJECTIVES: We conducted a preliminary study to examine the in vivo effects of lithium treatment on platelet membrane phosphoinositides in bipolar disorder subjects, in an attempt to examine further the hypothesis that lithium has significant in vivo effects on the PI pathway in these patients. METHODS: We quantitated PI, phosphatidylinositol-4-phosphate (PIP), and phosphatidylinositol-4,5-bisphosphate (PIP2) in platelet membranes of seven subjects (five male, two female; mean age= 27.9+/-5.7 years), initially while they were unmedicated, and a second time after at least 21 days of lithium treatment (mean+/-SD=28.7+/-7.1 days). RESULTS: The mean+/-SD values for PI were 5.63+/-2.25% and 5.21+/-1.06%; for PIP 0.68+/-0.20% and 0.55+/-0.11%; and for PIP2 0.60+/-0.21% and 0.38+/-0.15%, before and after lithium treatment, respectively. The decrease in PIP2 values after lithium treatment was statistically significant (Wilcoxon signed ranks test, Z=-2.37, P=0.02). CONCLUSION: This longitudinal study suggests that therapeutic doses of lithium significantly decrease platelet membrane PIP2 levels in vivo in bipolar disorder subjects, which may be related to lithium's mechanism of action in bipolar disorder.

Adult↗
PubMed2000

Allelic variation in the serotonin transporter promoter affects onset of paroxetine treatment response in late-life depression.

The relationship of the serotonin transporter gene promoter region polymorphism (5-HTTLPR) to antidepressant response was examined in 95 elderly patients receiving a protocolized treatment for depression with paroxetine or nortriptyline. Patients were treated for up to 12 weeks and assessed weekly with clinical ratings and measurements of plasma drug concentrations. Twenty-one of the paroxetine-treated subjects were found to have the ll genotype and 30 had at least one s allele. There were no baseline differences between these groups in pretreatment Hamilton Rating Scale for Depression (HRSD) scores or anxiety symptoms. During acute treatment with paroxetine, mean reductions from baseline in HRSD were significantly more rapid for patients with the ll genotype than for those possessing an s allele, despite equivalent paroxetine concentrations. Onset of response to nortriptyline was not affected. Allelic variation of 5-HTTLPR may contribute to the variable initial response of patients treated with a selective serotonin reuptake inhibitor.

Adrenergic alpha-Agonists↗
PubMed2000

Serotonin type-1A receptor imaging in depression.

Regional 5-hydroxytryptamine(1A) (5-HT(1A)) receptor binding potential (BP) of depressed subjects with primary, recurrent, familial mood disorders was compared to that of healthy controls by using positron emission tomography and [carbonyl-(11)C]WAY-100635 ¿[(11)C]N-(2-(4-(2-methoxyphenyl)-1-piperazin-1-yl)ethyl)-N-(2- pyridy l)cyclohexanecarboxamide¿. The mean 5-HT(1A) receptor BP was reduced 42% in the midbrain raphe and 25-33% in limbic and neocortical areas in the mesiotemporal, occipital, and parietal cortex. The magnitude of these abnormalities was most prominent in bipolar depressives and unipolar depressives who had bipolar relatives. These abnormal reductions in 5-HT(1A) receptor BP are consistent with in vivo evidence that 5-HT(1A) receptor sensitivity is reduced in major depressive disorder and postmortem data showing a widespread deficit of 5-HT(1A) receptor expression in primary mood disorders.

Adult↗