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Biomedical subjects

Ellen Frank

Publications and source records attributed to Ellen Frank.

At least 73 records · Page 4Linked to original sources
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

2002 Robert Ader New Investigator award. Relationship of cardiovascular reactivity, stressful life events, and multiple sclerosis disease activity.

Previous studies of stress in multiple sclerosis patients have suggested that life events may alter the onset and development of MS. However, results have been inconsistent because of infrequent monitoring and reporting bias. We followed fifty female MS patients for 1 year to determine characteristics of life events associated with MS exacerbations, and examine the influence of cardiovascular activity. Subjects completed weekly life-event checklists. The short- and long-term threat of each event was determined using the Life Events and Difficulties Schedule. Neurologic symptoms were also monitored weekly. MS exacerbations were confirmed by a neurologist blinded to psychosocial events. Cardiovascular reactivity to an acute psychological stressor was determined at study onset, and resting heart rate and blood pressure were monitored monthly. Forty-two percent of life events were associated with exacerbations in the subsequent 6 weeks. Logistic regression confirmed that exacerbations were more likely during at-risk periods following life events and were relatively independent of the threat level and type of stressor. Participants with higher cardiovascular reactivity to acute stress and higher baseline heart rate demonstrated a greater number of exacerbations and proportion of weeks ill. Using multiple regression, we found that disability level, medication usage, cardiovascular reactivity, baseline heart rate, and life event density explained approximately 30% of the variance in the proportion of weeks ill. These results are consistent with the hypothesis that stress is a potential trigger of MS disease activity and suggest that autonomic tone and stress reactivity may play a role in the development of stress-related exacerbations.

Adaptation, Psychological↗
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

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↗
PubMed2003

Integrated family and individual therapy for bipolar disorder: results of a treatment development study.

BACKGROUND: Several studies have established the efficacy of psychosocial interventions as adjuncts to pharmacotherapy in the symptom maintenance of bipolar disorder. This study concerned a new psychosocial approach - integrated family and individual therapy (IFIT) - that synthesizes family psychoeducational sessions with individual sessions of interpersonal and social rhythm therapy. METHOD: Shortly after an acute illness episode, 30 bipolar patients (DSM-IV criteria) were assigned to open treatment with IFIT (up to 50 weekly sessions of family and individual therapy) and mood-stabilizing medications in the context of a treatment development study. Their outcomes over 1 year were compared with the outcomes of 70 patients from a previous trial who received standard community care, consisting of 2 family educational sessions, mood-stabilizing medications, and crisis management (CM). Patients in both samples were evaluated as to symptomatic functioning at entry into the project and then every 3 months for 1 year. RESULTS: Patients in IFIT had longer survival intervals (time without relapsing) than patients in CM. They also showed greater reductions in depressive symptoms over 1 year of treatment relative to their baseline levels. The results could not be explained by group differences in baseline symptoms or pharmacologic treatment regimens. CONCLUSION: Combining family and individual therapy with medication may protect episodic bipolar patients from early relapse and ongoing depressive symptoms. Further examination of this integrative model within randomized controlled trials is warranted.

Adult↗
PubMed2002

Skating to where the puck is going to be: a plan for clinical trials and translation research in mood disorders.

As part of the National Institute of Mental Health Strategic Plan for Mood Disorders Research effort, the Clinical Trials and Translation Workgroup was asked to define priorities for clinical trials in mood disorders and for research on how best to translate the results of such research to clinical practice settings. Through two face-to-face meetings and a series of conference calls, we established priorities based on the literature to date and what was known about research currently in progress in this area. We defined five areas of priority that cut across developmental stages, while noting that research on adult mood disorders was at a more advanced stage in each of these areas than research on child or geriatric disorders. The five areas of priority are: 1) maximizing the effectiveness and cost-effectiveness of initial (acute) treatments for mood disorders already known to be efficacious in selected populations and settings when they are applied across all populations and care settings; 2) learning what further treatments or services are most likely to reduce symptoms and improve functioning when the first treatment is delivered well, but the mood disorder does not remit or show adequate improvement; 3) learning what treatments or services are most cost-effective in preventing recurrence or relapse and maintaining optimal functioning after a patient's mood disorder has remitted or responded maximally to treatment; 4) developing and validating clinical, psychosocial, biological, or other markers that predict: a) which treatments are most effective, b) course of illness, c) risk of adverse events/tolerability and acceptability for individual patients or well-defined subgroups of patients; 5) developing clinical trial designs and methods that result in lower research costs and greater generalizability earlier in the treatment development and testing process. A rationale for the importance of each of these priorities is provided.

Aged↗
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

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

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

Conceptual underpinnings and empirical support for the mood spectrum.

This article presents an overview of the conceptual basis and empirical support for a unitary view of mood disturbance. The authors consider this general conceptualization of psychiatric disturbance as consisting of an array of related symptoms and behavioral features that define the "spectrum" of each disorder. They discuss how this conceptual framework aids in overcoming what they believe to be the false dichotomy between unipolar and bipolar mood disorders and in evaluating subthreshold and unusual presentations. They also describe the structured clinical interview and self-report instrument that they have developed to facilitate systematic assessment of the proposed mood spectrum. Finally, they summarize the clinical utility of such an approach to the description and assessment of patients with mood disorders.

Humans↗
PubMed2002

The panic-agoraphobic spectrum: development, description, and clinical significance.

The results of the authors' research efforts to date support the idea that the panic-agoraphobic spectrum is a robust and culturally transferable construct with important clinical implications for patients with mood and anxiety disorders. In particular, their findings suggest the need for alternate treatment strategies to treat mood patients with comorbid panic features [50,52]. They maintain that the spectrum approach could add to the knowledge of course and outcome of mood and anxiety disorders and inform treatment decisions. The spectrum concept has other potential implications. For the purposes of neurobiologic research, reliable identification of phenotypes that map [Figure 3: see text] onto specific brain processes in crucial. The definition of the diathesis phenotype is also important if we are to elucidate the cause and pathophysiology of mental disorders at a molecular level. A panic-agoraphobic spectrum assessment incorporate temperamental features and trait-like manifestations into a comprehensive symptom assessment to provide a detailed picture of the clinical features of PD. Such an approach holds some promise for progress in studies of neurobiologic basis of panic and may be useful in further efforts to overcome the nagging problem of the ambiguous boundaries of DSM diagnostic categories [53].

Adult↗
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

Differential functioning of the Beck depression inventory in late-life patients: use of item response theory.

The present analyses examined age-related measurement bias in responses to items on the revised Beck Depression Inventory (BDI) in depressed late-life patients versus midlife patients. Item response theory (IRT) models were used to equate the scale and to differentiate true-group differences from bias in measurement in the 2 samples. Baseline BDI data (218 late life and 613 midlife) were used for the present analysis. IRT results indicated that late-life patients tended to report fewer cognitive symptoms, especially at low to average levels of depression. Conversely, they tended to report more somatic symptoms, especially at higher levels of depression. Adjusted cutoff scores in the late-life group are provided, and possible reasons for age-related differences in the performance of the BDI are discussed.

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↗