Biomedical subjects

Ellen M Whyte

Publications and source records attributed to Ellen M Whyte.

14 recordsLinked to original sources

PubMed2007

Onset of depression in elderly persons after hip fracture: implications for prevention and early intervention of late-life depression.

OBJECTIVES: To identify predictors of onset of major depressive disorder (MDD) and of depressive symptoms in subjects who suffered a hip fracture. DESIGN: Prospective naturalistic study. SETTING: University of Pittsburgh Medical Center-Shadyside, a large urban hospital in Pittsburgh, Pennsylvannia. PARTICIPANTS: One hundred twenty-six elderly patients who received surgical fixation for hip fracture and who were not experiencing a major depressive episode at the time of the fracture; severely cognitively impaired persons were excluded. MEASUREMENTS: Subjects were evaluated at the time of hospital discharge using a battery of clinical measures (including apathy measured using the Apathy Evaluation Scale (AES), delirium, cognitive measures, social support, and disability level). Depression was assessed at the end of the surgical stay, 2 weeks later, and then monthly for 6 months, using the Hamilton Rating Scale for Depression (Ham-D) to evaluate symptomatology and the Primary Care Evaluation of Mental Disorders to evaluate diagnosis of MDD. RESULTS: Eighteen of 126 subjects (14.3%) developed MDD after hip fracture. Of these, 11 developed MDD by the end of the hospitalization, and seven developed MDD between 2 and 10 weeks later. Logistic regression showed that baseline apathy score, as measured using the AES, was the only clinical measure associated with the development of MDD (odds ratio=1.09, 95% confidence interval=1.03-1.16, P=.003); 46.2% of those with high AES scores developed MDD, versus 10.9% of those with lower scores. In contrast, cognitive variables, delirium, disability after hip fracture, and other factors related to the fracture (e.g., fracture type) were not associated with MDD. A repeated-measures analysis with Ham-D over time as a dependent variable generally confirmed these findings; depressive symptoms were highest immediately after the fracture, and apathy and delirium scores were associated with higher depressive symptom levels. CONCLUSION: The onset of MDD is common after hip fracture, and the greatest period of risk is immediately after the fracture. Individuals with clinical evidence of apathy are at high risk for developing MDD, and evaluation and close follow-up of such individuals is warranted. However, further research is needed to examine other candidate variables (e.g., clinical measures or biomarkers) to model adequately the risk for MDD after hip fracture and other disabling medical events.

Affect↗

PubMed2006

Maintenance treatment of major depression in old age.

BACKGROUND: Elderly patients with major depression, including those having a first episode, are at high risk for recurrence of depression, disability, and death. METHODS: We tested the efficacy of maintenance paroxetine and monthly interpersonal psychotherapy in patients 70 years of age or older who had depression (55 percent of whom were having a first episode) in a 2-by-2, randomized, double-blind, placebo-controlled trial. Among patients with a response to treatment with paroxetine and psychotherapy, 116 were randomly assigned to one of four maintenance-treatment programs (either paroxetine or placebo combined with either monthly psychotherapy or clinical-management sessions) for two years or until the recurrence of major depression. Clinical-management sessions, conducted by the same nurses, social workers, and psychologists who provided psychotherapy, involved discussion of symptoms. RESULTS: Major depression recurred within two years in 35 percent of the patients receiving paroxetine and psychotherapy, 37 percent of those receiving paroxetine and clinical-management sessions, 68 percent of those receiving placebo and psychotherapy, and 58 percent of those receiving placebo and clinical-management sessions (P=0.02). After adjustment for the effect of psychotherapy, the relative risk of recurrence among those receiving placebo was 2.4 times (95 percent confidence interval, 1.4 to 4.2) that among those receiving paroxetine. The number of patients needed to be treated with paroxetine to prevent one recurrence was 4 (95 percent confidence interval, 2.3 to 10.9). Patients with fewer and less severe coexisting medical conditions (such as hypertension or cardiac disease) received greater benefit from paroxetine (P=0.03 for the interaction between treatment with paroxetine and baseline severity of medical illness). CONCLUSIONS: Patients 70 years of age or older with major depression who had a response to initial treatment with paroxetine and psychotherapy were less likely to have recurrent depression if they received two years of maintenance therapy with paroxetine. Monthly maintenance psychotherapy did not prevent recurrent depression. (ClinicalTrials.gov number, NCT00178100.).

Aged↗

PubMed2006

CYP2D6 genotype and venlafaxine-XR concentrations in depressed elderly.

INTRODUCTION: The elderly are at increased risk for medication-related adverse events. Recent reports indicate that venlafaxine may put the elderly at increased risk of cardio- and cerebrovascular adverse events. We investigated the relationship between the CYP2D6 polymorphism and steady-state plasma concentration of venlafaxine (VEN) and its primary metabolite o-desmethylvenlafaxine (ODV) in elderly participants receiving venlafaxine-XR for major depression in order to explore the contribution of pharmacogenetics to medication tolerability. METHODS: Forty-six elderly participants received venlafaxine-XR for the treatment of major depression. CYP2D6 genotype and steady-state plasma levels of VEN and ODV were determined. RESULTS: Sixty-five percent of participants were homozygous of the wild type (WT) allele, whereas 35% carried one or more variant alleles associated with intermediate and poor 2D6 metabolizer status. VEN concentration per unit dose was significantly higher and ODV concentration per unit dose was significantly lower in participants who carried one or more variant alleles compared to participants who were homozygous for the WT allele. The VEN and ODV concentrations per unit dose were also correlated with creatinine clearance. CYP2D6 genotype was not associated with medication associated side-effects. CONCLUSIONS: Plasma dose-corrected concentrations of VEN and ODV correlated with genetically determined CYP2D6 enzymatic activity in depressed elders treated with venlafaxine-XR. This relationship was not masked by the effects of age-related illness or polypharmacy. Future clinical application of pharmacogenetics to examine 2D6-dependent medications may help reduce the incidence of medication adverse events particularly in those elders at higher risk for medication adverse events due to impaired renal or cardiac function.

Aged↗

PubMed2006

Depression in late-life: shifting the paradigm from treatment to prevention.

Late-life depression is very common and is associated with high rates of morbidity and mortality. While the field of geriatric psychiatry is focused on depression treatment, prevention is an enticing option. Prevention of late-life depression would decrease both emotional suffering and depression-associated morbidity and mortality and may decrease dependence on non-mental health professionals to detect depression and to initiate a treatment referral. This paper will review current thinking on prevention research with a particular focus on its application to late-life depression. To illustrate these issues, we discuss recent and ongoing clinical trials of interventions to prevent depression in two populations of older persons: those with age-related macular degeneration (AMD) and those with cerebrovascular disease.

Aged↗

PubMed2006

Preventing depression after stroke.

Mental health prevention research is an emerging and intriguing field. Preventing mental disorders is attractive as successful prevention, as it could potentially avert both emotional suffering and illness related morbidity and mortality. Several studies have looked at preventing post-stroke depression, a common complication of stroke. In this review article, we will first provide a conceptual overview of mental health prevention research. Then, we will discuss recent research supporting the prevention of depression after stroke and the likely positive effect successful prevention may have on non-psychiatric outcomes.

Depression↗

PubMed2006

Impact of prior treatment exposure on response to antidepressant treatment in late life.

OBJECTIVE: The objective of this study was to describe the correlates of prior antidepressant exposure and its association with response to protocolized treatment in older patients with major depression. METHODS: Based on their prior antidepressant treatment exposure, 193 elderly patients with a major depressive episode were divided into three groups: those with no prior treatment for their current episode (not treated [TN]), those with antidepressant trials of inadequate dose or duration ("treatment-inadequate" [TI]), and those with at least one adequate trial but persisting depression ("treatment-resistant" [TR]). All patients then received protocolized treatment with interpersonal psychotherapy (IPT) and paroxetine plus pharmacologic augmentation if needed. The demographic, clinical, and outcome information were compared among these three groups. RESULTS: Approximately one-third of the patients referred to the study had been adequately treated (TR), one-third had been inadequately treated (TI), and one-third were not treated for the current episode (TN). Treatment completion rates and reasons for dropping out did not differ statistically among TR, TI, and TN patients. TR patients took longer to respond (13.0 weeks) than either TI or TN patients (7.6 and 8.0 weeks, respectively). TR and TI patients had lower response rates (67% and 71%) than TN patients (86%). CONCLUSIONS: Prior treatment exposure is an important correlate of course and outcome in late-life depression. Most TR and TI patients eventually respond, but TR patients may require more intensive and longer courses of treatment than TI and TN patients.

Aged↗

PubMed2005

Differential cortical atrophy in subgroups of mild cognitive impairment.

OBJECTIVE: To compare gray matter brain volumes in patients diagnosed with subtypes of mild cognitive impairment (MCI) (those with a focal amnestic disorder and those with more diffuse cognitive dysfunction) with those of elderly controls. DESIGN: Magnetic resonance imaging volumetric study of MCI subgroups (MCI-amnestic [MCI-A], and MCI-multiple cognitive domain [MCI-MCD]) using a whole brain voxel-based analysis. SETTING: Referral dementia clinic. Patients Thirty-seven patients with MCI (age range, 49-85 years; MCI-A, n = 9; MCI-MCD, n = 28) and 47 control subjects (age range, 55-81 years). MAIN OUTCOME MEASURES: Volumetric anatomical magnetic resonance imaging differences between MCI subgroups and normal controls, and between patients with MCI who progressed to dementia. Magnetic resonance imaging scans were analyzed using statistical software SPM99. RESULTS: Overall, the patients with MCI had significantly decreased volume in the hippocampus and middle temporal gyrus, bilaterally, compared with control subjects. Compared with patients with MCI-MCD, patients with MCI-A had significant volume loss of the left entorhinal cortex and inferior parietal lobe. Compared with patients with MCI-A, patients with MCI-MCD had significantly reduced volume of the right inferior frontal gyrus, right middle temporal gyrus, and bilateral superior temporal gyrus. Patients with MCI who progressed to Alzheimer disease during follow-up (mean interval 2 years, maximum 4.5 years), showed greater atrophy in the left entorhinal cortex, bilateral superior temporal gyri, and right inferior frontal gyrus compared with those who did not progress. CONCLUSIONS: These data provide evidence of distinct brain structural abnormalities in 2 groups of patients with MCI. While both have mesial temporal and cortical volume loss, those with a focal memory deficit have more involvement of the mesial temporal structures and less involvement of the neocortical heteromodal association areas than those patients with MCI with diffuse cognitive dysfunction. Thus, MCI may represent a more heterogeneous group than currently conceived, possibly reflecting 2 different etiological processes to dementia. These data also suggest that these structural abnormalities precede the development of Alzheimer disease.

Aged↗

PubMed2004

The nature and determinants of neuropsychological functioning in late-life depression.

CONTEXT: Cognitive impairment in late-life depression (LLD) is highly prevalent, disabling, poorly understood, and likely related to long-term outcome. OBJECTIVES: To determine the characteristics and determinants of neuropsychological functioning LLD. DESIGN: Cross-sectional study of groups of LLD patients and control subjects. SETTING: Outpatient, university-based depression research clinic. PARTICIPANTS: One hundred patients without dementia 60 years and older who met DSM-IV criteria for current episode of unipolar major depression (nonpsychotic) and 40 nondepressed, age- and education-equated control subjects. MAIN OUTCOME MEASURES: A comprehensive neuropsychological battery. RESULTS: Relative to control subjects, LLD patients performed poorer in all cognitive domains. More than half exhibited significant impairment (performance below the 10th percentile of the control group). Information processing speed and visuospatial and executive abilities were the most broadly and frequently impaired. The neuropsychological impairments were mediated almost entirely by slowed information processing (beta =.45-.80). Education (beta =.32) and ventricular atrophy (beta =.28) made additional modest contributions to variance in measures of language ability. Medical and vascular disease burden, apolipoprotein E genotype, and serum anticholinergicity did not contribute to variance in any cognitive domain. CONCLUSIONS: Late-life depression is characterized by slowed information processing, which affects all realms of cognition. This supports the concept that frontostriatal dysfunction plays a key role in LLD. The putative role of some risk factors was validated (eg, advanced age, low education, depression severity), whereas others were not (eg, medical burden, age at onset of first depressive episode). Further studies of neuropsychological functioning in remitted LLD patients are needed to parse episode-related and persistent factors and to relate them to underlying neural dysfunction.

Age Factors↗

PubMed2004

Depression after stroke: a prospective epidemiological study.

OBJECTIVES: To elucidate the relationship between stroke and depressive symptoms and to determine whether disability or cerebrovascular risk factors mediate that relationship. DESIGN: A prospective longitudinal epidemiological survey. SETTING: The mid-Monongahela Valley, a rural, nonfarm, low-socioeconomic-status community. PARTICIPANTS: Random sample of 1,134 subjects aged 65 and older. MEASUREMENTS: The dependent variable was clinically significant depressive symptoms, as defined by five or more symptoms on the modified Center for Epidemiological Studies Depression scale. The independent variables were demographics (age, sex, education), stroke, number of impaired instrumental activities of daily living (IADLs), diabetes mellitus, hypertension, atherosclerotic heart disease, and smoking. Logistic regression analyses were conducted for cross-sectional and longitudinal models examining whether stroke was associated with or predicted depressive symptoms, with other associated factors included as covariates. RESULTS: Clinically significant depressive symptoms were cross-sectionally associated with stroke (odds ratio (OR)=3.5, 95% confidence interval (CI)=1.4-8.3), diabetes mellitus (OR=2.8, 95% CI=1.7-4.6; P</=.05), and IADL impairment (OR=1.6, 95% CI=1.4-1.8; P<.05). Longitudinal analysis demonstrated that stroke (OR=6.3, 95% CI=1.7-23.2) and depressive symptoms at baseline (OR=15, 95% CI=7.7-29.5) predicted subsequent clinically significant depressive symptoms measured 2 years later, whereas education was protective (OR=0.4, 95% CI=0.2-0.8). CONCLUSION: Stroke survivors have a greatly elevated risk for clinically significant depressive symptoms even 2 or more years after index stroke, independent of functional disability, cerebrovascular risk factors, and previous depressive symptoms.

Activities of Daily Living↗

PubMed2004

Time course of response to antidepressants in late-life major depression: therapeutic implications.

In the treatment of depression, there is considerable interest in the time course of response and, in particular, the speed with which individuals recover from depressive episodes. Examination of the time course and speed of response is critical for assessing the usefulness of specific treatments. However, while this issue has received attention in mid-life adult populations, it has received little consideration in the context of late-life major depression. The synthesis of empirical reports indicates that, while older adults with depression seem to respond with the same speed as mid-life adults, several factors have consistently been associated with reduced speed of response to antidepressant treatment, including greater severity of depressive symptoms and co-occurring anxiety symptoms. Limited evidence suggests that sleep impairment and genetic factors (e.g. presence of the s allele of the serotonin transporter gene promoter region) may also be associated with reduced speed of response. Some factors have consistently been found to be unrelated to speed of response (demographic characteristics, nonpsychiatric physical illnesses) whereas other factors have only mixed evidence supporting any effect (psychosocial and other clinical factors). While there is little work available to date, some evidence suggests that time course and speed of response affect longer-term outcomes of depression pharmacotherapy; thus, older adults with more rapid versus slower patterns of response may differ in the types of maintenance treatment needed to avert additional depressive episodes. None of potential strategies for accelerating speed of response have been clearly shown to be effective in late-life depression. Future treatment studies for late-life depression should routinely consider not only overall efficacy of a given pharmacotherapy (i.e. total rate of response), but time course and speed of response. To this end, new investigations must be designed to overcome the methodological limitations of prior studies that have examined time course and they should include a range of potential covariates and outcomes of between-patient differences in speed of response. Better understanding of factors related to such differences may suggest new intervention strategies to accelerate response.

Aged↗

PubMed2004

Geriatric depression treatment in nonresponders to selective serotonin reuptake inhibitors.

BACKGROUND: Up to a third of elderly patients with major depressive disorder are treatment resistant, yet little objective evidence is available to guide the clinician in managing these patients. We report here our experience with elderly subjects with prospectively defined treatment-resistant depression in 2 separate research studies: one entailing an augmentation strategy, the other a change to venlafaxine extended release (XR). METHOD: Fifty-three elderly subjects with major depressive disorder according to DSM-IV criteria who failed treatment with paroxetine plus interpersonal psychotherapy received 1 to 3 trials of augmentation with bupropion sustained release, nortriptyline, or lithium. Successively fewer subjects entered each sequential trial of augmentation. Twelve subjects subsequently received venlafaxine XR monotherapy. Response to treatment was defined as a 17-item Hamilton Rating Scale for Depression score of < 10 for 3 weeks. RESULTS: Sixty percent of subjects (N = 32) responded to some form of augmentation, with 45% (24/53), 31% (5/16), and 43% (3/7) responding to the first, second, and third augmentation trials, respectively. The mean time to response after starting the first augmentation trial was 6.0 (SD = 5.8) weeks. Forty-two percent (N = 5) of the venlafaxine XR-treated subjects responded with the mean time to response of 6.4 (SE = 0.9) weeks. Adverse effects leading to treatment discontinuation and falls were more common in the augmentation subjects than in the venlafaxine XR subjects. CONCLUSION: We observed similar rates and speed of response with an augmentation strategy and a strategy of switching to venlafaxine XR in elderly subjects with prospectively defined treatment-resistant major depressive disorder. Venlafaxine XR was generally better tolerated than the augmentation strategies. Further investigation of venlafaxine XR as a preferred strategy for treatment-resistant geriatric depression is warranted.

Aged↗

PubMed2002

Post stroke depression: epidemiology, pathophysiology, and biological treatment.

Depression is a common occurrence after stroke and is associated with excess disability, cognitive impairment, and mortality. The authors undertook a systematic review of the English language literature to review several aspects of this illness, including the prevalence of this disorder, the debate on its etiology, and the current understanding of the biological treatment of poststroke depression. Methodological problems encountered in the study of poststroke depression are highlighted throughout the manuscript. The authors conclude that the available evidence supports poststroke depression as being multifactorial in origin and consistent with the biopsychosocial model of mental illness.

Aged↗

PubMedDate not supplied

The relation of white matter hyperintensities to cognitive performance in the normal old: education matters.

This study examined whether the severity of cerebral white matter abnormalities (evident on MR images as white matter hyperintensities (WMH)) was related to the cognitive performance of 141 high-functioning older adults. The elderly showed the typical age decrement on measures of processing speed, working memory, and inhibition; however WMH severity was significantly related only to processing speed. The strength of this relationship was, however, influenced by the educational level of the participants, such that processing speed was more associated with WMH severity in less-educated than in well-educated participants. This is consistent with recent concepts of cognitive reserve, but does raise a question as to the underlying source of the cognitive decrement found in the sort of well-educated elders typically used in cognitive-aging studies.

Adolescent↗

PubMedDate not supplied

Cognitive and behavioral correlates of low vitamin B12 levels in elderly patients with progressive dementia.

Vitamin B12 deficiency is common in elderly persons, yet its role in dementia and psychiatric illness is unclear. The authors examined the relationship between vitamin B12 serum levels and cognitive and neuropsychiatric symptoms in dementia. Community-dwelling elderly subjects (N=643) meeting NINCDS-ADRDA criteria for probable or possible Alzheimer disease (AD) underwent comprehensive neuropsychiatric evaluation and measurement of vitamin B12 serum levels. Thirty-seven subjects (5.7%) had low B12 serum levels (200 pcg/ml or less). Subjects with low B12 levels were significantly older and had significantly lower scores on the Mini-Mental State Exam and higher scores on the Blessed Dementia Scale, but not a different pattern of cognitive or behavior disturbances compared with the normal-B12 subjects. In AD, the prevalence of low vitamin B12 serum levels is consistent with that found in community-dwelling elderly persons in general but is associated with greater overall cognitive impairment.

Aged↗