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Biomedical subjects

David C Steffens

Publications and source records attributed to David C Steffens.

At least 73 records · Page 4Linked to original sources
PubMed2003

Associations among the NEO Personality Inventory, Revised and the serotonin transporter gene-linked polymorphic region in elders: effects of depression and gender.

OBJECTIVE: The short variant of the serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) has been associated with personality traits related to anxiety, hostility, and depression. We attempted to replicate findings suggesting a positive relation between the short allele variant of 5-HTTLPR and Neuroticism, and a negative association between the short allele variant and Agreeableness. METHODS: Participants in the present study were 103 geriatric depressed patients and 99 non-depressed age matched controls. Depression status and gender were examined as potential modifiers of the association between 5-HTTLPR and personality. RESULTS: Neuroticism was associated with allele frequency such that individuals with the short variant of the allele (ss or sl, group S) were significantly lower on Neuroticism ( P<0.04) compared with individuals with the long allele variant (group L), a pattern opposite to that of previous reports. The association did not vary by clinical group (depressed or controls) but was conditional on gender ( P<0.01): the mean Neuroticism for males in group S was 48.2, whereas the mean Neuroticism for males in group L was 55.9; and the mean Neuroticism for females did not differ by allele group. In the total sample, Agreeableness was not associated with allele frequency; however, there was a significant allele groupxclinical groupxgender interaction ( P<0.01). CONCLUSIONS: The present findings failed to replicate prior work suggesting that the short variant of the 5-HTTLPR allele is associated with higher Neuroticism and lower Agreeableness.

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PubMed2003

The incidence of mental and behavioral disturbances in dementia: the cache county study.

A population-based prevalence sample of 355 residents of Cache County, Utah, who were diagnosed with dementia, was rated on the Neuropsychiatric Inventory (NPI). Of the 355 residents, 119 had no neuropsychiatric symptoms at baseline and were, consequently, at risk for incident mental and behavioral disturbances. The NPI was readministered approximately 18 months later to 61 surviving participants. Sixty-nine percent developed at least one mental or behavioral symptom. Delusions were most common (28%), followed by apathy (21%), and aberrant motor behavior (21%). When this incidence rate of 69% was combined with a previously estimated prevalence rate of 61%, the cumulative 18-month prevalence approached 90%. These results argue for a routine assessment of psychiatric disturbances in all patients with dementia, even among those who have never experienced symptoms of mental or behavioral disturbances.

Aged↗
PubMed2003

Serial MR imaging of volumes of hyperintense white matter lesions in elderly patients: correlation with vascular risk factors.

OBJECTIVE: The purpose of the study was to examine change in volume of hyperintense white matter lesions in a cohort of community-dwelling elderly subjects without neuropsychiatric disease. SUBJECTS AND METHODS. One hundred seventeen volunteers underwent brain MR imaging on a 1.5-T scanner. Demographic data and the presence of specific medical illnesses were recorded at the time of the initial scanning. Hyperintense white matter lesion volume was measured using a supervised semiautomated technique that seeded lesions and then created a segmented lesion image. Subjects underwent repeated MR imaging at a mean of 25 months. Mean change in lesion volume and mean percentage of change were determined between the two time points. Logistic regression models were used to examine the differential effects of age, sex, race, and self-reported medical morbidity. RESULTS: Mean baseline volume of cerebral hyperintense lesions was 4.91 cc, and at 2-year follow-up, it was 6.42 cm(2) (p < 0.0001), for a mean increase of 26.7%. Comparable results were seen in separate analyses of hemispheric hyperintense lesion volumes. Neither sex, race, nor baseline hyperintense lesion volume was significantly associated with an interval increase in lesion volume. Age (p = 0.0117) and presence of diabetes (p = 0.0215) were associated with greater change. CONCLUSION: Elderly subjects exhibited approximately a 27% increase in hyperintense lesion volume over a 2-year period, a finding influenced by both age and medical comorbidity rates. Because hyperintense lesions can be associated with several neuropsychiatric conditions, further research is needed to determine if interventions designed to slow hyperintense lesion disease progression may improve neuropsychiatric outcomes.

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PubMed2003

Cholesterol-lowering medication and relapse of depression.

This study sought to examine the effects of taking cholesterol-lowering medication on outcomes of depression among older depressed adults. 243 elderly depressed patients were treated using an antidepressant algorithm by a geriatric psychiatrist who administered the Montgomery-Asberg Depression Rating Scale (MADRS) at clinical visits up to six years. We defined remission and relapse as achieving MADRS scores less than 7 and greater than 15, respectively. There were no between-group differences on time to remission. Among 167 remitted patients with follow-up data, 61.4% on cholesterol-lowering medication, and 39.8% not on cholesterol medications experienced a relapse during the follow-up period (p<0.032), and remitted patients taking cholesterol medications relapsed more quickly than did others in adjusted analyses (hazard ratio=1.791, p<0.018). These results add to the literature linking cholesterol and mood, and they support the "vascular depression" hypothesis in geriatric depression. Future studies of depression outcomes in the elderly will need to include serial examination of cholesterol levels.

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PubMed2002

Hormone replacement therapy and incidence of Alzheimer disease in older women: the Cache County Study.

CONTEXT: Previous studies have shown a sex-specific increased risk of Alzheimer disease (AD) in women older than 80 years. Basic neuroscience findings suggest that hormone replacement therapy (HRT) could reduce a woman's risk of AD. Epidemiologic findings on AD and HRT are mixed. OBJECTIVE: To examine the relationship between use of HRT and risk of AD among elderly women. DESIGN, SETTING, AND PARTICIPANTS: Prospective study of incident dementia among 1357 men (mean age, 73.2 years) and 1889 women (mean age, 74.5 years) residing in a single county in Utah. Participants were first assessed in 1995-1997, with follow-up conducted in 1998-2000. History of women's current and former use of HRT, as well as of calcium and multivitamin supplements, was ascertained at the initial contact. MAIN OUTCOME MEASURE: Diagnosis of incident AD. RESULTS: Thirty-five men (2.6%) and 88 women (4.7%) developed AD between the initial interview and time of the follow-up (3 years). Incidence among women increased after age 80 years and exceeded the risk among men of similar age (adjusted hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.22-3.86). Women who used HRT had a reduced risk of AD (26 cases among 1066 women) compared with non-HRT users (58 cases among 800 women) (adjusted HR, 0.59; 95% CI, 0.36-0.96). Risk varied with duration of HRT use, so that a woman's sex-specific increase in risk disappeared entirely with more than 10 years of treatment (7 cases among 427 women). Adjusted HRs were 0.41 (95% CI, 0.17-0.86) for HRT users compared with nonusers and 0.77 (95% CI, 0.31-1.67) compared with men. No similar effect was seen with calcium or multivitamin use. Almost all of the HRT-related reduction in incidence reflected former use of HRT (9 cases among 490 women; adjusted HR, 0.33 [95% CI, 0.15-0.65]). There was no effect with current HRT use (17 cases among 576 women; adjusted HR, 1.08 [95% CI, 0.59-1.91]) unless duration of treatment exceeded 10 years (6 cases among 344 women; adjusted HR, 0.55 [95% CI, 0.21-1.23]). CONCLUSIONS: Prior HRT use is associated with reduced risk of AD, but there is no apparent benefit with current HRT use unless such use has exceeded 10 years.

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PubMed2002

Investigation of Notch3 as a candidate gene for bipolar disorder using brain hyperintensities as an endophenotype.

The purpose of the study was to consider MRI hyperintensities as a potential endophenotype for bipolar disorder (BPD) and to investigate Notch3 (CADASIL) as a candidate gene for BPD. MRI scans were performed on 21 members of a family with a high incidence of BPD. Two-point and multipoint linkage analyses were performed and two exons of Notch3 were investigated with SSCP. Fifteen of 21 family members had MRI hyperintensities, including all bipolar patients and six family members with no affective illness. Two-point linkage analysis yielded negative results for all models. Multipoint linkage analysis yielded negative results except for Model 1a, in which a maximal LOD score was -1.24. A mutation screen of Exons 3 and 4 was negative. Notch3 does not appear to be a candidate gene for BPD in this family.

Adolescent↗
PubMed2002

APOE genotype and hippocampal volume change in geriatric depression.

BACKGROUND: Apolipoprotein E has been associated with hippocampal volume loss in Alzheimer's disease and in elderly controls. In this study, we examined the role of apolipoprotein E and hippocampal volume change in 45 older nondemented depressed subjects. All had baseline and 2-year magnetic resonance imaging scans. METHODS: Hippocampal volumes were determined using a semiautomated method. RESULTS: Compared with 36 depressed subjects without an apolipoprotein E epsilon4 allele, 9 subjects with at least one APOE epsilon4 allele showed significant decline in hippocampal volume, particularly in the right hippocampus. In a logistic model, percent change in right hippocampal volume remained associated with presence of an APOE epsilon4 allele after controlling for age, gender, Mini-Mental State Examination score, and baseline total cerebral volume. CONCLUSIONS: Future studies are needed to explain this association and to determine whether the finding for the right hippocampus has a biological basis, or if it is merely a function of small sample size.

Aged↗
PubMed2002

Head injury in early adulthood and the lifetime risk of depression.

BACKGROUND: Depressive symptoms are common and can be debilitating in the months after head injury. Head injury can also have long-term cognitive effects, but little is known about the long-term risk of depression associated with head injury. We investigated the lifetime rates of depressive illness 50 years after closed head injury. METHODS: Participants were male World War II veterans who served during 1944-1945 and were hospitalized at that time for a head injury, pneumonia, or laceration, puncture, or incision wounds. We used military medical records to establish the presence and severity of closed head injuries. Veterans with (n = 520) and without (n = 1198) head injuries were interviewed in 1996-1997 for their lifetime history of depressive illness. Men with dementia were excluded. RESULTS: Veterans with head injury were more likely to report major depression in subsequent years and were more often currently depressed. Using logistic regression and controlling for age and education, the lifetime prevalence of major depression in the head injured group was 18.5% vs 13.4% in those with no head injury (odds ratio = 1.54, 95% confidence interval = 1.17-2.04). Current major depression was detected in 11.2% of the veterans with head injuries vs 8.5% of those without head injury (odds ratio = 1.63, 95% confidence interval = 1.07-2.50). This increase in depression could not be explained by a history of myocardial infarction, a history of cerebrovascular accident, or history of alcohol abuse. The lifetime risk of depression increased with severity of the head injury. CONCLUSION: The risk of depression remains elevated for decades following head injury and seems to be highest in those who have had a severe head injury.

Adult↗
PubMed2002

Subcortical white matter lesions and functional impairment in geriatric depression.

Geriatric depression is associated with significant functional impairment. There is also growing evidence linking vascular brain changes to depression in late life. We sought to examine the relationship between cerebrovascular disease and impairment in basic activities of daily living (BADL) and instrumental activities of daily living (IADL) in a group of older depressives. The sample consisted of 224 depressed adults aged 60 years and above enrolled in Duke's Mental Health Clinical Research Center. All subjects had unipolar major depression and were free of other major psychiatric and neurological illness, including dementia. In a structured interview, subjects reported their medical history and ability to perform both BADL and IADL. Geriatric psychiatrists assessed cognition using the Mini Mental State Examination (MMSE) and depression severity using the Montgomery Asberg Depression Rating Scale (MADRS). Subjects had a standardized magnetic resonance imaging (MRI) brain scan. MRI scans were processed using a semi-automated method to determine volumes of subcortical white matter lesions (WML) and subcortical gray matter lesions (GML). Logistic regression was used to examine effects of WML and GML controlling for demographic and clinical factors. Greater volume of WML was associated with impairment in both BADL and IADL, while GML was associated with IADL impairment. In logistic models, WML remained significantly associated with IADL after controlling for the effects of age, gender, depression severity, and medical comorbidity. We concluded that white matter lesions are independently associated with functional impairment. Further studies are needed to understand how these lesions affect function, e.g., through effects on cognition or motor skills.

Activities of Daily Living↗
PubMed2002

Psychosocial and clinical predictors of unipolar depression outcome in older adults.

BACKGROUND: This study examined psychosocial and clinical predictors of depression non-remittance among a sample of initially clinically depressed elders. METHODS: Incident and prevalent unipolar depression cases (n = 166) were enrolled into the MHCRC for the Study of Depression in Late Life and followed for 12 months while undergoing treatment using a standardized algorithm. The outcome was remission vs non-remission (<6 vs > 7 on the Montgomery-Asberg Depression Rating Scale (MADRS)) at one-year follow-up. Baseline predictor variables included psychosocial factors, such as four domains of social support, basic and instrumental activities of daily living (ADLs), and clinical factors, which included use of ECT, past history of depression, comorbidities, and antidepressant treatment. RESULTS: At one-year follow-up, 45% of the sample was in remission based upon MADRS scores. In bivariate analyses, non-remitted patients were more likely at baseline to use benzodiazepines, anxiolytic/sedatives, and/or MAO inhibitors than patients in remission, and have more depressive episodes. Among psychosocial factors, non-remitted patients had at baseline, more ADL and IADL problems and decreased subjective social support as compared to patients in remission. In logistic regression analyses more depression episodes, using anxiolytic/sedatives, more IADL problems and decreased subjective social support predicted poor depression outcome after one-year. CONCLUSIONS: While clinical and diagnostic variables were related to improvement, baseline psychosocial factors were also important.

Activities of Daily Living↗
PubMed2002

Hippocampal volume and antidepressant response in geriatric depression.

BACKGROUND: Biological markers of treatment response may include structural brain changes seen on neuroimaging. While most imaging studies have focused on cerebrovascular disease, evidence is growing that the hippocampus may play a role in depression, particularly geriatric depression. METHOD: We studied 60 depressed elderly patients enrolled in a longitudinal study who were treated with antidepressant medications using a treatment guideline-based approach. Baseline and 12-week Montgomery-Asberg Depression Rating Scale (MADRS) scores were obtained via interview with a geriatric psychiatrist. All subjects had a baseline magnetic resonance imaging (MRI) brain scan. MRI scans were processed using standard protocols to determine total cerebral volume and right and left hippocampal volumes. Hippocampal volumes were standardized for total cerebral volume. MADRS scores less than 10 were used to define remission. RESULTS: When the group with the lowest quartile of standardized hippocampal volumes was compared to those above the first quartile, those with small right and total hippocampal volumes were less likely to achieve remission. In a subsequent logistic regression model controlling for age small standardized right hippocampal volumes remained significantly associated with remission. CONCLUSION: Further studies with larger sample are needed to determine if left-right hippocampal volume differences do exist in depression, and basic neuroscience studies will need to elucidate the role of the hippocampus in geriatric depression.

Aged↗
PubMed2002

Anatomic location and laterality of MRI signal hyperintensities in late-life depression.

OBJECTIVES: Evidence is mounting linking cerebrovascular disease with the development of major depression in the elderly. Lesions in both white and gray matter have been associated with geriatric depression. In addition, the literature on poststroke depression suggests that left-sided lesions are associated with depression. We sought to examine the severity and location of white- and gray-matter lesions in a group of elderly depressives and nondepressed control subjects. METHOD: 115 depressed patients (69 with late onset, 46 with early onset) and 37 controls, all over age 45, received magnetic resonance imaging (MRI). Semiquantitative severity ratings and quantitative measurements of number and size of MRI hyperintensities were obtained, and groups were compared using Cochran-Mantel-Haenszel (CMH) analyses and repeated-measures analyses of covariance adjusting for age. RESULTS: Late-onset depressed patients had more severe hyperintensity ratings in deep white matter than early-onset patients and controls. Late- and early-onset patients had more severe subcortical gray-matter hyperintensities (particularly in the putamen) compared with controls. Left-sided white-matter lesions were significantly associated with older age of depression onset, whereas right-anterior white matter and left-subcortical lesions (particularly in the putamen) were associated with melancholia in the depressed group. CONCLUSION: These findings extend previous reports of an association between cerebrovascular disease and depression, as well as recent studies showing lateralized lesion involvement in geriatric depression. Such vascular pathology may disrupt neural pathways involved in affective processing and the maintenance of a normal mood and psychomotor state.

Age of Onset↗
PubMed2002

Behavioral medicine and aging.

A brief history of behavioral medicine and aging is followed by a series of perspectives that help to understand how age is used as a variable in this research, the relative importance of age to declines in cognitive functioning, and the impact of behavioral risk indicators on healthy survival. The authors discuss Alzheimer's disease and the role of age in clinical practice. Also discussed are potential problems in age-related research, ways to improve the knowledge base in behavioral medicine and aging, and thoughts about future challenges to enhance work in behavioral medicine and aging.

Age Factors↗
PubMed2002

Cerebrovascular disease and evolution of depressive symptoms in the cardiovascular health study.

BACKGROUND AND PURPOSE: Previous studies have reported an association between cerebrovascular disease and depressive symptoms. The Cardiovascular Health Study (CHS) provides an opportunity to examine the relationship between vascular brain pathology seen on neuroimaging and changes in depressive symptoms. METHODS: The sample included 3236 CHS participants who had an MRI brain scan. Demographic variables, medical history, functional status, and apolipoprotein E genotype were obtained at baseline. Annual scores on a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale were obtained initially and up to 7 years subsequently. RESULTS: After controlling for important covariates, occurrence of depressive symptoms (defined as modified CES-D score of >7) was associated with small lesions in the basal ganglia, large cortical white-matter lesions, and severe subcortical white-matter grade. Neuroimaging variables did not predict incident depression among those who were nondepressive at the time of MRI. Persistence of depressive symptoms across 2 consecutive time points was associated with small basal ganglia lesions and large cerebral cortical white-matter lesions. Worsening of depression (increase in CES-D score of > or =5) was associated with subcortical white-matter lesions. CONCLUSIONS: These findings suggest that cerebrovascular disease at baseline is related to depression symptoms over time. Further studies are needed to investigate the differential effects of subcortical white- versus gray-matter lesions on mood.

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PubMed2002

The Duke Somatic Treatment Algorithm for Geriatric Depression (STAGED) approach.

Although there have been previously published algorithms for the treatment of depression, few have been rigorously studied in terms of outcome. We present the Duke Somatic Treatment Algorithm for Geriatric Depression (STAGED) approach, developed by clinicians in the Duke Mood Disorders Program. The algorithm consists of five stages based on treatment history. In developing the approach, we enrolled 228 depressed elderly patients in a National Institute of Mental Health-funded longitudinal study of depression. Patients were treated by geriatric psychiatrists using the algorithm as a guideline for treatment. Initially, 174 patients were treated with antidepressant medications, and 54 patients were treated with electroconvulsive therapy. Over the course of 18 months of treatment, 88.6% of patients responded, and 65.35% of patients were able to achieve full remission of symptoms. The STAGED approach appears to be a clinically useful method of successfully treating elderly depressed patients.

Aged↗
PubMedDate not supplied

Implementing a disease management intervention for depression in primary care: a random work sampling study.

We describe the daily work activities of 13 Depression Clinical Specialists (DCSs) at 7 national sites who served as care managers in an effective multisite randomized trial of a disease management model for depression in primary care. DCSs carried portable random-reminder beepers for a total of 147 consecutive workdays and recorded 4,030 work activities. Patient care activity comprised the largest percentage of the workday, 49.4% (95% confidence interval [CI], 42.0 to 56.7%), followed by research-related activity, 18.3 % (95% CI, 14.7 to 21.9%), administrative work, 17.9% (95% CI, 12.2 to 23.7%), personal time, 9.4% (95% CI, 5.4 to 13.4%), and time in transit, 5.1% (95% CI, 2.8 to 7.4%). The DCSs delivered 19.2% (95% CI, 14.4 to 24.1%) of direct patient care by telephone. The DCSs spent a significant portion of the day alone 48.7% (95% CI, 43.3 to 54.1%), followed by time spent with patients, 37.5% (95% CI, 31.6 to 43.3%). Less than 10% (7.8%) (95% CI, 5.1 to 10.6%) of their time was spent with local study staff. Less than 4% of their time was spent with other health care providers. Our results demonstrate that the DCSs' time was primarily devoted to clinical care, a significant portion of which was delivered by telephone. They functioned independently, making efficient use of the limited amount of time that they interacted with other health care providers. This information will be helpful to those who may wish to implement this disease management strategy.

Depressive Disorder↗
PubMedDate not supplied

MRI lesion severity and mortality in geriatric depression.

OBJECTIVE: The authors correlated magnetic resonance imaging (MRI) lesion severity and mortality among depressed elderly patients. METHOD: They examined the association of mortality and deep white-matter hyperintensity (DWMH), periventricular hyperintensity (PVH), and subcortical gray-matter hyperintensity (SGH) ratings in 259 subjects. RESULTS: DWMH and PVH were significantly associated with mortality initially, and, in final modeling, DWMH remained significant. CONCLUSION: These findings suggest that there is a relationship between cerebrovascular disease severity and mortality among depressed patients. More studies, with larger sample sizes, comparing depressed patients and control subjects are needed to further elucidate this relationship.

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