Biomedical subjects

David C Steffens

Publications and source records attributed to David C Steffens.

At least 55 records · Page 3Linked to original sources

PubMed2005

Predictors of partial remission in older patients treated for major depression: the role of comorbid dysthymia.

OBJECTIVE: The authors studied demographic, clinical, social, and perceived health and well-being factors as predictors of partial remission in older patients treated for major depressive disorder (MDD). METHODS: The sample included 186 patients who met DSM-IV criteria for MDD and underwent naturalistic treatment. Remission status was determined by Montgomery-Asberg Depression Rating Scale score. Ordinal logistic-regression was used to model the relationship between predictors and remission on an ordinal scale. RESULTS: A total of 26.9% patients were in partial remission (score: 7-15), and 25.8% were not in remission (score: 16-60) 1 year after the index evaluation. In bivariate analyses, the odds of partial/no remission were significantly increased for those with comorbid MDD and dysthymia and for those with higher baseline depression scores, and decreased for those with higher perceived social support. Other factors potentially associated with outcome included number of mobility/IADL limitations, perceived stress, self-perceived health, life dissatisfaction, and heart trouble. Controlling for these potential confounders, comorbid MDD and dysthymia significantly predicted outcome. The effect of mobility/IADL limitations differed for those with comorbid dysthymia. CONCLUSIONS: Among older adults treated for MDD, factors predicting partial remission appear to be similar to those predicting no remission. Patients with comorbid MDD and dysthymia are at increased risk for poor outcome, and predictors may vary by dysthymia status.

Activities of Daily Living↗

PubMed2005

Symptomatic remission in patients with bipolar mania: results from a double-blind, placebo-controlled trial of risperidone monotherapy.

BACKGROUND: The purpose of this analysis was to assess rates of symptomatic remission in patients with bipolar mania receiving risperidone in a double-blind, parallel-group, multicenter, placebo-controlled trial conducted in India. METHOD: Two hundred ninety-one adult patients who met DSM-IV criteria for bipolar I disorder manic or mixed episode were randomly assigned to flexible doses of risperidone (1-6 mg/day, N = 146) or placebo (N = 145) for up to 3 weeks. An entry Young Mania Rating Scale (YMRS) score of >or= 20 was required at trial screening and baseline. Remission was defined as achieving and maintaining a YMRS score <or= 8 for the remainder of the trial or until censor. Time to first onset of remission was assessed using Cox proportional hazards model. Presence or absence of remission was analyzed using logistic regression. Data were collected from March 2001 to December 2001. RESULTS: Of the 291 patients randomly assigned to treatment, 290 received at least 1 postbaseline assessment and were included in the analysis. The patients' mean YMRS score at baseline was 37.2 +/- 7.9. Remission was achieved by 42% of patients in the risperidone group and 13% of patients in the placebo group. After adjusting for psychosis, baseline YMRS score, sex, number of mood cycles in the previous year, and treatment, the odds of remission for patients receiving risperidone was 5.6 (95% CI = 3.0 to 10.4; chi(2) = 29.9, p < .0001). Similarly, the adjusted hazard of remission for the risperidone patients was 4.0 (95% CI = 2.3 to 6.8; chi(2) = 25.9, p < .0001). CONCLUSION: A significant proportion of acutely manic patients receiving risperidone monotherapy achieved symptomatic remission within 3 weeks.

Adult↗

PubMed2004

Establishing diagnostic criteria for vascular depression.

We have proposed a subtype of vascular depression with two key elements: (1) presence of major depression and (2) presence of cerebrovascular disease on neuroimaging. Future studies are needed to refine these diagnostic criteria. There must be a consensus as to whether requiring major depression criteria is acceptable, or possibly too stringent. There are several methodological issues regarding cerebrovascular disease, including defining severity and thresholds, importance of location and system of assessment. Once agreement is reached on a working diagnosis of vascular depression, researchers will be in a position to estimate prevalence of the disorder, determine conditions that represent risk factors, and examine important outcomes in patients with vascular depression.

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PubMed2004

Clinical characteristics of magnetic resonance imaging-defined subcortical ischemic depression.

BACKGROUND: There is a substantial body of research supporting the vascular depression hypothesis of late-life depression. To update this hypothesis so it incorporates recent research, we propose that the term subcortical ischemic vascular depression may be a more accurate representation of the disease process. We sought to investigate this diagnosis as a construct by examining differences between depressed subjects with and without magnetic resonance imaging defined subcortical ischemic vascular depression. METHODS: This case-control study examined 139 depressed elderly subjects. Demographic data, psychiatric, medical, and family history, depressive symptomatology, and functional impairment were compared between groups dichotomized based on neuroimaging findings. RESULTS: Seventy-five (54%) of the subjects met neuroimaging criteria for subcortical ischemic vascular depression. Age was most strongly associated with increased prevalence of subcortical ischemic vascular depression. Lassitude and a history of hypertension were also positively associated with the diagnosis; a family history of mental illness and loss of libido were negatively associated with the diagnosis. CONCLUSIONS: These data support that subcortical ischemic vascular depression may be a specific syndrome from other types of late-life depression. Further research is needed to further characterize this disorder, particularly in regards to cognitive function and treatment implications.

Age Factors↗

PubMed2004

The persistence of neuropsychiatric symptoms in dementia: the Cache County Study.

OBJECTIVE: To estimate the 18-month persistence of neuropsychiatric symptoms in dementia in a population-based sample, and to compare the severity of neuropsychiatric symptoms at baseline to the severity at 18-month follow-up. METHODS: A population-based sample of 329 residents of Cache County, Utah, diagnosed with dementia was rated on the Neuropsychiatric Inventory (NPI). Of the 204 participants with neuropsychiatric symptoms at baseline (defined as total NPI score >0), NPI data were obtained approximately 18 months later on 117 who were alive and available for follow-up. RESULTS: Eighty-one percent of those with neuropsychiatric symptoms at baseline (defined as total NPI score>0) continued to have at least one symptom at follow-up. Sixty-seven percent of participants with a clinically significant total NPI score (defined as > or = 4) at baseline continued to have a clinically significant total NPI score at follow-up. Among the ten neuropsychiatric domains assessed at baseline, delusions persisted in 65.5% of individuals, followed by depression (58.3%), and aberrant motor behavior (55.6%), while hallucinations and disinhibition persisted in only 25.0% and 11.1% respectively. In participants who were symptomatic at both baseline and follow-up, the mean severity scores at the two observation points were comparable in all ten neuropsychiatric domains. CONCLUSIONS: Neuropsychiatric symptoms in dementia overall were highly persistent. Among those in whom symptoms did persist, symptom severity a year and a half later appeared to be comparable.

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PubMed2004

Is there a definition of remission in late-life depression that predicts later relapse?

Remission of depressive symptoms is the goal of all antidepressant therapy. Rating scales define remission in clinical trials, but it is unclear how well these definitions predict risk of later relapse. We measured the sensitivity and specificity of a range of Montgomery-Asberg Depression Rating Scale (MADRS) cutoff scores at 3- and 6-months, wherein scores above a given cutoff would predict relapse over an 18-month period. We examined 153 elderly depressed subjects exhibiting a MADRS < or = 15 after 3 or 6 months of antidepressant therapy. Subjects who subsequently exhibited a MADRS > 15 during the 18-month study period were defined as relapsed. Receiver operating characteristic (ROC) curves were developed and area under the curve (AUC) values calculated for the sensitivity and specificity of 3- and 6-month MADRS scores to predict future relapse. The 3-month ROC had an AUC value of 0.63; the 6-month ROC had an AUC value of 0.66. There was no MADRS cutoff found that could predict likelihood of relapse with good sensitivity and specificity. A post hoc analysis where relapse rate was adjusted by controlling for medical comorbidity, disability, and social support showed no change in the ROCs or AUC values. The higher the MADRS score at 3 and 6 months, the greater the likelihood of relapse. With no clean MADRS cutoff score, the goal of antidepressant therapy should be the lowest possible degree of depressive symptomatology to minimize risk of later relapse. Definitions of remission that are better associated with longer-term outcomes are needed.

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PubMed2004

Prefrontal neuropsychological predictors of treatment remission in late-life depression.

Recent studies suggest that neuropsychological measures involving the prefrontal cortex are associated with treatment remission in late-life depression. To further explore this issue, we studied the neuropsychological performance of 110 depressed individuals aged 60 years and over who are participating in an ongoing pharmacologic treatment study. Participants were clinically depressed at entry to the study as rated by the Montgomery-Asberg Depression Rating Scale (MADRS > or = 15), at which time they also completed a neuropsychological assessment that included measures of prefrontal/executive functions. A geriatric psychiatrist treating the participant using a standardized pharmacologic treatment algorithm evaluated the participant at baseline and 3-month follow-up, completing a MADRS at both visits. Using logistic discriminative procedures to predict depression remission at 3 months while controlling for age, gender, education, ethnicity, and baseline MADRS severity, we found that perseverative responses during verbal initiation tasks significantly predicted remission status (MADRS < 7). This finding is consistent with previous single-agent treatment studies suggesting a relationship between prefrontal neuropsychological function and treatment response in late-life depression. The current results, however, appear to differentiate verbal perseveration from verbal initiation as the cognitive process that is most associated with poor treatment response. By extension, we suggest that orbitofrontal prefrontal cortex may play a role in sustaining perseverative processing in geriatric depression.

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PubMed2004

Late-life depression and microstructural abnormalities in dorsolateral prefrontal cortex white matter.

OBJECTIVE: The purpose of this study was to determine whether microstructural abnormalities in the white matter of the dorsolateral prefrontal cortex are associated with late-life depression. METHOD: Seventeen elderly depressed subjects were compared with 16 elderly subjects who were not depressed. Diffusion tensor imaging was used to measure the fractional anisotropy of the white matter in the dorsolateral prefrontal cortex's superior and middle frontal gyri bilaterally and in the left occipital lobe as a control region. The authors compared results between groups while controlling for age, sex, and comorbid medical disorders. RESULTS: Even after controlling for age, sex, hypertension, and heart disease, the authors found significantly lower fractional anisotropy values in the right superior frontal gyrus white matter of depressed patients than comparison subjects. CONCLUSIONS: Microstructural changes in the white matter of the right superior frontal gyrus are associated with late-life depression. Further work is needed to determine how these changes contribute to depression outcomes.

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PubMed2004

Methodology and preliminary results from the neurocognitive outcomes of depression in the elderly study.

A methodology is presented for following a cohort of older depressed patients to examine neurocognitive outcomes of depression. A total of 265 depressed individuals and 138 healthy, nondepressed controls age 60 and older who completed at least 1 year of follow-up data underwent periodic clinical evaluation by a geriatric psychiatrist. A subset of 141 patients and 137 controls had neuropsychological testing. A consensus panel of experts reviewed 63 depressed subjects with suspected cognitive impairment. Twenty-seven individuals in the depressed group were assigned diagnoses of dementia, including 11 with Alzheimer's disease, 8 with vascular dementia, and 8 with dementia of undetermined etiology. In addition, 25 individuals had other forms of cognitive impairment, and 11 were considered cognitively normal. Among elderly controls, 2 developed substantial cognitive impairment with clinical diagnoses of dementia. Among the depressed group, the incidence rates for dementia for this age are much higher than would be expected. These results are consistent with prior evidence linking depression and later dementia. Future studies are needed to examine neuroimaging and genetic, clinical, and social predictors of neurocognitive decline in depression.

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PubMed2003

Apolipoprotein E genotype and subcortical vascular lesions in older depressed patients and control subjects.

BACKGROUND: Several studies have linked geriatric depression with cerebrovascular disease. The apolipoprotein E gene (APOE) epsilon 4 allele has been associated with a variety of late-life neuropsychiatric disorders, including Alzheimer's disease, vascular dementia, and depression. METHODS: The sample consisted of 145 elderly depressive individuals and 100 nondepressed elderly control subjects. After a standardized clinical assessment, all subjects underwent a magnetic resonance imaging brain scan. Volumes of subcortical white and gray matter lesions were determined using a semi-automated method. Apolipoprotein E genotype was determined on blood sample using a standard protocol. A series of linear regression models were developed to assess the relationships between APOE genotype and white and gray matter lesion volumes. RESULTS: Older age, lower Mini-Mental State Examination score, and having any APOE epsilon 4 allele were each correlated with gray-matter lesion volume in depressed patients. Apolipoprotein E genotype was not associated with any lesion volume among control subjects. In a subsequent linear regression model, gray matter lesion volume was associated with older age, having at least one APOE epsilon 4 allele, and white matter lesion volume among depressed patients. CONCLUSIONS: These results are consistent with previous reports linking cerebrovascular disease and APOE genotype. Further studies are needed to replicate this finding in elderly depressive individuals and to explain the relationship between the APOE locus and development of central nervous system vascular pathology.

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PubMed2003

Subcortical lesion severity and orbitofrontal cortex volume in geriatric depression.

Previous studies have shown a reduction of orbital frontal cortex volume and an increase in magnetic resonance imaging signal hyperintensities in geriatric depression. We aimed to assess the relationship between subcortical gray- and deep white-matter lesions and orbital frontal cortex volume in elderly depressives and controls. The study included 41 elderly depressed patients and 41 age-matched control subjects. The orbital frontal cortex volume was measured in both hemispheres using a standardized MRI procedure. Signal hyperintensities were rated on (T2)-weighted MRI with qualitative lesion analyses performed according to an established hyperintensity classification system. After controlling for total cerebral hemisphere, age and sex, the geriatric depressed subjects had significant reduction in orbital frontal cortex volume and compared with the control group. Multiple linear regression modeling indicated that reduced orbital frontal cortex volumes were significantly associated with increased subcortical gray-matter lesions. Our study confirmed the reduction of OFC volume in geriatric depressed subjects. We also suggest that subcortical lesions may decrease OFC volume. Further studies are needed to understand how subcortical lesions may be related to OFC volume changes.

Aged↗

PubMed2003

Smaller orbital frontal cortex volumes associated with functional disability in depressed elders.

BACKGROUND: Depression is associated with significant functional impairment. Recent evidence has linked the orbital frontal cortex (OFC) with depression. We examined the relationship between OFC volumes in older subjects and impairment in the basic (BADL) and instrumental (IADL) activities of daily living. METHODS: The sample consisted of 81 subjects aged 60 years or older; 41 were depressed subjects and 40 healthy control subjects. In a structured interview, subjects reported their medical history and ability to perform both BADL and IADL. Subjects then had a brain magnetic resonance imaging (MRI) scan; the OFC was manually traced bilaterally using neuroanatomical landmarks. Logistic regression was used to examine the effect of OFC volume on BADL and IADL while controlling for the effects of total brain volume, subject status, medical comorbidity, and demographic factors. RESULTS: Smaller OFC volumes, along with greater cognitive impairment as measured by the Mini-Mental State Examination, were significantly associated with BADL impairment. Smaller OFC volumes and being depressed were significantly associated with IADL impairment. CONCLUSIONS: Smaller OFC volumes are independently associated with functional impairment, supporting its role in depression. Further studies are needed to determine how smaller OFC volumes are related to other MRI abnormalities associated with depression and functional impairment.

Activities of Daily Living↗

PubMed2003

White matter hyperintensity progression and late-life depression outcomes.

CONTEXT: White matter hyperintensities (WMHs) are bright foci seen in the parenchyma of the brain on T2-weighted cranial magnetic resonance imaging (MRI) scans and are associated with geriatric depression. Because they are associated with age, they should increase in number and size over time. To our knowledge, this is the first longitudinal, volumetric MRI study of WMHs in depression. OBJECTIVE: To determine if WMH progression over 2 years influences depression outcomes. DESIGN: Over 2 years, depressed subjects received antidepressant treatment according to a naturalistic somatic treatment algorithm designed to offer the best possible treatment to the individual. After the treatment period, depressed subjects were dichotomized based on whether they had reached and sustained remission during this period. PARTICIPANTS: One hundred thirty-three subjects aged 60 years or older meeting DSM-IV criteria for major depressive disorder. MEASURES: Cranial MRI was obtained at baseline and approximately 2 years later. White matter hyperintensity volume was measured in each hemisphere using a semiautomated segmentation process. OUTCOMES: Subjects were dichotomized based on achieving or not achieving remission of depressive symptoms, defined as a Montgomery-Asberg Depression Rating Scale score of 8 or less. RESULTS: The depressed subgroup that achieved and sustained remission had significantly less increases in WMH volume (11.5%) than did the group that did not achieve or sustain remission (31.6%) (P =.01). In a regression model, greater change in WMH volume was significantly associated with failure to sustain remission (P =.004) even when controlling for baseline depression severity, medical illness severity, age, sex, and race. Education was associated with achieving and sustaining remission (P =.02). CONCLUSIONS: Greater progression of WMH volume is associated with poor outcomes in geriatric depression. Future work is needed to develop means of slowing the rate of WMH progression and to determine whether this will lead to improved depression outcomes in elderly persons.

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PubMed2003

The association of psychosocial factors and depression with hypertension among older adults.

OBJECTIVE: To examine the relationship between depression and hypertension in an elderly population and how psychosocial variables influence this relationship. METHODS: The study included 293 subjects, who met DSM-IV criteria for unipolar depression, and 151 subjects with no psychiatric disorder. All subjects were over the age of 58. Participants were administered the Duke Depression Evaluation Schedule at baseline and at yearly intervals for 3 years. RESULTS: Cross-sectional analyses of baseline data showed that hypertensive patients were more likely to be depressed and of non-white race. Bivariate analyses provided evidence that hypertension was associated with higher amounts of total stressors and lower social support. No differences in the prevalence of hypertension were found between men and women. In addition, there was no evidence of change in hypertension status over time. CONCLUSION: Patients, especially minorities, who experience depression, stress, or a lack of social support, are at an increased likelihood of having hypertension and clinicians should consider this risk when treating this population.

Age Factors↗

PubMed2003

A three-factor analytic model of the MADRS in geriatric depression.

OBJECTIVE: Major depression is a heterogeneous disorder, perhaps comprising several clinical subtypes or subgroups of symptoms. This study examined whether items on the Montgomery-Asberg Depression Rating Scale (MADRS) form distinct symptom subgroups among geriatric depressive patients that might form the basis of new outcome measures for tracking treatment effects. METHOD: The study examined a sample of 225 adults age 59 and older diagnosed with major depression. Factor analysis with oblique rotation was used to analyze baseline MADRS item scores. RESULTS: Three distinct interpretable factors were obtained; all ten items loaded <0.60 on a domain. The first factor, dysphoric apathy/retardation, comprised five items: apparent sadness, reported sadness, lassitude, reduced concentration, and inability to feel. Psychic anxiety, the second factor, included three items: inner tension, pessimistic thoughts, and suicidal thoughts. The third factor, vegetative symptoms, resulted from items involving sleep and appetite. CONCLUSIONS: The study produced three interpretable MADRS factors reflecting geriatric depression dimensions that may be useable to monitor focused treatment outcomes.

Affect↗

PubMed2003

The impact of religious practice and religious coping on geriatric depression.

OBJECTIVE: Both religiousness and social support have been shown to influence depression outcome, yet some researchers have theorized that religiousness largely reflects social support. We set out to determine the relationship of religiousness with depression outcome after considering clinical factors. METHODS: Elderly patients (n=114) in the MHCRC for the Study of Depression in Late Life while undergoing treatment using a standardized algorithm were examined. Patients completed measures of public and religious practice, a modified version of Pargament's RCOPE to measure religious coping, and subjective and instrument social support measures. A geriatric psychiatrist completed the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and six months. RESULTS: Both positive and negative religious coping were related to MADRS scores in treated individuals, and positive coping was related to MADRS six months later, independent of social support measures, demographic, and clinical measures (e.g. use of electro-convulsive therapy, number of depressed episodes). Public religious practice, but not private religious practice was independently related to MADRS scores at the time of completion of the religiousness measures. Religious coping was related to social support, but was independently related to depression outcome. CONCLUSIONS: Clinicians caring for older depressives should consider inquiring about spirituality and religious coping as a way of improving depressive outcomes.

Adaptation, Psychological↗

PubMed2003

Localization of age-associated white matter hyperintensities in late-life depression.

OBJECTIVE: Deep white matter hyperintense lesions are associated with advanced age and late-life depression. The authors examined where age-related cerebral lesions occurred in elderly depressed and healthy control subjects. METHODS: Eighty-seven depressed subjects and 47 control subjects underwent 1.5 T cranial magnetic resonance imaging (MRI). Utilizing a semiautomated method, a segmented image was created containing only white matter lesions. We created a statistical parametric map (SPM) separately for each subject group that displayed the association between lesions in any voxel and advanced age. RESULTS: The SPM analysis in depressed subjects demonstrates a significant association between age and lesions found in bilateral, frontal, and left parietal regions. The analysis in control subjects found significant associations only in bilateral parieto-temporal regions, not frontal regions. CONCLUSIONS: This study demonstrates a different pattern of age-related lesion location between depressed and control subjects. It further supports the theory that frontostriatal disconnection contributes to late-life depression.

Age Factors↗

PubMed2003

Left orbital frontal cortex volume and performance on the benton visual retention test in older depressives and controls.

Changes within the prefrontal cortex (PFC) have been associated with both mood disorders and with specific impairments in cognitive testing. The left PFC has been implicated in relational processing, that is, binding different pieces of information. We hypothesized that among older depressives and elderly controls, lower performance on one test of relational processing would be associated with smaller volume of the orbital frontal cortex (OFC). A total of 30 depressed and 40 control subjects were included in the study. All subjects were administered the Benton Visual Retention Test (BVRT). Subjects received a standardized magnetic resonance imaging, for which volumes of the OFC and total brain were calculated. We found that, controlling for age and education, total correct on BVRT was associated with left OFC volume normalized for total brain volume among the entire sample. For the depressed sample only, the number of perseverative errors was negatively associated with left OFC volume normalized for total brain volume after controlling for age and education. These results add to the literature linking mood and cognitive disturbances to the PFC. Future studies with a larger sample employing functional measures are warranted.

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