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Biomedical subjects

K R Krishnan

Publications and source records attributed to K R Krishnan.

At least 19 recordsLinked to original sources
PubMed2005

Psychiatric disease in the genomic era: rational approach.

Although the introduction of explicit diagnostic criteria and rule-based classifications, such as Research Diagnostic Criteria, Diagnostic and Statistical Manual Ed 3 and Ed 4, has dramatically influenced teaching and research psychiatric practice, it has significant limitations. As new knowledge is developed with genetic, imaging and metabolomic technologies, a method to incorporate this research in a systematic manner with current classification systems is needed. The current approach, which is essentially nominalist in character, has to be developed where new data and new concepts of disease can be integrated and tested. Examples of how this could happen is shown in the context of Alzheimer's disease and subcortical ischemic disease. It is likely that a standardized approach that can develop and modify classification systems in a timely manner, based on science and free of societal and political influence, can enhance research, teaching and clinical practice.

Alzheimer Disease↗
PubMed2002

Quality of life in patients with spinal cord injury--basic issues, assessment, and recommendations.

INTRODUCTION: Spinal cord injury (SCI) often causes severe disabilities. The degree of functional impairment strongly depends on the level and completeness of lesion (tetraplegic, paraplegic). But evaluation of outcomes also needs to consider the broader concept of health-related quality of the life (HRQL) for SCI patients. A multinational group of clinicians and researchers assessed this concept and reviewed the available instruments for measurement of quality of life in this group of patients. TIME POINTS: Phase I is in the acute clinic; phase II during rehabilitation; phase III after discharge home. Annual follow-up investigations should be maintained. The phase of initial care (phase 0) is important for prognosis and should, therefore, be part of the documentation. INSTRUMENTS: Criteria used to evaluate current QoL measures: reliability, validity, responsiveness, availability of translations, application in SCI patients, existing population norms. Several specific instruments or subscales exist for the following domains: physical and psychological functioning, pain, and handicap. Well-known generic measures of HRQL also have been applied to SCI patients, and a disease-specific instrument has been developed (SCIQL-23). A variety of subjective quality of life measures were evaluated as well. GROUP CONSENSUS/GUIDELINE: Prior to discharge from rehabilitation, the group suggested the use of the Functional Independence Measure, the Hospital Anxiety and Depression Scale and a Visual Analogue Scale for pain. Following discharge from the acute clinic, the SF-36, the Craig Handicap Assessment and Reporting Technique, the Quality of Well-being Scale, or the Life Satisfaction questionnaire were proposed. However, the evidence supporting the use of these instruments is sparse.

Disability Evaluation↗
PubMed2001

Performance feedback deficit in geriatric depression.

BACKGROUND: The orbital frontal cortex is involved with processing of performance feedback. This study tests the hypothesis that older depressed subjects, compared with elderly control subjects, commit more subsequent errors after receiving feedback from an initial error. METHODS: We administered 116 older depressed patients and 139 control subjects the Trail Making Test Part B (TRAILS-B). Subjects who committed an error on TRAILS-B were immediately given feedback on performance. We then measured the frequency of making an error on the subsequent three tries. The likelihood of making any subsequent error was examined. RESULTS: After controlling for the overall initial error rate, more depressed patients than control subjects made subsequent errors. This association remained significant in later regression models. When the depressed group was examined in additional models, severity of depression was not associated with increased subsequent errors. CONCLUSIONS: These results extend previous findings suggesting a performance feedback deficit in geriatric depression. The findings support previous studies linking the orbital frontal cortex and depression.

Aged↗
PubMed2001

MRI correlates of suicide attempt history in unipolar depression.

BACKGROUND: Suicide represents a major health problem in the United States, and prediction of suicide attempts is difficult. No structural neuroimaging studies have been done to specifically examine findings in patients who have attempted suicide. The objective of this study was to compare MRI findings in unipolar patients with and without a history of a suicide attempt. METHODS: In this post hoc analysis, 20 unipolar subjects with a history of a suicide attempt were matched by age and gender to unipolar subjects without a history of an attempt. Subjects were also matched on parameters such as cardiovascular history, electroconvulsive treatment history, and history of psychosis. Subjects with a history of any neurologic condition were excluded. There were no significant differences in age of onset of depression, number of episodes of depression, and Hamilton Depression scores between the two groups. T2-weighted magnetic resonance imaging (MRI) scans were rated using the Coffey and Boyko rating scales. RESULTS: Unipolar patients with a history of a suicide attempt demonstrated significantly more subcortical gray matter hyperintensities compared with patients without such a history. CONCLUSIONS: Patients with abnormal MRI findings may be at higher risk for mood disorders and suicide attempts because of disruption of critical neuroanatomic pathways. Gray matter hyperintensities in the basal ganglia may be especially associated with risk for suicide attempts.

Aged↗
PubMed2001

Evidence of white matter tract disruption in MRI hyperintensities.

BACKGROUND: Diffusion tensor imaging (DTI) of brain tissue measures the apparent diffusion coefficient (ADC), or isotropic diffusion, and anisotropy, or diffusion as influenced by tissue structure. We hypothesized that hyperintensities, when compared with normal tissue by DTI, would show evidence of damage through an increased ADC and decreased anisotropy. We also hypothesized that DTI changes in hyperintensities would be similar between depressed subjects and control subjects. METHODS: Fourteen depressed geriatric patients and nineteen control subjects received DTI. The ADC and aniso-tropy of normal tissue from standard regions were compared with hyperintensities from these regions. The Students' t test compared individual regions and averaged white matter results. RESULTS: Hyperintensities showed higher ADC and lower anisotropy than normal regions. Gray matter exhibited similar trends. There was no significant difference in diffusion characteristics of hyperintensities between subjects and control subjects. CONCLUSIONS: Hyperintensities damage the structure of brain tissue, and do so comparably in depressed subjects and control subjects.

Aged↗
PubMed2001

Medial orbital frontal lesions in late-onset depression.

BACKGROUND: Early studies using magnetic resonance (MR) imaging suggested that subcortical vascular changes are more prevalent in late-life depression and that they may play a role in the pathophysiology of depression. Studying the location of the lesion relative to the occurrence of depression could be critical in delineating the neuroanatomic substrates of depression. Our purpose was to characterize these lesions in terms of location by development of statistical parametric maps of lesions that differentiate patients from control subjects. METHODS: Magnetic resonance images were acquired on 88 elderly depressed subjects ("patients," unipolar major depression assessed using the Duke Depression Evaluation Schedule, age range 63-80 years) enrolled in the Duke University Clinical Research Center for the Study of Late-Life Depression and 47 age- and gender-matched nondepressed subjects ("control subjects"). The MR protocol includes a volumetric, dual-contrast fast spin-echo pulse sequence. A statistical parametric map was formed from a two-group t test to test for differences in lesion density between patients and control subjects. Additional testing was performed to evaluate whether there were regions that correlated with the severity of depression using the 17-item Hamilton Depression rating. RESULTS: The statistical parametric mapping analysis between groups showed two major regions of increased lesion density in the patients in the medial orbital prefrontal white matter. Severity of depression among depressed patients was correlated with lesions in the medial orbital region. CONCLUSIONS: This study supports recent evidence implicating the medial orbital frontal cortex in depression.

Age of Onset↗
PubMed2001

Association between selective serotonin-reuptake inhibitor therapy and heart valve regurgitation.

The identification of an association between fenfluramines and valvular disease has raised the possibility of a similar association between another class of medications that increases local levels of serotonin, the selective serotonin-reuptake inhibitors (SSRIs). The objective of this study was to examine the association between heart valve regurgitation and treatment with SSRIs. We examined 5,437 consecutive patients who underwent echocardiography. Patients with a similar likelihood of SSRI treatment were identified by propensity models. The prevalence of regurgitation according to treatment was compared after adjusting for clinical characteristics associated with regurgitation. We also blindly reinterpreted a subset of 2,000 echocardiograms to identify characteristics associated with fenfluramine-associated valvular heart disease such as posterior mitral leaflet restriction. Among 5,437 consecutively hospitalized patients, we identified 292 who had taken SSRIs before admission. Patients taking SSRIs tended to be younger, female, Caucasian, unmarried, and more likely to have psychiatric illness and hypertension (p < or = 0.05). The overall prevalence of regurgitation meeting Food and Drug Administration criteria (at least moderate mitral regurgitation or mild aortic regurgitation) was 30%, with no significant difference in prevalence between those receiving SSRIs (26.7%) and controls (30.4%) (p = 0.19). The association remained negative when comparing SSRI-treated patients to controls with similar characteristics. Furthermore, the prevalence of features described in conjunction with fenfluramine exposure, such as posterior mitral leaflet restriction, was not higher in SSRI-treated patients. Among a large consecutive cohort of patients, the prevalence of mitral and aortic regurgitation in patients taking SSRIs was not different from that of controls, suggesting that SSRIs are not associated with valvular disease.

Aortic Valve Insufficiency↗
PubMed2001

Clinical and treatment response characteristics of late-life depression associated with vascular disease: a pooled analysis of two multicenter trials with sertraline.

1. The safety and efficacy of sertraline in the treatment of moderate-to-severe major depression in elderly outpatients, aged 60 years and older, with comorbid vascular disease was evaluated. 2. An analysis of the pooled results for the sertraline treatment group drawn from two prospective, randomized, double-blind studies (sertraline vs. fluoxetine, and sertraline vs. nortriptyline) was done. Patients were retrospectively categorized into one of 3 clinical groups: 1) patients with a current diagnosis of hypertension but no other past or present cardiovascular illness (HTN), 2) patients reporting a current or past history of cardiovascular illness, but excluding hypertension (VASC), and 3) patients with no hypertension, and no other comorbid vascular illness (NoVASC). Patients received 12-3. weeks of double-blind treatment with sertraline in flexible daily doses in the range of 50 - 150 mg (in the nortriptyline comparator trial) or 50 - 100 mg (in the fluoxetine comparator trial). 4. Sertraline treatment yielded comparable levels of response in all 3 groups (response criterion: CGI-much or very much improved) at treatment endpoint on both a completer analysis (HTN, 86%; VASC, 89%; NoVASC, 77%) and significantly higher response rates on a 12-week endpoint analysis (HTN, 74%; VASC, 69%; NoVASC, 58%; p < 0.05). Sertraline treatment was well-tolerated, with no between-group differences in rates of adverse events, or in discontinuation due to adverse events. Patients taking 5 or more concomitant medications showed no difference, when compared with patients taking none-or-one concomitant medication, either in rates of adverse events, or in discontinuation due to adverse events. 5. Sertraline was found to be a safe, well-tolerated, and effective as an antidepressant in elderly patients suffering from hypertension and other forms of vascular comorbidity.

Age of Onset↗
PubMed2001

Bupropion for weight loss: an investigation of efficacy and tolerability in overweight and obese women.

OBJECTIVE: On the basis of the clinical observations that bupropion facilitated weight loss, we investigated the efficacy and tolerability of this drug in overweight and obese adult women. RESEARCH METHODS AND PROCEDURES: A total of 50 overweight and obese (body mass index: 28.0 to 52.6 kg/m(2)) women were included. The core component of the study was a randomized, double-blind, placebo-controlled comparison for 8 weeks. Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily. All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries. Responders continued the same treatment in a double-blind manner for an additional 16 weeks to a total of 24 weeks. There was additional single-blind follow-up treatment for a total of 2 years. RESULTS: Subjects receiving bupropion achieved greater mean weight loss (last-observation-carried-forward analysis) over the first 8 weeks of the study (p = 0.0001): 4.9% +/- 3.4% (n = 25) for bupropion treatment compared with 1.3% +/- 2.4% (n = 25) for placebo treatment. For those who completed the 8 weeks, the comparison was 6.2% +/- 3.1% (n = 18) vs. 1.6% +/- 2.9% (n = 13), respectively(p = 0.0002), with 12 of 18 of the bupropion subjects (67%) losing over 5% of baseline body weight compared with 2 of 13 in the placebo group (15%; p = 0.0094). In the continuation phase, 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9% +/- 5.6% with fat accounting for 73.5% +/- 3.7% of the weight lost and no change in bone mineral density as assessed by DXA. Bupropion was generally well-tolerated in this sample. DISCUSSION: Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study. Initial responders to bupropion benefited further in the continuation phase.

Adult↗
PubMed2001

A controlled study of MRI signal hyperintensities in older depressed patients with and without hypertension.

OBJECTIVES: To compare the frequency/severity of signal hyperintensities--likely markers of cerebrovascular disease--in the subcortical gray and deep white matter on magnetic resonance imaging (MRI) scans of brains of hypertensive and normotensive older depressed and nondepressed comparison subjects. DESIGN: Between-groups comparison of cross-sectional MRI data employing analyses of covariance controlling for the effects of age, gender, and height. SETTING: A comprehensive inpatient-outpatient geriatric psychiatry service in a university hospital. PARTICIPANTS: Nondemented older depressed (n = 81) and nondepressed comparison (n = 70) subjects divided into four groups (hypertensive depressed (n = 40), hypertensive normals (n = 21), normotensive depressed (n = 41), normotensive normals (n = 49)). MEASUREMENTS: Signal hyperintensities were rated on T-2 weighted MRI scans blind to patient diagnoses employing two standardized hyperintensity rating systems (Fazekas, Boyko). RESULTS: Hypertensive depressives had significantly more- severe hyperintensity ratings in both subcortical gray and deep white matter than did normotensive depressives and controls (P < .05) and significantly more-severe hyperintensity ratings only in subcortical gray matter (P < .05) than did hypertensive controls. Hypertensive controls had significantly more-severe ratings in deep white matter than either normotensive group (P < .05). CONCLUSIONS: Findings suggest a relationship between deep white matter hyperintensities and hypertension (regardless of depressive state), and a particular role of subcortical gray matter hyperintensities (possibly interacting with more-severe deep white matter lesions) in older depressed hypertensives, as compared with older depressed normotensives of similar ages and severity of depression. These data support possible heterogeneous pathogenic contributions in late-life depression subgroups, one of which appears to be influenced by cerebrovascular disease.

Analysis of Variance↗
PubMed2001

Delirium: diagnosis, neuropathogenesis, and treatment.

Delirium affects more than 2 million patients in the United States each year. The onset of delirium often occurs after hospitalization and in many cases is due to medications or procedures performed during the hospitalization. Unfortunately, delirium remains unrecognized in the majority of patients for several reasons. This review addresses the diagnostic criteria for delirium, the neurochemistry that is believed to be causative, risk factors, measures that may be taken to reduce the onset of delirium, and treatment options.

Journal Article↗
PubMed2001

Informant-rated cognitive symptoms in normal aging, mild cognitive impairment, and dementia. Initial development of an informant-rated screen (Brief Cognitive Scale) for mild cognitive impairment and dementia.

An informant-rated cognitive screen may have the potential to reliably help detect early dementia. A valuable scale should have good interitem associations and strong reliability when tested in groups with and without cognitive impairment. Our scale, the Brief Cognitive Scale (BCS), consists of 18 questions designed to assess cognitive function that affects everyday activities. Each question is coded with one of four levels, ranging from no impairment to severe impairment. We administered this screen to 120 subjects: 26 controls, 28 with a diagnosis of mild cognitive impairment (MCI), and 66 with a diagnosis of dementia. In addition, we administered a Folstein Mini-Mental Status Examination (MMSE) to each subject. Our results showed that the BCS scores were lowest in the control group and highest in the dementia group. In our sample, this scale was effective at discriminating between subjects with no cognitive impairment, MCI, and dementia. However, the scale needs further refinement before it can be employed in a clinical setting.

Aged↗
PubMed2001

Clinical trials in Alzheimer's disease. Calculating Alzheimer's Disease Assessment Scale-cognitive subsection with the data from the consortium to establish a registry for Alzheimer's disease.

The database of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is a seminal work in the field of cognitive dysfunction and Alzheimer's disease. This 24-center study of 1,094 patients with Alzheimer's disease who received no treatment for their cognitive dysfunction and 463 normal control subjects is rich in neurobehavioral data and contains extensive imaging and neuropathologic findings. However, the Alzheimer's Disease Assessment Scale (ADAS) was not administered as part of the CERAD study, which limits the study's applicability to modern drug trials, in which the ADAS-cognitive subsection (ADAS-cog) is a popular end point. The purpose of this investigation was to develop a derived ADAS-cog score from the neurobehavioral data obtained from subjects during their evaluation in the CERAD study. Two calculated ADAS-cog scores were developed. The first was based on clinically mapping the items on the ADAS-cog to assessments that were performed in the CERAD study. The second was based on rescaling the Mini-Mental Status Exam (MMSE), using published results correlating the ADAS-cog to the MMSE. Standard characteristics of both calculated ADAS-cog scores were calculated and compared with each other and with the literature. Both calculated ADAS-cog scores performed comparably to published characteristics of the ADAS-cog. The clinically based calculated ADAS-cog outperformed the rescaled MMSE. Using the CERAD database, it is now possible to model the progression of an untreated (placebo) population of patients with Alzheimer's disease and correlate it to a study using ADAS-cog.

Aged↗
PubMed2000

Reduction of orbital frontal cortex volume in geriatric depression.

BACKGROUND: Postmortem studies have documented abnormalities in the medial orbital frontal cortex in depressed patients. In this study we evaluated whether atrophy of this region can be identified in older depressed patients using magnetic resonance imaging. METHODS: Twenty elderly patients meeting DSM-IV criteria for major depression and 20 matched control subjects were studied. The orbital frontal cortex was measured in both hemispheres using magnetic resonance imaging. RESULTS: Depressive patients had reduced volume in the total orbital frontal cortex, right orbital frontal cortex, and left orbital frontal cortex. CONCLUSIONS: Our finding of a reduction in orbital frontal cortex volume in both sides of the brain suggests that this region of the brain may have a critical role in the development of depression and raises questions about the etiology of the changes.

Aged↗
PubMed2000

Hippocampal volume in geriatric depression.

BACKGROUND: There is a growing literature on the importance of hippocampal volume in geriatric depression. METHODS: We examined hippocampal volume in a group of elderly depressed patients and a group of elderly control subjects (N = 66 geriatric depressed patients and 18 elderly nondepressed control subjects) recruited through Duke's Mental Health Clinical Research Center for the Study of Depression in the Elderly. The subjects received a standardized evaluation, including a magnetic resonance imaging scan of the brain. Patients had unipolar major depression and were free of comorbid major psychiatric illness and neurologic illness. Differences were assessed using t tests and linear regression modeling. RESULTS: Accounting for the effects of age, gender, and total brain volume, depressed patients tended to have smaller right hippocampal volume (p =.014) and left hippocampal volume (p =.073). Among depressed patients, age of onset was negatively but not significantly related to right hippocampal volume (p =.052) and to left hippocampal volume (p =.062). We noted that among subjects with either right or left hippocampal volume of 3 mL or less, the vast majority were patients rather than control subjects. CONCLUSIONS: These results support a role for hippocampal dysfunction in depression, particularly in late-age onset depression. Longitudinal studies examining both depressive and cognitive outcomes are needed to clarify the relationships between the hippocampus, depression, and dementia.

Aged↗
PubMed2000

Hippocampal sulcal cavities on MRI: relationship to age and apolipoprotein E genotype.

Hippocampal sulcal cavities are usually considered incidental findings on brain MRI. In a group of 92 elderly volunteers, the authors graded the number and size of hippocampal sulcal cavities with brain MRI to obtain a cavity score. Cavity scores increased with age, and were higher in subjects carrying the APOE epsilon4 or epsilon2 alleles than in subjects with the epsilon3/3 genotype. Age-related morphologic changes in the hippocampus may be mediated by the APOE genotype.

Age Factors↗