Biomedical subjects
Publications and source records attributed to K R Krishnan.
This brief discussion summarizes possible trial design changes that could be utilized to reduce the number of subjects exposed to ineffective treatment--in this case placebo; however, these designs are fairly complex and have not been implemented sufficiently to judge their utility. Clearly, such studies are essential before embarking on these paradigms as a primary method for assessing antidepressant efficacy.
BACKGROUND: Between 10% and 30% of patients with symptoms similar to angina and sufficient to justify cardiac catheterization are found to have normal coronary angiograms. Treatment of patients with chest pain with no apparent cardiac cause is a major clinical problem. Our hypothesis was that sertraline would reduce the severity of pain in patients with chest pain of noncardiac origin. METHODS AND RESULTS: This was a single-site, double-blind, placebo-controlled study of the efficacy, tolerability, and safety of sertraline in the treatment of noncardiac chest pain in outpatients. Thirty patients were enrolled in the study. After 1 week of single-blind placebo washout, patients were randomly assigned in a double-blind fashion either to drug or placebo. The Beck Depression Inventory was administered at baseline and at completion of study. Daily pain diaries (visual analogue scale, rating pain on a scale of 1 to 10) were selfadministered and evaluated at baseline and at follow-up visits. Statistical measures were performed with an intention-to-treat approach. Patients who received sertraline over the course of the study showed a statistically significant reduction in pain compared with those who were receiving placebo. CONCLUSIONS: The use of sertraline in patients with noncardiac chest pain produced clinically significant reduction of daily pain. These results suggest the need for further studies of the efficacy and tolerability of sertraline and other selective serotonin reuptake inhibitors in the long-term management of noncardiac chest pain.
Stroke is a leading cause of morbidity and mortality in the United States. Physical and psychological impairment from stroke may negatively affect quality of life. From a psychological perspective, depression, which is common in stroke patients, may influence functional recovery and possibly mortality after a stroke. Although somewhat controversial, the risk of poststroke depression may be related to lesion location, specifically left anterior or left basal ganglia lesions. Because poststroke depression can affect recovery, treatment with antidepressants may be warranted. Emerging evidence suggests that nortriptyline and fluoxetine may be effective; paroxetine, sertraline, and other selective serotonin reuptake inhibitors have shown efficacy in treating a related phenomenon known as pathologic crying. The influence of depression on the risk of stroke has not been extensively studied; however, several epidemiologic studies raise the possibility that a relation exists. In one study of elderly individuals, higher depressive symptoms increased the risk of stroke. Many older individuals who have depression develop later in life have evidence of subtle cerebrovascular disease. Specifically, silent strokes that do not involve the sensory or motor parts of the brain are quite common in the elderly population. Vascular depression is depression that occurs in patients with cerebrovascular or ischemic changes in the brain. Preliminary evidence indicates that these vascular changes may be related to atherosclerosis, hypertension, or myocardial infarction. However, additional studies are needed to gain a better profile of these patients and to explore potential treatment modalities.
BACKGROUND: There has been a paucity of well-designed studies comparing selective serotonin reuptake inhibitor (SSRI) medications in the treatment of depression in the elderly. This multicenter study was designed to examine the efficacy and safety of sertraline and fluoxetine in depressed elderly outpatients. A secondary objective was to examine the effects of SSRI treatment on quality of life and cognitive function. METHOD: Two hundred thirty-six outpatients 60 years of age and older who met DSM-III-R criteria for major depressive disorder received 1 week of single-blind placebo before being randomly assigned to 12 weeks of double-blind, parallel-group treatment with flexible daily doses of either sertraline (range, 50-100 mg) or fluoxetine (range, 20-40 mg). Primary efficacy measures consisted of the 24-item Hamilton Rating Scale for Depression and Clinical Global Impressions scale ratings. Secondary outcome assessments included clinician- and patient-rated measures of depression symptoms and factors, cognitive functioning, and quality of life, as well as plasma drug concentrations, which were correlated with clinical response. RESULTS: Both drugs produced a similarly positive response on the primary efficacy measures, with 12-week responder rates of 73% for sertraline and 71% for fluoxetine. Sertraline-treated patients showed statistically greater cognitive improvement on several measures. Both drugs were safe and well tolerated. CONCLUSION: Data indicate that both drugs are effective antidepressants for the treatment of depressed elderly outpatients. Differences in cognitive performance effects deserve further investigation.
BACKGROUND: Previous observational and interventional studies have suggested that regular physical exercise may be associated with reduced symptoms of depression. However, the extent to which exercise training may reduce depressive symptoms in older patients with major depressive disorder (MDD) has not been systematically evaluated. OBJECTIVE: To assess the effectiveness of an aerobic exercise program compared with standard medication (ie, antidepressants) for treatment of MDD in older patients, we conducted a 16-week randomized controlled trial. METHODS: One hundred fifty-six men and women with MDD (age, > or = 50 years) were assigned randomly to a program of aerobic exercise, antidepressants (sertraline hydrochloride), or combined exercise and medication. Subjects underwent comprehensive evaluations of depression, including the presence and severity of MDD using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and Hamilton Rating Scale for Depression (HAM-D) and Beck Depression Inventory (BDI) scores before and after treatment. Secondary outcome measures included aerobic capacity, life satisfaction, self-esteem, anxiety, and dysfunctional cognitions. RESULTS: After 16 weeks of treatment, the groups did not differ statistically on HAM-D or BDI scores (P = .67); adjustment for baseline levels of depression yielded an essentially identical result. Growth curve models revealed that all groups exhibited statistically and clinically significant reductions on HAM-D and BDI scores. However, patients receiving medication alone exhibited the fastest initial response; among patients receiving combination therapy, those with less severe depressive symptoms initially showed a more rapid response than those with initially more severe depressive symptoms. CONCLUSIONS: An exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons. Although antidepressants may facilitate a more rapid initial therapeutic response than exercise, after 16 weeks of treatment exercise was equally effective in reducing depression among patients with MDD.
The goal of this study was to compare the clinical, demographic and social characteristics of psychotic and non-psychotic depression in the elderly and younger age groups. Depressed patients (n = 674) meeting DSM-III-R criteria for major depressive episode were classified into two groups, psychotic and non-psychotic, based on the presence of delusions or hallucinations. The patients with psychotic and non-psychotic depression were compared on clinical, demographic, and social characteristics. Bivariate analyses revealed that younger age, psychomotor retardation, guilt, feelings of worthlessness, history of delusions in the past, and increased suicidal ideation and intent were found more commonly in psychotic as compared to non-psychotic depression. A fully adjusted logistic regression model also confirmed younger age, history of past delusions, and increased feelings of worthlessness to be associated more with psychotic than with non-psychotic depression. Trends were observed for psychotic depression to be associated with poor subjective social support and with bipolar illness. Cerebrovascular risk factors and gender composition did not differ significantly in the psychotic vs. non-psychotic groups. The study confirms previously described findings such as increased guilt, increased psychomotor retardation and increased suicidality in psychotic depression in a large sample of depressed patients. The study also introduces the concept of age as an important variable influencing psychotic depression. The limitation of this finding is that it is applicable to tertiary care samples. Further studies are needed to confirm this finding in other subgroups.
BACKGROUND: To examine the magnetic resonance (MR) images of bipolar patients across a wide age range for the presence of hyperintense lesions compared to age- and gender-matched control subjects. METHODS: Consecutive admissions to a mood disorders unit over a 2-year period were evaluated retrospectively for the presence of bipolar disorder by DSM-III-R criteria and whether they received an MR scan. Bipolar patients (n = 70, mean age = 49.9 +/- 19.7 years) were age- and gender-matched to control subjects (n = 70, mean age = 53.2 +/- 18.1 years) and the MR scans were rated to assess for the presence of hyperintensites. RESULTS: Compared to control subjects, the bipolar patients demonstrated hyperintense lesions in the subependymal region, subcortical gray nuclei, and the deep white matter. CONCLUSIONS: Hyperintense lesions in bipolar patients are found in both the subcortical white matter and gray nuclei and may play an important role in the etiology of bipolar illness.
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BACKGROUND: A number of studies have concluded that the perceived quality of support is more strongly associated with mental health than with the actual structure of personal networks. This study examined clinical, historical, and phenomenological variables associated cross-sectionally and longitudinally with perceived social support. METHODS: Participants included elderly, middle-aged, and young-adult depressed samples derived from the Duke Clinical Research Center for the Study of Depression in Late Life. RESULTS: Cross-sectional multivariate analyses revealed that perceived social support was: (1) for the elderly associated with pessimistic thinking, being divorced, having strange ideas, the degree of social interaction, and instrumental support; (2) for middle-age associated with dysthymia, divorce, pessimistic thoughts, social interaction, and instrumental support; and (3) among young adults with instrumental support only. Longitudinal multivariate analyses indicated that only perceived social support at Time 1 predicted perceived social support 1 year later among elderly and middle-aged subjects, whereas only instrumental support predicted perceived social support 1 year later among the young-adult sample. LIMITATIONS: The small number of subjects among the young-adult sample limit conclusions regarding this group. In addition, only patients provided data. Future studies should consider using multiple informants to enhance the accuracy of reported social support. CONCLUSIONS: Our findings indicate that in addition to whatever else they do for depressed patients, clinicians must endeavor to address relationship or social support difficulties, especially in the elderly.
1. Emotion and mood, once thought to be governed solely by the limbic system of the brain, now are thought to be influenced by numerous nonlimbic central nervous system structures as well. 2. The present review discusses several important brain structures and neuroanatomic pathways thought to be involved in affect and mood disorders, including the amygdala, frontal neocortex, cingulate gyrus, basal ganglia, and the monoamine systems. 3. The authors propose a specific neuroanatomic model for depression that emphasizes that a distributed system of extensively interconnected CNS structures mediates emotion and affect.
1. The authors investigated the candidate neuroanatomic substrates underlying delusional thought disorder in old-aged depressed patients by using magnetic resonance imaging (MRI), and examined the relationship between volumes for individual brain structures and clinical correlates of particular relevance to depression: executive cognitive impairment and global severity of depression. 2. MR morphometry was performed on nineteen deluded depressed patients and 26 non-deluded depressed patients, all older than 55 years of age. Subjects were administered a neuropsychological test battery and measures of depression. 3. The absolute volume of prefrontal cortex (PFC) was smaller in the deluded depressed group than in non-deluded depressed group (131.79 +/- 37.26 ml vs. 152.65 +/- 26.13 ml, p = 0.03); a difference that was statistically significant even after adjusting for the effect of whole brain volume (p = 0.01). No group differences were observed in the volumes of the basal ganglia, the temporal lobes, the superior temporal gyri, the amygdala-hippocampal complex, the lateral ventricles, or whole brain. The relative volume of PFC correlated inversely and significantly with the index of Wisconsin Card Sorting Test (WCST) performance (r = -0.76, p < 0.01) in depressed patients. 4. PFC may be one of the candidate neuroanatomic substrates underlying delusional thought disorder in old-aged depression.
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OBJECTIVE: To examine the effect of major depression on reported functional status in a group of patients with coronary artery disease (CAD). SETTING: An inpatient cardiology service. PARTICIPANTS: Three hundred thirty-five inpatients with coronary artery disease who were free of dementia, Parkinson's disease, and other primary neurological illnesses. MEASUREMENTS: Duke Depression Evaluation Schedule, a structured psychiatric interview which included the Diagnostic Interview Schedule depression subscale, the Cumulative Illness Rating Scale, and two scales for measuring instrumental and self-maintenance activities of daily living. RESULTS: Twenty-seven subjects met DSM-IV criteria for major depression. Compared with subjects without major depression, depressed subjects were more than twice as likely to report a self-maintenance ADL deficit and were significantly more likely to report an IADL deficit than were nondepressed subjects (93 vs 71%). In regression models, female gender, older age, greater medical illness severity, and presence of major depression were significant predictors of self-maintenance ADL disability; and female gender, older age, greater medical severity, and presence of major depression significantly predicted greater IADL impairment. CONCLUSION: The presence of major depression was associated with functional disability in patients with CAD. Further research is needed to clarify whether antidepressant treatment significantly impacts both affective symptoms and functional status in patients with coronary heart disease.
BACKGROUND AND PURPOSE: Evidence is mounting linking cerebrovascular disease with depressive symptoms in the elderly. Lesions in both white and gray matter have been associated with depressive symptoms and major depression. We sought to investigate the relationship between depressive symptoms and white and gray matter lesions in subjects participating in the Cardiovascular Health Study. METHODS: In a sample of 3660 men and women who underwent a standardized interview, physical examination, and MRI scan, we examined the association between number of white and gray matter lesions and white matter grade (a measure of severity) and reported depressive symptoms using a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale. We controlled for a variety of demographic and medical variables as well as functional status and Modified Mini-Mental State Examination score. RESULTS: The number of small (<3 mm) basal ganglia lesions was significantly associated with reported depressive symptoms, but white matter grade was not. In subsequent logistic regression models, number of basal ganglia lesions remained a significant predictor after controlling for non-MRI variables and severity of white matter lesions. CONCLUSIONS: Our findings extend previous reports that linked cerebrovascular changes to depressive symptoms in clinical populations to a large community-based population. This report provides further evidence of the importance of basal ganglia lesions in geriatric depression.
OBJECTIVE: The authors investigated the links between depression, cardiac disease, and microcirculatory cerebral blood flow (CBF). METHOD: A magnetic resonance imaging technique based on arterial spin tagging was used to estimate microcirculatory CBF in depressed (N = 5) and comparison (N = 14) elderly subjects with coronary artery disease. Signal intensity ratios corresponding to relative microcirculatory CBF were calculated for four regions on two axial images through the upper and lower halves of the lateral ventricles. RESULTS: On the superior image, estimates of microcirculatory CBF were statistically significantly lower on the left side in the depressed subjects than in the nondepressed group. When the ratios in the superior and inferior images were averaged, the depressed subjects had lower values for both left periventricular regions of interest and the parietal region. CONCLUSIONS: Despite the small study group and indirect estimates of blood flow, these preliminary findings suggest that a relative cerebral hypoperfusion may underlie depression in elderly cardiac patients.
OBJECTIVE: The purpose of this study was to examine the relationship between signal hyperintensities--a probable marker of underlying pathology--on T2-weighted magnetic resonance brain scans and neuropsychological test findings in elderly depressed and normal subjects. METHOD: Elderly subjects with a DSM-III-R diagnosis of major depression (N=41) and normal elderly comparison subjects (N=38) participated in a magnetic resonance imaging study (1.0-T) of signal hyperintensities in periventricular, deep white matter, and subcortical gray matter. Hard copies of scans were rated in random order by research psychiatrists blind to diagnosis; the modified Fazekas hyperintensity rating scale was used. Cognitive performance was independently assessed with a comprehensive neuropsychological battery. Clinical and demographic differences between groups were assessed by t tests and chi-square analysis. Relationships between neuropsychological performance and diagnosis and hyperintensities and their interaction were analyzed by using analysis of covariance, with adjustment for age and education. RESULTS: Elderly depressed subjects manifested poorer cognitive performance on several tests than normal comparison subjects. A significant interaction between hyperintensity location/severity and presence/absence of depression on cognitive performance was found: depressed patients with moderate-to-severe deep white matter hyperintensities demonstrated worse performance on general and delayed recall memory indices, executive functioning and language testing than depressed patients without such lesions and normal elderly subjects with or without deep white matter changes. CONCLUSIONS: Findings validate cognitive performance decrements in geriatric depression and suggest possible neuroanatomic vulnerabilities to developing particular neuropsychological dysfunction in depressed subjects.
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Because aggressive behavior occurs in so many psychiatric disorders, it is important to have an understanding of the aggression complex of symptoms, which occurs in posttraumatic stress disorder, bipolar disorder, depression, dementia, schizophrenia, attention-deficit/hyperactivity disorder, and the obsessive-compulsive spectrum of disorders. The effective treatment of aggression symptoms would benefit from the identification of the neuroanatomical circuitry implicated in aggression, and a number of studies in humans and animals using magnetic resonance imaging (MRI) and computed tomography provide evidence that helps identify this circuitry. However, future research still must address several questions.