Biomedical subjects

K Ranga Rama Krishnan

Publications and source records attributed to K Ranga Rama Krishnan.

At least 19 recordsLinked to original sources

PubMed2006

Concept of disease in geriatric psychiatry.

The concept of disease in geriatric psychiatry has to keep up with the rapid expansion in knowledge about the putative etiology of various diseases of interest. This article reviews the new knowledge that has been acquired about dementia. The proposed classification system has two axes: one for clinical manifestations and the other for etiology. Implementing this nomenclature will allow rapid adaptation of new knowledge for causation while at the same time communicating information on the clinical state. This should improve our ability to incorporate and communicate new knowledge in a dynamic format. In turn, this strategy should improve our ability to discern particular features of a disease and refine our notion of its clinical presentation and lead toward novel and improved treatments for our patients.

Alzheimer Disease↗

PubMed2005

Lobar distribution of lesion volumes in late-life depression: the Biomedical Informatics Research Network (BIRN).

White matter hyperintense lesions on T2-weighted images are associated with late-life depression. Little work has been carried out examining differences in lesion location between elderly individuals with and without depression. In contrast to previous studies examining total brain white matter lesion volume, this study examined lobar differences in white matter lesion volumes derived from brain magnetic resonance imaging. This study examined 49 subjects with a DSM-IV diagnosis of major depression and 50 comparison subjects without depression. All participants were age 60 years or older. White matter lesion volumes were measured in each hemisphere using a semiautomated segmentation process and localized to lobar regions using a lobar atlas created for this sample using the imaging tools provided by the Biomedical Informatics Research Network (BIRN). The lobar lesion volumes were compared against depression status. After controlling for age and hypertension, subjects with depression exhibited significantly greater total white matter lesion volume in both hemispheres and in both frontal lobes than did control subjects. Although a similar trend was observed in the parietal lobes, the difference did not reach a level of statistical significance. Models of the temporal and occipital lobes were not statistically significant. Older individuals with depression have greater white matter disease than healthy controls, predominantly in the frontal lobes. These changes are thought to disrupt neural circuits involved in mood regulation, thus increasing the risk of developing depression.

Aged↗

PubMed2005

Prominent reduction in pyramidal neurons density in the orbitofrontal cortex of elderly depressed patients.

BACKGROUND: Elderly depressed patients have more vascular hyperintensities in frontal white matter and basal ganglia than elderly control subjects. Cell pathology that might be related to increased vascular hyperintensities has not been examined. METHODS: Postmortem samples from the orbitofrontal cortex (ORB) were collected in 15 elderly subjects with major depressive disorder (MDD) and 11 age-matched control subjects. Cell packing density of neurons and glia, density of pyramidal and nonpyramidal neurons, and cortical and laminar width were measured. RESULTS: The overall (layers I-VI) packing density of ORB neurons with pyramidal morphology was markedly decreased in MDD (by 30%) as compared with control subjects. Further laminar analysis of pyramidal neurons density revealed significant reductions in layers IIIc and V in MDD. In contrast, in MDD the density of nonpyramidal neurons and glia and cortical and laminar width were comparable to control values. CONCLUSIONS: In elderly subjects with depression, the density of pyramidal neurons in the ORB was particularly low in cortical layers V and III, the origin of prefronto-striatal and prefronto-cortical and prefronto-amygdalar projections. Degeneration of neurons furnishing these projections might be related to the white matter hyperintensities previously observed. Neuronal pathology seems to be more severe in elderly than in younger subjects with MDD.

Age Factors↗

PubMed2005

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Acquired Immunodeficiency Syndrome↗

PubMed2005

Residual symptoms in older patients treated for major depression.

OBJECTIVE: The purpose of this study was to identify residual symptoms in a sample of older adults treated for major depression and compare individual symptoms present at baseline with those at three months by remission status. METHODS: The sample was comprised of 229 patients with DSM-IV major depression who were participants in the NIMH Mental Health Clinical Research Center at Duke University. Symptoms were measured using the Montgomery-Asberg Depression Rating Scale (MADRS). RESULTS: At three months, 86 patients (37.6%) had remitted, or had a MADRS score less than or equal to 9. In the remitted group, the most frequently reported symptoms at three months were inner tension and lassitude. Among nonremitters, the most frequently reported symptoms were reported and apparent sadness, as well as lassitude and inner tension. In the sample as a whole, the symptoms most likely to be present at baseline but not three months were pessimistic and suicidal thoughts, while the most frequently reported emergent symptoms were reduced appetite and inner tension. Patients were much more likely to no longer have a particular symptom than to acquire a new symptom. Overall, the symptoms present at three months were not severe in either group. CONCLUSIONS: In older adults treated for major depression, residual symptoms at three months may include emergent symptoms as well as persistent symptoms, and are likely to include symptoms of anxiety as well as sadness. These findings have clinical implications for the treatment of late-life depression.

Affect↗

PubMed2005

Magnitude of placebo response and drug-placebo differences across psychiatric disorders.

BACKGROUND: Placebo response, drug response, and drug-placebo differences appear to vary among psychiatric conditions. METHOD: We evaluated the Food and Drug Administration (FDA) Summary Basis of Approval (SBA) reports to compare the magnitude of placebo response, magnitude of psychotopic drug response, and drug placebo differences among various diagnostic groups such as depression, anxiety, and psychotic disorders. RESULTS: Six diagnostic groups (psychosis, obsessive-compulsive disorder (OCD), generalized anxiety disorder (GAD), depression, post-traumatic stress disorder, panic) varied in response to both placebo and active drug treatments. Response to placebo was high among patients participating in GAD, depression, and panic disorder clinical trials. Conversely, patients participating in psychotic disorder and OCD trials experienced low response to placebo. CONCLUSION: Our findings indicate that the magnitude of placebo response and drug response were heterogeneous and were statistically significantly different among various psychiatric disorders. Although a noticeable degree of heterogeneity was detected in the drug-placebo ratio among various disorders, the differences did not reach statistical significance. This finding suggests that placebo use should be continued for newer agents being tested for all of the psychiatric disorders. These findings may help in the development of psychopharmacology trial designs and in the deliberations of ethics committees.

Humans↗

PubMed2005

Treatment of depression in the medically ill.

Most studies on treatment methods in elderly depressive patients have included primarily patients in good physical health, excluding medical comorbidity, despite the fact that depression with medical comorbidity is the norm rather than the exception. In addition, depression is known to increase disability and mortality among the medically ill. This, therefore, becomes an extremely important issue. Although data are limited, the available evidence suggests that depression concomitant with medical illness can be treated. One or more of the selective serotonin reuptake inhibitors have demonstrated potential usefulness in depressed patients with ischemic heart disease, diabetes, dementia, and Parkinson's disease and in patients after stroke and after myocardial infarction. Large-scale trials are needed to assess not only the safety and effectiveness of agents for the treatment of depression in comorbid illness, but also the effects of depression on the course of the medical illness itself.

Antidepressive Agents↗

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

Diffusion tensor imaging: background, potential, and utility in psychiatric research.

Diffusion tensor imaging is a variation of magnetic resonance imaging that measures the diffusion of water in tissues. This can help measure and quantify a tissue's orientation and structure, making it an ideal tool for examining cerebral white matter and neural fiber tracts. It is only beginning to be utilized in psychiatric research. This article reviews the theory behind diffusion tensor imaging, its potential to map fiber tracts in the brain, and its recent use in psychiatric research.

Body Water↗

PubMed2004

Medical comorbidity in late-life depression.

OBJECTIVES: Medical comorbidity is common in elderly patients with depression, however the difference between depressed and non-depressed elderly populations is not well established. Additionally, differences between subgroups of depressed populations, including those with MRI-defined vascular depression and those with late-onset compared with early-onset depression are not well described. METHODS: We compared self-report of medical disorders between 370 depressed elders and 157 non-depressed control subjects. Subjects were additionally dichotomized based on presence or absence of subcortical MRI lesions and age of onset. Medical comorbidity was assessed by self report only, and depressed subjects were additionally assessed by the clinician-rated Cumulative Illness Rating Scale. RESULTS: When compared with the non-depressed group, depressed subjects were significantly more likely to report the presence of hypertension, heart disease, gastrointestinal ulcers, and 'hardening of the arteries'. Analyses of subjects with subcortical disease demonstrated they were significantly older, more likely to have depression, and more likely to report the presence of hypertension. Finally, the depressed cohort with late-onset depression (occurring after age 50 years) had more male subjects, exhibited greater CIRS scores, and greater prevalence of hypertension, but these did not reach a level of statistical significance after applying a Bonferroni correction. CONCLUSIONS: Vascular comorbidities are common in depressed elders. The differences in the report of hypertension supports past work investigating a vascular contribution to late-life depression. Given the association between depression and poor medical outcomes of cardiac disease, this population deserves clinical scrutiny and further research.

Age Factors↗

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.

Aged↗

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.

Aged↗

PubMed2004

Research design features and patient characteristics associated with the outcome of antidepressant clinical trials.

OBJECTIVE: The authors examined which, if any, research design features and patient characteristics would significantly differ between successful and unsuccessful antidepressant trials. METHOD: Clinical trial data were reviewed for nine antidepressants approved by the Food and Drug Administration between 1985 and 2000. From the antidepressant research programs on these medications, 52 clinical trials were included in the study. The authors evaluated trial design features, patient characteristics, and difference in response between placebo and antidepressant. RESULTS: Nine trial design features and patient characteristics were present in the research programs for all nine of the antidepressants. The severity of depressive symptoms before patient randomization, the dosing schedule (flexible versus fixed), the number of treatment arms, and the percentage of female patients were significantly associated with the difference in response to antidepressant and placebo. The duration of the antidepressant trial, number of patients per treatment arm, number of sites, and mean age of the patients were similar in successful trials (with a greater antidepressant-placebo difference) and less successful trials (with a smaller antidepressant-placebo difference). CONCLUSIONS: These findings may help in the design of future antidepressant trials.

Antidepressive Agents↗

PubMed2004

Antidepressant pharmacotherapy in the treatment of depression in the very old: a randomized, placebo-controlled trial.

OBJECTIVE: This study determined the efficacy of antidepressant medication for the treatment of depression in the "old-old." METHOD: This randomized 8-week medication trial compared citalopram, 10-40 mg/day, to placebo in the treatment of patients 75 and older with unipolar depression. RESULTS: A total of 174 patients who were 58% women with a mean age of 79.6 years (SD=4.4) and a mean baseline Hamilton Depression Rating Scale score of 24.3 (SD=4.1) were randomly assigned to treatment at 15 sites. There was a main effect for site but not for treatment condition. The remission rate, defined as a final Hamilton depression scale score <10, was 35% for the citalopram and 33% for the placebo groups. However, patients with severe depression (baseline Hamilton depression scale score >24) tended to have a higher remission rate with medication than with placebo (35% versus 19%). CONCLUSIONS: In the oldest group of community-dwelling patients to be studied to date, medication was not more effective than placebo for the treatment of depression. However, given the considerable psychosocial support received by all patients, the placebo condition represents more than the ingestion of an inactive pill. Across sites, there was considerable range in response to medication, 18% to 82%, and to placebo, 16% to 80%.

Age Factors↗

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.

Aged↗

PubMed2003

Focal and lateralized subcortical abnormalities in unipolar major depressive disorder: an automated multivoxel proton magnetic resonance spectroscopy study.

BACKGROUND: The results of prior proton magnetic resonance spectroscopy ((1)H-MRS) studies in unipolar major depressive disorder (MDD) evaluating choline (Cho)/creatine (Cr) and N-acetyl-L-aspartate (NAA)/Cr ratios are mixed. These single-voxel or one-dimensional chemical-shift imaging (CSI) nonautomated (1)H-MRS studies has been unable to evaluate global or lateralized abnormalities in neuronal or membrane function. Using automated multivoxel two-dimensional CSI (1)H-MRS techniques, we tested the hypothesis that patients with MDD have focal neuronal and membrane abnormalities localized in the subcortical region. METHODS: Whole brain and subcortical measures of Cho, NAA, Cr, and myo-inositol (mI) were obtained in 18 patients with MDD and 20 control subjects using automated two-dimensional CSI (1)H-MRS. RESULTS: Compared with control subjects, MDD patients had a significantly lower mean NAA/Cr amplitude in the caudate and a significantly higher mean Cho/Cr amplitude in the putamen, particularly on the right side. No differences were observed for global whole brain measurements. CONCLUSIONS: The findings support reduced neuronal viability or function in the caudate and altered membrane phospholipid metabolism in the putamen for patients with MDD. Our results are consistent with prior magnetic resonance imaging, positron emission tomography, and postmortem reports of focal and lateralized abnormalities of the basal ganglia in MDD.

Adult↗

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

Predicting suicidal risk in schizophrenic and schizoaffective patients in a prospective two-year trial.

BACKGROUND: Enhanced ability to reliably identify risk factors for suicidal behavior permits more focused decisions concerning treatment interventions and support services, with potential reduction in lives lost to suicide. METHODS: This study followed 980 patients at high risk for suicide in a multicenter prospective study for 2 years after randomization to clozapine or olanzapine. A priori predictors related to diagnosis, treatment resistance, and clinical constructs of disease symptoms were evaluated as possible predictors of subsequent suicide-related events. RESULTS: Ten baseline univariate predictors were identified. Historical predictors were diagnosis of schizoaffective disorder, history or current use at baseline of alcohol or substance abuse, cigarette smoking, number of lifetime suicide attempts, and the number of hospitalizations in the previous 36 months to prevent suicide. Predictive clinical features included greater baseline scores on the InterSePT scale for suicidal thinking, the Covi Anxiety Scale, the Calgary Depression Scale (CDS), and severity of Parkinsonism. Subsequent multivariate analysis revealed the number of hospitalizations in the previous 36 months, baseline CDS, severity of Parkinson's, history of substance abuse, and lifetime suicide attempts. Clozapine, in general, was more effective than olanzapine in decreasing the risk of suicidality, regardless of risk factors present. CONCLUSIONS: This is the first prospective analysis of predictors of suicide risk in a large schizophrenic and schizoaffective population judged to be at high risk for suicide. Assessment of these risk factors may aid clinicians in evaluating risk for suicidal behaviors so that appropriate interventions can be made.

Adult↗