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Biomedical subjects

R Ramasubbu

Publications and source records attributed to R Ramasubbu.

At least 19 recordsLinked to original sources
PubMed2003

Serotonin transporter gene functional polymorphism: a plausible candidate gene for increased vascular risk in depression.

The evidence of increased vascular morbidity and mortality associated with depression has generated research interest in studying the mechanisms or causal pathways underlying this association. Recent advances in molecular genetics have demonstrated that serotonin transporter gene functional polymorphism may confer susceptibility for affective disorder as well as for some cardiovascular risk factors. Taking into account these genetic findings, this article proposes a hypothesis that serotonin transporter gene functional polymorphism may be a plausible candidate gene to study the genetic mechanisms of depression-related increased vascular morbidity and mortality. Future research projects to test this hypothesis is warranted.

Aged↗
PubMed2002

Insulin resistance: a metabolic link between depressive disorder and atherosclerotic vascular diseases.

The association of depression with insulin resistance (IR) and athersclerotic vascular diseases has been well documented. This review examines the relevance of IR as a link between depressive disorder and atherosclerotic vascular diseases. Relevant articles collected from Medline database over the period of 1966-2001 were reviewed. Studies have shown that IR is a state-dependent abnormality in depression and depression increases the risk of vascular morbidity and mortality. Given that IR is a central component of cardiovascular risk factors, depression-related IR might play a role in the development and progression of coronary and cerebral atherosclerosis in chronic-resistant depression. Further, IR may contribute to the pathophysiology of depressive disorder. In conclusion IR could account for the linkage between depression and atherosclerotic vascular diseases. More studies are needed to examine the importance of improving insulin sensitivity in the treatment of chronic-resistant depression and prevention of depression-related vascular morbidity and mortality.

Antidepressive Agents↗
PubMed2001

Dose-response relationship of selective serotonin reuptake inhibitors treatment-emergent hypomania in depressive disorders.

OBJECTIVE: The notion that antidepressant treatment-associated hypomania or mania being pharmacologically induced has been challenged. To determine whether selective serotonin reuptake inhibitors (SSRI) induced hypomania is secondary to medication effects, we examined the dose-response relationship of SSRI-induced hypomania in two patients with depressive disorder. METHOD: Case study. RESULT: Hypomanic symptoms emerged during treatment with sertraline at the dose of 300 mg per day in a 45-year-old male with major depression. Paroxetine treatment at the dose of 80 mg per day induced hypomania in a 37-year-old female with dysthymia and trichitillomania. These patients have no family or personal history of bipolar disorder. Hypomania resolved when sertraline was decreased to 200 mg per day and paroxetine to 40 mg per day. No hypomanic switch was observed during 18-24 months follow-up. CONCLUSION: In the absence of risk factors for manic switch, SSRI-induced hypomania may be dose-dependent medication effects.

Adult↗
PubMed2000

Neurohormonal responses to D-fenfluramine in healthy elderly subjects. A placebo-controlled study.

Considering age-related changes in serotonin (5HT) function, we examined normative data of prolactin (PRL) and cortisol (CORT) responses to D-fenfluramine (D-FEN) in healthy elderly subjects. Twenty-three healthy male and female volunteers aged 60-86 participated in a single-blind, placebo-controlled, fixed-order, crossover-design challenge test. Two baseline PRL and CORT values and the responses of these hormones to 30 mg of oral D-FEN and placebo over a 4 h period were measured on two separate sessions. PRL and CORT responses were significantly greater following D-FEN than after placebo. Peak PRL responses (maximum change from baseline following D-FEN) were relatively robust compared to peak CORT responses. Peak PRL concentration was positively correlated with plasma D-nor-FEN concentration. Gender and aging had no effect on hormonal responses in the elderly. Although the weight adjusted dose used in this study was higher than the therapeutic dose of D-FEN, PRL responses were modest and only two participants experienced side effects. D-FEN is a safe serotonergic probe and PRL responsivity to D-FEN is a reliable index of central 5HT function in the elderly. An age-related decline in serotonergic function must be considered in determining the dose requirement for maximal hormonal responses to D-FEN challenge tests in the elderly.

Aged↗
PubMed2000

Serotonin and dopamine antagonism in obsessive-compulsive disorder: effect of atypical antipsychotic drugs.

BACKGROUND: Previous reports suggest that some atypical antipsychotics may have obsessogenic as well as antiobsessional effects. Given their higher affinity for serotonin 5HT2 receptors than dopamine D2 receptors, it has been speculated that atypical antipsychotics may induce obsessive-compulsive (OC) symptoms, even at low doses, due to high 5HT2 antagonism, whereas improvement in OC symptoms is thought to occur only at high doses due to high D2 antagonism. METHOD: In this open case series, the dose-response relationship of atypical antipsychotic augmentation in the treatment of obsessive compulsive disorder (OCD), and the dose-severity relationship in atypical anti psychotic-induced OC symptoms were examined. Three patients were identified who had either refractory OCD or OC symptoms following administration of atypical antipsychotics such as olanzapine and risperidone. RESULTS: Case 1: A linear dose-response relationship between increasing doses of olanzapine and improvement in OC symptoms was observed in an OCD patient resistant to 5-HT reuptake inhibitors. 2: OC symptoms induced by low doses of risperidone (1 mg) were reversed by increasing the doses of risperidone (3 mg) in a bipolar disorder patient suggesting an inverse dose-severity relationship. 3: No inverse dose-severity relationship was noted between olanzapine induced OC symptoms and its dosage in an asymptomatic OCD patient. Tretment-emergence OC symptoms responded to increasing the doses of maintanance clomipramine treatment. CONCLUSIONS: Controlled studies are needed to investigate the dose-response or dose-severity relationships between OCD and atypical antipsychotics.

Adult↗
PubMed1999

Switching to moclobemide to reverse fluoxetine-induced sexual dysfunction in patients with depression.

OBJECTIVE: To determine the efficacy of substituting moclobemide, a reversible monoamine oxidase-A inhibitor, for fluoxetine to reverse fluoxetine-induced sexual dysfunction in patients with depression. DESIGN: Prospective open trial. SETTING: Outpatient treatment. PARTICIPANTS: Five patients with depressive disorder who experienced sexual side effects during treatment with standard doses of fluoxetine (20 to 40 mg per day). INTERVENTION: Discontinuation of fluoxetine and replacement with moclobemide (300 to 600 mg per day) after a 2-week washout period. OUTCOME MEASURES: Libido, orgasmic function (in women) or erectile and ejaculatory function (in men), and overall improvement in sexual function during a follow-up period of 2 months to 3 years. RESULTS: Among patients receiving fluoxetine questioned about sexual side effects, 4 (1 man and 3 women) had treatment-related diminished libido with poor orgasmic response or partial erectile failure, and 1 female patient had enhanced sexual desire with intense clitoral stimulation. In all patients, sexual disturbances resolved completely after a 2-week washout period and a switch to treatment with moclobemide. Moclobemide was well tolerated. The antidepressant effect of moclobemide was comparable to that of fluoxetine. CONCLUSIONS: Moclobemide may be preferred as a treatment for depression in patients with fluoxetine-induced sexual dysfunction.

Adult↗
PubMed1998

Diminished serotonin-mediated prolactin responses in nondepressed stroke patients compared with healthy normal subjects.

BACKGROUND AND PURPOSE: The purpose of this study was to use hormonal responsiveness to d-fenfluramine (d-FEN) challenge as a measure of central serotonin (5-HT) function in a comparative evaluation of serotonergic abnormalities between stroke patients and healthy elderly normal subjects to test the hypothesis that stroke may be associated with diminished serotonergic functioning. METHODS: Eight nondepressed medically stable stroke patients and 12 healthy volunteers completed a single-blind, placebo-controlled, fixed-order, crossover design challenge test with 30 mg of oral d-FEN. Baseline prolactin (PRL) and cortisol (CORT) and hormonal responses to d-FEN and placebo were measured at hourly intervals over a 4-hour period. Cardiovascular responses (pulse and blood pressure) and behavioral responses were also recorded at the same time points. RESULTS: The 2 groups were comparable in demographics, body weight, plasma drug concentration, and behavioral and CORT responses. A 3-way ANOVA for repeated measures showed group differences for baseline adjusted PRL responses (change of scores from baseline). Peak PRL responses (maximal PRL change from baseline scores after treatment with d-FEN) in nondepressed stroke patients were attenuated compared with healthy elderly subjects, suggesting diminished serotonergic responsiveness in stroke patients. CONCLUSIONS: The demonstrated serotonergic hypofunctioning poststroke may contribute to the high incidence of depressive disorders in stroke patients. Serotonergic agents may have a role in augmentation of stroke recovery.

Administration, Oral↗
PubMed1998

Functional impairment associated with acute poststroke depression: the Stroke Data Bank Study.

To examine the independent association of depression following acute stroke with impairment in activities of daily living (ADL), the authors conducted a cross-sectional analysis of stroke patients enrolled in the Stroke Data Bank (U.S.A.) who had completed the Center for Epidemiological Studies Depression Scale (CES-D). Scores on the Barthel Index, a measure of ADL, were compared between depressed (CES-D > or = 16) and nondepressed patients (CES-D < or = 15) at 7-10 days after stroke. Of the 626 who completed CES-D, 160 were depressed. Depressed stroke patients evidenced greater impairment in ADL than nondepressed patients, independently of all other factors that influenced poststroke physical disabilities. CES-D scores were negatively correlated with Barthel scores in the entire stroke population. Neurological factors, greater age, poor prestroke physical activity, and prestroke disturbances in sexual functioning were also independently associated with limitations in functional status of stroke patients.

Activities of Daily Living↗
PubMed1994

Factors complicating the diagnosis of depression in cerebrovascular disease, Part I--Phenomenological and nosological issues.

Depression is frequently associated with cerebrovascular disease. Early detection and intervention in depression may enhance rehabilitation potential. Difficulties encountered by clinicians in identifying depression in patients with cerebrovascular disease are numerous. This two part review focuses on issues related to the diagnosis of depression with emphasis on recognition of depressive symptoms and their relevance to the diagnosis of depressive syndromes in the presence of vascular lesions and associated neurological deficits. Furthermore, the value of diagnostic instruments and biological markers in identifying depression following stroke has been critically evaluated. In this first part of this two part paper, phenomenological and nosological aspects are considered with an emphasis on symptom profile, significance of vegetative symptoms and other related emotional responses such as catastrophic reaction, emotionalism and apathy in the diagnosis of depression following stroke. The applicability of diagnostic subcategories to define depressive syndromes associated with cerebrovascular disease and its clinical relevance is also discussed. The authors stress that knowledge on phenomenology of depression and other emotional responses related to cerebrovascular disease will facilitate better understanding of its clinical presentation and may improve diagnostic acumen.

Adaptation, Psychological↗
PubMed1994

Factors complicating the diagnosis of depression in cerebrovascular disease, Part II--Neurological deficits and various assessment methods.

Neurological deficits associated with cerebrovascular disease such as aphasia, dementia, anosognosia and aprosodia may impair the ability to express or experience depressive symptoms. Identification of depression in the absence of verbal report on subjective mood state is a difficult task. The value of various diagnostic methods including depressive rating scales, standard psychiatric interviews and biological variables in the diagnosis of depression in cerebrovascular disease is considered. This review concludes by focusing on the deficiencies of existing approaches in the diagnostic assessment of depression in patients with severe communication and comprehension deficits and emphasizes the importance of devising a standard diagnostic method with less reliance on verbal responses.

Agnosia↗