Antidepressant treatment of cytokine-induced mood disorders

2002 ◽  
Vol 14 (6) ◽  
pp. 336-343 ◽  
Author(s):  
Charles L Raison ◽  
Michael Marcin ◽  
Andrew H Miller
Keyword(s):  
Major Depression ◽  
Immune Cell ◽  
Antidepressant Treatment ◽  
Sickness Behavior ◽  
Laboratory Animals ◽  
Interferon Α ◽  
Medical Illness ◽  
Hepatitis C Infection ◽  
Induced Mood ◽  
Second Messenger Pathways

Significant evidence suggests that the immune system is capable of profoundly affecting central nervous system (CNS) functioning in ways that may contribute to the development and expression of neuropsychiatric disorders, including disorders of mood. This paper reviews evidence that the production of proinflammatory cytokines, whether in the context of therapeutic administration (e.g. interferon-α-2b for hepatitis C infection) or medical illness, induces a state of sickness behavior that closely resembles major depression. Antidepressants have been shown to abolish or attenuate cytokine-induced sickness behavior in laboratory animals and to protect against the development of major depression in the context of therapeutic cytokine administration in humans. Potential mechanisms by which antidepressants ameliorate depressive and/or sickness symptoms in the context of immune activation include direct effects on immune cell functioning, as well as modulatory effects on monoamine neurotransmitters, intracellular second messenger pathways and the neuroendocrine system, in particular the hypothalamic–pituitary–adrenal axis.

scholarly journals 332 - Electroconvulsive therapy in older adults with major depression was not associated with cognitive decline during a 15-year follow-up

2020 ◽  
Vol 32 (S1) ◽  
pp. 91-91
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Major Depression ◽  
Cognitive Decline ◽  
Electroconvulsive Therapy ◽  
Antidepressant Treatment ◽  
Community Sample ◽  
Control Group

AUTHORS:Kerstin Johansson, Karolina Thömkvist, Ingmar Skoog and Sacuiu SF* (*presenter)OBJECTIVE:To determine the effects of electroconvulsive therapy (ECT) in major depression in relation to the development of dementia during long-term follow-up.METHOD:In an observational clinical prospective study of consecutive patients 70 years and older diagnosed with major depression at baseline 2000-2004 (n=1090), who were free of dementia and received antidepressant treatment, with or without ECT, we sought to determine if cognitive decline (mild cognitive impairment and dementia) during 15 -year follow-up was associated with receiving ECT at baseline. The control group was selected among the participants in the Gothenburg H70 Birth Cohort Studies matched by age group and sex 1:1.RESULTS:Among patients with affective syndromes 7% received ECT. During follow-up, 157 patients were diagnosed with dementia, equal proportions among those who received ECT (14.5%) and those who did not receive ECT (14.5%). The relation between ECT and cognitive decline remained non-significant irrespective antidepressive medication or presence of mild cognitive impairment at baseline.CONCLUSION:Preliminary results indicate that ECT was not associated with the development of cognitive decline in the long-term in a hospital-based cohort of 70+ year-olds. The results remain to verify against controls from a representative community sample.

scholarly journals Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse Model

2010 ◽  
Vol 84 (21) ◽  
pp. 11089-11100 ◽  
Author(s):  
Dennis A. Bente ◽  
Judie B. Alimonti ◽  
Wun-Ju Shieh ◽  
Gaëlle Camus ◽  
Ute Ströher ◽  
...  
Keyword(s):  
Animal Model ◽  
Mouse Model ◽  
Immune Cell ◽  
Hemorrhagic Fever ◽  
Fever Virus ◽  
Interferon Response ◽  
Laboratory Animals ◽  
Crimean Congo Hemorrhagic Fever ◽  
Hemorrhagic Fever Virus ◽  
Elevated Liver Enzymes

ABSTRACT Tick-borne Crimean-Congo hemorrhagic fever virus (CCHFV) causes a severe hemorrhagic syndrome in humans but not in its vertebrate animal hosts. The pathogenesis of the disease is largely not understood due to the lack of an animal model. Laboratory animals typically show no overt signs of disease. Here, we describe a new small-animal model to study CCHFV pathogenesis that manifests clinical disease, similar to that seen in humans, without adaptation of the virus to the host. Our studies revealed that mice deficient in the STAT-1 signaling molecule were highly susceptible to infection, succumbing within 3 to 5 days. After CCHFV challenge, mice exhibited fever, leukopenia, thrombocytopenia, and highly elevated liver enzymes. Rapid viremic dissemination and extensive replication in visceral organs, mainly in liver and spleen, were associated with prominent histopathologic changes in these organs. Dramatically elevated proinflammatory cytokine levels were detected in the blood of the animals, suggestive of a cytokine storm. Immunologic analysis revealed delayed immune cell activation and intensive lymphocyte depletion. Furthermore, this study also demonstrated that ribavirin, a suggested treatment in human cases, protects mice from lethal CCHFV challenge. In conclusion, our data demonstrate that the interferon response is crucial in controlling CCHFV replication in this model, and this is the first study that offers an in-depth in vivo analysis of CCHFV pathophysiology. This new mouse model exhibits key features of fatal human CCHF, proves useful for the testing of therapeutic strategies, and can be used to study virus attenuation.

scholarly journals Quality of life, diagnosis, and treatment of patients with major depression: a prospective cohort study in primary care

2011 ◽  
Vol 33 (3) ◽  
pp. 245-251 ◽  
Author(s):  
Ana Flávia Barros da Silva Lima ◽  
Marcelo Pio de Almeida Fleck
Keyword(s):  
Quality Of Life ◽  
Primary Care ◽  
Cohort Study ◽  
Major Depression ◽  
Antidepressant Treatment ◽  
Epidemiologic Studies ◽  
World Health ◽  
World Health Organization Quality

OBJECTIVE: To describe the demographic and clinical characteristics, adequacy of antidepressant treatment, and changes in quality of life of patients with major depression receiving follow-up care from primary care centers. METHOD: A cohort study was performed in which major depression patients were followed-up over a nine-month period. Several evaluation instruments were used, including the World Health Organization Quality of Life and the Quality of Life-Depression, Centers for Epidemiologic Studies-Depression questionnaires. RESULTS: The sample comprised 179 individuals, mostly female (73%), with a mean age of 38 years and mean education of 9 years. At the end of the follow-up period, 42% of the individuals still presented with major depression, 25% had complete symptom remission, and only 9% were properly treated with antidepressants. In relation to quality of life, there were significant differences especially between baseline and after nine months in almost all measures. CONCLUSION: This study demonstrated that depressive symptoms are poorly recognized and that treatment is often inadequate for patients followed-up in primary care units in the south of Brazil. Most of the patients continued to have symptoms of depression over the nine-month period which were associated with impaired quality of life.

Comparative Efficacy and Safety of Sertraline Versus Nortriptyline in Major Depression in Patients 70 and Older

1999 ◽  
Vol 11 (1) ◽  
pp. 85-99 ◽  
Author(s):  
Sanford I. Finkel ◽  
Ellen M. Richter ◽  
Cathryn M. Clary
Keyword(s):  
Major Depression ◽  
Rating Scale ◽  
Antidepressant Treatment ◽  
Change Score ◽  
Attrition Rate ◽  
Double Blind ◽  
Almost All ◽  
Positive Effect ◽  
Population Segment

Background. Few randomized, double-blind studies that examine antidepressant treatment in patients 70 years and older are available. To provide additional data on the safety and efficacy of antidepressants in this rapidly growing population segment, a subgroup analysis of a larger sertraline vs. nortriptyline elderly depression treatment study was performed. Methods. Outpatients (N = 76) who met DSM-III-R criteria for major depression with a minimum Hamilton Depression Rating Scale (HAM-D) severity score of 18 were randomized to 12 weeks of flexible dose treatment with sertraline (50–150 mg) or nortriptyline (25–100 mg). Results. Both treatments significantly improved depression as measured by the HAM-D and Clinical Global Impression scales. At Weeks 10, 12, and endpoint, sertraline demonstrated a significantly greater reduction in depression severity compared to nortriptyline as measured by improvement on the 24-item HAM-D (mean adjusted change score of 14.8 vs. 7.6, respectively, at Week 12; p = .001). Sixty-five percent of sertraline-treated patients were responders by Week 12 (50% or greater reduction from baseline in 24-item HAM-D score) compared to 26% of nortriptyline-treated patients (p < .05). Sertraline treatment had a significantly more positive effect, when compared to nortriptyline, across almost all associated measures of cognitive function, energy, anxiety, and quality of life and was better tolerated than nortriptyline, with a lower attrition rate/side effect burden. Conclusion. The efficacy advantage of sertraline appeared to be even greater in this subgroup of older patients drawn from a larger treatment study of depression that included elderly individuals over the age of 60.

The Efficacy and Tolerability of Combined Antidepressant Treatment in Different Depressive Subgroups

1993 ◽  
Vol 162 (3) ◽  
pp. 363-368 ◽  
Author(s):  
Sinead O'brien ◽  
Patrick McKeon ◽  
Myra O'regan
Keyword(s):  
Treatment Group ◽  
Side Effects ◽  
Major Depression ◽  
Orthostatic Hypotension ◽  
Antidepressant Treatment ◽  
Combined Treatment ◽  
Endogenous Depression ◽  
Double Blind Study ◽  
Double Blind ◽  
Global Improvement

Eighty patients admitted to hospital with major depression were randomly allocated to six weeks of treatment with tranylcypromine, amitriptyline, or tranylcypromine and amitriptyline in combination, in a double-blind study. Scores on the HRSD improved significantly in all three groups, but there were no differences between the three groups. Patients on tranylcypromine and amitriptyline combined improved more according to their self-ratings after six weeks, and response was earlier as measured by a clinical global improvement scale. Those with endogenous depression improved more than those with neurotic depression, irrespective of treatment group. Combined treatment was less well tolerated than single treatments and gave rise to more side-effects, although there was no serious toxicity. Orthostatic hypotension was observed more frequently in patients on combined treatment. This group also experienced a significant increase in weight and prolongation of the P-R interval on ECG.

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