19 research outputs found
Rationale and design of the participant, investigator, observer, and data-analyst-blinded randomized AGENDA trial on associations between gene-polymorphisms, endophenotypes for depression and antidepressive intervention: the effect of escitalopram versus placebo on the combined dexamethasone-corticotrophine releasing hormone test and other potential endophenotypes in healthy first-degree relatives of persons with depression
<p>Abstract</p> <p>Background</p> <p>Endophenotypes are heritable markers, which are more prevalent in patients and their healthy relatives than in the general population. Recent studies point at disturbed regulation of the hypothalamic-pituitary-adrenocortical axis as a possible endophenotype for depression. We hypothesize that potential endophenotypes for depression may be affected by selective serotonin re-uptake inhibitor antidepressants in healthy first-degree relatives of depressed patients. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test from baseline to the end of intervention.</p> <p>Methods</p> <p>The AGENDA trial is designed as a participant, investigator, observer, and data-analyst-blinded randomized trial. Participants are 80 healthy first-degree relatives of patients with depression. Participants are randomized to escitalopram 10 mg per day versus placebo for four weeks. Randomization is stratified by gender and age. The primary outcome measure is the change in plasma cortisol in the dexamethasone-corticotrophin releasing hormone test at entry before intervention to after four weeks of intervention. With the inclusion of 80 participants, a 60% power is obtained to detect a clinically relevant difference in the primary outcome between the intervention and the placebo group. Secondary outcome measures are changes from baseline to four weeks in scores of: 1) cognition and 2) neuroticism. Tertiary outcomes measures are changes from baseline to four weeks in scores of: 1) depression and anxiety symptoms; 2) subjective evaluations of depressive symptoms, perceived stress, quality of life, aggression, sleep, and pain; and 3) salivary cortisol at eight different timepoints during an ordinary day. Assessments are undertaken by assessors blinded to the randomization group.</p> <p>Trial registration</p> <p>Local Ethics Committee: H-KF 307413</p> <p>Danish Medicines Agency: 2612-3162.</p> <p>EudraCT: 2006-001750-28.</p> <p>Danish Data Agency: 2006-41-6737.</p> <p>ClinicalTrials.gov: NCT 00386841</p
Cerebral Functional Magnetic Resonance Imaging Activation Modulated by a Single Dose of the Monoamine Neurotransmission Enhancers Fluoxetine and Fenozolone during Hand Sensorimotor Tasks
Fluoxetine normalizes disrupted light-induced entrainment, fragmented ultradian rhythms and altered hippocampal clock gene expression in an animal model of high trait anxiety- and depression-related behavior
Fluoxetine Inhibits Inflammatory Response and Bone Loss in a Rat Model of Ligature-Induced Periodontitis
Modification of Virtual Reality Combined with a Mental Task Stimulates Cortisol in Volunteers
D-serine, a novel uremic toxin, induces senescence in human renal tubular cells via GCN2 activation
Effects of antidepressants on the performance in the forced swim test of two psychogenetically selected lines of rats that differ in coping strategies to aversive conditions
Psychopharmacology (Berl). 2010 Sep;211(4):403-14. Epub 2010 Jun 30.
Effects of antidepressants on the performance in the forced swim test of two
psychogenetically selected lines of rats that differ in coping strategies to
aversive conditions.
Piras G, Giorgi O, Corda MG.
Department of Toxicology, University of Cagliari, Via Ospedale 72, 09124,
Cagliari, Italy.
INTRODUCTION: The selective breeding of Roman low-avoidance (RLA) and
high-avoidance (RHA) rats for, respectively, poor versus rapid acquisition of
active avoidance in a shuttle-box has produced two phenotypes that differ
drastically in the reactivity to stressful stimuli: in tests used to assess
emotionality, RLA rats display passive ("reactive") coping and robust
hypothalamus-pituitary-adrenal (HPA) axis reactivity, whereas RHA rats show
proactive coping and blunted HPA axis responses. The behavioral and
neuroendocrine traits that distinguish these lines suggest that RLA rats may be
prone, whereas RHA rats may be resistant to develop depression-like behavior when
exposed to stressful experimental conditions.
OBJECTIVE AND METHODS: To evaluate the performance of the Roman lines in the
forced swim test, immobility, climbing, and swimming were assessed under baseline
conditions (i.e., pretest in naĂŻve animals or test after the administration of
vehicle), and after subacute treatment with desipramine, fluoxetine, and
chlorimipramine.
RESULTS: Under baseline conditions, RLA rats displayed greater immobility and
fewer climbing counts than RHA rats. In RLA rats, desipramine, fluoxetine, and
chlorimipramine decreased immobility; moreover, desipramine and chlorimipramine
increased climbing, whereas fluoxetine increased swimming. In RHA rats, none of
these drugs affected immobility, swimming, or climbing.
CONCLUSIONS: RLA and RHA rats represent two divergent phenotypes respectively
susceptible and resistant to display depression-like behavior in the forced swim
test. Hence, comparative studies in these lines may help to develop novel working
hypotheses on the relationships among genotype, temperament traits, and neural
mechanisms underlying the vulnerability or resistance to stress-induced
depression in humans.
PMID: 20589496 [PubMed - indexed for MEDLINE