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

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 naïve 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