Clinical observations and experimental data (Gorenstein et al., 1998; Knutson et al., 1998) suggest that low or moderate doses of antidepressants administered to normal volunteers are associated with improvement that go beyond classical therapeutic effects, with respect to self-confidence, mood and well being, reduced irritability, and higher tolerance to aversive stimuli increased sociability, and subjective improvement in cognitive processing and decision making. Besides that side effects such as: weight gain and increased alimentary appetite, particularly for carbohydrates, interference with and desinhibiton of certain sleep with frequent awakenings in the absence of significant hangover, impulsive behavior suggest widespread action in brain and behaviour. The strategy of studying the effects of antidepressants in normal subjects is justified by the need to discriminate primary actions from therapeutic effects in clinical states. Such studies are still scarce and several aspects must be investigated. The aim of the current project is to replicate and extend the scope of our previous investigations of the effects of low doses of antidepressants on the emotional response of normal subjects and patients with psychiatric disorders, in order to contribute to the understanding of the "extra-therapeutic" effects of such drugs and the mechanisms of mood regulation.The first phase involves clinical trials in normal volunteers without previous psychiatric diagnosis and studies with animals. The volunteers, grouped into assymptomatic and symptomatic normals, will receive flexible-doses of clomipramine ranging from 10 to 50 mg or active placebo in a parallel group design, under doubleblind conditions, during six weeks, and will be evaluated before and at the end of treatment. This study will be carried out in blocks of 20 subjects for each treatment condition, repeated as many times as necessary to obtain the samples required for the various associated experiments. The main objectives are:a) Assess the effects of antidepressants on personality characteristics, mood and other psychological variables, as well as, their relationship to cognitive processing, circadian rhythms, alimentary behavior and neuroimage;b) Explore the effects on the sleep-wakefulness cycle, evaluating the macro and microstructure of nocturnal sleep, and the objective and subjective parameters of daytime sleepiness, circadian temperature, activity and mood cycle, and effects on the secretion of melatonin;c) Study the effects of antidepressants on appetite and their relationship with weight gain and craving. Studies in rats will determine the effects of clornipramine on the ingestion of macronutrients, sucrose and sucralose, and sacarose craving;d) Explore the anatomic-functional correlates of emotional and motivational states before and after treatment with antidepressants. Measures of Functional magnetic resonance imaging will be obtained in different emotional conditions, before and after treatment with clomipramine.Depending on the results of these experiments, a series of clinical trials with antidepressants will be run in normal volunteers and psychiatric patients to test hypothesis regarding issues of specificity, validity and reproducibility of such effects. If findings similar to those found in our previous studies in normal subjects are confirmed, they may have important clinical and social implications. The improvement of the emotional responses of emotionally unstable individuals is a longstanding clinical goal with many favorable consequences for personal, family and social interactions. These studies may also help clarifying aspects of the limits of the pharmacological and psychological therapeutic interventions. (AU)
Articles published in Agência FAPESP Newsletter about the research grant:
BOFFINO, CATARINA C.;
CARDOSO DE SA, CRISTINA S.;
BROWN, RICHARD G.;
BASILE, LUIS F. H.;
RAMOS, RENATO T.
Fear of heights: cognitive performance and postural control.
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE,
Web of Science Citations: 19.