1985 — 1990 |
Depue, Richard A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Studies of Persons At Risk For Depressive Disorders @ University of Minnesota Twin Cities
This proposal incorporates three foci that elaborate the behavioral high-risk paradigm as applied to affective disorders. The first concerns further refinement of the item set and case-identification properties of an inventory which is used to identify cyclothymic individuals who are at risk for developing full syndromal bipolar affective disorder. These aspects of the inventory are evaluated in a major interview validation study, the goal of which is to define a highly stable inventory so that other investigators may use it. The second focus involved the extension of the behavioral high-risk paradigm to the identification of certain forms of dysthymia which have been related to cyclothymia via a multiple-threshold model of inheritance. These studies include two independent validations of new Dysthymic Inventory developed by the PI. The goal of these studies is to provide a stable inventory that will allow comparitive research on cyclothymia and dysthymia. The third focus of the proposal concerns the application of the behavioral high-risk paradigm in a manner for which it was developed: to assess the psychobiologic factors in subsyndromal affective disorders which may serve as predictors of future clinical outcome. In this case, circadian rhythm functioning in cyclothymia, and later in the period dysthymia, is proposed. Several rhythms of subjects are monitored continuously for approximately 60 days while they live in their natural environment under changing conditions of life stress. It is through the latter type of work, in particular, that predispositional nature of bipolar disorder may be investigated. Without an adequate high-risk paradigm, predispositional variables will not be accessible to investigation. The behavioral high-risk paradigm provides one promising means to this end.
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0.914 |
1992 |
Depue, Richard A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Biology and the Structures of Personality and Emotion @ University of Minnesota Twin Cities
This proposal draws a comparison between a neurobehavioral emotional system described in practically all species, and a higher order factor that is one major component of the structure of personality. The former is the Behavioral Facilitation System (BFS), and the latter is Positive Emotionality (PE), similar to extraversion. Behaviorally, the two systems are described quite similarly: both social and sexual interaction by signals of reward. The neurobiology of the BFS has been studied extensively in animals: it is based on the ascending dopamine (DA) projections originating in the ventral tegmental area and terminating in the limbic striatum and forebrain, and neocortex. Because the neurobiology associated with PE is unknown, analogy between the animal BFS and human PE constructs has not progressed. The preliminary and proposed studies described herein attempt to assess DA functioning in normal twins naturally distributed across the dimension of PE, as measured by Tellegen's (1982) Multidimensional Personality Questionnaire (MPQ). A strictly correlational nature of the study is circumvented in part by the use of a challenge protocol employing a direct DA D2 receptor agonist. DA functioning is assessed via the action of a DA agonist on prolactin (PRL) secretion, the rate of spontaneous eye blinking, and spatial delayed-response performance, all variables being strongly influenced by DA D2 receptor action. Preliminary studies demonstrated an extremely strong correlation between PE and the DA agonist's effects on these variables. Three major aims of the proposed studies are: 1) To determine, by sex, the range of three DA agonist doses that is most sensitive to individual differences in DA agonist effects on the DA indices; 2) To determine the degree of genetic influence on (a) each DA variable, and (b) pairs of DA and personality variables via use of a twin population in a dose-response design; and 3) To determine the relationship between a host of personality inventories (having convergent and divergent constructs to the BFS or PE constructs) and DA reactivity to the agonist. The best set of DA-related personality subdomains will be identified in order to revise the MPQ PE scale for selection of research subjects in future studies. Also, major hypotheses concerning the interaction of personality traits will be tested with the DA variables being the predicted criterion, which is the first such analysis where biology is incorporated. The potential significance of these studies for mental health issues lies in the detailed explication of a personality-neurobehavioral system that, when incorporating genetic vulnerabilities, may contribute to (a) abuse of substances that depend on DA function for their psychogenic effects, including alcohol, and (b) certain forms of affective disorder that are DA-related, most particularly bipolar affective disorders.
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0.914 |
1997 — 2003 |
Depue, Richard A |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Neurobiology of Personality and Emotion @ Cornell University Ithaca
The goal of this research is to discover the most precise means of measuring individual differences in dopamine (DA) functioning, and then to test the relation of DA reactivity to personality traits. Using a pharmacological challenge protocol with hormonal and behavioral indicators as responses to tee challenge, several preliminary studies have demonstrated a strong relation between DA and extraversion or positive emotionality (PEM). The proposed study aims to establish a standard pharmacological challenge protocol that can be used by us and the scientific community to study DA, extraversion or PEM, and behavior. The most powerful means of expressing individual differences in DA trait levels is to assess the slope of DA reactivity across a series of incentive stimulus magnitudes -(i.e., DA-agonist challenge doses), providing a stimulus-DA dose-response function. The proposed study uses a randomized, cross-over design under double-blind conditions to establish a dose-response challenge protocol based on a set of 3 (out of 4) methylphenidate (MP) doses (iv .05, .15, .3, .5 mg/kg) as a function of sex. Indicators of MP effects are prolactin (PRL), growth hormone (GH), mood ratings, and working memory. Using the final 3 selected MP doses slope will be calculated across doses for each subject for each variable (GH, PRL, mood) to provide dose- response indicators of DA-reactivity to MP challenge. We will assess the extent to which the final set of indicators represents a similar MP-induced process by factor analyzing them in order to define one or more DA-reactivity factors. The DA-reactivity factor will then be intercorrelated with, first, the major personality traits, and, secondly, with the subdomains of the major traits that correlate significantly with DA reactivity. In this way, a "DA" inventory will be derived. These studies are designed to enlighten several psychiatric problems that may involve a relation between DA and behavior. Recent research suggests that determination of DA- behavior relations could have benefit in understanding, and perhaps in treating, pathological forms of personality, especially of the Cluster B type, some forms of affective disorders, schizophrenic positive symptoms, and genetic-experience interactive liabilities to substance abuse that may depend on sensitivity of DA receptor types.
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0.958 |