2000 — 2002 |
Mcgeary, John E |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Stress Induced Increases in Alcohol Effects @ University of Colorado At Boulder
This application proposes three studies that investigate the role of the stress in mediating alcohol's positive reinforcement effects. Alcohol's positive reinforcement is partly provided by the mesolimbic dopamine system. Corticosteroids (cort), stress hormones released during conditions of stress and after alcohol use, have been shown to moderate dopamine activation. A blockade of cort synthesis leads to decreased self administration of alcohol and other drugs of abuse, perhaps by disrupting the positive reinforcement and subjective experience of euphoria. To test this hypothesis in humans, three studies are proposed: 1) Study 1, with 23 subjects per condition, will cross alcohol/placebo with shock/no shock to determine if cortisol release is additive and to establish its effects on self- reported euphoria; and, 2) Study 2 will use a blockade of cortisol by Metyrapone to investigate the role of HPA activation in response to alcohol, stress and their interaction.
|
0.966 |
2008 |
Mcgeary, John E |
S10Activity Code Description: To make available to institutions with a high concentration of NIH extramural research awards, research instruments which will be used on a shared basis. |
Brown University Shared Dna Sequencer
[unreadable] DESCRIPTION (provided by applicant): This application proposes to replace outdated DNA sequencing technology (discontinued by manufacturer on 6/30/06) with a state of the art machine. The broad objectives of this proposal are to enrich ongoing psychiatric and behavioral research at Brown University and collaborating institutions through the integration of molecular genetics with the intensive phenotypic and environmental data currently being collected. The specific aim of the is proposal is to replace the no-longer supported Applied Biosystems 377 DNA Sequencer with a state-of-the-art Applied Biosystems 3130xl Genetic Analyzer. Obtaining a new genetic analyzer would allow uninterrupted progress in identifying genetic moderators of drug's effects (e.g., McGeary et al 2004), defining genetic contributions to gene by environment interactions (e.g., Gibb et al, 2006) and defining psychiatric subtypes (e.g., McGeary et al., 2006). Current research projects that would benefit from this acquisition include numerous trials of medications for alcohol and nicotine dependence with the goal of improving pharmacological treatments through the identification of genetic variation that predicts positive response (good treatment outcome) and negative response (side effects). There are 19 research proposals currently under review that would benefit from access to this equipment. These projects span multiple methodologies and include neuroimaging assessment studies, human lab challenge studies of multiple drugs of abuse, assessments of obesity, depression and anxiety disorders and investigations of genetic influences on human sleep. [unreadable] [unreadable] [unreadable]
|
1 |
2016 |
Allen, John J. (co-PI) [⬀] Beevers, Christopher G [⬀] Mcgeary, John E |
R56Activity Code Description: To provide limited interim research support based on the merit of a pending R01 application while applicant gathers additional data to revise a new or competing renewal application. This grant will underwrite highly meritorious applications that if given the opportunity to revise their application could meet IC recommended standards and would be missed opportunities if not funded. Interim funded ends when the applicant succeeds in obtaining an R01 or other competing award built on the R56 grant. These awards are not renewable. |
Contribution of Genome-Wide Variation to Cognitive Vulnerability to Depression @ University of Texas, Austin
Abstract Depression is a leading cause of disability worldwide among adults. Cognitive models of depression, which have received strong empirical support, posit that individuals' characteristic ways of attending to, interpreting, and remembering stimuli in their environment may contribute to the development and maintenance of the disorder. To understand the etiology of these biases, many genetic association studies have been completed. However, findings so far (including those from our own work) have been somewhat limited. Although genetic association studies have value, we strongly believe that whole genome methods will provide new insights into the role of genetic variation in psychopathology. Aim 1 is to comprehensively measure phenotypes related to negative cognitive bias in a community sample of 1500 adults of European ancestry. We propose to use established behavioral, eye tracking, and electrophysiological tasks to comprehensively measure negatively biased attention, interpretation, and memory?central features of contemporary cognitive models of depression. Aim 2 is to quantify the aggregate contribution of genetic variation across the genome to cognitive vulnerability. We propose to use genomic-relatedness-matrix restricted maximum likelihood to estimate the aggregate genetic effect of approximately 900,000 polymorphisms that measure exomic and common genetic variation across the entire genome. This will provide an answer to the fundamental question of how much variance in these key phenotypes is due to variation in measured polymorphisms. Aim 3 is to develop biologically plausible cumulative genetic scores (CGS) to identify linkages between specific genetic variation and our phenotypes. We have created gene sets derived from a database of known and predicted protein interactions and from human brain atlases with genetic and anatomic information. Importantly, our large sample allows us to perform a confirmatory study for these gene sets. Upon study conclusion, we will make our data publically available so investigators can develop additional gene sets that putatively relate to cognitive vulnerability. In sum, the proposed study will provide much needed insight into the degree to which these theoretically motivated intermediate phenotypes for depression are associated with genetic variation. Although twin studies point to the possibility of a genetic etiology, no attempts have been made to quantify the contribution of measured genetic variation to these cognitive phenotypes. This will provide much needed guidance about how much variance in cognitive vulnerability to depression can be predicted with genome- wide based analyses and may help account for some of the missing heritability often associated with candidate polymorphism studies.
|
0.966 |
2018 — 2019 |
Mcgeary, John E Metrik, Jane Miller, Mary Elizabeth [⬀] Miller, Mary Elizabeth [⬀] |
R21Activity Code Description: To encourage the development of new research activities in categorical program areas. (Support generally is restricted in level of support and in time.) |
The Impact of Cbt For Insomnia On Alcohol Treatment Outcomes Among Veterans
PROJECT SUMMARY / ABSTRACT Alcohol use disorders (AUDs) are prevalent among Veterans and result in significant physical and psychological burden. Among those who receive treatment for AUDs, 1 in 3 relapses to problematic drinking within one year of treatment. Thus, additional strategies are needed to enhance alcohol treatment outcomes. One promising approach involves providing concurrent treatment for a common complaint ? difficulty falling or staying asleep. As many as 63% of Veterans with AUDs report co-occurring symptoms of insomnia. Given the negative impact of insomnia on attention and emotion regulation, insomnia symptoms may decrease patients? abilities to attend to alcohol treatment and manage negative emotions that lead to craving and relapse. Moreover, approximately 50% of individuals with AUDs report using alcohol to help them sleep, making relapse more likely for those with no other tools or skills to help them sleep. Indeed, sleep disturbance has been identified as a risk factor for relapse among individuals in alcohol treatment. Thus, effective treatment of sleep problems may enhance alcohol treatment for a substantial number of individuals with AUDs. Cognitive Behavioral Therapy for Insomnia (CBTi) has been effective in reducing insomnia severity in individuals with AUDs; however, no investigations have examined the efficacy of CBTi delivered concurrently with AUD treatment to determine its impact on treatment engagement. This R21 aims to examine the feasibility, acceptability, and initial efficacy of a CBTi supplement to ongoing outpatient alcohol treatment at the VA. We will conduct a randomized pilot trial with 80 Veterans who meet DSM-5 criteria for AUD and the episodic criterion for Insomnia Disorder. Participants will be randomly assigned to a minimal-treatment (education) control involving sleep hygiene education in addition to treatment as usual (eTAU; n = 40) or TAU+CBTi (n = 40). Outcomes will be assessed at the end of the active intervention period (6 weeks) and 6 weeks post- intervention. Outcomes of interest include recruitment and retention rates, treatment satisfaction, percentage of abstinent days, percentage of heavy drinking days, alcohol-related consequences, use of alcohol as a sleep aid, sleep efficiency, ability to sustain attention, working memory, negative affect, and emotion regulation. Data analyses will focus on size of treatment effects. Results will inform an R01 application to examine the efficacy, cost-effectiveness, and potential mechanisms of CBTi in preventing or delaying relapse to problematic drinking among Veterans with insomnia and AUDs. This study will provide initial evidence that treatment of insomnia not only improves sleep but also allows participants to derive greater benefit from intensive outpatient alcohol treatment.
|
1 |