1993 — 1994 |
Allen, John J. |
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.) |
Acupuncture Treatment For Unipolar Depression
Severe depression is an unfortunately common condition, especially among women, and one which for many persons have sought alternative treatments. This may reflect that for many persons depression is a chronic or episodic rather than an acute condition, one for which conventional treatments fail to provide full or lasting remission. The efficacy of the alternative treatments that persons seek for the symptoms of depression has not been empirically assessed. This proposal presents a preliminary, yet controlled, study to test the efficacy of acupuncture as a treatment for unipolar depression in women. This interdisciplinary collaborative project involves the principal collaboration between a faculty member from the psychology department at the University of Arizona and the Director of and acupuncturist for the Kwan Yin Center for the Healing Arts. Additional collaborators include another faculty member from the department of psychology, a medical doctor affiliated with the University of Arizona Medical Center, and four local acupuncturists who will serve as consultants. The project involves assessing depression from the perspectives of both Western and Chinese medicine, and developing treatment plans according to the principles of Chinese medicine that accommodate each individual's specific pattern of disharmony. Additionally, these individually-tailored treatments will consider the phase of the menstrual cycle as an important determinant of the selected treatment points. The main objective of the study is to determine if the efficacy of acupuncture as a treatment depression is substantial enough to warrant a large-scale clinical trial. Specifically, there are four objectives: a) to evaluate the efficacy as well as the clinical significance of acupuncture as a treatment for symptoms of unipolar depression; b) to evaluate the comparative efficacy of individually- tailored acupuncture treatments relative to treatment using a set of points nonspecific to depression and relative to a wait-list control group; c) to assess stability of or changes in electroencephalographic asymmetries as a function of treatment; and d) to compare Western and Chinese medicine-based diagnostic procedures to identify those patterns of disharmony that are subsumed under the diagnosis of unipolar depression.
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0.936 |
1997 — 2001 |
Allen, John J. |
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. |
Acupuncture in the Treatment of Depression
DESCRIPTION (Applicant's Abstract): Depression is an unfortunately common condition for which people often seek alternative (non-western) treatments, perhaps because conventional treatments do not consistently provide lasting relief. A pilot study (Allen, Schnyer, & Hitt, 1996) suggests that acupuncture, a popular but under-researched alternative treatment derived from Chinese medicine, holds sufficient promise as a treatment for depression to warrant a larger-scale clinical trial. We propose to test the efficacy acupuncture designed specifically to treat depression by comparing it to acupuncture treatment designed to treat symptoms that are not part of the depressive symptom picture and to a wait list control group. Because relapse and recurrence of Major Depression are quite common, we also propose to assess the clinical status of participants for 18 months after treatment concludes, to examine whether the dose of treatment predicts the likelihood of relapse or recurrence. In the first phase of this double-blind randomized clinical trial, 150 men and women meeting DSM-IV criteria for Major Depression will be randomly assigned to one of three conditions: (a) eight weeks of acupuncture designed specifically to address depression; (b) eight weeks of nonspecific acupuncture treatments designed to treat valid symptom pattens other than depression; (c) or a waitlist control condition. At the end of this first phase, blind assessments will be used to compare treatment effects from the perspectives of both western psychiatry and Chinese medicine. After this phase, all participants will receive specific treatment. This experimental design will thus address the following specific aims: (1) to evaluate the efficacy of acupuncture treatments for Major Depression relative to both a waitlist control and to nonspecific acupuncture treatments desired to treat symptoms that are not part of depression; (2) to evaluate the clinical significance of acupuncture as a treatment for Major Depression by assessing the impact of acupuncture not only on depression but also on functioning in social and work arenas; and (3) to examine whether a dose-response relationship exists, such that the number of specific acupuncture treatments is related to the likelihood of remission during treatment, or the likelihood of recurrence or relapse following treatment. Secondary aims are: (1) to assess the efficacy of acupuncture treatments using measures of outcome derived from the principles of Chinese medicine; (2) to examine the convergence of western-based and Chinese-medicine-based outcome measures in terms of clinical significance; (3) to determine whether changes in energetic pattern mediate changes in western defined depression severity; and (4) to explore whether patient and history variables predict response to acupuncture treatments.
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0.936 |
2004 — 2008 |
Allen, John J. |
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. |
Trait and State Frontal Brain Asymmetry in Depression
DESCRIPTION (provided by applicant): Asymmetrical frontal brain activity holds promise as a marker of risk for depression. Over 40 studies suggest that resting frontal electroencephalographic (EEG) asymmetry may serve as an indicator of a trait-like diathesis to respond to emotional situations with a pattern of emotional negativity and behavioral withdrawal. Moreover, resting frontal EEG asymmetry distinguishes depressed individuals -- those currently symptomatic as well those as in remission -- from never-depressed individuals. These findings suggest that frontal EEG asymmetry is more than a correlate of a depressive episode, potentially serving as a liability marker for the development of depression. Such a marker could have prognostic and etiological value, but superimposed on the trait-like stability are fluctuations that vary as a function of occasion of assessment or experimentally manipulated emotion. Estimates of the stability of frontal EEG asymmetry are in the range of.60, suggesting that trait factors are substantial, but that variation across assessments may limit the utility of asymmetrical frontal brain activity as a trait-like risk indicator for depression. Such factors may underlie the few inconsistent findings in this literature. The present proposal represents a necessary step in the programmatic investigation of frontal EEG asymmetry as a potential risk indicator for depression, by evaluating three distinct sources of variability in frontal EEG asymmetry: 1) Stable trait consistency across multiple assessments; 2) Occasion-specific fluctuations from one assessment to the next; and, 3) State-dependent changes within a single assessment. During four visits, trait resting as well as state manipulated frontal EEG asymmetry will be assessed in depressed and nondepressed subjects. This design will allow us to address several specific aims, including: 1) To assess the relative contributions of trait, occasion, and state variance in frontal EEG asymmetry; 2) To assess whether frontal EEG asymmetry has characteristics that suggest it may profitably serve as a marker of risk for major depressive disorder; and, 3) To assess the acute impact of a widely used selective serotonin reuptake inhibitor on frontal EEG asymmetry, as medication effects have been largely unexplored. Secondary aims address methodological and treatment-related questions, as well as assessing gender and menstrual cycle effects that may moderate the relationship between frontal EEG asymmetry and depression.
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0.936 |
2014 — 2015 |
Allen, John J. Schnyer, David (co-PI) [⬀] |
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.) |
Identifying Eeg Indices of Neural Systems Underlying Risk For Mdd
DESCRIPTION (provided by applicant): Major Depressive Disorder (MDD) is unfortunately common with substantial burden of disease, economically and personally. Given the prevalence of depression and its debilitating course, [developing biomarkers that that have predictive value for the development, maintenance, and treatment of MDD and related disorders is of high scientific significance. Biomarkers that link deficits in neural systems to specific psychological processes that are dysfunctional in MDD] are especially valuable because they can reveal risk-to-symptom pathways that may be future targets for treatments and preventions. Although neuroimaging in MDD has generated impressive returns, imaging procedures such as functional magnetic resonance imaging (fMRI) are not well- suited for studying prospective of risk for MDD, given the relatively high cost of fMRI and the large samples required for prospective studies. A cost-effective and promising strategy would be to link less costly and more widely-available electroencephalographic (EEG) indices of brain activity to specific neural systems involved in MDD, [and subsequently to use these EEG biomarkers in assessing risk in research and clinical settings. Future prospective research using cost-effective EEG in large samples would have a clear link to established neural systems identified with fMRI approaches. Moreover, such easily-assessed biomarkers can promote premorbid risk assessment, facilitate early diagnosis, and lead to individually-tailored treatment and] prevention approaches for high-risk populations. With these goals in mind, [and motivated by a cognitive-neural emotion- regulation framework of depressive vulnerability,] we propose to collect simultaneous resting-state (RS) fMRI and 64-channel EEG data [from never-depressed and previously-depressed young adults], to identify associations between surface-recorded EEG and regional connectivity assessed via RSfMRI. We will apply cutting-edge approaches to the examination of RSfMRI networks and EEG data, including independent components analysis and multivariate vector approaches. We will examine EEG features motivated by extant EEG MDD literature, such as frontal EEG asymmetry, and also conduct broader exploratory analyses, to identify which EEG features index aspects of resting state network connectivity that have previously been identified as dysregulated in MDD. We can then assess whether these EEG features differentiate individuals with a lifetime history of MDD from those without - which would be expected of a risk indicator for MDD - using [the present sample and also] our extant sample of 306 individuals (143 with a history of MDD), all of whom have provided resting EEG data. In addition to the RSfMRI, high resolution T1 structural images as well as diffusion tensor images (DTI) will be collected to provide structural correlates of EEG and RSfMRI connectivity that can be examined in a highly exploratory manner. In this application we provide pilot data showing the feasibility o this approach, but consistent with the R21 mechanism, we consider our exploratory approach to be a strength of this proposal.
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0.936 |
2016 |
Allen, John J. Beevers, Christopher G [⬀] Mcgeary, John E (co-PI) [⬀] |
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.
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0.902 |