Helena C Kraemer

Stanford University, Palo Alto, California, United States

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Publications (265)1448.37 Total impact

  • Helena Chmura Kraemer
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    ABSTRACT: To understand the process by which a treatment (T) achieves an effect on outcome (O) and thus to improve the effect of T on O, it is vital to detect mediators, to compare the impact of different mediators, and to develop hypotheses about the causal factors (all mediators) linking T and O. An index is needed to facilitate interpretation of the potential clinical importance of a mediator (M) of choice of T on treatment O in randomized clinical trials (RCTs). Ideally such a mediator effect size should (1) be invariant under any rescaling of M and O consistent with the model used, and (2) reflect the difference between the overall observed effect of T on O and what the maximal effect of T on O could be were the association between T and M broken. A mediator effect size is derived first for the traditional linear model, and then more generally for any categorical (ordered or non-ordered) potential mediator. Issues such as the problem of multiple treatments, outcomes and mediators, and of causal inferences, and the correspondence between this approach and earlier ones, are discussed. Illustrations are given of the application of the approach. Copyright © 2014 John Wiley & Sons, Ltd.
    International Journal of Methods in Psychiatric Research 06/2014; · 1.76 Impact Factor
  • Helena Chmura Kraemer
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    ABSTRACT: Reliability of clinical diagnosis is essential for good clinical decision making as well as productive clinical research. The current review emphasizes the distinction between a disorder and a diagnosis and between validity and reliability of diagnoses, and the relationships that exist between them. What is crucial is that reliable diagnoses are essential to establishing valid diagnoses. The present review discusses the theoretical background underlying the evaluation of diagnoses, possible designs of reliability studies, estimation of the reliability coefficient, the standards for assessment of reliability, and strategies for improving reliability without compromising validity. Expected final online publication date for the Annual Review of Clinical Psychology Volume 10 is March 20, 2014. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.
    Annual Review of Clinical Psychology 01/2014; · 12.42 Impact Factor
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    ABSTRACT: Separate bodies of literature report that elevated pro-inflammatory cytokines and cortisol negatively affect hippocampal structure and cognitive functioning, particularly in older adults. Although interactions between cytokines and cortisol occur through a variety of known mechanisms, few studies consider how their interactions affect brain structure. In this preliminary study, we assess the impact of interactions between circulating levels of IL-1Beta, IL-6, IL-8, IL-10, IL-12, TNF-alpha, and waking cortisol on hippocampal volume. Twenty-eight community-dwelling older adults underwent blood draws for quantification of circulating cytokines and saliva collections to quantify the cortisol awakening response. Hippocampal volume measurements were made using structural magnetic resonance imaging. Elevated levels of waking cortisol in conjunction with higher concentrations of IL-6 and TNF-alpha were associated with smaller hippocampal volumes. In addition, independent of cortisol, higher levels of IL-1beta and TNF-alpha were also associated with smaller hippocampal volumes. These data provide preliminary evidence that higher cortisol, in conjunction with higher IL-6 and TNF-alpha, are associated with smaller hippocampal volume in older adults. We suggest that the dynamic balance between the hypothalamic-pituitary adrenal axis and inflammation processes may explain hippocampal volume reductions in older adults better than either set of measures do in isolation.
    Frontiers in Aging Neuroscience 01/2014; 6:153. · 5.20 Impact Factor
  • Sleep Medicine. 01/2014;
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    ABSTRACT: Despite depressive disorders being very common there has been little research to guide primary care physicians on the choice of treatment for patients with mild to moderate depression. To evaluate the efficacy of interpersonal counselling compared with selective serotonin reuptake inhibitors (SSRIs), in primary care attenders with major depression and to identify moderators of treatment outcome. A randomised controlled trial in nine centres (DEPICS, Australian New Zealand Clinical Trials Registry number: ACTRN12608000479303). The primary outcome was remission of the depressive episode (defined as a Hamilton Rating Scale for Depression score ≤7 at 2 months). Daily functioning was assessed using the Work and Social Adjustment Scale. Logistic regression models were used to identify moderators of treatment outcome. The percentage of patients who achieved remission at 2 months was significantly higher in the interpersonal counselling group compared with the SSRI group (58.7% v. 45.1%, P = 0.021). Five moderators of treatment outcome were found: depression severity, functional impairment, anxiety comorbidity, previous depressive episodes and smoking habit. We identified some patient characteristics predicting a differential outcome with pharmacological and psychological interventions. Should our results be confirmed in future studies, these characteristics will help clinicians to define criteria for first-line treatment of depression targeted to patients' characteristics.
    The British journal of psychiatry: the journal of mental science 12/2013; · 6.62 Impact Factor
  • Meredith L Wallace, Ellen Frank, Helena C Kraemer
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    ABSTRACT: IMPORTANCE Identifying treatment moderators may help mental health practitioners arrive at more precise treatment selection for individual patients and can focus clinical research on subpopulations that differ in treatment response. OBJECTIVE To demonstrate a novel exploratory approach to moderation analysis in randomized clinical trials. DESIGN, SETTING, AND PARTICIPANTS A total of 291 adults from a randomized clinical trial that compared an empirically supported psychotherapy with selective serotonin reuptake inhibitor (SSRI) pharmacotherapy as treatments for depression. MAIN OUTCOMES AND MEASURES We selected 8 relatively independent individual moderators out of 32 possible variables. A combined moderator, M*, was developed as a weighted combination of the 8 selected individual moderators. M* was then used to identify individuals for whom psychotherapy may be preferred to SSRI pharmacotherapy or vice versa. RESULTS Among individual moderators, psychomotor activation had the largest moderator effect size (0.12; 95% CI, <.01 to 0.24). The combined moderator, M*, had a larger moderator effect size than any individual moderator (0.31; 95% CI, 0.15 to 0.46). Although the original analyses demonstrated no overall difference in treatment response, M* divided the study population into 2 subpopulations, with each showing a clinically significant difference in response to psychotherapy vs SSRI pharmacotherapy. CONCLUSIONS AND RELEVANCE Our results suggest that the strongest determinations for personalized treatment selection will likely require simultaneous consideration of multiple moderators, emphasizing the value of the methods presented here. After validation in a randomized clinical trial, a mental health practitioner could input a patient's relevant baseline values into a handheld computer programmed with the weights needed to calculate M*. The device could then output the patient's M* value and suggested treatment, thereby allowing the mental health practitioner to select the treatment that would offer the greatest likelihood of success for each patient.
    JAMA Psychiatry 09/2013; · 12.01 Impact Factor
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    ABSTRACT: OBJECTIVE This article describes the clinical utility and feasibility of proposed DSM-5 criteria and measures as tested in the DSM-5 Field Trials in Routine Clinical Practice Settings (RCP). METHODS RCP data were collected online for six months (October 2011 to March 2012). Participants included psychiatrists, licensed clinical psychologists, clinical social workers, advanced practice psychiatric-mental health nurses, licensed counselors, and licensed marriage and family therapists. Clinicians received staged, online training and enrolled at least one patient. Patients completed self-assessments of cross-cutting symptom domains, disability measures, and an evaluation of these measures. Clinicians conducted diagnostic interviews and completed DSM-5 and related assessments and a clinical utility questionnaire. RESULTS A total of 621 clinicians provided data for 1,269 patients. Large proportions of clinicians reported that the DSM-5 approach was generally very or extremely easy for assessment of both pediatric (51%) and adult (46%) patients and very or extremely useful in routine clinical practice for pediatric (48%) and adult (46%) patients. Clinicians considered the DSM-5 approach to be better (57%) or much better (18%) than that of DSM-IV. Patients, including children age 11 to 17 (47%), parents of children age six to ten (64%), parents of adolescents age 11 to 17 (72%), and adult patients (52%), reported that the cross-cutting measures would help their clinicians better understand their symptoms. Similar patterns in evaluations of feasibility and clinical utility were observed among clinicians from various disciplines. CONCLUSIONS The DSM-5 approach was feasible and clinically useful in a wide range of routine practice settings and favorably received by both clinicians and patients.
    Psychiatric services (Washington, D.C.) 07/2013; · 2.81 Impact Factor
  • Helena Chmura Kraemer
    International Journal of Eating Disorders 07/2013; 46(5):412-5. · 3.03 Impact Factor
  • Helena Chmura Kraemer
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    ABSTRACT: The quality of all clinical decision-making, as well as power and precision in clinical research results, depends fundamentally on the quality of the measures used. Yet evaluations of the quality of clinical measures likely to be used either in clinic or research applications are difficult to execute or to critique because the criteria for judging such studies are so ill-defined. Here a set of guidelines is proposed, modeled on CONSORT guidelines for randomized clinical trials, first defining the terms often inconsistently used in the research literature and then identifying certain errors that seem to recur in evaluation studies.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 07/2013; 21(7):589-95. · 3.35 Impact Factor
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  • American Journal of Psychiatry 06/2013; 170(6):680a-681. · 14.72 Impact Factor
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    ABSTRACT: Objective Results of the NIMH Collaborative Multisite Multimodal Treatment Study of Children With Attention-Deficit/Hyperactivity Disorder (MTA) were analyzed to determine whether a double-blind, placebo-controlled methylphenidate (MPH) titration trial identified the best MPH dose for each child with attention-deficit/hyperactivity disorder (ADHD).
  • American Journal of Psychiatry 04/2013; 170(4):443-4. · 14.72 Impact Factor
  • Helena Chmura Kraemer
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    ABSTRACT: No one treatment is likely to affect all patients with a disorder in the same way. A treatment highly effective for some may be ineffective or even harmful for others. Statistically significant or not, the effect sizes of many treatments tend to be small. Consequently, emphasis in clinical research is gradually shifting (1) to increased focus on effect sizes and (2) to discovery and documentation of moderators of treatment effect on outcome in randomized clinical trials, that is, personalized medicine, in which individual differences between patients are explicitly acknowledged. How to test a null hypothesis of moderation of treatment outcome is reasonably well known. The focus here is on how, under parametric assumptions, to define the strength of moderation, that is, a moderator effect size, either for scientific purposes or for assessment of clinical significance, in order to compare moderators and choose among them and to develop a composite moderator, which might more strongly moderate the effect of a treatment on outcome than any single moderator that might ultimately provide guidance for clinicians as to whom to prescribe what treatment. Copyright © 2013 John Wiley & Sons, Ltd.
    Statistics in Medicine 01/2013; · 2.04 Impact Factor
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    ABSTRACT: Objective: This article captures the proceedings of a meeting aimed at defining clinically meaningful effects for use in randomized controlled trials for psychopharmacological agents. Design: Experts from a variety of disciplines defined clinically meaningful effects from their perspectives along with viewpoints about how to design and interpret randomized controlled trials. Setting: The article offers relevant, practical, and sometimes anecdotal information about clinically meaningful effects and how to interpret them. Participants: The concept for this session was the work of co-chairs Richard Keefe and the late Andy Leon. Faculty included Richard Keefe, PhD; James McNulty, AbScB; Robert S. Epstein, MD, MS; Shelby D. Reed, PhD; Juan Sanchez, MD; Ginger Haynes, PhD; Andrew C. Leon, PhD; Helena Chmura Kraemer, PhD; Ellen Frank, PhD, and Kenneth L. Davis, MD. Results: The term clinically meaningful effect is an important aspect of designing and interpreting randomized controlled trials but can be particularly difficult in the setting of psychopharmacology where effect size may be modest, particularly over the short term, because of a strong response to placebo. Payers, regulators, patients, and clinicians have different concerns about clinically meaningful effects and may describe these terms differently. The use of moderators in success rate differences may help better delineate clinically meaningful effects. Conclusion: There is no clear consensus on a single definition for clinically meaningful differences in randomized controlled trials, and investigators must be sensitive to specific concerns of stakeholders in psychopharmacology in order to design and execute appropriate clinical trials.
    Innovations in clinical neuroscience. 01/2013; 10(5-6 Suppl A):4S-19S.
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    ABSTRACT: OBJECTIVE There is growing public health interest in understanding and promoting successful aging. While there has been some exciting empirical work on objective measures of physical health, relatively little published research combines physical, cognitive, and psychological assessments in large, randomly selected, community-based samples to assess self-rated successful aging. METHOD In the Successful AGing Evaluation (SAGE) study, the authors used a structured multicohort design to assess successful aging in 1,006 community-dwelling adults in San Diego County, ages 50-99 years, with oversampling of people over 80. A modified version of random-digit dialing was used to recruit subjects. Evaluations included a 25-minute telephone interview followed by a comprehensive mail-in survey of physical, cognitive, and psychological domains, including positive psychological traits and self-rated successful aging, scaled from 1 (lowest) to 10 (highest). RESULTS The mean age of the respondents was 77.3 years. Their mean self-rating of successful aging was 8.2, and older age was associated with a higher rating, despite worsening physical and cognitive functioning. The best multiple regression model achieved, using all the potential correlates, accounted for 30% of the variance in the score for self-rated successful aging and included resilience, depression, physical functioning, and age (entering the regression model in that order). CONCLUSIONS Resilience and depression had significant associations with self-rated successful aging, with effects comparable in size to that for physical health. While no causality can be inferred from cross-sectional data, increasing resilience and reducing depression might have effects on successful aging as strong as that of reducing physical disability, suggesting an important role for psychiatry in promoting successful aging.
    American Journal of Psychiatry 12/2012; · 14.72 Impact Factor
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    ABSTRACT: OBJECTIVE: To compare longer-term safety and effectiveness of the 4 most commonly used atypical antipsychotics (aripiprazole, olanzapine, quetiapine, and risperidone) in 332 patients, aged > 40 years, having psychosis associated with schizophrenia, mood disorders, posttraumatic stress disorder, or dementia, diagnosed using DSM-IV-TR criteria. METHOD: We used equipoise-stratified randomization (a hybrid of complete randomization and clinician's choice methods) that allowed patients or their treating psychiatrists to exclude 1 or 2 of the study atypical antipsychotics due to past experience or anticipated risk. Patients were followed for up to 2 years, with assessments at baseline, 6 weeks, 12 weeks, and every 12 weeks thereafter. Medications were administered employing open-label design and flexible dosages, but with blind raters. The study was conducted from October 2005 to October 2010. OUTCOME MEASURES: Primary metabolic markers (body mass index, blood pressure, fasting blood glucose, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), percentage of patients who stay on the randomly assigned atypical antipsychotic for at least 6 months, psychopathology, percentage of patients who develop metabolic syndrome, and percentage of patients who develop serious and nonserious adverse events. RESULTS: Because of a high incidence of serious adverse events, quetiapine was discontinued midway through the trial. There were significant differences among patients willing to be randomized to different atypical antipsychotics (P < .01), suggesting that treating clnicians tended to exclude olanzapine and prefer aripiprazole as one of the possible choices in patients with metabolic problems. Yet, the atypical antipsychotic groups did not differ in longitudinal changes in metabolic parameters or on most other outcome measures. Overall results suggested a high discontinuation rate (median duration 26 weeks prior to discontinuation), lack of significant improvement in psychopathology, and high cumulative incidence of metabolic syndrome (36.5% in 1 year) and of serious (23.7%) and nonserious (50.8%) adverse events for all atypical antipsychotics in the study. CONCLUSIONS: Employing a study design that closely mimicked clinical practice, we found a lack of effectiveness and a high incidence of side effects with 4 commonly prescribed atypical antipsychotics across diagnostic groups in patients over age 40, with relatively few differences among the drugs. Caution in the use of these drugs is warranted in middle-aged and older patients. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00245206.
    The Journal of Clinical Psychiatry 11/2012; · 5.81 Impact Factor
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    ABSTRACT: OBJECTIVE The authors sought to document, in adult and pediatric patient populations, the development, descriptive statistics, and test-retest reliability of cross-cutting symptom measures proposed for inclusion in DSM-5. METHOD Data were collected as part of the multisite DSM-5 Field Trials in large academic settings. There were seven sites focusing on adult patients and four sites focusing on child and adolescent patients. Cross-cutting symptom measures were self-completed by the patient or an informant before the test and the retest interviews, which were conducted from 4 hours to 2 weeks apart. Clinician-report measures were completed during or after the clinical diagnostic interviews. Informants included adult patients, child patients age 11 and older, parents of all child patients age 6 and older, and legal guardians for adult patients unable to self-complete the measures. Study patients were sampled in a stratified design, and sampling weights were used in data analyses. The mean scores and standard deviations were computed and pooled across adult and child sites. Reliabilities were reported as pooled intraclass correlation coefficients (ICCs) with 95% confidence intervals. RESULTS In adults, test-retest reliabilities of the cross-cutting symptom items generally were good to excellent. At the child and adolescent sites, parents were also reliable reporters of their children's symptoms, with few exceptions. Reliabilities were not as uniformly good for child respondents, and ICCs for several items fell into the questionable range in this age group. Clinicians rated psychosis with good reliability in adult patients but were less reliable in assessing clinical domains related to psychosis in children and to suicide in all age groups. CONCLUSIONS These results show promising test-retest reliability results for this group of assessments, many of which are newly developed or have not been previously tested in psychiatric populations.
    American Journal of Psychiatry 10/2012; · 14.72 Impact Factor
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    ABSTRACT: OBJECTIVE This article discusses the design, sampling strategy, implementation, and data analytic processes of the DSM-5 Field Trials. METHOD The DSM-5 Field Trials were conducted by using a test-retest reliability design with a stratified sampling approach across six adult and four pediatric sites in the United States and one adult site in Canada. A stratified random sampling approach was used to enhance precision in the estimation of the reliability coefficients. A web-based research electronic data capture system was used for simultaneous data collection from patients and clinicians across sites and for centralized data management. Weighted descriptive analyses, intraclass kappa and intraclass correlation coefficients for stratified samples, and receiver operating curves were computed. The DSM-5 Field Trials capitalized on advances since DSM-III and DSM-IV in statistical measures of reliability (i.e., intraclass kappa for stratified samples) and other recently developed measures to determine confidence intervals around kappa estimates. RESULTS Diagnostic interviews using DSM-5 criteria were conducted by 279 clinicians of varied disciplines who received training comparable to what would be available to any clinician after publication of DSM-5. Overall, 2,246 patients with various diagnoses and levels of comorbidity were enrolled, of which over 86% were seen for two diagnostic interviews. A range of reliability coefficients were observed for the categorical diagnoses and dimensional measures. CONCLUSIONS Multisite field trials and training comparable to what would be available to any clinician after publication of DSM-5 provided "real-world" testing of DSM-5 proposed diagnoses.
    American Journal of Psychiatry 10/2012; · 14.72 Impact Factor
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    ABSTRACT: OBJECTIVE The DSM-5 Field Trials were designed to obtain precise (standard error <0.1) estimates of the intraclass kappa as a measure of the degree to which two clinicians could independently agree on the presence or absence of selected DSM-5 diagnoses when the same patient was interviewed on separate occasions, in clinical settings, and evaluated with usual clinical interview methods. METHOD Eleven academic centers in the United States and Canada were selected, and each was assigned several target diagnoses frequently treated in that setting. Consecutive patients visiting a site during the study were screened and stratified on the basis of DSM-IV diagnoses or symptomatic presentations. Patients were randomly assigned to two clinicians for a diagnostic interview; clinicians were blind to any previous diagnosis. All data were entered directly via an Internet-based software system to a secure central server. Detailed research design and statistical methods are presented in an accompanying article. RESULTS There were a total of 15 adult and eight child/adolescent diagnoses for which adequate sample sizes were obtained to report adequately precise estimates of the intraclass kappa. Overall, five diagnoses were in the very good range (kappa= 0.60-0.79), nine in the good range (kappa= 0.40-0.59), six in the questionable range (kappa= 0.20-0.39), and three in the unacceptable range (kappa values <0.20). Eight diagnoses had insufficient sample sizes to generate precise kappa estimates at any site. CONCLUSIONS Most diagnoses adequately tested had good to very good reliability with these representative clinical populations assessed with usual clinical interview methods. Some diagnoses that were revised to encompass a broader spectrum of symptom expression or had a more dimensional approach tested in the good to very good range.
    American Journal of Psychiatry 10/2012; · 14.72 Impact Factor

Publication Stats

12k Citations
1,448.37 Total Impact Points


  • 1979–2014
    • Stanford University
      • • Department of Psychiatry and Behavioral Sciences
      • • Department of Health Research and Policy
      Palo Alto, California, United States
  • 2012
    • Norfolk and Norwich University Hospitals NHS Foundation Trust
      Norwich, England, United Kingdom
  • 2010–2012
    • University of California, San Diego
      • Department of Psychiatry
      San Diego, CA, United States
  • 2011
    • University of Pittsburgh
      • Department of Psychiatry
      Pittsburgh, Pennsylvania, United States
  • 2010–2011
    • Kaiser Permanente
      • Center for Health Research (Oregon, Hawaii, and Georgia)
      Oakland, CA, United States
    • University of Chicago
      • Department of Psychiatry and Behavioral Neuroscience
      Chicago, IL, United States
  • 2005–2010
    • Wesleyan University
      • Department of Psychology
      Middletown, CT, United States
    • Cornell University
      • Department of Psychiatry
      Ithaca, NY, United States
    • Oregon Health and Science University
      Portland, Oregon, United States
  • 2009
    • Rutgers, The State University of New Jersey
      • Graduate School of Applied and Professional Psychology
      New Brunswick, NJ, United States
    • University at Buffalo, The State University of New York
      Buffalo, New York, United States
    • University of California, San Francisco
      • Department of Anthropology, History and Social Medicine
      San Francisco, CA, United States
    • Haukeland University Hospital
      Bergen, Hordaland, Norway
  • 2007–2009
    • CSU Mentor
      Long Beach, California, United States
    • University Center Rochester
      Rochester, Minnesota, United States
    • Medical University of Vienna
      Wien, Vienna, Austria
    • University of California, Berkeley
      Berkeley, California, United States
  • 2002–2009
    • University of Wisconsin, Madison
      • Department of Psychiatry
      Madison, MS, United States
    • Loyola University Maryland
      • Department of Psychology
      Baltimore, MD, United States
    • St. John's University
      • Department of Psychology
      New York City, NY, United States
    • University of Minnesota Twin Cities
      • Department of Psychiatry
      Minneapolis, MN, United States
    • University of California, Los Angeles
      • Department of Family Medicine
      Los Angeles, CA, United States
  • 1979–2009
    • Stanford Medicine
      • • Division of Cardiovascular Medicine
      • • Department of Psychiatry and Behavioral Sciences
      • • Laboratory for the Study of Behavioral Medicine
      Stanford, California, United States
  • 2008
    • University of California, Irvine
      • Department of Pediatrics
      Irvine, CA, United States
    • University of Toronto
      • Department of Psychiatry
      Toronto, Ontario, Canada
  • 2006
    • University of Louisville
      • Department of Psychological and Brain Sciences
      Louisville, KY, United States
    • Palo Alto University
      Palo Alto, California, United States
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
  • 2005–2006
    • Northeastern University
      • Department of Applied Psychology
      Boston, MA, United States
  • 2003–2005
    • Boston University
      Boston, Massachusetts, United States
  • 2004
    • University of South Florida
      • School of Aging Studies
      Tampa, Florida, United States
    • Universität Trier
      • Department of Psychology
      Trier, Rhineland-Palatinate, Germany
  • 2003–2004
    • The Ohio State University
      • Department of Psychiatry
      Columbus, OH, United States
  • 2002–2003
    • Washington University in St. Louis
      • Department of Psychiatry
      Saint Louis, MO, United States
  • 2001
    • Purdue University
      • Department of Psychological Sciences
      West Lafayette, Indiana, United States
  • 1990
    • Palo Alto Medical Foundation
      Palo Alto, California, United States