Charles F Reynolds

University of Pittsburgh, Pittsburgh, PA, USA

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Publications (262)1344.81 Total impact

  • Article: Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies.
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    ABSTRACT: Late-life depression may increase the risk of incident dementia, in particular of Alzheimer's disease and vascular dementia. To conduct a systematic review and meta-analysis to evaluate the risk of incident all-cause dementia, Alzheimer's disease and vascular dementia in individuals with late-life depression in population-based prospective studies. A total of 23 studies were included in the meta-analysis. We used the generic inverse variance method with a random-effects model to calculate the pooled risk of dementia, Alzheimer's disease and vascular dementia in older adults with late-life depression. Late-life depression was associated with a significant risk of all-cause dementia (1.85, 95% CI 1.67-2.04, P<0.001), Alzheimer's disease (1.65, 95% CI 1.42-1.92, P<0.001) and vascular dementia (2.52, 95% CI 1.77-3.59, P<0.001). Subgroup analysis, based on five studies, showed that the risk of vascular dementia was significantly higher than for Alzheimer's disease (P = 0.03). Late-life depression is associated with an increased risk for all-cause dementia, vascular dementia and Alzheimer's disease. The present results suggest that it will be valuable to design clinical trials to investigate the effect of late-life depression prevention on risk of dementia, in particular vascular dementia and Alzheimer's disease.
    The British journal of psychiatry: the journal of mental science 05/2013; 202:329-35. · 6.62 Impact Factor
  • Article: Dynamic Prediction of Treatment Response in Late-Life Depression.
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    ABSTRACT: OBJECTIVE: To identify actionable predictors of remission to antidepressant pharmacotherapy in depressed older adults and to use signal detection theory to develop decision trees to guide clinical decision making. METHOD: We treated 277 participants with current major depression using open-label venlafaxine XR (up to 300 mg/day) for 12 weeks, in an NIMH-sponsored randomized, placebo-controlled augmentation trial of adjunctive aripiprazole. Multiple logistic regression and signal detection approaches identified predictors of remission in both completer and intent-to-treat samples. RESULTS: Higher baseline depressive symptom severity (odds ratio [OR]: 0.86, 95% confidence interval [CI]: 0.80-0.93; p <0.001), smaller symptom improvement during the first two weeks of treatment (OR: 0.96, 95% CI: 0.94-0.97; p <0.001), male sex (OR: 0.41 95% CI: 0.18-0.93; p = 0.03), duration of current episode ≥2 years (OR: 0.26, 95% CI: 0.12-0.57; p <0.001) and adequate past depression treatment (ATHF ≥3) (OR: 0.34, 95% CI: 0.16-0.74; p = 0.006) predicted lower probability of remission in the completer sample. Subjects with Montgomery Asberg (MADRS) decreasing by greater than 27% in the first 2 weeks and with baseline MADRS scores of less than 27 (percentile rank = 51) had the best chance of remission (89%). Subjects with small symptom decrease in the first 2 weeks with adequate prior treatment and younger than 75 years old had the lowest chance of remission (16%). CONCLUSION: Our results suggest the clinical utility of measuring pre-treatment illness severity and change during the first 2 weeks of treatment in predicting remission of late-life major depression.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 02/2013; · 3.35 Impact Factor
  • Article: Impaired Executive Function in Contemplated and Attempted Suicide in Late Life.
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    ABSTRACT: OBJECTIVE: Executive deficits may play an important role in late-life suicide. Yet, current evidence in this area is inconclusive and does not indicate whether these deficits are broadly associated with suicidal ideation or are specific to suicidal behavior. This study examined global cognition and specifically executive function impairments as correlates of suicidal ideation and suicidal behavior in depressed older adults, with the goal of extending an earlier preliminary study. DESIGN: Case-control study. SETTING: University-affiliated psychiatric hospital. PARTICIPANTS: All participants were age 60+: 83 depressed suicide attempters, 43 depressed individuals having suicidal ideation with a specific plan, 54 nonsuicidal depressed participants, and 48 older adults with no history of psychiatric disorders. MEASUREMENTS: Global cognitive function was assessed with Dementia Rating Scale (DRS) and executive function with Executive Interview (EXIT). RESULTS: Both suicide attempters and suicide ideators performed worse than the two comparison groups on the EXIT, with no difference between suicide attempters and suicide ideators. On the DRS total score, as well as on Memory and Attention subscales, suicide attempters and ideators and nonsuicidal depressed subjects performed similarly and were impaired relative to nonpsychiatric control subjects. Controlling for education, substance use disorders, and medication exposure did not affect group differences in performance on either the EXIT or the DRS. CONCLUSIONS: Executive deficits, captured with a brief instrument, are associated broadly with suicidal ideation in older depressed adults but do not appear to directly facilitate suicidal behavior. Our data are consistent with the idea that different vulnerabilities may operate at different stages in the suicidal process.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 02/2013; · 3.35 Impact Factor
  • Article: Economic Inequalities in the Effectiveness of a Primary Care Intervention for Depression and Suicidal Ideation.
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    ABSTRACT: BACKGROUND:: Economic disadvantage is associated with depression and suicide. We sought to determine whether economic disadvantage reduces the effectiveness of depression treatments received in primary care. METHODS:: We conducted differential-effects analyses of the Prevention of Suicide in Primary Care Elderly: Collaborative Trial, a primary-care-based randomized, controlled trial for late-life depression and suicidal ideation conducted between 1999 and 2001, which included 514 patients with major depression or clinically significant minor depression. RESULTS:: The intervention effect, defined as change in depressive symptoms from baseline, was stronger among persons reporting financial strain at baseline (differential effect size = -4.5 Hamilton Depression Rating Scale points across the study period [95% confidence interval = -8.6 to -0.3]). We found similar evidence for effect modification by neighborhood poverty, although the intervention effect weakened after the initial 4 months of the trial for participants residing in poor neighborhoods. There was no evidence of substantial differences in the effectiveness of the intervention on suicidal ideation and depression remission by economic disadvantage. CONCLUSIONS:: Economic conditions moderated the effectiveness of primary-care-based treatment for late-life depression. Financially strained individuals benefited more from the intervention; we speculate this was because of the enhanced treatment management protocol, which led to a greater improvement in the care received by these persons. People living in poor neighborhoods experienced only temporary benefit from the intervention. Thus, multiple aspects of economic disadvantage affect depression treatment outcomes; additional work is needed to understand the underlying mechanisms.
    Epidemiology (Cambridge, Mass.) 01/2013; 24(1):14-22. · 5.51 Impact Factor
  • Source
    Dataset: Reynolds etal 2012 Ann Rev Public Health
  • Article: Social inequalities in depression and suicidal ideation among older primary care patients.
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    ABSTRACT: PURPOSE: Depression and suicide are major public health concerns, and are often unrecognized among the elderly. This study investigated social inequalities in depressive symptoms and suicidal ideation among older adults. METHODS: Data come from 1,226 participants in PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial), a large primary care-based intervention trial for late-life depression. Linear and logistic regressions were used to analyze depressive symptoms and suicidal ideation over the 2-year follow-up period. RESULTS: Mean Hamilton Depression Rating Scale (HDRS) scores were significantly higher among participants in financial strain [regression coefficient (b) = 1.78, 95 % confidence interval (CI) = 0.67-2.89] and with annual incomes below $20,000 (b = 1.67, CI = 0.34-3.00). Financial strain was also associated with a higher risk of suicidal ideation (odds ratio = 2.35, CI = 1.38-3.98). CONCLUSIONS: There exist marked social inequalities in depressive symptoms and suicidal ideation among older adults attending primary care practices, the setting in which depression is most commonly treated. Our results justify continued efforts to understand the mechanisms generating such inequalities and to recognize and provide effective treatments for depression among high-risk populations.
    Social Psychiatry 09/2012; · 2.05 Impact Factor
  • Article: Early intervention to reduce the global health and economic burden of major depression in older adults.
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    ABSTRACT: Randomized trials for selective and indicated prevention of depression in both mixed-aged and older adult samples, conducted in high-income countries (HICs), show that rates of incident depression can be reduced by 20-25% over 1-2 years through the use of psychoeducational and psychological interventions designed to increase protective factors. Recurrence of major depression can also be substantially reduced through both psychological and psychopharmacological strategies. Additional research is needed, however, to address the specific issues of depression prevention in older adults in low- and middle-income countries (LMICs). The growing number of older adults globally, as well as workforce issues and the expense of interventions, makes it important to develop rational, targeted, and cost-effective risk-reduction strategies. In our opinion, one strategy to address these issues entails the use of lay health counselors (LHCs), a form of task shifting already shown to be effective in the treatment of common mental disorders in LMICs. We suggest in this review that the time is right for research into the translation of depression-prevention strategies for use in LMICs.
    Annual Review of Public Health 04/2012; 33:123-35. · 5.45 Impact Factor
  • Article: Social emotion recognition, social functioning, and attempted suicide in late-life depression.
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    ABSTRACT: : Lack of feeling connected and poor social problem solving have been described in suicide attempters. However, cognitive substrates of this apparent social impairment in suicide attempters remain unknown. One possible deficit, the inability to recognize others' complex emotional states has been observed not only in disorders characterized by prominent social deficits (autism-spectrum disorders and frontotemporal dementia) but also in depression and normal aging. This study assessed the relationship between social emotion recognition, problem solving, social functioning, and attempted suicide in late-life depression. DESIGN, PARTICIPANTS, MEASUREMENTS:: There were 90 participants: 24 older depressed suicide attempters, 38 nonsuicidal depressed elders, and 28 comparison subjects with no psychiatric history. We compared performance on the Reading the Mind in the Eyes test and measures of social networks, social support, social problem solving, and chronic interpersonal difficulties in these three groups. : Suicide attempters committed significantly more errors in social emotion recognition and showed poorer global cognitive performance than elders with no psychiatric history. Attempters had restricted social networks: they were less likely to talk to their children, had fewer close friends, and did not engage in volunteer activities, compared to nonsuicidal depressed elders and those with no psychiatric history. They also reported a pattern of struggle against others and hostility in relationships, felt a lack of social support, perceived social problems as impossible to resolve, and displayed a careless/impulsive approach to problems. : Suicide attempts in depressed elders were associated with poor social problem solving, constricted social networks, and disruptive interpersonal relationships. Impaired social emotion recognition in the suicide attempter group was related.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 03/2012; 20(3):257-65. · 3.35 Impact Factor
  • Article: A positive 2-item Patient Health Questionnaire depression screen among hospitalized heart failure patients is associated with elevated 12-month mortality.
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    ABSTRACT: Given the association of depression with poorer cardiac outcomes, an American Heart Association Science Advisory has advocated routine screening of cardiac patients for depression using the 2-item Patient Health Questionnaire (PHQ-2) "at a minimum." However, the prognostic value of the PHQ-2 among HF patients is unknown. We screened hospitalized HF patients (ejection fraction [EF] <40%) that staff suspected may be depressed with the PHQ-2, and then determined vital status at up to 12-months follow-up. At baseline, PHQ-2 depression screen-positive patients (PHQ-2+; n = 371), compared with PHQ-2 screen-negative patients (PHQ-2-; n = 100), were younger (65 vs 70 years) and more likely to report New York Heart Association (NYHA) functional class III/IV than class II symptoms (67% vs. 39%) and lower levels of physical and mental health-related quality of life (all P ≤ .002); they were similar in other characteristics (65% male, 26% mean EF). At 12 months, 20% of PHQ-2+ versus 8% of PHQ-2- patients had died (P = .007) and PHQ-2 status remained associated with both all-cause (hazard ratio [HR] 3.1, 95% confidence interval [CI] 1.4-6.7; P = .003) and cardiovascular (HR 2.7, 95% CI 1.1-6.6; P = .03) mortality even after adjustment for age, gender, EF, NYHA functional class, and a variety of other covariates. Among hospitalized HF patients, a positive PHQ-2 depression screen is associated with an elevated 12-month mortality risk.
    Journal of cardiac failure 03/2012; 18(3):238-45. · 3.25 Impact Factor
  • Article: Communication profiles of psychiatric residents and attending physicians in medication-management appointments: a quantitative pilot study.
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    ABSTRACT: The authors quantitatively examined differences in psychiatric residents' and attending physicians' communication profiles and voice tones. Audiotaped recordings of 49 resident-patient and 35 attending-patient medication-management appointments at four ambulatory sites were analyzed with the Roter Interaction Analysis System (RIAS). Nonparametric tests were used to compare differences in proportions of speech devoted to relationship-building, activating, and partnering in decision-making processes, and data-gathering/counseling/patient education. Differences in affect expressed by psychiatrists' voice tones were also examined. Residents' visits were twice as long as Attendings' visits (28.2 versus 14.1 minutes), and residents devoted a significantly greater proportion of their talk to relationship-building (23% versus 20%) and activating/partnering (36% versus 28%) aspects of communication, whereas Attendings devoted a greater proportion to biomedically-related data-gathering/counseling/patient education (31% versus 20%). Analysis of voice tones revealed that residents were perceived as sounding significantly friendlier and more sympathetic, versus Attendings, who were rated as sounding more dominant and rushed. These findings show distinct communication profiles and voice-tone differences. Future psychiatric communication research should address the influence of appointment length, psychiatrist/patient characteristics, and other potential confounders on psychiatrist-patient communication.
    Academic Psychiatry 03/2012; 36(2):96-103. · 0.81 Impact Factor
  • Article: Cognition in older adults with bipolar disorder versus major depressive disorder.
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    ABSTRACT: Bipolar disorder (BD) and major depressive disorder (MDD) are associated with cognitive dysfunction in older age during both acute mood episodes and remitted states. The purpose of this study was to investigate for the first time the similarities and differences in the cognitive function of older adults with BD and MDD that may shed light on mechanisms of cognitive decline. A total of 165 subjects with BD (n = 43) or MDD (n = 122), ages ≥ 65 years [mean (SD) 74.2 (6.2)], were assessed when euthymic, using comprehensive measures of cognitive function and cognitive-instrumental activities of daily living (C-IADLs). Test results were standardized using a group of mentally healthy individuals (n = 92) of comparable age and education level. Subjects with BD and MDD were impaired across all cognitive domains compared with controls, most prominently in Information Processing Speed/Executive Function. Despite the protective effects of having higher education and lower vascular burden, BD subjects were more impaired across all cognitive domains compared with MDD subjects. Subjects with BD and MDD did not differ significantly in C-IADLs. In older age, patients with BD have worse overall cognitive function than patients with MDD. Our findings suggest that factors intrinsic to BD appear to be related to cognitive deterioration and support the understanding that BD is associated with cognitive decline.
    Bipolar Disorders 03/2012; 14(2):198-205. · 5.29 Impact Factor
  • Article: Addressing both depression and pain in late life: the methodology of the ADAPT study.
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    ABSTRACT: To describe the methodology of the first NIH-funded clinical trial for seniors with comorbid depression and chronic low back pain. Randomized controlled effectiveness trial using stepped care methodology. Participants are ≥60 years old. Phase 1 (6 weeks) is open treatment with venlafaxine xr 150 mg/day and supportive management (SM). Response is 2 weeks of PHQ-9 ≤5 and at least 30% improvement in the average numeric rating scale for pain. Nonresponders progress to phase 2 (14 weeks) in which they are randomized to high-dose venlafaxine xr (up to 300 mg/day) with problem solving therapy for depression and pain (PST-DP) or high-dose venlafaxine xr and continued SM. Primary outcomes are the univariate pain and depression response and both observed and self-reported disability. Survival analytic techniques will be used, and the clinical effect size will be estimated with the number needed to treat. We hypothesize that self-efficacy for pain management will mediate response for subjects randomized to venlafaxine xr and PST-DP. Not applicable. The results of this trial will inform the care of these complex patients and further understanding of comorbid pain and depression in late life.
    Pain Medicine 02/2012; 13(3):405-18. · 2.35 Impact Factor
  • Article: Prognostic factors, course, and outcome of depression among older primary care patients: the PROSPECT study.
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    ABSTRACT: We sought to examine whether there are patterns of evolving depression symptoms among older primary care patients that are related to prognostic factors and long-term clinical outcomes. Primary care practices were randomly assigned to Usual Care or to an intervention consisting of a depression care manager offering algorithm-based depression care. In all, 599 adults 60 years and older meeting criteria for major depression or clinically significant minor depression were randomly selected. Longitudinal analysis via growth curve mixture modeling was carried out to classify patients according to the patterns of depression symptoms across 12 months. Depression diagnosis determined after a structured interview at 24 months was the long-term clinical outcome. Three patterns of change in depression symptoms over 12 months were identified: high persistent course (19.1% of the sample), high declining course (14.4% of the sample), and low declining course (66.5% of the sample). Being in the intervention condition was more likely to be associated with a course of high and declining depression symptoms than high and persistent depression symptoms (OR = 2.53, 95% CI [1.01, 6.37]). Patients with a course of high and persistent depression symptoms were much more likely to have a diagnosis of major depression at 24 months compared with patients with a course of low and declining depression symptoms (adjusted OR = 16.46, 95% CI [7.75, 34.95]). Identification of patients at particularly high risk of persistent depression symptoms and poor long-term clinical outcomes is important for the development and delivery of interventions.
    Aging and Mental Health 02/2012; 16(4):452-61. · 1.37 Impact Factor
  • Article: Insomnia and objectively measured sleep disturbances predict treatment outcome in depressed patients treated with psychotherapy or psychotherapy-pharmacotherapy combinations.
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    ABSTRACT: Insomnia and objectively measured sleep disturbances predict poor treatment outcomes in patients with major depressive disorder (MDD). However, prior research has utilized individual clinical trials with relatively small sample sizes and has focused on insomnia symptoms or objective measures, but not both. The present study is a secondary analysis that examines the degree to which insomnia, objective sleep disturbances, or their combination predicts depression remission following pharmacotherapy and/or psychotherapy treatment. Participants were 711 depressed (DSM criteria) patients drawn from 6 clinical trials. Remission status, defined as a score of ≤ 7 on the Hamilton Depression Rating Scale (HDRS) over 2 consecutive months, served as the primary outcome. Insomnia was assessed via the 3 sleep items on the HDRS. Objectively measured short sleep duration (total sleep time ≤ 6 hours) and prolonged sleep latency (> 30 minutes) or wakefulness after sleep onset (> 30 minutes) were derived from in-laboratory polysomnographic sleep studies. Logistic regression predicted the odds of nonremission according to insomnia, each of the objective sleep disturbances, or their combination, after adjusting for age, sex, treatment modality, and baseline depressive symptoms. Prolonged sleep latency alone (OR = 3.53; 95% CI, 1.28-9.73) or in combination with insomnia (OR = 2.11; 95% CI, 1.13-3.95) predicted increased risk of nonremission. In addition, insomnia and sleep duration individually and in combination were each associated with a significantly increased risk of nonremission (P values < .05). Findings suggest that objectively measured prolonged sleep latency and short sleep duration independently or in conjunction with insomnia are risk factors for poor depression treatment outcome.
    The Journal of Clinical Psychiatry 11/2011; 73(4):478-85. · 5.80 Impact Factor
  • Article: Course of depression and mortality among older primary care patients.
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    ABSTRACT: : Depression is a treatable illness that disproportionately places older adults at increased risk for mortality. : We sought to examine whether there are patterns of course of depression severity among older primary care patients that are associated with increased risk for mortality. : Our study was a secondary analysis of data from a practice-based randomized controlled trial within 20 primary care practices located in greater New York City, Philadelphia, and Pittsburgh. : The study sample consisted of 599 adults aged 60 years and older recruited from primary care settings. Participants were identified though a two-stage, age-stratified (60-74 years; older than 75 years) depression screening of randomly sampled patients. Severity of depression was assessed using the 24-item Hamilton Depression Rating Scale (HDRS). : Longitudinal analysis via growth curve mixture modeling was carried out to classify patterns of course of depression severity across 12 months. Vital status at 5 years was ascertained via the National Death Index Plus. : Three patterns of change in course of depression severity over 12 months were identified: 1) persistent depressive symptoms, 2) high but declining depressive symptoms, 3) low and declining depressive symptoms. After a median follow-up of 52.0 months, 114 patients had died. Patients with persistent depressive symptoms were more likely to have died compared with patients with a course of high but declining depressive symptoms (adjusted hazard ratio 2.32, 95% confidence interval [1.15-4.69]). : Persistent depressive symptoms signaled increased risk of dying in older primary care patients, even after adjustment for potentially influential characteristics such as age, smoking status, and medical comorbidity.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 10/2011; 20(10):895-903. · 3.35 Impact Factor
  • Article: Treating post-CABG depression with telephone-delivered collaborative care: does patient age affect treatment and outcome?
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    ABSTRACT: To determine the nature of telephone-delivered collaborative care intervention provided to patients younger than and older than 60 years experiencing clinically significant depressive symptoms after coronary artery bypass graft (CABG) surgery and whether patient age is related to response and remission rates and delivery of care at 8-month follow-up. : Exploratory post-hoc analysis of data collected in a randomized controlled trial (RCT). Seven Pittsburgh-area general hospitals. Fifty-eight depressed post-CABG patients younger than 60 and 92 comparable patients age 60 years and older randomized to the RCT's intervention arm. : Components of collaborative care provided to patients over the 8-month study period and Hamilton Rating Scale for Depression scores at 8-month follow-up to determine response and remission status. There were no differences in the cumulative 8-month rates at which the components of collaborative care were delivered to the two age groups. Similar response and remission rates were also achieved by these groups. Older and younger patients experiencing clinical depression after CABG surgery can be treated with comparable components of collaborative care, and both age groups will achieve clinical outcomes that do not differ significantly from each other.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 10/2011; 19(10):871-80. · 3.35 Impact Factor
  • Article: Anticipatory grief in new family caregivers of persons with mild cognitive impairment and dementia.
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    ABSTRACT: Anticipatory grief is the process of experiencing normal phases of bereavement in advance of the loss of a significant person. To date, anticipatory grief has been examined in family caregivers to individuals who have had Alzheimer disease (AD) an average of 3 to 6 years. Whether such grief is manifested early in the disease trajectory (at diagnosis) is unknown. Using a cross-sectional design, we examined differences in the nature and extent of anticipatory grief between family caregivers of persons with a new diagnosis of mild cognitive impairment (MCI, n=43) or AD (n=30). We also determined whether anticipatory grief levels were associated with caregiver demographics, caregiving burden, depressive symptoms, and marital quality. The mean anticipatory grief levels were high in the total sample, with AD caregivers endorsing significantly more anticipatory grief than MCI caregivers. In general, AD caregivers endorsed difficulty in functioning, whereas MCI caregivers focused on themes of "missing the person" they once knew. Being a female caregiver, reporting higher levels of objective caregiving burden, and higher depression levels each had independent, statistically significant relationships with anticipatory grief. Given these findings, family caregivers of individuals with mild cognitive deficits or a new AD diagnosis may benefit from interventions specifically addressing anticipatory grief.
    Alzheimer disease and associated disorders 09/2011; 26(2):159-65. · 2.88 Impact Factor
  • Article: Default-mode network connectivity and white matter burden in late-life depression.
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    ABSTRACT: The brain's default-mode network has been the focus of intense research. This study characterizes the default-mode network activity in late-life depression and the correlation of the default-mode network activity changes with the white-matter hyperintensities burden. We hypothesized that elderly depressed subjects would have altered default-mode network activity, which would correlate with the increased white-matter hyperintensities burden. Twelve depressed subjects (mean Hamilton Depression Rating Scale 19.8±4.1, mean age 70.5±4.9) and 12 non-depressed, comparison subjects (mean age 69±6.5) were included. Functional magnetic resonance imaging (fMRI) data were collected while subjects performed a low cognitive load, event-related task. We compared the default-mode network activity in these groups (including depressed subjects pre- and post-antidepressant treatment). We analyzed the resting connectivity patterns of the posterior cingulate cortex. Deconvolution was used to evaluate the correlation of resting-state connectivity scores with the white-matter hyperintensities burden. Compared with non-depressed elderly, depressed subjects pretreatment had decreased connectivity in the subgenual anterior cingulate cortex and increased connectivity in the dorsomedial prefrontal cortex and the orbito-frontal cortex. The abnormal connectivity was significantly correlated with the white-matter hyperintensities burden. Remitted elderly depressed subjects had improved functional connectivity compared to pretreatment, although alterations persisted in the anterior cingulate and the prefrontal cortex when remitted elderly depressed subjects were compared with non-depressed elderly. Our study provides evidence for altered default-mode network connectivity in late-life depression. The correlation between white-matter hyperintensities burden and default-mode network connectivity emphasizes the role of vascular changes in late-life depression etiopathogenesis.
    Psychiatry Research 08/2011; 194(1):39-46. · 2.52 Impact Factor
  • Article: fMRI correlates of white matter hyperintensities in late-life depression.
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    ABSTRACT: This study tests whether or not the structural white matter lesions that are characteristic of late-life depression are associated with alterations in the functional affective circuits of late-life depression. This study used an emotional faces paradigm that has been shown to engage the affective limbic brain regions. Thirty-three elderly depressed patients and 27 nondepressed comparison subjects participated in this study. The patients were recruited through the NIMH-sponsored Advanced Center for Interventions and Services Research for the Study of Late-Life Mood Disorders at the University of Pittsburgh Center for Bioethics and Health Law. Structural and functional MRI was used to assess white matter hyperintensity (WMH) burden and functional magnetic resonance imaging (fMRI) blood-oxygen-level-dependent (BOLD) response on a facial expression affective-reactivity task in both elderly participants with nonpsychotic and nonbipolar major depression (unmedicated) and nondepressed elderly comparison subjects. As expected, greater subgenual cingulate activity was observed in the depressed patients relative to the nondepressed comparison subjects. This same region showed greater task-related activity associated with a greater burden of cerebrovascular white matter change in the depressed group. Moreover, the depressed group showed a significantly greater interaction of WMH by fMRI activity effect than the nondepressed group. The observation that high WMH burden in late-life depression is associated with greater BOLD response on the affective-reactivity task supports the model that white matter ischemia in elderly depressed patients disrupts brain mechanisms of affective regulation and leads to limbic hyperactivation.
    American Journal of Psychiatry 07/2011; 168(10):1075-82. · 12.54 Impact Factor
  • Article: The default mode network in late-life anxious depression.
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    ABSTRACT: The aim of this exploratory study is to examine the default mode network (DMN) functional connectivity pattern in elderly depressed subjects with and without comorbid anxiety. Functional magnetic resonance imaging data were collected for 11 elderly depressed subjects with high comorbid anxiety and eight elderly depressed subjects with low anxiety. We analyzed the resting-connectivity patterns of the posterior cingulate cortex. We compared the DMN activity in the elderly depressed subjects with high versus low comorbid anxiety. Depressed elderly with high comorbid anxiety had increased functional connectivity in the posterior regions of the DMN and decreased functional connectivity in the anterior regions of the DMN. Elderly depressed subjects with high anxiety display a dissociative pattern of connectivity in the DMN when compared with elderly depressed subjects with low anxiety. These results suggest a unique biologic signature of the anxiety symptoms in the context of late-life depression.
    The American journal of geriatric psychiatry: official journal of the American Association for Geriatric Psychiatry 07/2011; 19(11):980-3. · 3.35 Impact Factor

Institutions

  • 1996–2013
    • University of Pittsburgh
      • • Department of Psychiatry
      • • School of Medicine
      • • Health and Community Systems
      Pittsburgh, PA, USA
  • 2005–2012
    • University of Pennsylvania
      • Department of Family Medicine and Community Health
      Philadelphia, PA, USA
  • 2008–2011
    • Washington University in St. Louis
      • Department of Psychiatry
      Saint Louis, MO, USA
    • Massachusetts General Hospital
      • Department of Psychiatry
      Boston, MA, USA
  • 2004–2011
    • Weill Cornell Medical College
      • Department of Psychiatry
      New York City, NY, USA
    • University of Cincinnati
      • Department of Emergency Medicine
      Cincinnati, OH, USA
  • 2010
    • University of California, San Diego
      • Department of Psychiatry
      San Diego, CA, USA
  • 2009
    • Washington School of Psychiatry
      Washington, D. C., DC, USA
    • RAND Corporation
      Arlington, WA, USA
    • North Shore-Long Island Jewish Health System
      • Department of Psychiatry Research
      New York City, NY, USA
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, MI, USA
  • 2008–2009
    • University of Toronto
      • Department of Psychiatry
      Toronto, Ontario, Canada
  • 2006
    • Nathan Kline Institute
      Orangeburg, NY, USA
    • Harvard University
      Boston, MA, USA
    • University Center Rochester
      • Department of Psychiatry
      Rochester, MN, USA
  • 2004–2005
    • Cornell University
      • Department of Psychiatry
      Ithaca, NY, USA