Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Depression: HELP
Articles by George S. Alexopoulos
Based on 80 articles published since 2008
||||

Between 2008 and 2019, G. S. Alexopoulos wrote the following 80 articles about Depression.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Editorial Neuroimaging in geriatric psychiatry. 2009

Smith, Gwenn S / Alexopoulos, George S. · ·Int J Geriatr Psychiatry · Pubmed #19593778.

ABSTRACT: -- No abstract --

2 Editorial Personalizing the care of geriatric depression. 2008

Alexopoulos, George S. · ·Am J Psychiatry · Pubmed #18593780.

ABSTRACT: -- No abstract --

3 Review Vascular depression and the death of Queen Victoria. 2018

Abrams, Robert C / Alexopoulos, George S. ·Division of Geriatrics and Palliative Medicine, Weill Cornell Medicine, New York, NY, USA. · Department of Psychiatry, Weill Cornell Medicine, New York, NY, USA. ·Int J Geriatr Psychiatry · Pubmed #30276875.

ABSTRACT: OBJECTIVES: The aim of this article was to examine relationships between the neurological events that were the immediate cause of the death of Queen Victoria and the late-life depression that preceded it. METHODS/DESIGN: The authors closely reviewed the surviving medical notes of Queen Victoria's personal physician, Sir James Reid, RESULTS: The depression that Queen Victoria experienced over the 5 months prior to her death and during her final 10 days from 13 January 1901 until 22 January likely had a vascular etiology. CONCLUSIONS: Although conclusions from this study are necessarily speculative given the lack of neuroimaging and other diagnostic tools available in 1901, it emerged that Queen Victoria had experienced early-onset depression followed in later life by an acute depressive episode associated with vascular risk factors and personal losses, a sequence also encountered by today's geriatricians. In addition, etiological connections between the Queen's early-onset and late-life depressions appeared probable. Underlined for contemporary practitioners are the suffering experienced by patients with vascular depression at the end of their lives, as well as the struggles of physicians like Sir James Reid to provide clinical wisdom and emotional support.

4 Review Amyloid Hypothesis: Is There a Role for Antiamyloid Treatment in Late-Life Depression? 2016

Mahgoub, Nahla / Alexopoulos, George S. ·Department of Psychiatry, Weill Cornell Medical College, White Plains, NY. · Department of Psychiatry, Weill Cornell Medical College, White Plains, NY. Electronic address: gsalexop@med.cornell.edu. ·Am J Geriatr Psychiatry · Pubmed #26946981.

ABSTRACT: Antidepressants have modest efficacy in late-life depression (LLD), perhaps because various neurobiologic processes compromise frontolimbic networks required for antidepressant response. We propose that amyloid accumulation is an etiologic factor for frontolimbic compromise that predisposes to depression and increases treatment resistance in a subgroup of older adults. In patients without history of depression, amyloid accumulation during the preclinical phase of Alzheimer disease (AD) may result in the prodromal depression syndrome that precedes cognitive impairment. In patients with early-onset depression, pathophysiologic changes during recurrent episodes may promote amyloid accumulation, further compromise neurocircuitry required for antidepressant response, and increase treatment resistance during successive depressive episodes. The findings that support the amyloid hypothesis of LLD are (1) Depression is a risk factor, a prodrome, and a common behavioral manifestation of AD; (2) amyloid deposition occurs during a long predementia period when depression is prevalent; (3) patients with lifetime history of depression have significant amyloid accumulation in brain regions related to mood regulation; and (4) amyloid deposition leads to neurobiologic processes, including vascular damage, neurodegeneration, neuroinflammation, and disrupted functional connectivity, that impair networks implicated in depression. The amyloid hypothesis of LLD is timely because availability of ligands allows in vivo assessment of amyloid in the human brain, a number of antiamyloid agents are relatively safe, and there is evidence that some antidepressants may reduce amyloid production. A model of LLD introducing the role of amyloid may guide the design of studies aiming to identify novel antidepressant approaches and prevention strategies of AD.

5 Review Diagnosis and treatment of depression and cognitive impairment in late life. 2015

Morimoto, Sarah Shizuko / Kanellopoulos, Dora / Manning, Kevin J / Alexopoulos, George S. ·Institute of Geriatric Psychiatry, Weill Cornell Medical College, White Plains, New York. · Department of Psychiatry, University of Connecticut Health Center, Farmington, Connecticut. ·Ann N Y Acad Sci · Pubmed #25655026.

ABSTRACT: Cognitive impairment in late-life depression is prevalent, disabling, and heterogeneous. Although mild cognitive impairment in depression does not usually progress to dementia, accurate assessment of cognition is vital to prognosis and treatment planning. For example, executive dysfunction often accompanies late-life depression, influences performance across cognitive domains, and is associated with poor antidepressant treatment outcomes. Here, we review how assessment can capture dysfunction across cognitive domains and discuss cognitive trajectories frequently observed in late-life depression in the context of the neurobiology of this disorder. We also review the efficacy of a sample of interventions tailored to specific cognitive profiles.

6 Review Depression and anxiety in patients with COPD. 2014

Yohannes, Abebaw M / Alexopoulos, George S. ·Dept of Health Professions, The Research Institute for Health and Social Care, Manchester Metropolitan University, Manchester, UK. Weill Cornell Institute of Geriatric Psychiatry, Weill Cornell Medical College, White Plains, NY, USA A.yohannes@mmu.ac.uk. · Dept of Health Professions, The Research Institute for Health and Social Care, Manchester Metropolitan University, Manchester, UK. Weill Cornell Institute of Geriatric Psychiatry, Weill Cornell Medical College, White Plains, NY, USA. ·Eur Respir Rev · Pubmed #25176970.

ABSTRACT: Under-recognised and untreated depression and anxiety symptoms have deleterious effects on physical functioning and social interaction increasing fatigue and healthcare utilisation in patients with chronic obstructive pulmonary disease (COPD). Depression and anxiety are challenging to identify and treat because their symptoms often overlap with those of COPD. The cause(s) of depression and anxiety symptoms are multifactorial and include behavioural, social and biological factors. Less than one-third of COPD patients with comorbid depression or anxiety symptoms are receiving appropriate treatment. Factors that contribute to the lack of provision of treatment are varied, they include patient perceived barriers, for example lack of knowledge and reluctance to receive antidepressant drug therapy; poor treatment compliance and lack of a standardised diagnostic approach; and scarcity of adequate resources for mental health treatment. The evidence for the efficacy of antidepressant drug therapy in patients with COPD with comorbid depression and anxiety is inconclusive. There are some promising findings regarding pulmonary rehabilitation, psychological therapy and the collaborative care model in reducing depression and anxiety symptoms in patients with COPD, but these findings are limited by short-term follow-up periods. Further work is required to examine the efficacy of these interventions in randomised controlled trials with larger samples and long-term follow-up.

7 Review Pharmacological treatment of depression in older patients with chronic obstructive pulmonary disease: impact on the course of the disease and health outcomes. 2014

Yohannes, A M / Alexopoulos, G S. ·Department of Health Professions, Research Institute for Health and Social Care, Manchester Metropolitan University, Manchester, M13 0JA, UK, a.yohannes@mmu.ac.uk. ·Drugs Aging · Pubmed #24902934.

ABSTRACT: Over 40 % of older chronic obstructive pulmonary disease (COPD) patients suffer from clinically significant depressive symptoms, which may interfere with their daily activities. Untreated depression may increase physical disability, social isolation, hopelessness and healthcare utilization. This review examined the impact of depression on the course of COPD, and the efficacy of antidepressant drug therapy and its implications for clinical practice. The efficacy of antidepressants in published trials in patients with COPD has been inconclusive. Specifically, there has been no clear evidence that antidepressants can induce remission of depression or ameliorate dyspnoea or physiological indices of COPD. Both selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepressant (TCA) studies conducted in depressed COPD patients have been significantly limited by methodological weaknesses including small sample size, sample heterogeneity and variability in the scales used to diagnose and monitor the treatment of depression. For this reason, it remains unclear which SSRIs or TCAs should be favoured in the treatment of depressed COPD patients and what are appropriate dosages and duration ranges. Simply offering antidepressant drugs to older depressed COPD patients is unlikely to improve their condition. Promising treatment strategies such as a collaborative treatment approach and cognitive behavioural therapy should be considered for depressed COPD patients, with or without antidepressant drug therapy. Further studies are needed, including large, randomized, controlled trials with long-term follow-up, to examine the efficacy of antidepressants in patients with COPD.

8 Review Cognitive deficits in geriatric depression: clinical correlates and implications for current and future treatment. 2013

Morimoto, Sarah Shizuko / Alexopoulos, George S. ·Department of Psychiatry, Institute of Geriatric Psychiatry, Weill Cornell Medical College, 21 Bloomingdale Road, White Plains, NY 10605, USA. Electronic address: ssm9006@med.cornell.edu. ·Psychiatr Clin North Am · Pubmed #24229654.

ABSTRACT: The purpose of this article is to identify the cognitive deficits commonly associated with geriatric depression and describe their clinical significance. The complex relationship between geriatric depression and dementia is summarized and possible shared mechanisms discussed. Evidence regarding whether the cognitive deficits in depression may be mitigated with medication or with computerized cognitive remediation is presented.

9 Review The vascular depression hypothesis: mechanisms linking vascular disease with depression. 2013

Taylor, W D / Aizenstein, H J / Alexopoulos, G S. ·Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University, Nashville, TN 37212, USA. Warren.d.taylor@vanderbilt.edu ·Mol Psychiatry · Pubmed #23439482.

ABSTRACT: The 'Vascular Depression' hypothesis posits that cerebrovascular disease may predispose, precipitate or perpetuate some geriatric depressive syndromes. This hypothesis stimulated much research that has improved our understanding of the complex relationships between late-life depression (LLD), vascular risk factors, and cognition. Succinctly, there are well-established relationships between LLD, vascular risk factors and cerebral hyperintensities, the radiological hallmark of vascular depression. Cognitive dysfunction is common in LLD, particularly executive dysfunction, a finding predictive of poor antidepressant response. Over time, progression of hyperintensities and cognitive deficits predicts a poor course of depression and may reflect underlying worsening of vascular disease. This work laid the foundation for examining the mechanisms by which vascular disease influences brain circuits and influences the development and course of depression. We review data testing the vascular depression hypothesis with a focus on identifying potential underlying vascular mechanisms. We propose a disconnection hypothesis, wherein focal vascular damage and white matter lesion location is a crucial factor, influencing neural connectivity that contributes to clinical symptomatology. We also propose inflammatory and hypoperfusion hypotheses, concepts that link underlying vascular processes with adverse effects on brain function that influence the development of depression. Testing such hypotheses will not only inform the relationship between vascular disease and depression, but also provide guidance on the potential repurposing of pharmacological agents that may improve LLD outcomes.

10 Review Neuroplasticity-based computerized cognitive remediation for geriatric depression. 2012

Morimoto, Sarah Shizuko / Wexler, Bruce E / Alexopoulos, George S. ·Department of Psychiatry, Institute of Geriatric Psychiatry, Weill Cornell Medical College, White Plains, NY, USA. ssm9006@med.cornell.edu ·Int J Geriatr Psychiatry · Pubmed #22451346.

ABSTRACT: OBJECTIVE: This article describes a novel treatment model designed to target specific neurocognitive deficits in geriatric depression with neuroplasticity-based computerized cognitive remediation (NBCCR). METHOD: The recent National Institute of Mental Health (NIMH) report "From Discovery to Cure" calls for studies focusing on mechanisms of treatment response with the goal of arriving at new interventions for those who do not respond to existing treatments. We describe the process that led to the identification of specific executive deficits and their underlying neurobiology, as well as the rationale for targeting these symptoms as a part of a strategy intended to improve both executive dysfunction and depression. We then propose a strategy for further research in this emerging area. RESULTS AND CONCLUSIONS: Despite significant developments, conventional antidepressant treatments leave many older adults still depressed and suffering. Psychotherapy may be effective in some depressed elders, although a recent review concluded that none of the available treatment studies meets stringent criteria for efficacy in the acute treatment of geriatric depression. Appropriately developed and targeted NBCCR, has the potential to serve as a novel treatment intervention for geriatric depression. Pathophysiological changes associated with executive dysfunction may be an appropriate target for NBCCR. Examining both behavioral changes and indices of structural integrity and functional change of networks related to cognitive and emotional regulation may lead to a novel treatment and elucidate the role of specific cerebral networks in geriatric depression.

11 Review Immunity, aging, and geriatric depression. 2011

Morimoto, Sarah Shizuko / Alexopoulos, George S. ·Weill Cornell Institute of Geriatric Psychiatry, 21 Bloomingdale Road, White Plains, NY 10605, USA. ·Psychiatr Clin North Am · Pubmed #21536167.

ABSTRACT: Inflammatory processes are likely to play a causal role in geriatric depression. Geriatric depression occurs in the context of illnesses in which inflammatory processes are part of the pathogenesis. Both aging and depression are associated with immune responses, and the connectivity among mood-regulating structures may be modulated by inflammatory responses. Geriatric depression exacerbates the symptoms of comorbid disorders. Geriatric depression often occurs in persons exposed to chronic stress, a state precipitating geriatric depression and triggering proinflammatory responses. The successful treatment of comorbid conditions that increase central nervous system inflammatory responses has general health benefits and should be part of clinical practice.

12 Review The inflammation hypothesis in geriatric depression. 2011

Alexopoulos, George S / Morimoto, Sarah Shizuko. ·Weill Cornell Institute of Geriatric Psychiatry, White Plains, New York, USA. gsalexop@med.cornell.edu. ·Int J Geriatr Psychiatry · Pubmed #21370276.

ABSTRACT: BACKGROUND: A large body of research has focused on "mediating mechanisms" and predisposing brain abnormalities to geriatric depression, but little is known about its etiology. This paper examines whether age-related and comorbid disease-related immune deregulation is an etiologic contributor to geriatric depression. METHODS: This article reviews findings on neuroinflammation during the aging process and depression as well as studies of anti-inflammatory actions of classical antidepressants and antidepressant actions of anti-inflammatory agents. RESULTS: Aging results in increased peripheral immune responses, impaired peripheral-CNS immune communication, and a shift of the CNS into a pro-inflammatory state. These exaggerated and prolonged immune responses may lead to changes in the function of emotional and cognitive networks pertinent to geriatric depression and to behavioral changes reminiscent of the depressive and cognitive symptoms of geriatric depression. Some antidepressants may reduce the expression of inflammation markers. Limited data suggest that some anti-inflammatory agents may have antidepressant properties. CONCLUSIONS: A synthesis of available findings suggests that aging-related and comorbid disease-related inflammatory processes may promote changes in the neural systems predisposing to geriatric depression or facilitating metabolic changes that mediate depressive syndromes. The "inflammation hypothesis" in geriatric depression cannot be tested in its entirety, but it can lead to testable hypotheses and data on mechanisms by which inflammatory processes promote geriatric depression. The significance of such an effort is that it may lead to a novel treatment development model bringing to bear recent advances of anti-inflammatory pharmacology to the treatment of depressed elderly patients.

13 Review Treating depression in disabled, low-income elderly: a conceptual model and recommendations for care. 2010

Areán, Patricia A / Mackin, Scott / Vargas-Dwyer, Eleanor / Raue, Patrick / Sirey, Jo Anne / Kanellopolos, Dora / Alexopoulos, George S. ·Weill Cornell Institute of Geriatric Psychiatry, Weill Cornell Medical College, University of California, San Francisco, USA. pata@lppi.ucsf.edu ·Int J Geriatr Psychiatry · Pubmed #20602424.

ABSTRACT: BACKGROUND: The treatment of depression in low-income older adults who live in poverty is complicated by several factors. Poor access to resources, disability, and mild cognitive impairment are the main factors that moderate treatment effects in this population. Interventions that not only address the depressive syndrome but also manage social adversity are sorely needed to help this patient population recover from depression. METHODS: This paper is a literature review of correlates of depression in late life. In the review we propose a treatment model that combines case management (CM) to address social adversity with problem solving treatment (PST) to address the depressive syndrome. RESULTS: We present the case of Mr Z, an older gentleman living in poverty who is also depressed and physically disabled. In this case we illustrate how the combination of CM and PST can work together to ameliorate depression. CONCLUSIONS: The combination of age, disability, and social adversity complicates the management and treatment of depression. CM and PST are interventions that work synergistically to overcome depression and manage social problems.

14 Review Psychotherapy for late-life depression. 2010

Alexopoulos, George S. ·Department of Psychiatry, Weill Medical College of Cornell University and New York Presbyterian Hospital, New York, USA. ·J Clin Psychiatry · Pubmed #20573323.

ABSTRACT: Few data on treating geriatric patients with depression are available. In 2001, a panel of experts reached consensus on preferred treatment strategies for older adults with depression, and guidelines were published to aid clinicians in treating these patients. This activity reviews the recommendations and provides updated evidence on the use of psychotherapy in the treatment of older adults with depression, including the development of a problem-solving therapy designed to increase patient functioning and address symptoms seen in depressed patients with executive dysfunction.

15 Review A model for intervention research in late-life depression. 2009

Alexopoulos, George S / Bruce, Martha L. ·Weill Cornell Institute of Geriatric Psychiatry, Weill Cornell Medical College, 21 Bloomingdale Road, White Plains, NY, USA. gsalexop@med.cornell.edu ·Int J Geriatr Psychiatry · Pubmed #19391184.

ABSTRACT: OBJECTIVE: To serve as a conceptual map of the role of new interventions designed to reduce the burden of late-life depression. METHODS: We identified three needs to be addressed by intervention research: (1) the need for novel interventions given that the existing treatments leave many older adults depressed and disabled; (2) the need for procedures enabling community-based agencies to offer interventions of known efficacy with fidelity; and (3) the need to increase access of depressed older adults to care. RESULTS: Our model orders novel interventions according to their role in serving depressed older adults and according to their position in the efficacy, effectiveness, implementation, and dissemination testing continuum. We describe three interventions designed by our institute to exemplify intervention research at different level of the model. A common element is that each intervention personalizes care both at the level of the individuals served and the level of community agencies providing care. To this end, each intervention is designed to accommodate the strengths and limitations of both patients and agencies and introduces changes in the patients' environment and community agencies needed in order to assimilate the new intervention. CONCLUSIONS: We suggest that this model provides conceptual guidance on how to shorten the testing cycle and bring urgently needed novel treatments and implementation approaches to the community. While replication studies are important, propose that most of the support should be directed to those projects that take rational risks, and after adequate preliminary evidence, make the next step along the testing continuum.

16 Review Problem solving therapy for the depression-executive dysfunction syndrome of late life. 2008

Alexopoulos, George S / Raue, Patrick J / Kanellopoulos, Dora / Mackin, Scott / Arean, Patricia A. ·Department of Psychiatry, Weill Cornell Medical College, White Plains, NY 10605, USA. gsalexop@med.cornell.edu ·Int J Geriatr Psychiatry · Pubmed #18213605.

ABSTRACT: BACKGROUND: The 'depression executive dysfunction syndrome' afflicts a considerable number of depressed elderly patients and may be resistant to conventional pharmacotherapy. Non-pharmacological approaches addressing their behavioral deficits may reduce disability and experienced stress and improve depression. METHODS: This paper focuses on problem solving therapy (PST) because it targets concrete problems that can be understood by patients with executive dysfunction and trains patients to address them using an easy to comprehend structured approach. RESULTS: We suggest that PST is a suitable treatment for patients with the depression-executive dysfunction syndrome because it has been found effective in uncomplicated geriatric major depression and in other psychiatric disorders accompanied by severe executive dysfunction. Furthermore, PST can address specific clinical features of depressed patients with executive dysfunction, especially when modified to address difficulties with affect regulation, initiation and perseveration. CONCLUSIONS: A preliminary study suggests that appropriately modified PST improves problem solving skills, depression and disability in elderly patients with the depression-executive dysfunction syndrome of late life. If these findings are confirmed, PST may become a therapeutic option for a large group of depressed elderly patients likely to be drug resistant.

17 Clinical Trial Comparing engage with PST in late-life major depression: a preliminary report. 2015

Alexopoulos, George S / Raue, Patrick J / Kiosses, Dimitris N / Seirup, Joanna K / Banerjee, Samprit / Arean, Patricia A. ·Weill Cornell Institute of Geriatric Psychiatry, White Plains, NY. Electronic address: gsalexop@med.cornell.edu. · Weill Cornell Institute of Geriatric Psychiatry, White Plains, NY. · Department of Psychiatry, University of California, San Francisco, CA. ·Am J Geriatr Psychiatry · Pubmed #25081818.

ABSTRACT: OBJECTIVE: The complexity of psychotherapies has been a barrier to community implementation. We used the Research Domain Criteria consensus as a guide to develop Engage, a streamlined, neurobiology-based psychotherapy for late-life depression that may match the skill set of practicing clinicians. This proof of concept study tested the hypotheses that Engage is bioequivalent to Problem Solving Therapy (PST) in reducing depressive symptoms, inducing remission, and ameliorating disability. METHODS: Engage assumes that abnormal function of the positive valence systems fuels depression and uses "reward exposure" (engagement in meaningful, rewarding activities) as its principal intervention. Negativity bias, apathy, and emotional dysregulation are expressions of abnormalities in the negative valence, arousal and regulatory, and cognitive control systems, respectively. Engage targets each of them with simple interventions only if they interfere with reward exposure. We treated openly, with 9 weekly sessions of Engage, 39 older adults with unipolar major depression. We compared their course of depression (HAM-D), remission rate (HAM-D<10), and disability (WHODAS) with those of a historical comparison group (N = 97) treated with 9 weekly sessions of PST. RESULTS: Community social workers and research therapists required one third as much training time in Engage as in PST. Engage was non-inferior to PST in reducing HAM-D and WHODAS. Remission rates for Engage at 6 and 9 weeks were 18.2% and 41.1%, respectively. The corresponding figures for PST were 13.7% and 35.0%, respectively. CONCLUSION: These initial observations suggest that Engage has comparable efficacy with PST in reducing depressive symptoms and disability and warrants a randomized controlled trial.

18 Clinical Trial Neuroplasticity-based computerized cognitive remediation for treatment-resistant geriatric depression. 2014

Morimoto, Sarah Shizuko / Wexler, Bruce E / Liu, Jiacheng / Hu, Willie / Seirup, Joanna / Alexopoulos, George S. ·Weill Cornell Medical College, Institute of Geriatric Psychiatry, New York, New York 10605, USA. · Department of Psychiatry, Yale Medical School, New Haven, Connecticut 06519, USA. · 1] Department of Psychiatry, Yale Medical School, New Haven, Connecticut 06519, USA [2] Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China. ·Nat Commun · Pubmed #25093396.

ABSTRACT: Executive dysfunction (ED) in geriatric depression (GD) is common, predicts poor clinical outcomes and often persists despite remission of symptoms. Here we develop a neuroplasticity-based computerized cognitive remediation-geriatric depression treatment (nCCR-GD) to target ED in GD. Our assumption is that remediation of these deficits may modulate the underlying brain network abnormalities shared by ED and depression. We compare nCCR-GD to a gold-standard treatment (escitalopram: 20 mg per 12 weeks) in 11 treatment-resistant older adults with major depression; and 33 matched historical controls. We find that 91% of participants complete nCCR-GD. nCCR-GD is equally as effective at reducing depressive symptoms as escitalopram but does so in 4 weeks instead of 12. In addition, nCCR-GD improves measures of executive function more than the escitalopram. We conclude that nCCR-GD may be equally effective as escitalopram in treating GD. In addition, nCCR-GD participants showed greater improvement in executive functions than historical controls treated with escitalopram.

19 Clinical Trial Executive function and short-term remission of geriatric depression: the role of semantic strategy. 2011

Morimoto, Sarah Shizuko / Gunning, Faith M / Murphy, Christopher F / Kanellopoulos, Dora / Kelly, Robert E / Alexopoulos, George S. ·Weill Cornell Medical College, Department of Psychiatry, Institute of Geriatric Psychiatry, White Plains, NY 10605, USA. ·Am J Geriatr Psychiatry · Pubmed #20808124.

ABSTRACT: BACKGROUND: This study tested the hypothesis that use of semantic organizational strategy in approaching the Mattis Dementia Rating Scale (MDRS) complex verbal initiation/perseveration (CV I/P) task, a test of semantic fluency, is the function specifically associated with remission of late-life depression. METHOD: Seventy elders with major depression participated in a 12-week escitalopram treatment trial. Neuropsychologic performance was assessed at baseline after a 2-week drug washout period. Patients with a Hamilton Depression Rating Scale Score ≤7 for 2 consecutive weeks and who no longer met Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were considered to be remitted. Cox's proportional hazards survival analysis was used to examine the relationship between subtests of the I/P, other neuropsychologic domains, and remission rate. Participants' performance on the CV I/P subscale was coded for perseverations, and use of semantic strategy. RESULTS: The relationship between the performance on the CV I/P subscale and remission rate was significant. No other subtest of the MDRS I/P evidenced this association. There was no significant relationship between speed, confrontation naming, verbal memory, or perseveration with remission rate. Remitters' use of verbal strategy was significantly greater than nonremitters. CONCLUSIONS: Geriatric depressed patients who showed decrements in performance on a semantic fluency task showed poorer remission rates than those who showed adequate performance on this measure. Executive impairment in verbal strategy explained performance. This finding supports the concept that executive functioning exerts a "top down" effect on other basic cognitive processes, perhaps as a result of frontostriatal network dysfunction implicated in geriatric depression.

20 Clinical Trial Microstructural white matter abnormalities and remission of geriatric depression. 2008

Alexopoulos, George S / Murphy, Christopher F / Gunning-Dixon, Faith M / Latoussakis, Vassilios / Kanellopoulos, Dora / Klimstra, Sibel / Lim, Kelvin O / Hoptman, Matthew J. ·Weill Cornell Institute of Geriatric Psychiatry, Weill Cornell Medical College, New York, NY, USA. gsalexop@med ·Am J Psychiatry · Pubmed #18172016.

ABSTRACT: OBJECTIVE: White matter abnormalities may interfere with limbic cortical balance and lead to chronic depressive syndromes. The authors used diffusion tensor imaging to test the hypothesis that depressed elders who fail to achieve remission have microstructural white matter abnormalities in cortico-striato-limbic networks implicated in geriatric depression. METHOD: The subjects were nondemented individuals with nonpsychotic major depression. After a 2-week placebo period, those subjects who had a Hamilton Depression Rating Scale (HAM-D) score of 18 or greater received escitalopram, 10 mg daily, for 12 weeks. Remission was defined as a HAM-D score of 7 or below for 2 consecutive weeks. Diffusion tensor imaging was performed at a 1.5 Tesla scanner, and voxel-based analysis of fractional anisotropy was conducted using age as the covariate. RESULTS: Subjects who failed to achieve remission (N=23) had lower fractional anisotropy in multiple frontal limbic brain areas, including the rostral and dorsal anterior cingulate, dorsolateral prefrontal cortex, genu of the corpus callosum, white matter adjacent to the hippocampus, multiple posterior cingulate cortex regions, and insular white matter, relative to those who achieved remission (N=25). In addition, lower fractional anisotropy was detected in the neostriatum and midbrain as well as select temporal and parietal regions. CONCLUSIONS: Lower fractional anisotropy in distributed cerebral networks is associated with poor antidepressant response of geriatric depression and may represent a neuroanatomical substrate that predisposes to this disorder.

21 Article White matter abnormalities predict residual negative self-referential thinking following treatment of late-life depression with escitalopram: A preliminary study. 2019

Victoria, Lindsay W / Alexopoulos, George S / Ilieva, Irena / Stein, Aliza T / Hoptman, Matthew J / Chowdhury, Naib / Respino, Matteo / Morimoto, Sarah Shizuko / Kanellopoulos, Dora / Avari, Jimmy N / Gunning, Faith M. ·Weill Cornell Institute of Geriatric Psychiatry, Department of Psychiatry, Weill Cornell Medicine, 21 Bloomingdale Road, White Plains, NY, United States. Electronic address: liv3002@med.cornell.edu. · Weill Cornell Institute of Geriatric Psychiatry, Department of Psychiatry, Weill Cornell Medicine, 21 Bloomingdale Road, White Plains, NY, United States. · Department of Psychology, University of Texas at Austin, Austin, TX, United States. · Schizophrenia Research Division, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY, United States; Department of Psychiatry, New York University School of Medicine, New York, NY, United States. · Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, United States. ·J Affect Disord · Pubmed #30236759.

ABSTRACT: BACKGROUND: Negative self-referential thinking is a common symptom of depression associated with poor treatment response. In late-life depression, white matter abnormalities may contribute to negative self-referential thoughts following antidepressant treatment. We investigated the association of fractional anisotropy (FA) in select regions of the negative valence system (NVS) with residual negative self-referential thoughts following treatment with escitalopram for late-life depression. METHODS: The participants were older adults with major depression and psychiatrically normal controls. Depressed participants received 12 weeks of treatment with escitalopram. To assess self-referential thinking, participants completed a Trait Adjective Task at baseline and at week 12. Baseline MRI scans included a diffusion imaging sequence for FA analyses. RESULTS: Participants with late-life depression differed from controls on all performance measures of the Trait Adjective Task at baseline and at 12 weeks. Depressed participants endorsed fewer negative personality traits and more positive personality traits at week 12 compared to baseline. Lower FA in the dorsal anterior cingulate and in the uncinate fasciculus in depressed participants was correlated with residual negative self-referential thinking (e.g., more endorsed negative adjectives, fewer rejected negative adjectives) at treatment end. LIMITATIONS: The sample size is modest so the findings are preliminary. FA analyses were restricted to predetermined regions. CONCLUSIONS: Negative self-referential thinking improved in depressed older adults following 12 weeks of treatment with escitalopram. Baseline FA in select white matter regions of the NVS was associated with residual negative self-referential thinking. These findings may help identify treatment targets for residual negative self-referential thoughts.

22 Article Resting state functional connectivity in patients with remitted psychotic depression: A multi-centre STOP-PD study. 2018

Neufeld, Nicholas H / Mulsant, Benoit H / Dickie, Erin W / Meyers, Barnett S / Alexopoulos, George S / Rothschild, Anthony J / Whyte, Ellen M / Hoptman, Matthew J / Nazeri, Arash / Downar, Jonathan / Flint, Alastair J / Voineskos, Aristotle N. ·Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, 250 College Street, Toronto, ON M5T 1R8, Canada; Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada. · Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada. · Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, 250 College Street, Toronto, ON M5T 1R8, Canada; Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada. · Weill Cornell Medical College, 21 Bloomingdale Road, White Plains, NY 10605, USA. · University of Massachusetts Medical School and UMass Memorial Medical Centre, 55 Lake Avenue North, Worcester, MA 01655, USA. · University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. · Nathan Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, NY 10962, USA; Department of Psychiatry, NYU School of Medicine, 550 First Avenue, New York, NY 10016, USA; Department of Psychology, CUNY Graduate Centre, 365 Fifth Avenue, New York, NY 10016, USA. · Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, 250 College Street, Toronto, ON M5T 1R8, Canada; Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Mallinckrodt Institute of Radiology, Washington University School of Medicine, 510 South Kingshighway Boulevard, Saint Louis, MO 63110, USA. · Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada; University Health Network, 200 Elizabeth Street, Toronto, ON M5G 2C4, Canada. · Kimel Family Translational Imaging-Genetics Laboratory, Research Imaging Centre, 250 College Street, Toronto, ON M5T 1R8, Canada; Campbell Family Mental Health Research Institute, 250 College Street, Toronto, ON M5T 1R8, Canada; Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada. Electronic address: Aristotle.Voineskos@camh.ca. ·EBioMedicine · Pubmed #30287158.

ABSTRACT: BACKGROUND: There is paucity of neurobiological knowledge about major depressive disorder with psychotic features ("psychotic depression"). This study addresses this knowledge gap by using resting state functional magnetic resonance imaging (R-fMRI) to compare functional connectivity in patients with psychotic depression and healthy controls. METHODS: We scanned patients who participated in a randomized controlled trial as well as healthy controls. All patients achieved remission from depressive and psychotic symptoms with sertraline and olanzapine. We employed Independent Component Analysis in independent samples to isolate the default mode network (DMN) and compared patients and controls. FINDINGS: The Toronto sample included 28 patients (mean [SD], age 56·2 [13·7]) and 39 controls (age 55·1 [13·5]). The Replication sample included 29 patients (age 56·1 [17·7]) and 36 controls (age 48·3 [17·9]). Patients in the Toronto sample demonstrated decreased between-network functional connectivity between the DMN and bilateral insular, somatosensory/motor, and auditory cortices with peak activity in the right planum polare (t = 4·831; p = 0·001, Family Wise Error (FWE) corrected). A similar pattern of between-network functional connectivity was present in our Replication sample with peak activity in the right precentral gyrus (t = 4·144; p = 0·003, FWE corrected). INTERPRETATION: Remission from psychotic depression is consistently associated with an absence of increased DMN-related functional connectivity and presence of decreased between-network functional connectivity. Future research will evaluate this abnormal DMN-related functional connectivity as a potential biomarker for treatment trajectories. FUNDING: National Institute of Mental Health.

23 Article Reward learning impairment and avoidance and rumination responses at the end of Engage therapy of late-life depression. 2018

Victoria, Lindsay W / Gunning, Faith M / Bress, Jennifer N / Jackson, Danielle / Alexopoulos, George S. ·Weill Cornell Institute of Geriatric Psychiatry, Department of Psychiatry, Weill Cornell Medicine, White Plains, NY, USA. ·Int J Geriatr Psychiatry · Pubmed #29573471.

ABSTRACT: OBJECTIVES: This study examined the association between reward processing, as measured by performance on the probabilistic reversal learning (PRL) task and avoidance/rumination in depressed older adults treated with Engage, a psychotherapy that uses "reward exposure" to increase behavioral activation. METHODS: Thirty older adults with major depression received 9 weeks of Engage treatment. At baseline and treatment end, the 24-item Hamilton Depression Rating Scale (HAM-D) was used to assess depression severity and the Behavioral Activation for Depression Scale (BADS) to assess behavioral activation and avoidance/rumination. Participants completed the PRL task at baseline and at treatment end. The PRL requires participants to learn stimulus-reward contingencies through trial and error, and switch strategies when the contingencies unexpectedly change. RESULTS: At the end of Engage treatment, the severity of depression was lower (HAM-D: t(19) = -7.67, P < .001) and behavioral activation was higher (BADS: t(19) = 2.23, P = .02) compared to baseline. Response time following all switches (r(19) = -0.63, P = .003) and error switches (r(19) = -0.57, P = .01) at baseline was negatively associated with the BADS avoidance/rumination subscale score at the end of Engage treatment. CONCLUSIONS: Impaired reward learning, evidenced by slower response following all switches and error switches, contributes to avoidant, ruminative behavior at the end of Engage therapy even when depression improves. Understanding reward processing abnormalities of avoidance and rumination may improve the timing and targeting of interventions for these symptoms, whose persistence compromises quality of life and increases the risk of depression relapse.

24 Article "Engage" therapy: Prediction of change of late-life major depression. 2017

Alexopoulos, George S / O'Neil, Robert / Banerjee, Samprit / Raue, Patrick J / Victoria, Lindsay W / Bress, Jennifer N / Pollari, Cristina / Arean, Patricia A. ·Weill-Cornell Institute of Geriatric Psychiatry, United States. Electronic address: gsalexop@med.cornell.edu. · Weill Cornell Medical College, Department of Healthcare Policy and Research, United States. · Weill-Cornell Institute of Geriatric Psychiatry, United States; Weill Cornell Medical College, Department of Healthcare Policy and Research, United States. · University of Washington, Department of Psychiatry and Behavioral Sciences, United States. · Weill-Cornell Institute of Geriatric Psychiatry, United States. ·J Affect Disord · Pubmed #28647669.

ABSTRACT: OBJECTIVE: Engage grew out of the need for streamlined psychotherapies that can be accurately used by community therapists in late-life depression. Engage was based on the view that dysfunction of reward networks is the principal mechanism mediating depressive symptoms. Accordingly, Engage uses "reward exposure" (exposure to meaningful activities) and assumes that repeated activation of reward networks will normalize these systems. This study examined whether change in a behavioral activation scale, an index of reward system function, predicts change in depressive symptomatology. METHODS: The participants (N = 48) were older adults with major depression treated with 9 weekly sessions of Engage and assessed 27 weeks after treatment. Depression was assessed with the 24-item Hamilton Depression Rating Scale (HAM-D) and behavioral activation with the four subscales of Behavioral Activation for Depression Scale (activation, avoidance/rumination, work impairment, social impairment) at baseline, 6 weeks (mid-treatment), 9 weeks (end of treatment), and 36 weeks. RESULTS: Change only in the Activation subscale during successive periods of assessment predicted depression severity (HAM-D) at the end of each period (F LIMITATIONS: No comparison group. Partial overlap of Activation Subscale with HAM-D, lack of detailed neurocognitive assessment and social support. CONCLUSION: Change in behavioral activation predicts improvement of depressive symptoms and signs in depressed older adults treated with Engage.

25 Article Therapeutic relationship in the treatment of geriatric depression with executive dysfunction. 2017

Mace, Ryan A / Gansler, David A / Suvak, Michael K / Gabris, Carla M / Areán, Patricia A / Raue, Patrick J / Alexopoulos, George S. ·Department of Psychology, Suffolk University, 73 Tremont Street, Boston, MA 02114, USA. Electronic address: rmace@suffolk.edu. · Department of Psychology, Suffolk University, 73 Tremont Street, Boston, MA 02114, USA. Electronic address: dgansler@suffolk.edu. · Department of Psychology, Suffolk University, 73 Tremont Street, Boston, MA 02114, USA. Electronic address: msuvak@suffolk.edu. · Department of Psychology, Suffolk University, 73 Tremont Street, Boston, MA 02114, USA; Northwell Health Solutions, Great Neck, NY, USA. Electronic address: carla2939@gmail.com. · Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. Electronic address: parean@uw.edu. · Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA. Electronic address: praue@uw.edu. · Department of Psychiatry, Weill Cornell Medical College, New York, NY, USA. Electronic address: gsalexop@med.cornell.edu. ·J Affect Disord · Pubmed #28288407.

ABSTRACT: BACKGROUND: The effects of therapeutic relationship (TR) in elder mental health are understudied. A greater understanding of TR in geriatric psychotherapy is particularly needed for treating late-life depression with executive dysfunction, which predicts poor response to antidepressant medication and presents unique clinical challenges. METHODS: Participants were older patients (N = 220) with major depression and executive dysfunction who received 12 weeks of problem-solving therapy or supportive therapy in a randomized control trial. Multilevel growth curve modeling and latent change scores were used to analyze TR dimensions of Understanding and Accepting at the patient level (individual patient ratings, N = 194) and therapist level (ratings of each therapist averaged across participants, N = 10). RESULTS: TR predicted reduction of depression in both treatment groups, while treatment×TR interactions were not significant. Patients treated by therapists with higher average Understanding (patient and therapist level) and Accepting (therapist level) ratings had greater decreases in depression. The patient level×therapist level interaction for Understanding approached statistical significance (p=.065), suggesting a synergistic effect on treatment outcome. Together, Understanding and Accepting predicted 21% of variance in depression level changes. LIMITATIONS: TR was not assessed throughout the course of treatment (only after the first therapy session and at post-treatment) and did not include ratings from an objective evaluator. CONCLUSIONS: Assessment of patient's experience of the TR and of therapist ability to foster Understanding and Accepting can play a significant role in the delivery of geriatric psychosocial interventions.

Next