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Depression: HELP
Articles by David Carl Steffens
Based on 124 articles published since 2008
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Between 2008 and 2019, D. Steffens wrote the following 124 articles about Depression.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5
1 Editorial A Geriatrics Perspective on Dementia Prevention and Treatment. 2018

Steffens, David C. ·From the Department of Psychiatry, University of Connecticut Health Center, Farmington. ·Am J Psychiatry · Pubmed #29490494.

ABSTRACT: -- No abstract --

2 Editorial Editorial Comment: Is It Time to Take the "Sub" Out of Subsyndromal Depression? 2017

Springate, Beth A / Steffens, David C. ·Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT. · Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT. Electronic address: steffens@uchc.edu. ·Am J Geriatr Psychiatry · Pubmed #28600124.

ABSTRACT: -- No abstract --

3 Editorial Vascular depression consensus report - a critical update. 2016

Aizenstein, Howard J / Baskys, Andrius / Boldrini, Maura / Butters, Meryl A / Diniz, Breno S / Jaiswal, Manoj Kumar / Jellinger, Kurt A / Kruglov, Lev S / Meshandin, Ivan A / Mijajlovic, Milija D / Niklewski, Guenter / Pospos, Sarah / Raju, Keerthy / Richter, Kneginja / Steffens, David C / Taylor, Warren D / Tene, Oren. ·Department of Psychiatry, University of Pittsburgh Medical Center, Pittsburgh, PA, USA. · Memory Disorders Clinic, Riverside Psychiatric Medical Group, Riverside, CA, USA. · Department of Psychiatry, Columbia University, New York, NY, USA. · Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA. · Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, PA, USA. · Department of Psychiatry and Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX, USA. · Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, Columbia University, New York, NY, USA. · Institute of Clinical Neurobiology, Alberichgasse 5/13, Vienna, A-1150, Austria. kurt.jellinger@univie.ac.at. · Department of Geriatric Psychiatry of the St. Petersburg Psychoneurological Research Institute named after V. M. Bekhterev, Medical Faculty of St. Petersburg University, St. Petersburg, Russia. · Clinical Department, Scientific and Practical Center of Psychoneurology named after V. M. Soloviev, St. Petersburg, Russia. · Neurology Clinic, Clinical Center of Serbia, School of Medicine University of Belgrade, Belgrade, Serbia. · University Clinic for Psychiatry and Psychotherapy, Paracelsus Private Medical University, Nuremberg, Germany. · Consultant in Old Age Psychiatry, Cheshire and Wirral Partnership NHS Foundation Trust, Chester, UK. · Faculty for Social Sciences, Technical University of Nuremberg Georg Simon Ohm, Nuremberg, Germany. · Department of Psychiatry, University of Connecticut Health Center, Farmington, CT, USA. · Department of Psychiatry, The Center for Cognitive Medicine, Vanderbilt University Medical Center, Nashville, TN, USA. · Department of Veterans Affairs Medical Center, The Geriatric Research, Education, and Clinical Center (GRECC), Tennessee Valley Healthcare System, Nashville, TN, USA. · Departments of Neurology and Psychiatry, Tel Aviv Medical Center, Tel Aviv, Israel. · Tel Aviv University, Sackler Faculty of Medicine, Tel Aviv, Israel. ·BMC Med · Pubmed #27806704.

ABSTRACT: BACKGROUND: Vascular depression is regarded as a subtype of late-life depression characterized by a distinct clinical presentation and an association with cerebrovascular damage. Although the term is commonly used in research settings, widely accepted diagnostic criteria are lacking and vascular depression is absent from formal psychiatric manuals such as the Diagnostic and Statistical Manual of Mental Disorders, 5 DISCUSSION: This diagnosis, based on clinical and MRI findings, suggests that vascular lesions lead to depression by disruption of frontal-subcortical-limbic networks involved in mood regulation. However, despite multiple MRI approaches to shed light on the spatiotemporal structural changes associated with late life depression, the causal relationship between brain changes, related lesions, and late life depression remains controversial. While postmortem studies of elderly persons who died from suicide revealed lacunes, small vessel, and Alzheimer-related pathologies, recent autopsy data challenged the role of these lesions in the pathogenesis of vascular depression. Current data propose that the vascular depression connotation should be reserved for depressed older patients with vascular pathology and evident cerebral involvement. Based on current knowledge, the correlations between intra vitam neuroimaging findings and their postmortem validity as well as the role of peripheral markers of vascular disease in late life depression are discussed. CONCLUSION: The multifold pathogenesis of vascular depression as a possible subtype of late life depression needs further elucidation. There is a need for correlative clinical, intra vitam structural and functional MRI as well as postmortem MRI and neuropathological studies in order to confirm the relationship between clinical symptomatology and changes in specific brain regions related to depression. To elucidate the causal relationship between regional vascular brain changes and vascular depression, animal models could be helpful. Current treatment options include a combination of vasoactive drugs and antidepressants, but the outcomes are still unsatisfying.

4 Review Diffusion tensor imaging studies in late-life depression: systematic review and meta-analysis. 2014

Wen, Ming-Ching / Steffens, David C / Chen, Mei-Kuang / Zainal, Nur Hani. ·National Neuroscience Institute, Singapore. ·Int J Geriatr Psychiatry · Pubmed #24798480.

ABSTRACT: OBJECTIVES: Late-life depression (LLD) is the association with more cerebrovascular susceptibilities and white matter damage that can be assessed with diffusion tensor imaging (DTI). To better understand the white matter pathological alterations in LLD, we conducted a systematic review and meta-analysis. METHODS: We searched MEDLINE, EMBASE, PsycINFO, PubMed, and Google Scholar databases for DTI studies comparing patients with LLD and healthy controls. For each study, details regarding participants, imaging methods, and results were extracted. Fractional anisotropy, an index of white matter integrity, was the dependent variable for group comparison. Effect sizes indicating the degree of group difference were estimated by random-effects meta-analysis. RESULTS: A total of 15 eligible studies were included in the qualitative systematic review, nine of which were suitable for quantitative meta-analyses for the dorsolateral prefrontal cortex (DLPFC), corpus callosum, cingulum, and uncinate fasciculus (UF). Compared with the healthy control group, the LLD group showed lower fractional anisotropy in the DLPFC and UF with a large and a medium effect size, respectively, although heterogeneity and publication bias were found in the DLPFC. CONCLUSION: Diffusion tensor imaging studies of LLD consistently showed reduced anisotropy in the DLPFC and UF of patients with LLD. These damaged regions are located with the frontostriatal and limbic networks. Thus, our findings showed that the disruption of frontal and frontal-to-limbic white matter tracts contributes to the pathogenesis of LLD.

5 Review What are the causes of late-life depression? 2013

Aziz, Rehan / Steffens, David C. ·Department of Psychiatry, Institute of Living, Hartford Hospital, 200 Retreat Avenue, Hartford, CT 06106, USA; Department of Psychiatry, Yale University School of Medicine, 300 George Street, Suite 901, New Haven, CT 06511, USA; Department of Psychiatry, University of Connecticut Health Center, Building L, MC 1410, 263 Farmington Avenue, Farmington, CT 06030, USA. Electronic address: Rehan.Aziz@hhchealth.org. ·Psychiatr Clin North Am · Pubmed #24229653.

ABSTRACT: Although depression in old age is less common than depression in younger populations, it still affects more than 1 million community-living older adults. Depression in late life has been associated with reduced quality of life and increased mortality from both suicide and illness. Its causes are multifactorial but are prominently related to both biologic and social factors. Psychological factors, although less studied in elders, are also important in understanding its cause. In this article, multiple facets of late-life depression are reviewed, including its clinical presentation, epidemiology, and biopsychosocial causes.

6 Review Structural neuroimaging of geriatric depression. 2011

Benjamin, Sophiya / Steffens, David C. ·Department of Psychiatry, Duke University Medical Center, DHSP, Box 3837, Durham, 27710 NC, USA. ·Psychiatr Clin North Am · Pubmed #21536166.

ABSTRACT: There is a large literature on the neuroanatomy of late-life depression that continues to grow with the discovery of novel structural imaging techniques along with innovative methods to analyze the images. Such advances have helped identify specific areas, characteristic lesions, and changes in the chemical composition in these regions that might be important in the pathophysiology of this complex disease. This article reviews relevant findings by each structural neuroimaging technique. When validated across many studies, such findings can serve as neuroanatomic markers that can help generate rational hypotheses for future studies to further understanding of geriatric depression.

7 Review MRI-defined vascular depression: a review of the construct. 2011

Culang-Reinlieb, Michelle E / Johnert, Lauren C / Brickman, Adam M / Steffens, David C / Garcon, Ernst / Sneed, Joel R. ·The Graduate Center, City University of New York, NY, USA. ·Int J Geriatr Psychiatry · Pubmed #21192018.

ABSTRACT: OBJECTIVE: To review the construct of MRI-defined vascular depression and to examine the substantive and methodological issues that bear on its validity as a distinct subtype of depression in late life. DESIGN: Literature review. RESULTS: We identified three areas that are critical to establishing the validity of MRI-defined vascular depression: (1) understanding and delineating the relationship between MRI hyperintensities, executive dysfunction, and antidepressant treatment outcome; (2) understanding the relationship between, and establishing the validity of, qualitative and quantitative approaches to the measurement of MRI hyperintensities (the primary feature of the proposed subtype); (3) establishing the clinical presentation and course of the subtype in the context of other late-life disorders. CONCLUSIONS: Despite considerable data supporting the validity of MRI-defined vascular depression, there are a number of critical issues that remain, including establishing a causal relationship between cerebrovascular disease and late-life depression, establishing consistent diagnostic criteria, determining the importance of lesion type and location, and understanding the course of the disorder.

8 Review Depressive morbidity and gender in community-dwelling Brazilian elderly: systematic review and meta-analysis. 2010

Barcelos-Ferreira, Ricardo / Izbicki, Rafael / Steffens, David C / Bottino, Cássio M C. ·Old Age Research Group (Proter), Institute of Psychiatry, University of São Paulo Medical School, Brazil. barcelosfr@usp.br ·Int Psychogeriatr · Pubmed #20478096.

ABSTRACT: BACKGROUND: Although studies indicate that community-dwelling elderly have a lower prevalence of major depression compared with younger age groups, prevalence estimates in Brazil show that clinically significant depressive symptoms (CSDS) and depression are frequent in the older population. However, a systematic review and meta-analysis of prevalence of and factors associated with depressive disorders and symptoms in elderly Brazilians has not previously been reported. The aims were (i) to perform a survey of studies dating from 1991 to 2009 on the prevalence of depressive disorders and CSDS in elderly Brazilians residing in the community; (ii) to determine depression prevalence and identify associated factors; and (iii) develop a meta-analysis to indicate the combined prevalence and the influence of gender on depressive morbidity in this population. METHODS: Studies were selected from articles dated between January 1991 and May 2009, extracted from Medline, LILACS and SciELO databases. RESULTS: A total of 17 studies were found, 13 with CSDS, 1 with major depression alone and 3 with major depression and dysthymia, involving the evaluation of 15,491 elderly people. The average age of participants varied between 66.5 and 84.0 years. Prevalence rates of 7.0% for major depression, 26.0% for CSDS, and 3.3% for dysthymia were found. The odds ratios for major depression and CSDS were greater among women. There was a significant association between major depression or CSDS and cardiovascular diseases. CONCLUSION: The review indicates greater prevalence of both major depression and CSDS compared to rates reported in the international literature, while the prevalence of dysthymia was found to be similar. The high prevalence of CSDS and its significant association with cardiovascular diseases reinforces the importance of evaluating subthreshold depressive symptoms in the elderly in the community.

9 Review Quetiapine XR: current status for the treatment of major depressive disorder. 2010

Pae, Chi-Un / Sohi, Manmohandeep Singh / Seo, Ho-Jun / Serretti, Alessandro / Patkar, Ashwin A / Steffens, David C / Masand, Prakash S. ·Department of Psychiatry, Bucheon St. Mary's Hospital, The Catholic University of Korea College of Medicine, 2 Sosa-Dong, Wonmi-Gu, Pucheon, Kyounggi-Do 420-717, Republic of Korea. pae@catholic.ac.kr ·Prog Neuropsychopharmacol Biol Psychiatry · Pubmed #20307622.

ABSTRACT: Quetiapine fumarate extended release (XR) has been approved for treatment of schizophrenia and bipolar disorder. Quetiapine may have antidepressant effects through effects on 5-HT(2A) receptor, 5-HT(1A) receptor, dopamine receptor, glutamate receptor and norepinephrine transporter. Recently, 7 large-scale randomized, double-blind, placebo (2-studies with active comparator)-controlled clinical trials have demonstrated that quetiapine XR has clinically meaningful efficacy as monotherapy and adjunct therapy to antidepressants for the treatment of adult patients with major depressive disorder (MDD). In such clinical trials, quetiapine XR was generally well tolerated, although weight gain and changes in metabolic parameters, consistent with the known profile of quetiapine, were observed in some patients. As of December 2009, the United States Food and Drug Administration has approved quetiapine XR for the adjunct treatment of MDD. From the data of currently available clinical trials, this review provides an overview of the data and clinical implications for quetiapine XR in the treatment of MDD to enhance clinicians understanding of the use of quetiapine XR in the treatment of MDD.

10 Review A multiplicity of approaches to characterize geriatric depression and its outcomes. 2009

Steffens, David C. ·Division of Geriatric Psychiatry, Duke University Medical Center, Durham, North Carolina 27710, USA. steff001@mc.duke.edu ·Curr Opin Psychiatry · Pubmed #19625967.

ABSTRACT: PURPOSE OF REVIEW: Research in geriatric depression has always had a multidisciplinary bent, particularly in methods used to characterize depression. Understanding diagnosis, psychiatric comorbidities, and course continues to be a goal of clinical researchers. Those interested in cognitive neuroscience and basic neuroscience have more recently trained their sights on late-life depression. This review identifies recent progress in the characterization of geriatric depression using a variety of methodologies. RECENT FINDINGS: Depression in the elderly remains underdetected and underdiagnosed, particularly in nonmental health settings. Studies of the impact of psychiatric comorbidities and of the negative outcomes of depression in older adults demonstrate that geriatric depression is a serious medical condition that not only affects mood but can also lead to functional and cognitive decline. Advances in neuroimaging technology have demonstrated structural and functional changes in the brains of older depressed patients. With the advent of brain banks in neuropsychiatry, we are now seeing postmortem neuroanatomical studies that seek to extend findings from clinical practice and from neuroimaging research. SUMMARY: Clinicians should become more aware of advances in detection of depression, the effect of psychiatric comorbidities, the poor mood and cognitive outcomes associated with late-life depression and should keep abreast of recent neuroimaging and neuroanatomical findings.

11 Review Separating mood disturbance from mild cognitive impairment in geriatric depression. 2008

Steffens, David C. ·Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA. teff001@mc.duke.edu ·Int Rev Psychiatry · Pubmed #18925486.

ABSTRACT: Disentangling depression from dementia remains one of the most difficult clinical challenges for psychiatrists caring for older adults. The relationship between geriatric depression and dementia is complex for several reasons. First, cognitive impairment is often a prominent feature of depression in the elderly. Cognition may improve with successful treatment of depression but it may not normalize. Indeed, marked memory impairment in older depressed individuals may indicate a prodromal state of dementia. This review will examine issues related to depression and cognitive disorder in the elderly. The author will provide an evidence-based approach to separate mood disorder from cognitive disorder among older adults.

12 Review Does neurotropin-3 have a therapeutic implication in major depression? 2008

Pae, Chi-Un / Marks, David M / Han, Changsu / Patkar, Ashwin A / Steffens, David. ·Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea. pae@catholic.ac.kr ·Int J Neurosci · Pubmed #18853330.

ABSTRACT: Although several classes of antidepressants are used to treat major depression, there is an unmet need in real clinical practice because not all patients treated with an antidepressant fully recover from their functional impairment. Hence, the development of new antidepressants based on a novel therapeutic mechanism may help in the development of more effective and ideal antidepressive agents. There is emerging evidence suggesting that the etiopathogenesis of depression involves transmitters other than the major neurotransmitters such as serotonin, norepinephrine, and dopamine. Therefore, it has consistently been suggested that an alteration in neuroprotection and synaptic plasticity is associated with the pathogenesis and therapeutic mechanism of depression. Neurotropin-3 (NT3) is an interesting protein that regulates neuronal survival, synaptic plasticity, and neurotransmission. It is widely expressed in the hippocampus and facilitates hippocampal plasticity by regulating neurogenesis. It has been also reported that an infusion of NT3 increases the level of brain-derived neurotrophic factor (BDNF) mRNA expression in the cerebral cortex and produces BDNF-like effects that induce cortical tyrosine kinase B phosphorylation. BDNF has been consistently implicated in the pathogenesis of depression and the therapeutic mechanism of antidepressants. It has also been implicated in the treatment effect of mood stabilizers such as lithium. NT3 has demonstrated its possible antidepressant effect in a learned helpless animal model. Animal studies have shown that it also modulates the neurotransmitters, serotonin and noradrenaline, which are essential in the development and treatment of depression. Therefore, further studies on the therapeutic implications of NT3 for depression are warranted and are expected for the development of newer, effective antidepressants.

13 Clinical Trial Altered Synchronizations among Neural Networks in Geriatric Depression. 2015

Wang, Lihong / Chou, Ying-Hui / Potter, Guy G / Steffens, David C. ·Department of Psychiatry, University of Connecticut Health Center, 263 Farmington, CT 06119, USA ; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA ; Brain Imaging and Analysis Center, Duke University, Durham, NC, USA. · Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA ; Brain Imaging and Analysis Center, Duke University, Durham, NC, USA. · Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA. · Department of Psychiatry, University of Connecticut Health Center, 263 Farmington, CT 06119, USA ; Department of Psychiatry and Behavioral Sciences, Duke University, Durham, NC, USA. ·Biomed Res Int · Pubmed #26180795.

ABSTRACT: Although major depression has been considered as a manifestation of discoordinated activity between affective and cognitive neural networks, only a few studies have examined the relationships among neural networks directly. Because of the known disconnection theory, geriatric depression could be a useful model in studying the interactions among different networks. In the present study, using independent component analysis to identify intrinsically connected neural networks, we investigated the alterations in synchronizations among neural networks in geriatric depression to better understand the underlying neural mechanisms. Resting-state fMRI data was collected from thirty-two patients with geriatric depression and thirty-two age-matched never-depressed controls. We compared the resting-state activities between the two groups in the default-mode, central executive, attention, salience, and affective networks as well as correlations among these networks. The depression group showed stronger activity than the controls in an affective network, specifically within the orbitofrontal region. However, unlike the never-depressed controls, geriatric depression group lacked synchronized/antisynchronized activity between the affective network and the other networks. Those depressed patients with lower executive function has greater synchronization between the salience network with the executive and affective networks. Our results demonstrate the effectiveness of the between-network analyses in examining neural models for geriatric depression.

14 Clinical Trial Thyroid hormones affect recovery from depression during antidepressant treatment. 2009

Pae, Chi-Un / Mandelli, Laura / Han, Changsu / Ham, Byung-Joo / Masand, Prakash S / Patkar, Ashwin A / Steffens, David C / De Ronchi, Diana / Serretti, Alessandro. ·Department of Psychiatry, Holy Family Hospital, The Catholic University of Korea College of Medicine, Bucheon, Kyoung-gi Province, Republic of Korea. alessandro.serretti@unibo.it ·Psychiatry Clin Neurosci · Pubmed #19566761.

ABSTRACT: AIMS: The aim of the present study was to evaluate whether thyroid hormonal changes during menopause may affect the development and the course of major depressive disorder. METHODS: Thirty-nine female patients (n = 17 in pre-menopause; n = 22 in post-menopause) with major depressive disorder based on Diagnostic Statistical Manual of Mental Disorders (4th edition) criteria and who were euthyroid and not on hormonal replacement therapy, participated in a prospective, 6-week, open-label naturalistic study. The Hamilton Depression Rating Scale-17 item, the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression scale and the Cognitive Failure Questionnaire were administered at baseline, week 1, week 3, and week 6. Levels of thyroid stimulating hormone, total thyroxine and total triiodothyronine were collected at baseline visit. RESULTS: In the whole sample, particularly in pre-menopausal women, levels of thyroid stimulating hormone-potential markers of subclinical hypothyroidism were correlated with those of less severe but more resistant depressive form. Conversely, total thyroxine levels were correlated with a more severe depression, but high levels of this hormone favored the response to antidepressants. Overall, a diagnosis of subclinical hypothyroidism was associated with a poor response to antidepressant treatment. Finally, total triiodothyronine levels were associated with better cognitive functioning, though they did not influence improvement occurring with recovery. CONCLUSIONS: Our study suggests that thyroid hormones may have an impact on severity and efficacy of antidepressant treatment. However, our result should be considered with caution and merely as a suggestion due to some methodological limitations. Hence further studies are required to better ascertain the role of thyroid hormones in depression after menopause.

15 Clinical Trial Do estradiol levels influence on the cognitive function during antidepressant treatments in post-menopausal women with major depressive disorder? A comparison with pre-menopausal women. 2008

Pae, Chi-Un / Mandelli, Laura / Han, Changsu / Ham, Byung-Joo / Masand, Prakash S / Patkar, Ashwin A / Steffens, David C / De Ronchi, Diana / Serretti, Alessandro. ·Department of Psychiatry, The Catholic University of Korea College of Medicine, Seoul, South Korea. pae@catholic.ac.kr ·Neuro Endocrinol Lett · Pubmed #18766158.

ABSTRACT: OBJECTIVES: A hypo-estrogenic status, as that occurring with menopause, has been proposed to negatively affect cognitive function in post-menopause women. Nevertheless, little is known about the improvement of cognitive functions during antidepressant treatment in post-menopausal women with major depressive disorder (MDD) and its relation with hormonal changes. Hence, this study aimed to investigate the role of menopausal status including the level of sex hormones on cognitive function during antidepressant treatment. DESIGN AND SETTINGS: Thirty-nine female patients (n=17 in pre-menopause; n=22 in post-menopause) with MDD based on DSM-IV criteria and who were not on hormonal replacement therapies participated in a prospective, 6-week, open-label naturalistic study. All patients were recruited in a university-based hospital. The Hamilton rating scale for Depression (HAMD), Montgomery-Asberg Depression Rating Scale (MADRS) and the Cognitive Failure Questionnaire (CFQ) were administered at baseline, week 1, week 3, and week 6. Levels of follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) were collected at baseline visit. RESULTS: Cognitive functioning improved during antidepressant treatment in the overall sample (P=0.00001). In post-menopausal women, E2 levels were strongly correlated with CFQ scores at each measurement. After controlling for depression severity, E2 levels maintained a significant association with the baseline CFQ scores (regression analysis: beta= -0.55 P=0.010; correlation: R= -0.54). In addition, the reduction of CFQ scores during antidepressant treatment was significantly associated with E2 levels (P=0.021), independently from the improvement of depressive symptoms, which however had a strong effect (P=0.0003). Nevertheless, we failed to find any association of CFQ score with sex hormones in pre-menopausal women. MAIN FINDINGS: In post-menopausal women, the CFQ scores were correlated with E2 levels and the reduction of CFQ score during antidepressant treatment was also dependent on E2 levels, even controlling for depressive symptoms severity. CONCLUSION: The present study further supports a crucial role of E2 on the cognitive function in post-menopause women. Moreover, our results suggest that E2 may influence the improvement of cognitive function in post-menopause women with MDD, during treatment with antidepressants.

16 Article Predictors of recurrence in remitted late-life depression. 2018

Deng, Yi / McQuoid, Douglas R / Potter, Guy G / Steffens, David C / Albert, Kimberly / Riddle, Meghan / Beyer, John L / Taylor, Warren D. ·The Center for Cognitive Medicine, Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. · Department of Psychiatry, University of Connecticut Health Center, Farmington, CT, USA. · Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA. ·Depress Anxiety · Pubmed #29749006.

ABSTRACT: BACKGROUND: Late-life depression (LLD) is associated with a fragile antidepressant response and high recurrence risk. This study examined what measures predict recurrence in remitted LLD. METHODS: Individuals of age 60 years or older with a Diagnostic and Statistical Manual - IV (DSM-IV) diagnosis of major depressive disorder were enrolled in the neurocognitive outcomes of depression in the elderly study. Participants received manualized antidepressant treatment and were followed longitudinally for an average of 5 years. Study analyses included participants who remitted. Measures included demographic and clinical measures, medical comorbidity, disability, life stress, social support, and neuropsychological testing. A subset underwent structural magnetic resonance imaging (MRI). RESULTS: Of 241 remitted elders, approximately over 4 years, 137 (56.8%) experienced recurrence and 104 (43.2%) maintained remission. In the final model, greater recurrence risk was associated with female sex (hazard ratio [HR] = 1.536; confidence interval [CI] = 1.027-2.297), younger age of onset (HR = 0.990; CI = 0.981-0.999), higher perceived stress (HR = 1.121; CI = 1.022-1.229), disability (HR = 1.060; CI = 1.005-1.119), and less support with activities (HR = 0.885; CI = 0.812-0.963). Recurrence risk was also associated with higher Montgomery-Asberg Depression Rating Scale (MADRS) scores prior to censoring (HR = 1.081; CI = 1.033-1.131) and baseline symptoms of suicidal thoughts by MADRS (HR = 1.175; CI = 1.002-1.377) and sadness by Center for Epidemiologic Studies-Depression (HR = 1.302; CI, 1.080-1.569). Sex, age of onset, and suicidal thoughts were no longer associated with recurrence in a model incorporating report of multiple prior episodes (HR = 2.107; CI = 1.252-3.548). Neither neuropsychological test performance nor MRI measures of aging pathology were associated with recurrence. CONCLUSIONS: Over half of the depressed elders who remitted experienced recurrence, mostly within 2 years. Multiple clinical and environmental measures predict recurrence risk. Work is needed to develop instruments that stratify risk.

17 Article Putamen Volume Differences Among Older Adults: Depression Status, Melancholia, and Age. 2018

Sachs-Ericsson, Natalie J / Hajcak, Greg / Sheffler, Julia L / Stanley, Ian H / Selby, Edward A / Potter, Guy G / Steffens, David C. ·1 Department of Psychology, Florida State University, Tallahassee, FL, USA. · 2 Department of Psychology, Rutgers University, Piscataway, NJ, USA. · 3 Department of Psychiatry, Duke University Medical Center, Durham, NC, USA. · 4 Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT, USA. ·J Geriatr Psychiatry Neurol · Pubmed #29251178.

ABSTRACT: BACKGROUND: Individuals with major depressive disorder (MDD) may exhibit smaller striatal volumes reflecting deficits in the reward circuit. Deficits may change with age and be more pronounced among the melancholic subtype. Limited research has investigated striatal volume differences in older adults and by depression subtypes. METHOD: We used baseline data from the Neurocognitive Outcomes of Depression in the Elderly study. We examined volumetric differences in the putamen and caudate nucleus among older adults (60 years and older), comparing healthy control participants (n = 134) to depressed participants (n = 226), and comparing nonmelancholic depressed participants (n = 93) to melancholic depressed participants (n = 133). Group-by-age interactions were examined. RESULTS: There were no significant group differences for the caudate nucleus. For the left putamen, investigation of the significant group-by-age interaction revealed that volume size was greater for the healthy controls compared to the depressed participants but only at younger ages (60-65 years); group differences diminished with increasing age. Examining volume by depression subtype revealed that the melancholic depressed participants had a smaller left putamen compared to the nonmelancholic depressed participants. Anhedonia symptoms were related to both smaller left and right putamen. CONCLUSION: Structural abnormalities in reward regions may underlie the anhedonic phenotype. Volume loss associated with MDD may attenuate in older age.

18 Article Length of axons expressing the serotonin transporter in orbitofrontal cortex is lower with age in depression. 2017

Rajkowska, Grazyna / Mahajan, Gouri / Legutko, Beata / Challagundla, Lavanya / Griswold, Michael / Albert, Paul R / Daigle, Mireille / Miguel-Hidalgo, Jose J / Austin, Mark C / Blakely, Randy D / Steffens, David C / Stockmeier, Craig A. ·Department of Psychiatry and Human Behavior, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: grajkowska@umc.edu. · Department of Psychiatry and Human Behavior, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: gmahajan@umc.edu. · Department of Psychiatry and Human Behavior, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: beatalgtk0@gmail.com. · Department of Data Science, JD Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: lchallagundla@umc.edu. · Department of Data Science, JD Bower School of Population Health, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: mgriswold@umc.edu. · Ottawa Hospital Research Institute (Neuroscience) and UOttawa Brain and Mind Research Institute, Ottawa, ON K1H 8M5, Canada. Electronic address: palbert@uottawa.ca. · Ottawa Hospital Research Institute (Neuroscience) and UOttawa Brain and Mind Research Institute, Ottawa, ON K1H 8M5, Canada. Electronic address: Mireille.Daigle@uOttawa.ca. · Department of Psychiatry and Human Behavior, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA. Electronic address: jmiguel-hidalgo@umc.edu. · Department of Biological Sciences, Idaho State University, Pocatello, ID 83209, USA. Electronic address: austinm@isu.edu. · Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: Randy.Blakely@Vanderbilt.edu. · Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT 06030, USA. Electronic address: STEFFENS@uchc.edu. · Department of Psychiatry and Human Behavior, School of Medicine, University of Mississippi Medical Center, Jackson, MS 39216, USA; Department of Psychiatry, Case Western Reserve University, Cleveland, OH 44106, USA. Electronic address: cstockmeier@umc.edu. ·Neuroscience · Pubmed #28711621.

ABSTRACT: Studies of major depressive disorder (MDD) in postmortem brain tissue report enhanced binding to inhibitory serotonin-1A autoreceptors in midbrain dorsal raphe and reductions in length of axons expressing the serotonin transporter (SERT) in dorsolateral prefrontal cortex. The length density of axons expressing SERT in the orbitofrontal cortex (OFC) was determined in 18 subjects with MDD and 17 age-matched control subjects. A monoclonal antibody was used to immunohistochemically label the SERT in fixed sections of OFC. The 3-dimensional length density of SERT-immunoreactive (ir) axons in layer VI of OFC was estimated. The age of subjects with MDD was negatively correlated with SERT axon length (r=-0.77, p<0.0005). The significant effect of age persisted when removing four depressed subjects with an antidepressant medication present at the time of death, or when removing nine depressed subjects that had a recent prescription for an antidepressant medication. Neither gender, tissue pH, postmortem interval, 5-HTTLPR genotype, time in fixative, nor death by suicide had a significant effect on axon length. The age-related decrease in SERT-ir axon length in MDD may reflect pathology of ascending axons passing through deep white matter hyperintensities. Greater length of axons expressing SERT in younger subjects with MDD may result in a significant deficit in serotonin availability in OFC.

19 Article Late-Life Depression and the Prodromes of Dementia. 2017

Steffens, David Carl. ·Department of Psychiatry, University of Connecticut School of Medicine, Farmington. ·JAMA Psychiatry · Pubmed #28514459.

ABSTRACT: -- No abstract --

20 Article Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression. 2017

Riddle, Meghan / Potter, Guy G / McQuoid, Douglas R / Steffens, David C / Beyer, John L / Taylor, Warren D. ·Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC. · Department of Psychiatry, University of Connecticut Health Center, Farmington, CT. · Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN; Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center (WDT), Tennessee Valley Healthcare System, Nashville, TN. Electronic address: warren.d.taylor@vanderbilt.edu. ·Am J Geriatr Psychiatry · Pubmed #28479153.

ABSTRACT: OBJECTIVE: Late-life depression is associated with cognitive deficits and increased risk for cognitive decline. The purpose of the study was to determine whether clinical characteristics could serve as phenotypes informative of subsequent cognitive decline. Age at depression onset and antidepressant remission at 3 months (acute response) and 12 months (chronic response) were examined. METHODS: In a longitudinal study of late-life depression in an academic center, 273 depressed and 164 never-depressed community-dwelling elders aged 60 years or older were followed on average for over 5 years. Participants completed annual neuropsychological testing. Neuropsychological measures were converted to z-scores derived from the baseline performance of all participants. Cognitive domain scores at each time were then created by averaging z-scores across tests, grouped into domains of episodic memory, attention-working memory, verbal fluency, and executive function. RESULTS: Depressed participants exhibited poorer performance at baseline and greater subsequent decline in all domains. Early-onset depressed individuals exhibited a greater decline in all domains than late-onset or nondepressed groups. For remission, remitters and nonremitters at both 3 and 12 month exhibited greater decline in episodic memory and attention-working memory than nondepressed subjects. Three-month remitters also exhibited a greater decline in verbal fluency and executive function, whereas 12-month nonremitters exhibited greater decline in executive function than other groups. CONCLUSION: Consistent with past studies, depressed elders exhibit greater cognitive decline than nondepressed subjects, particularly individuals with early depression onset, supporting the theory that repeated depressive episodes may contribute to decline. Clinical remission is not associated with less cognitive decline.

21 Article Negative Affectivity, Aging, and Depression: Results From the Neurobiology of Late-Life Depression (NBOLD) Study. 2017

Steffens, David C / Wang, Lihong / Manning, Kevin J / Pearlson, Godfrey D. ·Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT. Electronic address: steffens@uchc.edu. · Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC; Olin Neuropsychiatry Research Center, Institute of Living of Hartford Hospital, Hartford, CT. · Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT. · Olin Neuropsychiatry Research Center, Institute of Living of Hartford Hospital, Hartford, CT; Departments of Psychiatry and Neuroscience, Yale University School of Medicine, New Haven, CT. ·Am J Geriatr Psychiatry · Pubmed #28457805.

ABSTRACT: OBJECTIVE: Neuroticism is a common yet understudied condition in older adults. We hypothesized that presence of high negativity affectivity (NA), a key feature of neuroticism, would be associated with different prefrontal cortex (PFC) activity and connectivity patterns in depressed and never-depressed older adults. METHODS: This is a baseline cross-sectional analysis of a cohort study of 52 depressed and 36 never-depressed older adults. Assessments included NA scores from the Type D Scale-14 and Montgomery-Åsberg Depression Rating Scale scores. All subjects had a 3T brain functional magnetic resonance imaging resting scan, neuronal activity determined by amplitude of low-frequency fluctuations (ALFFs) were obtained, and resting state functional connectivity (FC) analyses were performed. Analyses of covariance were conducted on ALFFs and FC to examine significant differences between groups. RESULTS: In the ALFF analyses there were clearly different patterns between depressed and comparison groups in the correlation of ALFFs and NA. The correlation differences between the two groups were significant in the dorsomedial PFC, insula, amygdala, and posterior cingulate cortex (PCC). FC analyses revealed different between-group connectivity patterns. Significantly higher ventromedial PFC-amygdala FC with NA correlation was found in the depressed group than that in the never-depressed group. CONCLUSION: This study confirms differential activity of the dorsal and ventral regions of the medial PFC in individuals with high neuroticism. Our findings suggest increased rostral medial PFC activity may be a marker of resilience to depression in the elderly and decreased anterior ventromedial PFC, PCC, and amygdala activity may be a result of successful emotion regulation in never-depressed higher NA individuals.

22 Article Effects of stressful life events on cerebral white matter hyperintensity progression. 2017

Johnson, Anne D / McQuoid, Douglas R / Steffens, David C / Payne, Martha E / Beyer, John L / Taylor, Warren D. ·The Center for Cognitive Medicine, Department of Psychiatry, Vanderbilt University Medical Center, Nashville, TN, USA. · Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, USA. · Department of Psychiatry, University of Connecticut Health Center, Farmington, CT, USA. · Office of Research Development, Duke University School of Medicine, Durham, NC, USA. · Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Tennessee Valley Healthcare System, Nashville, TN, USA. ·Int J Geriatr Psychiatry · Pubmed #28029184.

ABSTRACT: OBJECTIVE: Exposure to stressful events is associated with both occurrence of depression and also vascular disease. The objective of this study was to determine whether higher levels of stress exposure was related to measures of pathological brain aging, specifically white matter hyperintensity volumes, in older adults with and without depression. METHODS: The sample included 130 depressed and 110 never-depressed older adults aged 60 years or older enrolled in a longitudinal study at an academic medical center. Participants completed clinical assessments, assessment of stressful event exposure and perceived stress, and magnetic resonance imaging at baseline and after 2 years. Analyses examined both cross-sectional and longitudinal relationships between stress measures and white matter hyperintensity volumes. RESULTS: There were no statistically significant relationships observed between cross-sectional baseline stress measures and either baseline hyperintensity volume or 2-year change in hyperintensity volume. However, after controlling for demographic variables and baseline measures, change in stressor exposure was associated with change in hyperintensity volumes. In this analysis, increased stressor exposure was associated with greater increases in white matter hyperintensity volume, while reductions in stressor exposure were associated with less increase in hyperintensity volume. This relationship did not significantly differ based on the presence of either depression or medical comorbidities. CONCLUSIONS: This work adds to a growing literature associating exposure to stressful events in later life with more rapid pathological brain aging. Work is needed to understand the physiological mechanisms by which stress exposure has this effect and examine whether stress reduction techniques may modify these observed outcomes. Copyright © 2016 John Wiley & Sons, Ltd.

23 Article Neuroticism Traits Selectively Impact Long Term Illness Course and Cognitive Decline in Late-Life Depression. 2017

Manning, Kevin J / Chan, Grace / Steffens, David C. ·Department of Psychiatry, University of Connecticut Health Center, Farmington, CT. Electronic address: manning@uchc.edu. · Department of Psychiatry, University of Connecticut Health Center, Farmington, CT. ·Am J Geriatr Psychiatry · Pubmed #27825555.

ABSTRACT: OBJECTIVES: Neuroticism is a broad construct that conveys a predisposition to experience psychological distress and negative mood states. Vulnerability to stress (VS) is one neuroticism trait that has been linked to worse mood and cognitive outcomes in older adults. We hypothesized that elevated VS would be associated with worse illness course and cognitive decline in older adults with late-life major depression (LLD). DESIGN: Participants were enrolled in the Neurocognitive Outcomes of Depression in the Elderly (NCODE), a longitudinal investigation of the predictors of poor illness course and cognitive decline in LLD. Participants were followed upwards of 10 years. SETTING: NCODE operates in a naturalistic treatment milieu. PARTICIPANTS: 112 participants aged 60 and older with a current diagnosis of major depressive disorder. MEASUREMENTS: Treatment response was assessed at least every 3 months and more often if clinically needed. Participants also completed the NEO Personality Inventory-Revised (NEO PI-R) and an annual cognitive examination. Neuroticism traits from the NEO PI-R included anxiety, depression, anger-hostility, self-consciousness, impulsivity, and VS. RESULTS: Higher neuroticism traits of VS, impulsivity, anger-hostility, and anxiety were associated with worse treatment response over time. High VS was the only neuroticism trait significantly associated with cognitive functioning. High VS negatively influenced the rate of global cognitive decline over time. CONCLUSIONS: Individual personality traits within the neuroticism dimension are associated with treatment resistance and cognitive impairment in LLD. It remains to be seen whether these individual traits are associated with different neurobiological substrates and clinical characteristics of LLD.

24 Article Decreased between-hemisphere connectivity strength and network efficiency in geriatric depression. 2017

Li, Xuesong / Steffens, David C / Potter, Guy G / Guo, Hua / Song, Sen / Wang, Lihong. ·Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing, China. · Department of Psychiatry, University of Connecticut School of Medicine, Farmington, Connecticut. · Department of Psychiatry and Behavioral Science, Duke University, Durham, North Carolina. ·Hum Brain Mapp · Pubmed #27503772.

ABSTRACT: White matter (WM) lesions have been recognized as a key etiological factor in geriatric depression. However, little is known about the topological pattern changes of WM in geriatric depression in the remitted state (RGD) and its relationship to depressive episodes. To address these questions, we acquired diffusion tensor images in 24 RGD and 24 healthy participants. Among them, 10 patients and 19 healthy controls completed a 1-year follow up. Between-hemisphere connectivity and graph theoretical methods were used to analyze the data. We found significantly reduced WM connectivity between the left and right hemisphere in the RGD group compared with the control group. Those with multiple depression episodes had greater reduction in between-hemisphere connectivity strength than those with fewer episodes. In addition, the RGD group had a reduced global clustering coefficient, global efficiency, and network strength, and an increased shortest path length compared with the controls. A lower clustering coefficient was correlated with poorer memory function. The reduction of nodal clustering coefficient, global efficiency, and network strength in several regions were associated with slower information processing speed. At 1-year follow up, the network properties in the RGD subjects were significantly changed suggesting instability of WM network properties of depressed patients. Together, our study provides direct evidence of reduced between-hemisphere WM connectivity with greater depressive episodes, and of alterations of network properties with cognitive dysfunction in geriatric depression. Hum Brain Mapp 38:53-67, 2017. © 2016 Wiley Periodicals, Inc.

25 Article Appetite and Weight Loss Symptoms in Late-Life Depression Predict Dementia Outcomes. 2016

Saha, Sayoni / Hatch, Daniel J / Hayden, Kathleen M / Steffens, David C / Potter, Guy G. ·Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC. · Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC; Center for the Study of Aging and Human Development, Duke University, Durham, NC. · Department of Social Sciences and Health Policy, Wake Forest School of Medicine, Winston-Salem, NC. · Department of Psychiatry, University of Connecticut School of Medicine, Farmington, CT. · Joseph and Kathleen Bryan Alzheimer's Disease Research Center, Duke University, Durham, NC; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC. Electronic address: guy.potter@duke.edu. ·Am J Geriatr Psychiatry · Pubmed #27555110.

ABSTRACT: OBJECTIVE: Identify depression symptoms during active late-life depression (LLD) that predict conversion to dementia. METHODS: The authors followed a cohort of 290 participants from the Neurocognitive Outcomes of Depression in the Elderly study. All participants were actively depressed and cognitively normal at enrollment. Depression symptom factors were derived from prior factor analysis: anhedonia and sadness, suicidality and guilt, appetite and weight loss, sleep disturbance, and anxiety and tension. Cox regression analysis modeled time to Alzheimer disease (AD) and non-AD dementia onset on depression symptom factors, along with age, education, sex, and race. Significant dementia predictors were tested for interaction with age at depression onset. RESULTS: Higher scores on the appetite and weight loss symptom factor were associated with an increased hazard of both AD and non-AD dementia. This factor was moderated by age at first depression onset, such that higher scores were associated with higher risk of non-AD dementia when depression first occurred earlier in life. Other depression symptom factors and overall depression severity were not related to risk of AD or non-AD dementia. CONCLUSION: Results suggest greater appetite/weight loss symptoms in active episodes of LLD are associated with increased likelihood of AD and non-AD dementia, but possibly via different pathways moderated by age at first depression onset. Results may help clinicians identify individuals with LLD at higher risk of developing AD and non-AD dementia and design interventions that reduce this risk.

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