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Depression Plays a Moderating Role in the Cognitive Decline Associated With Changes of Brain White Matter Hyperintensities.
Park JH, Lee SB, Lee JJ, Yoon JC, Han JW, Kim TH, Jeong HG, Newhouse PA, Taylor WD, Kim JH, Woo JI, Kim KW
(2018) J Clin Psychiatry 79:
MeSH Terms: Aged, Brain, Cognitive Dysfunction, Depressive Disorder, Major, Female, Humans, Magnetic Resonance Imaging, Male, Neuroimaging, Neuropsychological Tests, White Matter
Show Abstract · Added March 26, 2019
OBJECTIVE - In the elderly, depression and white matter hyperintensities (WMH) are common and associated with cognitive impairment. This study investigated the possible interactions between depression and WMH in their influences on cognition of the elderly.
METHODS - Using multiple neuropsychological tests, we evaluated the cognitive function of 122 community-dwelling elders with depression at baseline between November 2008 and February 2009. Major depressive disorder, dysthymic disorder, and minor depressive disorder were diagnosed according to DSM-IV criteria. Subsyndromal depressive disorder was operationally defined using a modification of DSM-IV criteria. We visually rated WMH severity according to the modified Fazekas scale and calculated WMH volume using an automated method. We defined WMH (+) as having a score of 2 or higher on the modified Fazekas scale. In the 3-year follow-up study, baseline participants were reassessed between November 2011 and February 2013 with the same methodology.
RESULTS - Baseline depression was associated with a decline over 3 years in the Categorical Verbal Fluency Test (VFT) (P = .001), Word List Memory Test (WLMT) (P = .019), Trail Making Test A (TMT-A) (P = .018), and Mini-Mental State Examination (MMSE) (P = .017), while baseline WMH (+) was associated with a decline in WLMT (P = .039) only. An increase of WMH volume over 3 years was associated with a decline in the performances of VFT (P = .044), WLMT (P = .044), Word List Recall Test (P = .040), Word List Recognition Test (P = .036), and TMT-A (P = .001) over the same period only in the subjects with depression at baseline.
CONCLUSIONS - Depressive disorder and WMH are interactively associated with the poor performance of multiple cognitive functions. Depressive disorder may moderate the cognitive decline associated with the changes of brain WMH.
© Copyright 2018 Physicians Postgraduate Press, Inc.
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11 MeSH Terms
Transdermal Nicotine for the Treatment of Mood and Cognitive Symptoms in Nonsmokers With Late-Life Depression.
Gandelman JA, Kang H, Antal A, Albert K, Boyd BD, Conley AC, Newhouse P, Taylor WD
(2018) J Clin Psychiatry 79:
MeSH Terms: Administration, Cutaneous, Affect, Aged, Cognitive Dysfunction, Depressive Disorder, Major, Female, Humans, Late Onset Disorders, Male, Middle Aged, Nicotine, Nicotinic Agonists, Non-Smokers
Show Abstract · Added March 26, 2019
OBJECTIVE - Late-life depression (LLD) is characterized by poor antidepressant response and cognitive dysfunction. This study examined whether transdermal nicotine benefits mood symptoms and cognitive performance in LLD.
METHODS - In a 12-week open-label outpatient study conducted between November 2016 and August 2017, transdermal nicotine was given to 15 nonsmoking older adults (≥ 60 years of age). Eligible participants met DSM-IV-TR criteria for major depressive disorder with ≥ 15 on the Montgomery-Asberg Depression Rating scale (MADRS) and endorsed subjective cognitive impairment. Transdermal nicotine patches were applied daily and titrated in a rigid dose escalation strategy to a maximum dose of 21.0 mg/d, allowing dose reductions for tolerability. The primary mood outcome was MADRS change measured every 3 weeks, with response defined as ≥ 50% improvement from baseline and remission as MADRS score ≤ 8. The primary cognitive outcome was the Conners Continuous Performance Test (CPT), a test of attention.
RESULTS - Robust rates of response (86.7%; 13/15 subjects) and remission (53.3%; 8/15 subjects) were observed. There was a significant decrease in MADRS scores over the study (β = -1.51, P < .001), with improvement seen as early as 3 weeks (Bonferroni-adjusted P value = .004). We also observed improvement in apathy and rumination. We did not observe improvement on the CPT but did observe improvement in subjective cognitive performance and signals of potential drug effects on secondary cognitive measures of working memory, episodic memory, and self-referential emotional processing. Overall, transdermal nicotine was well tolerated, although 6 participants could not reach the maximum targeted dose.
CONCLUSIONS - Nicotine may be a promising therapy for depressed mood and cognitive performance in LLD. A definitive placebo-controlled trial and establishment of longer-term safety are necessary before clinical usage.
TRIAL REGISTRATION - ClinicalTrials.gov identifier: NCT02816138​.
© Copyright 2018 Physicians Postgraduate Press, Inc.
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13 MeSH Terms
Advocating for mutually beneficial access to shelved compounds.
Pulley JM, Jerome RN, Shirey-Rice JK, Zaleski NM, Naylor HM, Pruijssers AJ, Jackson JC, Bernard GR, Holroyd KJ
(2018) Future Med Chem 10: 1395-1398
MeSH Terms: Antidiuretic Hormone Receptor Antagonists, Anxiety Disorders, Depressive Disorder, Major, Drug Industry, Drug Repositioning, Humans, Indoles, Pyrrolidines, Receptors, Vasopressin
Added March 26, 2019
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MeSH Terms
Predictors of recurrence in remitted late-life depression.
Deng Y, McQuoid DR, Potter GG, Steffens DC, Albert K, Riddle M, Beyer JL, Taylor WD
(2018) Depress Anxiety 35: 658-667
MeSH Terms: Activities of Daily Living, Age of Onset, Aged, Antidepressive Agents, Brain, Comorbidity, Depressive Disorder, Major, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Prognosis, Proportional Hazards Models, Recurrence, Remission Induction, Sex Factors, Social Support, Stress, Psychological, Suicidal Ideation
Show Abstract · Added March 26, 2019
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.
© 2018 Wiley Periodicals, Inc.
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MeSH Terms
Cognitive performance in antidepressant-free recurrent major depressive disorder.
Albert KM, Potter GG, McQuoid DR, Taylor WD
(2018) Depress Anxiety 35: 694-699
MeSH Terms: Adult, Cognitive Dysfunction, Depressive Disorder, Major, Female, Humans, Male, Middle Aged, Young Adult
Show Abstract · Added March 26, 2019
BACKGROUND - Cognitive complaints are common in depression, and cognition may be an important treatment target as cognitive problems often remain during remission and may contribute to recurrence risk. Previous studies of cognitive performance in depression have mainly examined late-life depression, with a focus on older adults, or assessed performance in specific cognitive tasks rather than cognitive domains.
METHODS - This study examined cognitive performance across multiple cognitive domains in antidepressant-free depressed adults with early onset recurrent depression compared to never-depressed controls. Domain scores were calculated for episodic memory, executive function, processing speed, and working memory, and the effect of depression diagnosis, depression severity, and depression duration on each domain score was examined, including interactions with age, sex, and education.
RESULTS - Currently depressed adults (n = 91) exhibited poorer performance in the processing speed domain compared with never-depressed adults (n = 105). Additionally, there was an interactive effect of depression duration and age on processing speed and executive function domain performance, such that performance was worse with older age and longer duration of depression. There were no effects of depression severity on performance across the cognitive domains.
CONCLUSIONS - These findings support that processing speed deficits appear in young adults with early onset depression that may not be related to current mood. Additionally, the effects of cumulative depressive episodes may interact with aging such that cognitive performance deficits worsen with recurrence over the lifespan.
© 2018 Wiley Periodicals, Inc.
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MeSH Terms
Time-varying effects of income on hippocampal volume trajectories in adolescent girls.
Ellwood-Lowe ME, Humphreys KL, Ordaz SJ, Camacho MC, Sacchet MD, Gotlib IH
(2018) Dev Cogn Neurosci 30: 41-50
MeSH Terms: Adolescent, Adolescent Development, Adult, Child, Depressive Disorder, Major, Female, Hippocampus, Humans, Income, Longitudinal Studies, Male, Middle Aged, Mother-Child Relations, Organ Size, Parents, Time Factors, Young Adult
Show Abstract · Added March 3, 2020
Children from lower-SES families exhibit smaller hippocampal volume than do their higher-SES peers. Few studies, however, have compared hippocampal developmental trajectories as a function of SES. Thus, it is unclear whether initial rank-order stability is preserved, or whether volumes diverge/converge over the course of adolescence. In a sample of 101 girls ages 10-24 years, we examined the longitudinal association between family income and parental education, proxies for SES, and changes in hippocampal volume. Hippocampal volume was obtained using MRI; using mixed modeling, we examined the effects of income and education on hippocampal volume across age. As expected, changes in volume were non-linear across development. Further, trajectories diverged in mid-adolescence, with lower-income girls exhibiting reductions in hippocampal volume. Maximal income-related differences were observed at 18 years, and trajectories converged thereafter. This interaction remained significant when accounting for maternal hippocampal volume, suggesting a unique contribution of environment over potential heritable differences. In contrast, the association between parental education and offspring hippocampal volume appeared to be stable across adolescence, with higher levels of parental education predicting consistently larger hippocampal volume. These findings constitute preliminary evidence that girls from lower-income homes exhibit unique trajectories of hippocampal growth, with differences most evident in late adolescence.
Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Anterior-posterior gradient differences in lobar and cingulate cortex cerebral blood flow in late-life depression.
Abi Zeid Daou M, Boyd BD, Donahue MJ, Albert K, Taylor WD
(2018) J Psychiatr Res 97: 1-7
MeSH Terms: Aged, Cerebral Cortex, Cerebrovascular Circulation, Depressive Disorder, Female, Gyrus Cinguli, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Thalamus, White Matter
Show Abstract · Added March 14, 2018
Vascular pathology is common in late-life depression, contributing to changes in cerebral function. We examined whether late-life depression was associated with differences in cerebral blood flow (CBF) and whether such differences were related to vascular risk and cerebrovascular pathology, specifically white matter hyperintensity (WMH) volumes. Twenty-three depressed elders and 20 age- and sex-matched elders with no psychiatric history completed cranial 3T MRI. MRI procedures included a pseudo-continuous Arterial Spin Labeling (pcASL) acquisition obtained while on room air and during a hypercapnia challenge allowing for calculation of cerebrovascular reactivity (CVR). Brain segmentation identified frontal, temporal, parietal and cingulate sub-regions in which CBF and CVR were calculated. The depressed group exhibited an anterior-posterior gradient in CBF, with lower CBF throughout the frontal lobe but higher CBF in the parietal lobe, temporal lobe, thalamus and hippocampus. A similar anterior to posterior gradient was observed in the cingulate cortex, with anterior regions exhibiting lower CBF and posterior regions exhibiting higher CBF. We did not observe any group differences in CVR measures. We did not observe significant relationships between CBF and CVR with vascular risk or WMH volumes, aside from an isolated finding associating higher WMH volumes with lower CBF in the rostral anterior cingulate cortex. Decreased anterior CBF in depressed elders might reflect decreased metabolic activity in these regions, while increased posterior CBF may represent either compensatory processes or different activity of posterior intrinsic functional networks. Future work should examine how these findings are related to compensatory changes with aging.
Copyright © 2017. Published by Elsevier Ltd.
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13 MeSH Terms
Psychosocial co-morbidities in Interstitial Cystitis/Bladder Pain syndrome (IC/BPS): A systematic review.
McKernan LC, Walsh CG, Reynolds WS, Crofford LJ, Dmochowski RR, Williams DA
(2018) Neurourol Urodyn 37: 926-941
MeSH Terms: Anxiety Disorders, Comorbidity, Cystitis, Interstitial, Depressive Disorder, Humans, Pain, Prevalence
Show Abstract · Added September 16, 2019
AIMS - Psychosocial factors amplify symptoms of Interstitial Cystitis (IC/BPS). While psychosocial self-management is efficacious in other pain conditions, its impact on an IC/BPS population has rarely been studied. The objective of this review is to learn the prevalence and impact of psychosocial factors on IC/BPS, assess baseline psychosocial characteristics, and offer recommendations for assessment and treatment.
METHOD - Following PRISMA guidelines, primary information sources were PubMed including MEDLINE, Embase, CINAHL, and GoogleScholar. Inclusion criteria included: (i) a clearly defined cohort with IC/BPS or with Chronic Pelvic Pain Syndrome provided the IC/BPS cohort was delineated with quantitative results from the main cohort; (ii) all genders and regions; (iii) studies written in English from 1995 to April 14, 2017; (iv) quantitative report of psychosocial factors as outcome measures or at minimum as baseline characteristics.
RESULTS - Thirty-four of an initial 642 articles were reviewed. Quantitative analyses demonstrate the magnitude of psychosocial difficulties in IC/BPS, which are worse than average on all measures, and fall into areas of clinical concern for 7 out of 10 measures. Meta-analyses shows mean Mental Component Score of the Short-Form 12 Health Survey (MCS) of 40.80 (SD 6.25, N = 2912), where <36 is consistent with severe psychological impairment. Averaged across studies, the population scored in the range seen in clinical depression (CES-D 19.89, SD 13.12, N = 564) and generalized anxiety disorder (HADS-A 8.15, SD 4.85, N = 465).
CONCLUSION - The psychological impact of IC/BPS is pervasive and severe. Existing evidence of treatment is lacking and suggests self-management intervention may be helpful.
© 2017 Wiley Periodicals, Inc.
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7 MeSH Terms
Longitudinal Cognitive Outcomes of Clinical Phenotypes of Late-Life Depression.
Riddle M, Potter GG, McQuoid DR, Steffens DC, Beyer JL, Taylor WD
(2017) Am J Geriatr Psychiatry 25: 1123-1134
MeSH Terms: Age of Onset, Aged, Aging, Attention, Cognitive Dysfunction, Comorbidity, Depressive Disorder, Executive Function, Female, Humans, Longitudinal Studies, Male, Memory, Episodic, Memory, Short-Term, Middle Aged, Phenotype, Remission Induction
Show Abstract · Added March 14, 2018
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.
Published by Elsevier Inc.
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17 MeSH Terms
CADASIL as a Useful Medical Model and Genetic Form of Vascular Depression.
Park JH, Jeon BH, Lee JS, Newhouse PA, Taylor WD, Boyd BD, Kim KW, Kim MD
(2017) Am J Geriatr Psychiatry 25: 719-727
MeSH Terms: Adult, Aged, CADASIL, Depression, Depressive Disorder, Major, Female, Genotype, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuroimaging, Republic of Korea, White Matter
Show Abstract · Added March 14, 2018
OBJECTIVE - The main magnetic resonance imaging (MRI) findings of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) are white matter hyperintensities (WMHs), lacunar infarctions, and cerebral microbleeds (CMBs). The purpose of this study was to investigate the effects of these three neuroimaging markers of CADASIL on depression to determine whether CADASIL is a useful medical model supporting the vascular depression hypothesis.
METHODS - Eighty-four subjects with CADASIL, aged 34-86 years, participated in this study. They underwent comprehensive clinical evaluation, including 3T MRI and genotyping of NOTCH3. The effects of WMH, lacunar infarctions, and CMBs were analyzed by path analyses and multivariate logistic regression analyses.
RESULTS - Patients with CADASIL exhibited frequencies of 17.9% for major depressive disorder (MDD) and 10.7% for minor depressive disorder. The frequency of MDD increased from 5.0% to 46.2% as WMH volume increased from first quartile to fourth quartile. WMH volume (OR: 1.03, 95% CI: 1.003-1.06) in patients with CADASIL was associated with the current depressive disorder. Path analyses demonstrated that only WMH volume was associated with the Korean version of the short form Geriatric Depression Scale score, Center for Epidemiologic Studies Depression Scale score, and 17-item Hamilton depression scale score. The effects of lacunar infarctions and CMBs on depression were not significant in path analyses and multivariate logistic regression analyses.
CONCLUSIONS - This study demonstrates that WMHs are closely associated with depression in patients with CADASIL. This supports that CADASIL might be a useful medical model and genetic form of vascular depression.
Copyright © 2017. Published by Elsevier Inc.
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14 MeSH Terms