Who benefits most from expectancy effects? A combined neuroimaging and antidepressant trial in depressed older adults.
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ABSTRACT:
SUBMITTER: Zilcha-Mano S
PROVIDER: S-EPMC8443672 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Suicide is a public health concern in older adults. Recent cross sectional studies suggest that impairments in executive functioning, memory and attention are associated with suicidal ideation in older adults. It is unknown whether these neuropsychological features predict persistent suicidal ideation. We analyzed data from 468 individuals ≥ age 60 with major depression who received venlafaxine XR monotherapy for up to 16 weeks. We used latent class growth modeling to classify groups of individuals based on trajectories of suicidal ideation. We also examined whether cognitive dysfunction predicted suicidal ideation while controlling for time-dependent variables including depression severity, and age and education. The optimal model using a zero inflated Poisson link classified individuals into four groups, each with a distinct temporal trajectory of suicidal ideation: those with 'minimal suicidal ideation' across time points; those with 'low suicidal ideation'; those with 'rapidly decreasing suicidal ideation'; and those with 'high and persistent suicidal ideation'. Participants in the 'high and persistent suicidal ideation' group had worse scores relative to those in the "rapidly decreasing suicidal ideation" group on the Color-Word 'inhibition/switching' subtest from the Delis-Kaplan Executive Function Scale, worse attention index scores on the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and worse total RBANS index scores. These findings suggest that individuals with poorer ability to switch between inhibitory and non-inhibitory responses as well as worse attention and worse overall cognitive status are more likely to have persistently higher levels of suicidal ideation. CLINICALTRIAL.Gov numberNCT00892047.
| S-EPMC4738173 | biostudies-literature
Project description:RationalePremature discontinuation of antidepressant drugs is a frequent clinical problem. Adverse effects are common, occur early on in treatment and are reported to be one of the main reasons for discontinuation of antidepressant treatment.ObjectivesTo investigate the association between adverse effects occurring in the first 2 weeks of antidepressant treatment and discontinuation by 6 weeks as the outcome. To investigate the time profile of adverse effects induced by the selective serotonin reuptake inhibitor citalopram and the noradrenaline reuptake inhibitor reboxetine over 12 weeks of treatment.MethodsSix hundred and one depressed individuals were randomly allocated to either citalopram (20 mg daily) or reboxetine (4 mg twice daily). A modified version of the Toronto Side Effects Scale was used to measure 14 physical symptoms at baseline (medication free) and at 2, 6 and 12 weeks after randomisation.ResultsIndividuals randomised to reboxetine reported a greater number of adverse effects and were more likely to stop treatment than individuals receiving citalopram. Dizziness (OR 1.83; 95% CI 1.09, 3.09; p = 0.02) and the total number of adverse effects (OR 1.12; 95% CI 1.00, 1.25; p = 0.06) reported at 2 weeks were associated with discontinuation from overall antidepressant treatment by 6 weeks. Reports of adverse effects tended to reduce throughout the 12 weeks for both antidepressants.ConclusionsThe majority of adverse effects were not individually associated with discontinuation from antidepressant treatment. Reports of physical symptoms tended to reduce over time. The physical symptoms that did not reduce over time may represent symptoms of depression rather than antidepressant-induced adverse effects.
| S-EPMC4099525 | biostudies-literature
Project description:Placebo responses in depression exemplify how expectancies and appraisals impact mood. Cognitive and neural mechanisms underlying these responses are still poorly understood, partly due to the difficulty of simulating antidepressant effects and manipulating mood experimentally. To address these challenges, we developed an acute antidepressant placebo experiment involving the intravenous administration of a "fast-acting antidepressant" and a trial-by-trial sham fMRI "neurofeedback" manipulation, purporting to reveal mood-relevant neural responses. Twenty volunteers with major depression underwent this experiment while rating their expected and actual mood improvement. Mixed-effects analyses of trial-by-trial ratings revealed that the "drug" infusion cues induced higher expectancies of mood improvement, while both the "drug" infusion cue and the sham neurofeedback induced a reported mood improvement. Neurofeedback of greater magnitude, compared to lower magnitude, recruited the lateral prefrontal cortex (lPFC). Individuals with greater lPFC responses to neurofeedback displayed: (1) greater effect of previous mood improvement on expectancy ratings and (2) greater effect of sham neurofeedback on mood improvement. Behavioral antidepressant placebo effects were additionally moderated by changes in peripheral β-endorphin plasma levels and depressive symptomatology. These data demonstrate the feasibility of trial-by-trial manipulation of antidepressant placebo-associated expectancies and their reinforcement. We provide initial insights into the role of the lPFC in the interplay between placebo-induced expectancies and mood, as well as preliminary evidence for the role of the opioid system in antidepressant placebo effects.
| S-EPMC6189213 | biostudies-literature
Project description:BackgroundPatient expectancy of therapeutic improvement is a primary mediator of placebo effects in antidepressant clinical trials, but its mechanisms are poorly understood. This study employed a novel antidepressant trial design, with integrated functional magnetic resonance imaging (fMRI), to manipulate patient outcome expectancy and examine its neural mediators.MethodTwenty-three depressed outpatients, in a randomized controlled trial were assigned to either Open (high outcome expectancy) or Placebo-controlled (low outcome expectancy) treatment with citalopram for eight weeks. fMRI scans were acquired before and after the expectancy manipulation (before medication treatment), while participants performed a masked emotional face task. Focusing on an amygdala region-of-interest (ROI), we tested a model where reduction in amygdala activation mediated outcome expectancy effects on the slope of change in depressive symptoms.ResultsFollowing the manipulation, significant differences between conditions were found in neural activation changes in the amygdala, as well as in superior temporal gyrus, insula, and thalamus. Findings support the proposed mediation model according to which activation in the left amygdala ROI decreased significantly in the Open as opposed to the Placebo-controlled group following randomization (p = 0.009) for sad vs. neutral face contrast. The reduced left amygdala activation, in turn, was a significant predictor of decreased depressive symptoms during the trial (p = 0.007), and the mediation model was significant.ConclusionsResults from this study, the first designed to identify the neural mechanisms of expectancy augmentation in an antidepressant randomized control trial, suggest that therapeutic modulation of amygdala activity may be an important pathway by which patient outcome expectancy influences depressive symptoms. CLINICALTRIALS.Gov identifierNCT01919216; Trial name: Placebo Effects in the Treatment of Depression: Cognitive and Neural Mechanisms, URL: https://clinicaltrials.gov/ct2/show/NCT01919216.
| S-EPMC6790474 | biostudies-literature
Project description:ObjectivesThe Medicare Health Outcome Survey (HOS) is the largest longitudinal survey of the U.S. community-dwelling elderly population. This study estimated total life expectancy, active life expectancy (ALE), and disability-free life expectancy (DFLE) by disability status among HOS participants.MethodsData were from the Medicare HOS Cohort 15 (baseline 2012, follow-up 2014). We included respondents aged ≥ 65 years (n = 164,597). Participants' disability status was assessed based on the following six activities of daily living (ADL): bathing, dressing, eating, getting in or out of chairs, walking, and using the toilet. The multi-state models were used to estimate life expectancy, ALE, and DFLE by participants' baseline disability status and age.ResultsPersons who had higher-level ADL limitations had a shorter life expectancy, ALE, and DFLE. Also persons with disability had greater expected life years with disability than those with no limitations and those with mild limitations. For example, among 65-year old respondents with no limitations, mild limitations, and disability, life expectancy was 19.9, 18.6, and 17.1 years, respectively; ALE was 14.0, 9.5, and 7.2 years, respectively; DFLE was 17.3, 15.2, and 11.4 years, respectively; and expected years with disability was 2.6, 3.4, and 5.7 years, respectively.ConclusionsThis study demonstrated that greater levels of disability adversely impact life expectancy, ALE, DFLE, and expected number of years with a disability among U.S. older adults. Understanding levels of disability, and how these may change over time, would enhance health care quality and planning services related to home care and housing in this community-dwelling population.
| S-EPMC7518583 | biostudies-literature
Project description:Background To evaluate the training effects of whole body vibration (WBV) combined with weighted vest (WV) in older adults. Methods This randomized controlled trial study was conducted in healthy older adults living in the community. Fifty-one participants were randomly allocated into 3 groups: group 1 (n = 17), WBV alone, training on WBV at a frequency 30 Hz, amplitude 2 mm, 10 sets of 1 min squats, with 60 s rest, group 2 (n = 15), WV alone, squat exercise, 10 sets of 1 min, with 60 s rest, while WV loaded with 10% body weight and group 3 (n = 19), WBV + WV, combining WBV exercise with the addition of a WV. All groups completed training 3 times per week for 8 weeks. The outcomes were total muscle mass, muscle thickness, maximal isometric strength, single-leg-stance and timed-up-and-go evaluated at baseline and after training. Results As a result of training all groups improved their isometric muscle strength with little difference between groups. The single-leg-stance significantly improved only in WBV + WV group 25.1 ± 10.8 s (mean ± 95% CI, p < 0.01). The timed-up-and-go improved in all groups, but the improvement was significantly greater in the WBV + WV group (17.5 ± 6.9%) compared to the WV (8.5 ± 3.2%) and WBV groups (9.2 ± 5.4%, p = 0.043, 0.023 respectively). Rectus femoris muscle thickness and total muscle mass were significantly increased in all groups equally with little difference between groups. Conclusion The combined WBV + WV had a greater effect on the single-leg-stance and the timed-up-and-go compared to WV or WBV alone. Trial registration TCTR20190306001. Thai Clinical Trials Registry (www.thaiclinicaltrials.org). Date of registration: 6 March 2019. Supplementary Information The online version contains supplementary material available at 10.1186/s12877-022-03593-4.
| S-EPMC9703755 | biostudies-literature
Project description:The objective of the current study was to examine the relationship between the COMT Val(158)Met polymorphism and neuropsychological performance in depressed and nondepressed older adults.One hundred and twenty-six clinically depressed older adults and 105 nondepressed comparison participants were compared on neuropsychological performance and COMT Val(158)Met (Val/Val, Val/Met, Met/Met).Based on multivariate regression models, the COMT Val(158)Met polymorphism was not associated with cognitive performance among depressed or nondepressed individuals, nor did this polymorphism account for the fact that depressed individuals performed worse than nondepressed individuals on several neuropsychological tests that are typically affected by depression. There was also no difference in frequency of the COMT Val(158)Met alleles between depressed and nondepressed individuals.Although the current study found no association between COMT Val(158)Met polymorphism on a number of clinical neuropsychological tests that are typically found to be sensitive to depression, differential effects of the COMT Val(158)Met polymorphism on dopamine transmission in psychiatric and non-psychiatric populations may be further clarified by clinical research with neuroscience-based paradigms that segregate cognitive tasks into component processes with precise neural substrates, particularly with respect to the complex functions of the prefrontal cortex. Negative results can be important to narrowing down target processes and understanding the influence of clinical and demographic characteristics in studies of psychiatric genetics.
| S-EPMC3793427 | biostudies-other
Project description:Monoamine dysfunction, particularly of the serotonin system, has been the dominant hypothesis guiding research and treatment development in affective disorders. The majority of research has been performed in midlife depressed adults. The importance of understanding the neurobiology of depression in older adults is underscored by increased rates of mortality and completed suicide and an increased risk of Alzheimer's dementia. To evaluate the dynamic response of the serotonin system, the acute effects of citalopram infusion on cerebral glucose metabolism was measured in depressed older adults and control subjects. The hypothesis was tested that smaller decreases in metabolism would be observed in cortical and limbic regions in depressed older adults relative to control subjects.Sixteen depressed older adults and 13 control subjects underwent two resting positron emission tomography (PET) studies with the radiotracer [18F]-2-deoxy-2-fluoro-D-glucose after placebo and citalopram infusions.In control subjects compared with depressed older adults, greater citalopram-induced decreases in cerebral metabolism were observed in the right anterior cingulate, middle temporal (bilaterally), left precuneus, and left parahippocampal gyri. Greater decreases in the depressed older adults than control subjects were observed in left superior and left middle frontal gyri and increases in left inferior parietal lobule, left cuneus, left thalamus, and right putamen.In depressed older adults relative to control subjects, the cerebral metabolic response to citalopram is blunted in cortico-cortical and cortico-limbic pathways and increased in the left hemisphere (greater decrease interiorly and increases posteriorly). These findings suggest both blunted and compensatory cerebral metabolic responses to citalopram in depressed older adults.
| S-EPMC2706292 | biostudies-literature
Project description:BACKGROUND:Previous studies suggest that low emotional resilience may correspond with increased or over-active amygdala function. Complementary studies suggest that emotional resilience increases with age; older adults tend to have decreased attentional bias to negative stimuli compared to younger adults. Amygdala nuclei and related brain circuits have been linked to negative affect, and depressed patients have been demonstrated to have abnormal amygdala function. METHODS:In the current study, we correlated psychological resilience measures with amygdala function measured with resting-state arterial spin-labelled (ASL) and blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in older adults with and without depression. Specifically, we targeted the basolateral, centromedial, and superficial nuclei groups of the amygdala, which have different functions and brain connections. RESULTS:High levels of psychological resilience correlated with lower basal levels of amygdala activity measured with ASL fMRI. High resilience also correlated with decreased connectivity between amygdala nuclei and the ventral default-mode network independent of depression status. Instead, lower depression symptoms were associated with higher connectivity between the amygdalae and dorsal frontal networks. LIMITATIONS:Future multi-site studies with larger sample size and improved neuroimaging technologies are needed. Longitudinal studies that target resilience to naturalistic stressors will also be a powerful contribution to the field. CONCLUSIONS:Our results suggest that resilience in older adults is more closely related to function in ventral amygdala networks, while late-life depression is related to reduced connectivity between the amygdala and dorsal frontal regions.
| S-EPMC5995579 | biostudies-literature
Project description:BackgroundPrecision medicine, optimized interventions, and access to care are catchphrases for the future of behavioral treatments. Progress has been slow due to the dearth of clinical trials that optimize interventions' benefits, individually tailor interventions to meet individual needs and preferences, and lead to rapid implementation after effectiveness is demonstrated. Two innovations have emerged to meet these challenges: fully remote trials and precision clinical trials.ObjectiveThis paper provides a detailed description of Mindful MyWay, a study designed to test online mindfulness training in older adults with depression. Consistent with the concept of fully remote trials using a smartphone app, the study requires no in-person contact and can be conducted with participants anywhere in the United States. Based upon the precision medicine framework, the study assesses participants using high-frequency assessments of symptoms, cognitive performance, and patient preferences to both understand the individualized nature of treatment response and help individually tailor the intervention.MethodsMindful MyWay is an open-label early-phase clinical trial for individuals 65 years and older with current depression. A smartphone app was developed to help coordinate the study, deliver the intervention, and evaluate the acceptability of the intervention, as well as predictors and outcomes of it. The curriculum for the fully remote intervention parallels the mindfulness-based stress reduction curriculum, a protocolized group-based mindfulness training that is typically provided in person. After consent and screening, participants download The Healthy Mind Lab mobile health smartphone app from the Apple App Store, allowing them to complete brief smartphone-based assessments of depressive symptoms and cognitive performance 4 times each day for 4 weeks prior to and after completing the intervention. The intervention consists of an introduction video and 10 weekly mindfulness training sessions, with the expectation to practice mindfulness at home daily. The app collects participant preference data throughout the 10-week intervention period; these high-frequency assessments identify participants' individually dynamic preferences toward the goal of optimizing the intervention in future iterations.ResultsParticipant recruitment and data collection began in March 2019. Final end point assessments will be collected in May 2022. The paper describes lessons learned regarding the critical role of early-phase testing prior to moving to a randomized trial.ConclusionsThe Mindful MyWay study is an exemplar of innovative clinical trial designs that use smartphone technology in behavioral and neuropsychiatric conditions. These include fully remote studies that can recruit throughout the United States, including hard-to-access areas, and collect high-frequency data, which is ideal for idiographic assessment and individualized intervention optimization. Our findings will be used to modify our methods and inform future randomized controlled trials within a precision medicine framework.Trial registrationClinicalTrials.gov NCT03922217; https://clinicaltrials.gov/ct2/show/NCT03922217.International registered report identifier (irrid)DERR1-10.2196/39233.
| S-EPMC9650569 | biostudies-literature