Charles F Reynolds

• University of Pittsburgh

Objectives Ableism—discrimination and social prejudice against people with disabilities—defines people by their disability and assumes that disabled people require fixing. We sought to characterize ableism after critical illness and to describe its relationship with care delivery. Design A secondary analysis of semi-structured individual interview...

Background Late‐life depression (LLD) often coincides with cognitive decline, impacting antidepressant treatment outcomes. Investigating the genetic profile of cognitive function and its association with antidepressant response in individuals with LLD is crucial. Method In the Incomplete Response in Late‐Life Depression: Getting to Remission (IRL‐...

Background There is an urgent need to identify novel, accessible and affordable strategies to prevent cognitive decline and progression in the Alzheimer disease and related dementias (ADRD) continuum. Vitamin D3 and marine omega‐3 fatty acids (omega‐3s) supplements show promise for cognitive protection, with potential variations in their effects by...

Although evidence-based treatments for Prolonged Grief Disorder (PGD) exist, pretreatment characteristics associated with differential improvement trajectories have not been identified. To identify clinical factors relevant to optimizing PGD treatment outcomes, we used unsupervised and supervised machine learning to study treatment effects from a d...

As the numbers of older adults continue to increase globally, the need for facilitating healthy aging has become critical. While a physically healthy lifestyle, including exercise and diet, is important, recent research has highlighted a major impact of psychosocial determinants of health, such as resilience, wisdom, positive social connections, an...

Rationale: Individuals acting as surrogate decision-makers for critically ill patients frequently struggle in this role and experience high levels of long-term psychological distress. Prior interventions designed solely to improve information sharing between clinicians and family members have been ineffective. Objectives: To examine the impact o...

Late-life depression (LLD) is often accompanied by medical comorbidities such as psychiatric disorders and cardiovascular diseases, posing challenges to antidepressant treatment. Recent studies highlighted significant associations between treatment-resistant depression (TRD) and polygenic risk score (PRS) for attention deficit hyperactivity disorde...

Background/objective To examine the cognitive benefits of 6 months of prescribed intermittent exercise (10-min bouts totaling 150 weekly minutes) in community-dwelling older adults, comparing effects of low-intensity movement (LIM) and moderate-intensity aerobic exercise (aerobic exercise; AE) training; and exploring biological mechanisms of exerci...

Introduction Alcohol and substance use are increasing in older adults, many of whom have depression, and treatment in this context may be more hazardous. We assessed alcohol and other substance use patterns in older adults with treatment‐resistant depression (TRD). We examined patient characteristics associated with higher alcohol consumption and e...

Introduction Late-life treatment-resistant depression (LL-TRD) is common and increases risk for accelerated ageing and cognitive decline. Impaired sleep is common in LL-TRD and is a risk factor for cognitive decline. Slow wave sleep (SWS) has been implicated in key processes including synaptic plasticity and memory. A deficiency in SWS may be a cor...

Background To date, no intervention has definitively improved outcomes for families of critical illness survivors. An integrated perspective on caregivers’ needs after critical illness could help identify high-priority intervention targets and improve outcomes. Objectives To obtain diverse perspectives on the needs, barriers and facilitators, and...

Prolonged grief disorder (PGD) is associated with impairments in cognitive functioning, but the neuropsychological correlates of early grief in older adults are poorly understood. This preliminary study cross-sectionally examined neuropsychological functioning in bereaved adults with high and low grief symptoms and a non-bereaved comparison sample...

Objective:To test vitamin D3 and omega-3s for late-life depression prevention under the National Academy of Medicine framework for indicated (targeting subthreshold depression) and selective (targeting presence of high-risk factors) prevention. Methods:VITamin D and OmegA-3 TriaL (VITAL) is a 2x2 factorial trial of vitamin D3 (2000 IU/day) and/or o...

In this study, we aimed to improve upon a published population pharmacokinetic (PK) model for venlafaxine (VEN) in the treatment of depression in older adults, then investigate whether CYP2D6 metabolizer status affected model‐estimated PK parameters of VEN and its active metabolite O‐desmethylvenlafaxine. The model included 325 participants from a...

Many older adults lost their spouse or life partner to COVID-19. Despite the anticipated rise in the prevalence of prolonged grief disorder, the association between COVID-19 bereavement and symptoms of complicated (or pathological) grief in community-dwelling older adults remains unclear. This study compared six clinically meaningful complicated gr...

BACKGROUND Apolipoprotein E (APOE)-ε4 allele is associated with cognitive decline; however, its potential to modify effects of vitamin D3 and omega-3s supplementation on later-life cognition is unclear. Our objectives were to estimate among the in-clinic subset of a randomized trial: 1) associations between APOE-ε4 and global and domain-specific co...

Objective: To examine whether psychological well-being, sleep, and suicidality improved with treatment with intravenous (IV) ketamine for late-life treatment-resistant depression (TRD). Methods: This is an analysis of secondary outcomes in an open-label late-life TRD study examining the safety, tolerability, and feasibility of IV ketamine infusi...

Late-life depression (LLD) is a heterogenous mood disorder influenced by genetic factors. Cortical physiological processes such as cortical inhibition, facilitation, and plasticity may be markers of illness that are more strongly associated with genetic factors than the clinical phenotype. Thus, exploring the relationship between genetic factors an...

Background Associations between epigenetic aging with cognitive aging and neuropsychiatric measures are not well-understood. Objective 1) To assess cross-sectional correlations between second-generation DNA methylation (DNAm)-based clocks of healthspan and lifespan (i.e., GrimAge, PhenoAge, and DNAm-based estimator of telomere length [DNAmTL]) and...

This study: 1) examined cross-sectional and longitudinal relations of serum brain-derived neurotrophic factor (BDNF) to late-life depression (LLD); 2) tested effects of vitamin D3 and omega-3s on change in BDNF; 3) explored modifying or mediating roles of BDNF on effects of vitamin D3 and omega-3s for LLD. We selected 400 adults from a completed tr...

Background: The benefits and risks of augmenting or switching antidepressants in older adults with treatment-resistant depression have not been extensively studied. Methods: We conducted a two-step, open-label trial involving adults 60 years of age or older with treatment-resistant depression. In step 1, patients were randomly assigned in a 1:1:...

Background Over half of critical illness survivors have new or worsened functional impairments. Yet, the United States lacks wide-scale transitional care infrastructure to promote wellbeing and prevent rehospitalization after critical illness. Evidence-based transitional care interventions urgently need to be adapted to address this gap. Thus, as a...

Objective: To investigate the relationship between lean muscle mass and treatment response in treatment-resistant late-life depression (TR-LLD). We hypothesized that lower lean muscle mass would be associated with older age, higher physical comorbidities, higher depressive symptom severity, and poorer treatment response. Design: Secondary analys...

Bereaved older adults experiencing high grief in the first year after an attachment loss is at increased risk for prolonged grief disorder (PGD) via unknown mechanisms. Yearning, a core grief symptom, is linked to the ventral striatal (VS) brain function, but the role of this neuronal system in late-life grief is poorly understood. As a first step,...

Background : Evidence-based treatment options for late-life treatment-resistant depression (TRD) are limited. Ketamine is a promising treatment for TRD; however, there is a paucity of data on its safety and efficacy in older adults. Methods : In this pilot clinical trial, 25 adults aged ≥60 years with TRD received IV ketamine openly twice a week f...

Background: Late-life depression (LLD) is common and associated with excessive age-related medical morbidity, cognitive decline, and increased mortality risk. Previous research has suggested that at least a subset of individuals with LLD experience accelerated aging. In addition, previous studies have implicated the role of cellular senescence, a h...

Background Despite the high prevalence of depression and disruption to 24-h sleep-wake routines following the death of a spouse in late-life, no bereavement interventions have been developed to re-entrain a regular sleep-wake routine among older widow(er)s. We describe the rationale and methodology of the NIH-funded WELL Study (Widowed Elders' Life...

Background Predictors of antidepressant response in older patients with major depressive disorder (MDD) need to be confirmed before they can guide treatment. Objective To create decision trees for early identification of older patients with MDD who are unlikely to respond to 12 weeks of antidepressant treatment, we analysed data from 454 older par...

The world's population is aging, bringing about an ever‐greater burden of mental disorders in older adults. Given multimorbidities, the mental health care of these people and their family caregivers is labor‐intensive. At the same time, ageism is a big problem for older people, with and without mental disorders. Positive elements of aging, such as...

Importance: Evidence regarding the nature and prevalence of 24-hour activity pattern phenotypes in older adults, especially those related to depression symptoms and cognition, is needed to guide the development of targeted mechanism research and behavioral interventions. Objectives: To identify subgroups of older adults with similar 24-hour acti...

Objective In older adults, major depressive disorder (MDD) is associated with accelerated physiological and cognitive aging, generating interest in uncovering biological pathways that may be targetable by interventions. Growth differentiation factor-15 (GDF-15) plays a significant role in biological aging via multiple biological pathways relevant t...

Objective The purpose of the study was to develop and validate a model to predict the risk of experiencing a fall for nursing home residents utilizing data that are electronically available at the more than 15 000 facilities in the United States. Materials and Methods The fall prediction model was built and tested using 2 extracts of data (2011 th...

Within many societies and cultures around the world, older adults are too often undervalued and underappreciated. This exacerbates many key challenges that older adults may face. It also undermines the many positive aspects of late life that are of tremendous value at both an individual and societal level. We propose a new approach to elevate healt...

Objective: To identify critical illness survivors' perceived barriers and facilitators to resuming performance of meaningful activities when transitioning from hospital to home. Design: Secondary content analysis of semistructured interviews about patients' experiences of intensive care (primary analysis disseminated on the patient-facing websit...

Objective: Sleep changes over the human lifespan, and it does so across multiple dimensions. We used individual-level cross-sectional data to characterize age trends and sex differences in actigraphy and self-report sleep dimensions across the healthy human lifespan. Methods: The Pittsburgh Lifespan Sleep Databank (PLSD) consists of harmonized p...

Background The magnitude of the placebo response depends on both the modality used as the “placebo” and the intervention with which it is compared, both of which can complicate the interpretation of randomized controlled trials (RCTs) for depression in late life. Given that neurostimulation and pharmacotherapy are among the most common intervention...

Importance Marine omega-3 fatty acid (omega-3) supplements have been used to treat depression but their ability to prevent depression in the general adult population is unknown. Objective To test effects of omega-3 supplementation on late-life depression risk and mood scores. Design, Setting, and Participants A total of 18 353 adults participated...

Background: Loneliness is one of the most distressing grief symptoms and is associated with adverse mental health in bereaved older adults. The endocannabinoid signaling (ECS) system is stress-responsive and circulating endocannabinoid (eCB) concentrations are elevated following bereavement. This study examined the association between loneliness an...

Background: In the past few decades, there is growing evidence that the growth differentiation factor-15 (GDF-15) plays a significant role in aging and multi-system disease development. The GDF-15 has a largely pleotropic effect and has been associated with both the development of cancers, metabolic, inflammatory, and cardiovascular diseases. Emerg...

Background: Treatment-resistant depression in late-life (TRLLD) is common. Perspectives of primary care providers (PCPs) and psychiatrists treating TRLLD could give insights into the challenges and potential solutions for managing this condition. Methods: To identify perspectives of providers who treat TRLLD, we conducted a qualitative descripti...

Background Genome‐wide DNA methylation assay (DNAm) reflects epigenetic aging and differences in gene expression, and may help to elucidate the role of systemic aging in cognitive decline. Neuropsychiatric symptoms (NPS) are common in mild cognitive impairment (MCI) and may increase the risk of progression to dementia. However, few investigations h...

Machine-assisted treatment selection commonly follows one of two paradigms: a fully personalized paradigm which ignores any possible clustering of patients; or a sub-grouping paradigm which ignores personal differences within the identified groups. While both paradigms have shown promising results, each of them suffers from important limitations. I...

Objectives To determine associations between geographic region and late-life depression (LLD) severity, item-level symptom burden, and treatment; to evaluate whether racial/ethnic disparities in LLD, previously observed in the overall sample, vary by region. Methods We included 25,502 VITAL (Vitamin D and Omega-3 Trial) participants and administer...

Background The experimental therapeutics approach that combines a placebo-controlled clinical trial with translational neuroscience methods can provide a better understanding of both the clinical and physiological effects of pharmacotherapy. We aimed to test the efficacy and tolerability of low-dose augmentation with buprenorphine (BPN) for treatme...

Objectives Morning activation deficits (MADs) correlate with depression symptom persistence in older dementia caregivers. To clarify the potential of MADs as a target for depression interventions, we aimed to: (1) adapt an existing behavioral activation program, Engage therapy, to target mornings; and (2) evaluate effects on self-reported MADs and...

The Care Transitions Intervention (CTI) is an evidence-based intervention aimed at supporting the transition from hospital back to the community for patients to ultimately reduce preventable re-hospitalization. In a pilot randomized controlled trial, we examined the preliminary effectiveness of an Enhanced Care Transitions Intervention (ECTI), CTI...

Background Antidepressants are a first line treatment for depression. However, only a third of individuals remit after the first treatment. Common genetic variation likely regulates, in part, antidepressant response, yet the success of previous genome-wide association studies has been limited by sample size. This study performs the largest genetic...

Background Older adults with late-life depression (LLD) often experience incomplete or lack of response to first-line pharmacotherapy. The treatment of LLD could be improved using objective biological measures to predict response. Transcranial magnetic stimulation (TMS) can be used to measure cortical excitability, inhibition, and plasticity, which...

Objective: Posttraumatic stress disorder and prolonged grief disorder (PGD) arise following major life stressors and may share some overlapping symptomatology. This study aimed to examine the presence and response to treatment of posttraumatic stress symptoms (PTSS) in bereaved adults with a primary diagnosis of PGD. Methods: A randomized contro...

Introduction Accelerated biological aging is related to worse brain aging. However, the interface of Alzheimer's Disease (AD) and the biology of aging is little understood. The study of epigenetics and epigenetic aging may yield advances in prevention and treatment of AD by identifying new therapeutic targets or approaches. Further, signals from ep...

Introduction: System-level care coordination strategies can be the most effective to promote continuity of care among people with Alzheimer's disease; however, the evidence is lacking. The objective of this study is to determine whether accountable care organizations are associated with lower rates of potentially preventable hospitalizations for p...

Objective: Novel approaches are needed to assist rural primary care physicians (PCPs) in caring for older patients living with depression and pain who are at an elevated suicide risk. To refine and improve a model of care (PREDICTOR: Pharmacy Identification and Primary Care Intervention of Older Adults at Risk for Suicide), we conducted qualitativ...

Late-life depression (LLD) is associated with an increased risk of developing dementia; however, it is not known whether individuals with a history of LLD exhibit a more rapid rate of cognitive decline. We aimed to determine whether those with LLD experienced faster cognitive decline compared with never-depressed control (NDC) participants from the...

Background/objectives: The number of older adults with complex health needs is growing, and this population experiences disproportionate morbidity and mortality. Interventions led by community health workers (CHWs) can improve clinical outcomes in the general adult population with multimorbidity, but few studies have investigated CHW-delivered int...

Antidepressant outcomes in older adults with depression is poor, possibly because of comorbidities such as cerebrovascular disease. Therefore, we leveraged multiple genome-wide approaches to understand the genetic architecture of antidepressant response. Our sample included 307 older adults (≥60 years) with current major depression, treated with ve...

Rural communities need access to effective interventions that can prevent functional decline among a growing population of older adults. We describe the conceptual framework and rationale for a multicomponent intervention (“Mind, Mood, Mobility”) delivered by Area Agency on Aging staff for rural older adults at risk for functional decline due to ea...

We examined features of everyday activities (capacity and frequency) between older adults with and without cognitive impairment over 12 months. Participants aged ≥60 years and at risk for depression were included (n = 260); 26% ( n = 69) had an acquired cognitive impairment at baseline. Cognitive impairment was defined as one standard deviation bel...

Background/objectives: Gait speed and psychomotor speed slow with age and may predict neuropsychiatric disease such as depression and anxiety. We explored the relative predictive values of gait speed, psychomotor slowing, and a composite index of these two measures on time to new episode depression or anxiety in older adults at risk for these comm...

Background: Antipsychotic drugs are well established to alter serum prolactin levels, often resulting in adverse effects including amenorrhea, galactorrhea, osteoporosis, and loss of libido. There is growing preclinical evidence that prolactin-elevating drugs can instigate the progression of precancerous lesions to breast cancer and that genes act...

There is evidence of racial/ethnic disparities in late-life depression (LLD) burden and treatment in the US. Geographic region may be a novel social determinant; yet, limited data exist regarding the interplay of geographic region with racial/ethnic differences in LLD severity, item-level symptom burden and treatment. We conducted a cross-sectional...

We call on geriatric brain health care providers, executives and entrepreneurs to embrace our Brain Health Living Lab model-a user-centered, iterative ecosystem, integrating concurrent clinical care, research and innovation processes.

Purpose/background: Venlafaxine is a commonly used antidepressant with both serotonergic and noradrenergic activity. There are concerns that it may prolong the corrected QT interval (QTc), and older adults may be at higher risk for this adverse effect, especially at higher dosages of the medication. Methods/procedures: In this secondary analysis...

Background: Late-life depression is often associated with non-response or relapse following conventional antidepressant treatment. The pathophysiology of late-life depression likely involves a complex interplay between aging and depression, and may include abnormalities in cortical inhibition and plasticity. However, the extent to which these cort...

Background: Adherence to healthy lifestyles/behaviours promotes healthy ageing. However, little is known about whether age, sex and/or race/ethnicity moderate associations of lifestyle/behavioural factors with relative telomere length (RTL), a potential biomarker of ageing. Methods: We included 749 midlife to older non-Hispanic White (n = 254),...

Objective: There is a paucity of data on the effects of coprescribed benzodiazepines on treatment response variability and adherence to antidepressant pharmacotherapy for depression and anxiety in late life. The objective of this transdiagnostic analysis was to examine the effect of benzodiazepines on treatment outcomes in older patients with gene...

Background Venlafaxine, a serotonin–norepinephrine reuptake inhibitor, is often used as first- or second-line therapy for depression in older adults. It can be associated with adverse blood pressure (BP) effects. Methods Adults ⩾60 years of age in a current major depressive episode were treated in a protocolized manner with venlafaxine XR; 429 par...

Mitochondrial DNA copy number (mtDNAcn) is a putative biomarker of oxidative stress and biological aging. Modifiable factors, including physical activity (PA), avoidance of heavy alcohol use and smoking, and maintaining good mental health, may reduce oxidative stress and promote healthy aging. Yet, limited data exist regarding how these factors are...

Objectives: A lack of "morningness" predicts greater depression symptom severity over time, including in a vulnerable group of older adults: family dementia caregivers (dCGs). Evidence regarding the neurobiological basis of these correlations is needed to guide future research towards biomarker-informed detection and prevention approaches. We ther...

Importance Low levels of 25-hydroxyvitamin D have been associated with higher risk for depression later in life, but there have been few long-term, high-dose large-scale trials. Objective To test the effects of vitamin D3 supplementation on late-life depression risk and mood scores. Design, Setting, and Participants There were 18 353 men and wome...

Facing the change together: reflections of coping and resilience from American geriatric psychiatrists during COVID-19 - Carmen Black Parker, Malcolm P Forbes, Ipsit V Vahia, Brent P Forester, Dilip V Jeste, Charles F Reynolds

Objective To determine the effect of the COVID-19 pandemic on the mental health of older adults with pre-existing major depressive disorder (MDD). Participants Participants were 73 community-living older adults with pre-existing MDD (mean age 69 [SD 6]) in Los Angeles, New York, Pittsburgh, and St Louis. Design and Measurements During the first t...

Background We aimed to identify trajectories of inflammation in older adults at elevated risk for syndromal depression and anxiety and to determine whether baseline physical, cognitive, and psychosocial factors could distinguish 15-month longitudinal trajectories. Methods Older adults (N=195, mean age (±SD) = 74.4 years (9.0) participating in thre...

The article by Lee and colleagues¹ in this issue of JAMA Psychiatry explores 3 domains or components of wisdom: prosocial relations, emotional regulation, and spirituality. The authors’ basic hypothesis is that interventions may enhance these domains of wisdom (although they found no eligible studies that addressed wisdom as an inclusive or unitary...