scholarly journals Genome-wide analysis suggests the importance of vascular processes and neuroinflammation in late-life antidepressant response

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Victoria S. Marshe ◽  
Malgorzata Maciukiewicz ◽  
Anne-Christin Hauschild ◽  
Farhana Islam ◽  
Li Qin ◽  
...  
Keyword(s):  
Older Adults ◽  
Cerebrovascular Disease ◽  
Protein Degradation ◽  
Late Life ◽  
Cardioembolic Stroke ◽  
Symptom Improvement ◽  
Antidepressant Response ◽  
Polygenic Risk ◽  
Remission Status ◽  
Genome Wide

AbstractAntidepressant 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 venlafaxine extended-release for 12 weeks. A standard genome-wide association study (GWAS) was conducted for post-treatment remission status, followed by in silico biological characterization of associated genes, as well as polygenic risk scoring for depression, neurodegenerative and cerebrovascular disease. The top-associated variants for remission status and percentage symptom improvement were PIEZO1 rs12597726 (OR = 0.33 [0.21, 0.51], p = 1.42 × 10−6) and intergenic rs6916777 (Beta = 14.03 [8.47, 19.59], p = 1.25 × 10−6), respectively. Pathway analysis revealed significant contributions from genes involved in the ubiquitin-proteasome system, which regulates intracellular protein degradation with has implications for inflammation, as well as atherosclerotic cardiovascular disease (n = 25 of 190 genes, p = 8.03 × 10−6, FDR-corrected p = 0.01). Given the polygenicity of complex outcomes such as antidepressant response, we also explored 11 polygenic risk scores associated with risk for Alzheimer’s disease and stroke. Of the 11 scores, risk for cardioembolic stroke was the second-best predictor of non-remission, after being male (Accuracy = 0.70 [0.59, 0.79], Sensitivity = 0.72, Specificity = 0.67; p = 2.45 × 10−4). Although our findings did not reach genome-wide significance, they point to previously-implicated mechanisms and provide support for the roles of vascular and inflammatory pathways in LLD. Overall, significant enrichment of genes involved in protein degradation pathways that may be impaired, as well as the predictive capacity of risk for cardioembolic stroke, support a link between late-life depression remission and risk for vascular dysfunction.

UNRAVELING GENOMIC CONTRIBUTIONS TO VENLAFAXINE REMISSION IN OLDER ADULTS WITH LATE-LIFE DEPRESSION USING A GENOME-WIDE APPROACH

2019 ◽  
Vol 29 ◽  
pp. S865-S866
Author(s):  
Victoria Marshe ◽  
Malgorzata Maciukiewicz ◽  
Soham Rej ◽  
Arun Tiwari ◽  
Etienne Sibille ◽  
...  
Keyword(s):  
Older Adults ◽  
Late Life ◽  
Late Life Depression ◽  
Genome Wide ◽  
A Genome

scholarly journals New insights on the pharmacogenomics of antidepressant response from the GENDEP and STAR*D studies: rare variant analysis and high-density imputation

2017 ◽  
Author(s):  
Chiara Fabbri ◽  
Katherine E. Tansey ◽  
Roy H. Perlis ◽  
Joanna Hauser ◽  
Neven Henigsberg ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Antidepressant Treatment ◽  
Association Studies ◽  
Research Network ◽  
Antidepressant Effect ◽  
Symptom Improvement ◽  
Genome Wide Association Studies ◽  
Antidepressant Response ◽  
Genome Wide ◽  
Pathway Level

AbstractGenome-wide association studies have generally failed to identify polymorphisms associated with antidepressant response. Possible reasons include limited coverage of genetic variants that this study tried to address by exome genotyping and dense imputation.A meta-analysis of Genome-Based Therapeutic Drugs for Depression (GENDEP) and Sequenced Treatment Alternatives to Relieve Depression (STAR*D) studies was performed at SNP, gene and pathway level. Coverage of genetic variants was increased compared to previous studies by adding exome genotypes to previously available genome-wide data and using the Haplotype Reference Consortium panel for imputation. Standard quality control was applied. Phenotypes were symptom improvement and remission after 12 weeks of antidepressant treatment. NEWMEDS consortium samples and Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) served for replication.7,062,950 SNPs were analysed in GENDEP (n=738) and STAR*D (n=1409). rs116692768 (p=1.80e-08, ITGA9 (integrin alpha 9)) and rs76191705 (p=2.59e-08, NRXN3 (neurexin 3)) were significantly associated with symptom improvement during citalopram/escitalopram treatment. At gene level, no consistent effect was found. At pathway level, the Gene Ontology terms GO:0005694 (chromosome) and GO:0044427 (chromosomal part) were associated with improvement (corrected p=0.007 and 0.045, respectively). The association between rs116692768 and symptom improvement was replicated in PGRN-AMPS (p=0.047), while rs76191705 was not. The two SNPs did not replicate in NEWMEDS.ITGA9 codes for a membrane receptor for neurotrophins and NRXN3 is a transmembrane neuronal adhesion receptor involved in synaptic differentiation. Despite their meaningful biological rationale for being involved in antidepressant effect, no convincing replication was achieved. Further studies may help in clarifying their role.

Validation study of microRNAs previously associated with antidepressant response in older adults treated for late-life depression with venlafaxine

2020 ◽  
Vol 100 ◽  
pp. 109867
Author(s):  
Victoria S. Marshe ◽  
Farhana Islam ◽  
Malgorzata Maciukiewicz ◽  
Laura M. Fiori ◽  
Volodymyr Yerko ◽  
...  
Keyword(s):  
Older Adults ◽  
Validation Study ◽  
Late Life ◽  
Antidepressant Response ◽  
Late Life Depression

GENOME-WIDE ANALYSES OF REMISSION ON VENLAFAXINE TREATMENT IN OLDER ADULTS WITH LATE-LIFE DEPRESSION

2019 ◽  
Vol 29 ◽  
pp. S1045-S1046
Author(s):  
Daniel Mueller ◽  
Victoria Marshe ◽  
Malgorzata Maciukiewicz ◽  
Arun Tiwari ◽  
James L. Kennedy ◽  
...  
Keyword(s):  
Older Adults ◽  
Late Life ◽  
Late Life Depression ◽  
Genome Wide

scholarly journals Mortality and Obesity Among U.S. Older Adults: The Role of Polygenic Risk

2019 ◽  
Author(s):  
Justin M Vinneau ◽  
Brooke M Huibregtse ◽  
Thomas M Laidley ◽  
Joshua A Goode ◽  
Jason D Boardman
Keyword(s):  
Older Adults ◽  
Total Sample ◽  
Polygenic Risk Score ◽  
Polygenic Risk ◽  
Risk Of Death ◽  
Risk Of Mortality ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Cox Proportional Hazard Models ◽  
Using Data

Abstract Objectives To examine the relationship between obesity and mortality as a function of polygenic risk for obesity among older U.S. adults. Method Using data from the 1994–2014 Health and Retirement Study in conjunction with genome-wide data, we evaluated the risk of mortality as a function of obesity classification, an individual’s polygenic risk score (PGS) for obesity, and their interaction, stratified by sex. We conducted our analyses using cox proportional hazard models. Results Among those with an average PGS for obesity (8,143 [68.8%]), obese I (hazard ratio [HR] = 0.79, p = .336) adults show no difference in their risk for mortality and obese II/III (HR = 3.17, p = .000) adults present higher risk of mortality relative to non-obese adults. The interaction of obesity classification and PGS suggests that obese II/III respondents with low PGS in the total sample (HR = 2.71, p = .006) and among women (HR = 3.02, p = .023) are at significantly higher risk of death when compared to obese II/III respondents with average or high PGS. Discussion We posit that these findings suggest that the pathway to obesity, in this case, more socio-behavioral rather than genetic, may influence subsequent risk of death in older adults. We suggest that practitioners and population researchers be mindful of these pathways as to better identify and understand mortality risk.

Refining Evidence-Based Treatments for Late-Life Depression

GeroPsych ◽  
2015 ◽  
Vol 28 (2) ◽  
pp. 67-76
Author(s):  
Grace C. Niu ◽  
Patricia A. Arean
Keyword(s):  
Older Adults ◽  
Mental Illness ◽  
Brain Plasticity ◽  
Late Life ◽  
Aging Population ◽  
The United States ◽  
Future Research ◽  
Evidence Based ◽  
Late Life Depression ◽  
Evidence Based Treatments

The recent increase in the aging population, specifically in the United States, has raised concerns regarding treatment for mental illness among older adults. Late-life depression (LLD) is a complex condition that has become widespread among the aging population. Despite the availability of behavioral interventions and psychotherapies, few depressed older adults actually receive treatment. In this paper we review the research on refining treatments for LLD. We first identify evidence-based treatments (EBTs) for LLD and the problems associated with efficacy and dissemination, then review approaches to conceptualizing mental illness, specifically concepts related to brain plasticity and the Research Domain Criteria (RDoc). Finally, we introduce ENGAGE as a streamlined treatment for LLD and discuss implications for future research.

scholarly journals Sex in Late Life: Assessing Adults’ Expectations and the Role of Healthcare Professionals

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 313-313
Author(s):  
Jill Naar ◽  
Raven Weaver ◽  
Shelbie Turner
Keyword(s):  
Older Adults ◽  
Sexual Health ◽  
Health Behaviors ◽  
Healthcare Professionals ◽  
Late Life ◽  
Sexual History ◽  
Growth Curve Models ◽  
The Us ◽  
Sexual Health Behaviors ◽  
The Life Course

Abstract Sexual activity contributes to quality of life throughout the lifespan. However, stigma about sex in late life influences older adults’ perceptions and healthcare professionals’ perceptions of older adults’ sexual health/behaviors. Using a multi-methods approach, we examined attitudes and knowledge about sexual health/behaviors in late life. Using longitudinal data from the Midlife in the US Study (Wave 1-3; N=7049), we ran age-based growth curve models to analyze changes in levels of optimism about sex in their future. We also piloted a survey with healthcare professionals assessing attitudes, knowledge, and awareness of policy about sexual health/behaviors among older adults. Adults’ expectations became less optimistic with increased age (β = -0.1, SE = 0.003, p < .0001). Men were more optimistic than women at age 20 (p = 0.016), but men’s optimism decreased over the life course at a faster rate than did women’s (p < .0001), so that from ages 40-93, men were less optimistic than women. Among healthcare professionals (N=21), the majority indicated never or rarely asking their clients about sexual history or health/behaviors; however, they indicated some knowledge about issues relevant to older adults (e.g., safe-sex practices, sexual dysfunction). Few indicated awareness about policies related to sexual behavior among residents (i.e., issues of consent, STIs). Among adults, there is a need to address declining optimism for expectations about sex in late life. Health professionals are well-situated to raise awareness and normalize discussions about sexual health, thus countering negative stigma and contributing to increasing optimism for expectations to remain sexually active.

scholarly journals Longitudinal Association Between Education and Disability in Older Adults Living in Iceland

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 396-396
Author(s):  
Milan Chang ◽  
Olof Geirsdottir ◽  
Lenore Launer ◽  
Vilmundur Gudnasson ◽  
Palmi Jonsson ◽  
...  
Keyword(s):  
Older Adults ◽  
Low Socioeconomic Status ◽  
Late Life ◽  
Mobility Disability ◽  
College And University ◽  
Disability Status ◽  
Adl Disability ◽  
And Gender ◽  
Access To Medical Care ◽  
Life Education

Abstract BACKGROUND: Disabilities among older adults are associated with cumulative adversities such as low socioeconomic status (SES), poor nutrition, and lack of access to medical care and education. However, there is little evidence on the long-term association between education and disability status among older adults in Iceland. The aim of the study was to examine the association between mid-life education and prevalence of disability in activities of daily living (ADL) and mobility disability in late-life using 25 years of longitudinal data. METHODS: A large community-based population residing in Reykjavik, Iceland participated in a longitudinal study with an average of 25 years of follow-up (N=5764, mean age 77±6 yrs, 57.7% of women) Mid-life education was categorized into 2 groups (primary and secondary versus college and university). Disability status in late life was defined with ADL and mobility disability with a binary outcome (no difficulty versus any difficulty). Logistic regression analysis was used to examine the association. RESULTS: After controlling for age and gender, and midlife health risk factors, those who had high education at mid-life were less likely to have ADL disability (Odds Ratio (OR) = 0.75, 95% Confidence Interval (CI): 0.64 ~ 0.88, P ≤ 0.001) and mobility disability (OR = 0.72, 95% CI: 0.61 ~ 0.86, P < 0.001) compared with those who had low education in mid-life. CONCLUSION: People with high mid-life education were less likely to have ADL and mobility disability after 25 years later.

scholarly journals Health and social care service utilisation and associated expenditure among community-dwelling older adults with depressive symptoms

2021 ◽  
Vol 30 ◽  
Author(s):  
Shiyu Lu ◽  
Tianyin Liu ◽  
Gloria H. Y. Wong ◽  
Dara K. Y. Leung ◽  
Lesley C. Y. Sze ◽  
...  
Keyword(s):  
Older Adults ◽  
Depressive Symptoms ◽  
Symptom Severity ◽  
Social Care ◽  
Late Life ◽  
Community Dwelling ◽  
Service Utilisation ◽  
Late Life Depression ◽  
Social Care Service ◽  
Health And Social Care

Abstract Aims Late-life depression has substantial impacts on individuals, families and society. Knowledge gaps remain in estimating the economic impacts associated with late-life depression by symptom severity, which has implications for resource prioritisation and research design (such as in modelling). This study examined the incremental health and social care expenditure of depressive symptoms by severity. Methods We analysed data collected from 2707 older adults aged 60 years and over in Hong Kong. The Patient Health Questionnaire-9 (PHQ-9) and the Client Service Receipt Inventory were used, respectively, to measure depressive symptoms and service utilisation as a basis for calculating care expenditure. Two-part models were used to estimate the incremental expenditure associated with symptom severity over 1 year. Results The average PHQ-9 score was 6.3 (standard deviation, s.d. = 4.0). The percentages of respondents with mild, moderate and moderately severe symptoms and non-depressed were 51.8%, 13.5%, 3.7% and 31.0%, respectively. Overall, the moderately severe group generated the largest average incremental expenditure (US$5886; 95% CI 1126–10 647 or a 272% increase), followed by the mild group (US$3849; 95% CI 2520–5177 or a 176% increase) and the moderate group (US$1843; 95% CI 854–2831, or 85% increase). Non-psychiatric healthcare was the main cost component in a mild symptom group, after controlling for other chronic conditions and covariates. The average incremental association between PHQ-9 score and overall care expenditure peaked at PHQ-9 score of 4 (US$691; 95% CI 444–939), then gradually fell to negative between scores of 12 (US$ - 35; 95% CI - 530 to 460) and 19 (US$ -171; 95% CI - 417 to 76) and soared to positive and rebounded at the score of 23 (US$601; 95% CI -1652 to 2854). Conclusions The association between depressive symptoms and care expenditure is stronger among older adults with mild and moderately severe symptoms. Older adults with the same symptom severity have different care utilisation and expenditure patterns. Non-psychiatric healthcare is the major cost element. These findings inform ways to optimise policy efforts to improve the financial sustainability of health and long-term care systems, including the involvement of primary care physicians and other geriatric healthcare providers in preventing and treating depression among older adults and related budgeting and accounting issues across services.

Sign in / Sign up

Export Citation Format

Share Document