Breno Satler Diniz1, Charles F Reynolds2, Etienne Sibille3, Chien-Wei Lin4, George Tseng4, Francis Lotrich2, Howard J Aizenstein2, Meryl A Butters2. 1. Department of Psychiatry & Behavioral Sciences, University of Texas Health Science Center at Houston, Houston, TX. Electronic address: brenosatler@gmail.com. 2. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA. 3. Departments of Psychiatry and of Pharmacology and Toxicology, Campbell Family Mental Health Research Institute of CAMH, University of Toronto, Toronto, Ontario, Canada. 4. Department of Statistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA.
Abstract
OBJECTIVE: This study aims to investigate whether a systemic molecular pattern associated with aging (senescent-associated secretory phenotype [SASP]) is elevated in adults with late-life depression (LLD), compared with never-depressed elderly comparison participants. DESIGN: Cross-sectional study. PARTICIPANTS: We included 111 older adults (80 with LLD and 31 comparison participants) in this study. MEASUREMENT: A panel of 22 SASP-related proteins was extracted from a previous multiplex protein panel performed in these participants. We conducted a principal component analysis to create the SASP index based on individual weights of each of protein. RESULTS: Participants with LLD showed a significantly increased SASP index compared with comparison participants, after controlling for age, depressive symptoms, medical comorbidity (CIRS-G) scores, sex, and cognitive performance (F(1,98) = 7.3, p = 0.008). Correlation analyses revealed that the SASP index was positively correlated with age (r = 0.2, p = 0.03) and CIRS score (r = 0.27, p = 0.005), and negatively correlated with information processing speed (r = -0.34, p = 0.001), executive function (r = -0.27, p = 0.004) and global cognitive performance (r = -0.28, p = 0.007). CONCLUSIONS: To the best of our knowledge, this is the first study to show that a set of proteins (i.e., SASP index) primarily associated with cellular aging is abnormally regulated and elevated in LLD. These results suggest that individuals with LLD display enhanced aging-related molecular patterns that are associated with higher medical comorbidity and worse cognitive function. Finally, we provide a set of proteins that can serve as potential therapeutic targets and biomarkers to monitor the effects of therapeutic or preventative interventions in LLD.
OBJECTIVE: This study aims to investigate whether a systemic molecular pattern associated with aging (senescent-associated secretory phenotype [SASP]) is elevated in adults with late-life depression (LLD), compared with never-depressed elderly comparison participants. DESIGN: Cross-sectional study. PARTICIPANTS: We included 111 older adults (80 with LLD and 31 comparison participants) in this study. MEASUREMENT: A panel of 22 SASP-related proteins was extracted from a previous multiplex protein panel performed in these participants. We conducted a principal component analysis to create the SASP index based on individual weights of each of protein. RESULTS:Participants with LLD showed a significantly increased SASP index compared with comparison participants, after controlling for age, depressive symptoms, medical comorbidity (CIRS-G) scores, sex, and cognitive performance (F(1,98) = 7.3, p = 0.008). Correlation analyses revealed that the SASP index was positively correlated with age (r = 0.2, p = 0.03) and CIRS score (r = 0.27, p = 0.005), and negatively correlated with information processing speed (r = -0.34, p = 0.001), executive function (r = -0.27, p = 0.004) and global cognitive performance (r = -0.28, p = 0.007). CONCLUSIONS: To the best of our knowledge, this is the first study to show that a set of proteins (i.e., SASP index) primarily associated with cellular aging is abnormally regulated and elevated in LLD. These results suggest that individuals with LLD display enhanced aging-related molecular patterns that are associated with higher medical comorbidity and worse cognitive function. Finally, we provide a set of proteins that can serve as potential therapeutic targets and biomarkers to monitor the effects of therapeutic or preventative interventions in LLD.
Authors: Pia Gudmundsson; Ingmar Skoog; Margda Waern; Kaj Blennow; Henrik Zetterberg; Lars Rosengren; Deborah Gustafson Journal: Psychiatry Res Date: 2010-02-04 Impact factor: 3.222
Authors: George S Alexopoulos; Soo Borson; Bruce N Cuthbert; D P Devanand; Benoit H Mulsant; Jason T Olin; David W Oslin Journal: Biol Psychiatry Date: 2002-08-01 Impact factor: 13.382
Authors: Warren D Taylor; Douglas R McQuoid; Martha E Payne; Anthony S Zannas; James R MacFall; David C Steffens Journal: Am J Geriatr Psychiatry Date: 2013-11-22 Impact factor: 4.105
Authors: Jean-Philippe Coppé; Christopher K Patil; Francis Rodier; Yu Sun; Denise P Muñoz; Joshua Goldstein; Peter S Nelson; Pierre-Yves Desprez; Judith Campisi Journal: PLoS Biol Date: 2008-12-02 Impact factor: 8.029
Authors: Ana Paula Mendes-Silva; Benson Mwangi; Howard Aizenstein; Charles F Reynolds; Meryl A Butters; Breno S Diniz Journal: Am J Geriatr Psychiatry Date: 2019-06-22 Impact factor: 4.105
Authors: K Droppa; H T Karim; D L Tudorascu; J F Karp; C F Reynolds; H J Aizenstein; M A Butters Journal: J Psychiatr Res Date: 2017-08-08 Impact factor: 4.791