TY - JOUR
T1 - Late-Life Depression is Associated With Increased Levels of GDF-15, a Pro-Aging Mitokine
AU - Mastrobattista, Emma
AU - Lenze, Eric J.
AU - Reynolds, Charles F.
AU - Mulsant, Benoit H.
AU - Wetherell, Julie
AU - Wu, Gregory F.
AU - Blumberger, Daniel M.
AU - Karp, Jordan F.
AU - Butters, Meryl A.
AU - Mendes-Silva, Ana Paula
AU - Vieira, Erica L.
AU - Tseng, George
AU - Diniz, Breno S.
N1 - Funding Information:
Dr. Lenze is a consultant for Prodeo, Boehringer-Ingelheim, Pritikin ICR, and IngenioRxDr. Lenze has a patent application for sigma-1 agonists in COVID-19 treatment. He also receives research support from PCORI, the COVID Early Treatment Fund, Emergent Venture FastGrants, and MagStim. Dr. Wu is consultant for Genzyme, Novartis, Roche, and The Department of Justice. Dr. Karp reports receipt of honorarium from Otsuka for preparation and presentation of a webinar (disease-state, not product-focused) and from NightWare for scientific advising and equity from Aifred Health for scientific advising. Dr. Mulsant holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He also receives compensation from the Centre for Addiction and Mental Health (CAMH), Toronto, Ontario. He currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). Within the past three years, he has received research support from the Patient-Centered Outcomes Research Institute (PCORI) and he has been an unpaid consultant to Myriad Neuroscience. Dr. Blumberger receives research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for one sponsor-initiated study for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. The other co-authors do not have conflict of interest related to this study. This work was funded by NIH grants R01MH118311 (Diniz & Tseng), R01 MH083660 (Reynolds, Lenze, Mulsant), and R01AG049369 (Lenze & Wetherell).
Funding Information:
Dr. Lenze is a consultant for Prodeo, Boehringer-Ingelheim, Pritikin ICR, and IngenioRxDr. Lenze has a patent application for sigma-1 agonists in COVID-19 treatment. He also receives research support from PCORI, the COVID Early Treatment Fund, Emergent Venture FastGrants, and MagStim. Dr. Wu is consultant for Genzyme, Novartis, Roche, and The Department of Justice. Dr. Karp reports receipt of honorarium from Otsuka for preparation and presentation of a webinar (disease-state, not product-focused) and from NightWare for scientific advising and equity from Aifred Health for scientific advising. Dr. Mulsant holds and receives support from the Labatt Family Chair in Biology of Depression in Late-Life Adults at the University of Toronto. He also receives compensation from the Centre for Addiction and Mental Health (CAMH), Toronto, Ontario. He currently receives research support from Brain Canada, the Canadian Institutes of Health Research, the CAMH Foundation, the US National Institute of Health (NIH), Capital Solution Design LLC (software used in a study founded by CAMH Foundation), and HAPPYneuron (software used in a study founded by Brain Canada). Within the past three years, he has received research support from the Patient-Centered Outcomes Research Institute (PCORI) and he has been an unpaid consultant to Myriad Neuroscience. Dr. Blumberger receives research support from CIHR, NIH, Brain Canada and the Temerty Family through the CAMH Foundation and the Campbell Research Institute. He received research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for one sponsor-initiated study for Brainsway Ltd. He also receives in-kind equipment support from Magventure for investigator-initiated studies. He received medication supplies for an investigator-initiated trial from Indivior. The other co-authors do not have conflict of interest related to this study. This work was funded by NIH grants R01MH118311 (Diniz & Tseng), R01 MH083660 (Reynolds, Lenze, Mulsant), and R01AG049369 (Lenze & Wetherell).
Publisher Copyright:
© 2022 American Association for Geriatric Psychiatry
PY - 2023/1
Y1 - 2023/1
N2 - 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 to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance. Design: This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals. Results: After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression. Conclusion: Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging.
AB - 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 to age and age-related diseases. Elevated levels of GDF-15 correlate with increasing chronological age, decreased telomerase activity, and increased mortality risk in older adults. We sought to evaluate the circulating levels of GDF-15 in older adults with MDD and its association with depression severity, physical comorbidity burden, age of onset of first depressive episode, and cognitive performance. Design: This study assayed circulating levels of GDF-15 in 393 older adults (mean ± SD age 70 ± 6.6 years, male:female ratio 1:1.54), 308 with MDD and 85 non-depressed comparison individuals. Results: After adjusting for confounding variables, depressed older adults had significantly higher GDF-15 serum levels (640.1 ± 501.5 ng/mL) than comparison individuals (431.90 ± 223.35 ng/mL) (t=3.75, d.f.= 391, p=0.0002). Among depressed individuals, those with high GDF-15 had higher levels of comorbid physical illness, lower executive cognitive functioning, and higher likelihood of having late-onset depression. Conclusion: Our results suggest that depression in late life is associated with GDF-15, a marker of amplified age-related biological changes. GDF-15 is a novel and potentially targetable biological pathway between depression and accelerated aging, including cognitive aging.
KW - Aging
KW - GDF-15
KW - Geroscience
KW - Late life depression
KW - biological markers
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UR - http://www.scopus.com/inward/citedby.url?scp=85138808244&partnerID=8YFLogxK
U2 - 10.1016/j.jagp.2022.08.003
DO - 10.1016/j.jagp.2022.08.003
M3 - Article
C2 - 36153290
AN - SCOPUS:85138808244
SN - 1064-7481
VL - 31
SP - 1
EP - 9
JO - American Journal of Geriatric Psychiatry
JF - American Journal of Geriatric Psychiatry
IS - 1
ER -