Treating depression in later life
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Abstract Mutant isocitrate-dehydrogenase-1 (IDH1-R132H; mIDH1) is a hallmark of adult gliomas. Lower grade mIDH1 gliomas are classified into two molecular subgroups: (i) 1p/19q co-deletion/TERT-promoter mutations or (ii) inactivating mutations in α-thalassemia/mental retardation syndrome X-linked (ATRX) and TP53. This work, relates to the gliomas’ subtype harboring mIDH1, TP53 and ATRX inactivation. IDH1-R132H is a gain-of-function mutation that converts α-ketoglutarate into 2-hydroxyglutarate (D-2HG). The role of D-2HG within the tumor microenvironment of mIDH1/mATRX/mTP53 gliomas remains unexplored. Inhibition of 2HG, when used as monotherapy or in combination with radiation and temozolomide (IR/TMZ), led to increased median survival (MS) of mIDH1 glioma bearing mice. Also, 2HG inhibition elicited anti-mIDH1 glioma immunological memory. In response to 2HG inhibition, PD-L1 expression levels on mIDH1-glioma cells increased to similar levels as observed in wild-type-IDH1 gliomas. Thus, we combined 2HG inhibition/IR/TMZ with anti-PDL1 immune checkpoint-blockade and observed complete tumor regression in 60% of mIDH1 glioma bearing mice. This combination strategy reduced T-cell exhaustion and favored the generation of memory CD8+T-cells. Our findings demonstrate that metabolic reprogramming elicits anti-mIDH1 glioma immunity, leading to increased MS and immunological memory. Our preclinical data supports the testing of IDH-R132H inhibitors in combination with IR/TMZ and anti-PDL1 as targeted therapy for mIDH1/mATRX/mTP53 glioma patients. Brief Summary Inhibition of 2-Hydroxyglutrate in mutant-IDH1 glioma in the genetic context of ATRX and TP53 inactivation elicits metabolic-reprograming and anti-glioma immunity.
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Anxiety and depression are under-diagnosed and under-treated, specifically among older people.
“These disorders are under-diagnosed and under-treated, specifically among older people”
From Can support workers from AgeUK deliver an intervention to support older people with anxiety and depression? A qualitative evaluation (2019) · cites this paper as [19]
Depression is common in older people, particularly those with chronic physical illness, but tends to be under-diagnosed and inadequately managed.
“Depression is common in older people, particularly those with chronic physical illness, but tends to be under-diagnosed and inadequately managed [18,19].”
From Development and evaluation of culturally sensitive psychosocial interventions for under-served people in primary care (2014) · cites this paper as [18]
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- Authors
- Chew-Graham, C., Baldwin, R., & Burns, A.
- Affiliations
- Manchester Royal Infirmary (GB)
- Corresponding author
- Burns, Alistair
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2004-07-22
- Volume
- 329
- Issue
- 7459
- Pages
- 181-182
- ISSN
- 0007-1447 (ISSN-L)
- 0959-8138
- 1468-5833
- PMC
- PMC487719
- OpenAlex
- W2037682777
- Cited by
- 62
- References
- 12
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2021: 2 · 2019: 3 · 2018: 3 · 2017: 4 · 2016: 4 · 2015: 1 · 2014: 4 · 2013: 3 · 2012: 2
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy (tdm)
- Locations
- BMJ (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- later-life depression, geriatric depression, depression treatment, older adults
- MeSH terms
- Aged, Depressive Disorder, Humans, Middle Aged, Randomized Controlled Trials as Topic, Treatment Outcome
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