Medicalising unhappiness: new classification of depression risks more patients being put on drug treatment from which they will not benefit
Abstract
The coinhibitory receptor programmed death-1 (PD-1) maintains immune homeostasis by negatively regulating T cell function and survival. Blockade of PD-1 increases the severity of graft-versus-host disease (GVHD), but the interplay between PD-1 inhibition and T cell metabolism is not well studied. We found that both murine and human alloreactive T cells concomitantly upregulated PD-1 expression and increased levels of reactive oxygen species (ROS) following allogeneic bone marrow transplantation. This PD-1HiROSHi phenotype was specific to alloreactive T cells and was not observed in syngeneic T cells during homeostatic proliferation. Blockade of PD-1 signaling decreased both mitochondrial H2O2 and total cellular ROS levels, and PD-1–driven increases in ROS were dependent upon the oxidation of fatty acids, because treatment with etomoxir nullified changes in ROS levels following PD-1 blockade. Downstream of PD-1, elevated ROS levels impaired T cell survival in a process reversed by antioxidants. Furthermore, PD-1–driven changes in ROS were fundamental to establishing a cell’s susceptibility to subsequent metabolic inhibition, because blockade of PD-1 decreased the efficacy of later F1F0-ATP synthase modulation. These data indicate that PD-1 facilitates apoptosis in alloreactive T cells by increasing ROS in a process dependent upon the oxidation of fat. In addition, blockade of PD-1 undermines the potential for subsequent metabolic inhibition, an important consideration given the increasing use of anti–PD-1 therapies in the clinic.
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Social marketing seems to be effective in reducing the stigma of mental illness.
“While sustained population-wide improvements in attitudes toward depression have not been demonstrated, social marketing seems to be effective in reducing the stigma of mental illness. 361”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [361]
Sustained population-wide improvements in attitudes toward depression have not been demonstrated.
“While sustained population-wide improvements in attitudes toward depression have not been demonstrated, social marketing seems to be effective in reducing the stigma of mental illness. 361”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [361]
For students, social contact-based interventions usually achieve short-term attitudinal improvement.
“For people with mental illness, some grouplevel interventions show promise, while for students, social contact-based interventions usually achieve short-term attitudinal improvement. 361,362”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [361]
For people with mental illness, some group-level interventions show promise.
“For people with mental illness, some grouplevel interventions show promise, while for students, social contact-based interventions usually achieve short-term attitudinal improvement. 361,362”
From Time for united action on depression: a Lancet–World Psychiatric Association Commission (2022) · cites this paper as [361]
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Time for united action on depression: a Lancet–World Psychiatric Association Commission
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“”[6] For GPs, who are likely to see a more diverse and less uniformly unwell population, these issues are more pronounced.[6]”
BackgroundSelf-citation
- Authors
- Dowrick, C., & Frances, A.
- Affiliations
- University of Liverpool (GB)
- Duke Medical Center (US)
- Corresponding author
- Dowrick, C.
- ORCID
- Dowrick, C.
- Venue
- BMJ
- Publisher
- BMJ
- Published
- 2013-12-09
- Volume
- 347
- Issue
- dec09 7
- Pages
- f7140-f7140
- ISSN
- 1756-1833 (ISSN-L)
- OpenAlex
- W2032037496
- Cited by
- 167
- References
- 48
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 11 · 2023: 8 · 2022: 8 · 2021: 12 · 2020: 11 · 2019: 13 · 2018: 15 · 2017: 15 · 2016: 19 · 2015: 23 · 2014: 17 · 2013: 1
- FWCI
- 14.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- BMJ (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Social Psychology › Mental Health Treatment and Access
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Keywords
- depression, medicalization, antidepressant prescribing, overprescribing, mental health services
- MeSH terms
- Antidepressive Agents, Depression, Major Depressive Disorder, Diagnosis, Differential, Diagnostic Errors, Grief, Humans, Diagnostic and Statistical Manual of Mental Disorders, Inappropriate Prescribing
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