ReviewThe American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry2013
The age-by-disease interaction hypothesis of late-life depression.
Review in The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Cross-tissue analysis of blood and brain epigenome-wide association studies in Alzheimer's disease.Nature communications · 2022Pooled it
- Cortical inhibition, facilitation and plasticity in late-life depression: effects of venlafaxine pharmacotherapy.Journal of psychiatry & neuroscience : JPN · 2021Trial
- Brain-derived neurotrophic factor levels in late-life depression and comorbid mild cognitive impairment: a longitudinal study.Journal of psychiatric research · 2014Trial
- Influence of sarcopenia on functional independence and depression in older adults: a cross-sectional study.Journal of exercise rehabilitation · 2026Article
- Age matters: a narrative review and machine learning analysis on shared and separate multidimensional risk domains for early and late onset suicidal behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Review
- Changes in dementia risk along with onset age of depression: a longitudinal cohort study of elderly depressed patients.BMC psychiatry · 2025Article
- Awareness of the condition in people living with dementia in a long-term care facility: a systematic review.Dementia & neuropsychologia · 2025Review
- Fast-acting antidepressant-like effects of ketamine in aged male rats.Pharmacological reports : PR · 2024Article
- MIAMI-AD (Methylation in Aging and Methylation in AD): an integrative knowledgebase that facilitates explorations of DNA methylation across sex, aging, and Alzheimer's disease.Database : the journal of biological databases and curation · 2024Article
- Cannabidiol Modulates Emotional Function and Brain-Derived Neurotrophic Factor Expression in Middle-Aged Female Rats Exposed to Social Isolation.International journal of molecular sciences · 2023Article
- Exploratory genome-wide analyses of cortical inhibition, facilitation, and plasticity in late-life depression.Translational psychiatry · 2023Article
- Transcranial Magnetic Stimulation Indices of Cortical Excitability Enhance the Prediction of Response to Pharmacotherapy in Late-Life Depression.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2022Article
- Dose-Dependent Antidepressant-Like Effects of Cannabidiol in Aged Rats.Frontiers in pharmacology · 2022Article
- Evaluating the effects of 2-BFI and tracizoline, two potent INaunyn-Schmiedeberg's archives of pharmacology · 2021Article
- Enhancing Health Care in the Veteran Community Through Synergistic Research Funding.Frontiers in psychiatry · 2021Article
- Mental health and related influencing factors among rural elderly in 14 poverty state counties of Chongqing, Southwest China: a cross-sectional study.Environmental health and preventive medicine · 2020Article
- DNA methylation in the human frontal cortex reveals a putative mechanism for age-by-disease interactions.Translational psychiatry · 2019Article
- Reduced GABAergic cortical inhibition in aging and depression.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2018Article
- Assessment of neuroplasticity in late-life depression with transcranial magnetic stimulation.Journal of psychiatric research · 2018Article
- Differential effects of chronic stress in young-adult and old female mice: cognitive-behavioral manifestations and neurobiological correlates.Molecular psychiatry · 2018Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The phenomenologic diagnosis of depression is successful in increasing diagnostic reliability, but it is a classification scheme without biologic bases. One subtype of depression for which evidence suggests a unique biologic basis is late-life depression (LLD), with first onset of symptoms after the age of 65. LLD is common and poses a significant burden on affected individuals, caretakers, and society. The pathophysiology of LLD includes disruptions of the neural network underlying mood, which can be conceptualized as the result of dysfunction in multiple underlying biologic processes. Here, we briefly review current LLD hypotheses and then describe the characteristics of molecular brain aging and their overlap with disease processes. Furthermore, we propose a new hypothesis for LLD, the age-by-disease interaction hypothesis, which posits that the clinical presentation of LLD is the integrated output of specific biologic processes that are pushed in LLD-promoting directions by changes in gene expression naturally occurring in the brain during aging. Hence, the brain is led to a physiological state that is more susceptible to LLD, because additional pushes by genetic, environmental, and biochemical factors may now be sufficient to generate dysfunctional states that produce depressive symptoms. We put our propositions together into a decanalization model to aid in illustrating how age-related biologic changes of the brain can shift the repertoire of available functional states in a prodepression direction, and how additional factors can readily lead the system into distinct and stable maladaptive phenotypes, including LLD. This model brings together basic research on neuropsychiatric and neurodegenerative diseases more closely with the investigation of normal aging. Specifically, identifying biologic processes affected during normal aging may inform the development of new interventions for the prevention and treatment of LLD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.