Abstract: Depression symptom genetics mapped onto NMN-linked mouse aging pathways
In this abstract, genetic signals for individual depression symptoms were tested against 10 pathways from an NMN mouse re-analysis; fatty acid degradation was the broadest signal, and the authors call the results hypothesis-generating without establishing NMN effects. [1]
Automatic summary · not editorially reviewed
The key findings
The analysis used transcriptome-wide association outputs from the Adams et al. 2024 depression meta-analysis and 10 KEGG pathways from a Cheung 2026 re-analysis of the Mills et al. 2016 NMN mouse study. [1]
Fatty acid degradation was significant in 8 of 12 symptom dimensions and was the highest-degree pathway hub. [1]
The authors call the results hypothesis-generating and say they do not establish therapeutic effects of NMN. [1]
The source at a glance
- Study type / format
- Abstract of a transcriptome-wide association pathway analysis
- Population / context
- Genetic signals for major depression symptom dimensions, analyzed with brain tissue models
- Summary based on
- Study abstract
- Publication status
- Preprint · peer-review status not confirmed
- Original publication
- July 16, 2026
Depression symptom genetics tested against NMN mouse pathways
The authors asked whether symptom-level genetic signals for major depression converge on cellular pathways previously nominated from NMN aging biology. They analyzed transcriptome-wide association study outputs derived from the Adams et al. 2024 genome-wide meta-analysis of depression symptom dimensions, using brain tissue models and 10 KEGG pathways selected from a Cheung 2026 re-analysis of the Mills et al. 2016 NMN mouse study. These pathways were anchored in 35 cross-tissue robust genes whose age-associated expression shifts were reported to be rescued by NMN.
Supporting source [1]
Fatty acid degradation broadest; endocytosis tied to hypersomnia
Fatty acid degradation was the broadest pathway signal, significant in 8 of 12 symptom dimensions and the highest-degree pathway hub. The strongest individual association was endocytosis with hypersomnia (sleepMore), Stouffer Z = −6.42, bootstrap 95% CI −9.67 to −3.02, permutation p = 0.0004. Autophagy was strongly associated with weight loss, Z = −5.93, p = 0.0008. Weight loss and weight gain diverged biologically (mean Lin's concordance correlation coefficient −0.32), supporting their treatment as distinct dimensions rather than opposite ends of one scale.
Supporting source [1]
Hypothesis-generating; no NMN therapeutic effect shown
Symptom clustering separated atypical sleep-weight features from core affective-cognitive-fatigue symptoms. The authors conclude that the findings support a dimensional, pathway-informed model of major depression, with the strongest signals implicating mitochondrial fatty acid handling, endosomal trafficking and autophagy in symptom-specific genetic liability. They state the results are hypothesis-generating and do not establish therapeutic effects of NMN, but nominate pathways for replication and mechanism-targeted studies in biologically defined depression subgroups.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. The analysis is genetic and pathway-based, uses mouse-derived NMN pathway nominations, and the authors describe the findings as hypothesis-generating without establishing NMN therapeutic effects.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Cheung N. · europepmc.org · July 16, 2026