Cellular Energy Metabolism and Fatigue

1 Cullen et al. 2026 — ATP Bioenergetics and Fatigue in Depression vs. Controls

Full Citation:: Cullen K, Tye S, Varela R, et al. ATP bioenergetics and fatigue in young adults with and without major depression. Translational Psychiatry. 2026. (Cullen et al. 2026) DOI:: 10.1038/s41398-026-03904-y Study Design:: Cross-sectional comparison (depressed vs. non-depressed young adults) Sample Size:: \(n=18\) (preliminary) Key Findings::

- Cells from depressed individuals paradoxically produce more ATP at rest but show reduced capacity to upscale output under metabolic stress
- Authors term this pattern *stress-responsive mitochondrial failure*: maximum baseline engagement with no spare reserve capacity
- Pattern conceptually resembles ME/CFS post-exertional energy collapse

Relevance:: Adjacent (depression cohort). The “stress-responsive mitochondrial failure” model may be a more accurate framing than absolute ATP deficiency for ME/CFS. Suggests that near-normal resting measures can coexist with severely impaired energy stress-response capacity — explaining why routine metabolic tests appear normal in ME/CFS. Certainty Assessment::

- *Quality:* Medium (Translational Psychiatry, peer-reviewed)
- *Sample:* $n=18$ (very small; preliminary)
- *Relevance to ME/CFS:* Speculative cross-application
- *Certainty:* 0.40
- *Limitation:* Depression cohort; requires replication; ME/CFS applicability untested

References

Cullen, Katie, Susannah Tye, Roger Varela, et al. 2026. “ATP Bioenergetics and Fatigue in Young Adults with and Without Major Depression.” Translational Psychiatry. https://doi.org/10.1038/s41398-026-03904-y.