To the Editor In their article in JAMA Psychiatry, Janssen and colleagues1 describe an intriguing pilot study showing that whole-body hyperthermia was superior to sham in reducing depression. Their conjecture was that warm-sensitive afferent thermosensory pathways affect mood regulatory neural activity.1 However, these data support an alternate hypothesis, which is that depression is associated with dysregulated mitochondrial function, the extent of which correlates with symptom severity and is associated with decreased oxidative energy generation and cerebral glucose use. Multiple psychiatric disorders are associated with a shift from aerobic to glycolytic energy generation. If it is shown that a therapy that increases mitochondrial energy generation also improves depressive symptoms, this would be useful, albeit indirect, proof of principle of this hypothesis.
Berk M, Tye S, Walder K, McGee S. Hyperthermia for Major Depressive Disorder? JAMA Psychiatry. 2016;73(10):1095–1096. doi:10.1001/jamapsychiatry.2016.1532
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