November 2020. In 2019, Nature Neuroscience published a brief review article by Niethard and Born1 entitled “Back to baseline: sleep recalibrates synapses.” They focused on the evidence supporting the “synaptic homeostasis hypothesis,” a theory that “proposes that sleep … promotes the downscaling and renormalization of synapses following wakefulness to maintain network plasticity within an optimal range” (p149). Information is encoded during the waking state, which leads to a general synaptic upscaling, followed, during sleep, by synaptic downscaling. The authors summarize a large body of research reflecting advances in our understanding of the brain’s activity during sleep, at the cellular level. This scientific progress is increasingly relevant as we learn more about the role of sleep at the macrolevel, in health and in disease. For example, sleep disturbance is a hallmark feature of depression, a clinical state that involves changes in neural plasticity.2 Furthermore, the mechanisms of action of therapeutic interventions such as antidepressants are thought to involve alterations in neural plasticity.
In this issue of the Journal, Centorino and colleagues present a fascinating discussion on “The relationship of transcranial magnetic stimulation with sleep and plasticity.” They reflect on the therapeutic mechanism of action of repetitive transcranial magnetic stimulation (rTMS) for patients with depression, considering that it may have to do with its effect on brain plasticity. However, they point out the many complexities of this question still to be understood. For example, low-frequency inhibitory rTMS and high-frequency excitatory rTMS produce different neurological effects, and the effects may differ if the intervention is administered in the waking state versus the sleeping state. They also refer to the well-established rapid antidepressant effect of sleep deprivation, an effect that is brief and transient, lasting only until resumption of sleep. In contrast, ketamine, also rapid-acting, has a more enduring effect. These and other avenues for further exploration are discussed.
Also in this issue of the Journal, Thekiso and collaborators report on the effectiveness of a specialized mood disorders service designed for patients with first-admission depression. The features of the specialized service are described in detail, and the favorable results of this intensive treatment service are presented, although on follow-up, a substantial proportion of patients experienced recurrences, especially those with longer mood episodes and those with co-occurring conditions. Another article in this issue, by Giles and colleagues, is a feasibility study on the use of exercise as a treatment for major depression in youth. This pilot project demonstrated that a 12-week program, which combined motivational interviewing with both aerobic exercise and resistance training, successfully reduced the severity of depression in a majority of the young adults in the study.
John M. Oldham, MD
1. Niethard N, Born J. Back to baseline: sleep recalibrates synapses. Nat Neurosci. 2019;22:149–153.
2. Zhang M-Q, Li R, Wang Y-Q, et al. Neural plasticity is involved in physiological sleep, depressive sleep disturbances, and antidepressant treatments. Hindawi Neural Plasticity. 2017:5870735. doi: https://doi.org/10.1155/2017/5870735