Major Depressive Disorder Research Roundup: August 29, 2024

In this Research Roundup, we explore new studies on major depressive disorder (MDD).

The Effects of Physical Activity on MDD

Physical activity has a significant ameliorative effect on MDD; however, there may be variations in the effects of different types of exercise. Investigators evaluated the following types of exercise:

• Endurance continuous training: aerobics exercise or moderate-intensity continuous training that utilizes oxygen as a metabolic pathway to meet the body’s energy needs through oxidative phosphorylation
• Explosive interval training: vigorous physical activity, with high intensity
• Resistance strength training: exercise that involves working against resistance to enhance muscle strength and volume
• Mind–body trainings: physical activities designed to improve the connection between the mind and body, promoting relaxation, stress reduction, and positive thinking

Using multimodal monitoring, the investigators found that physical activity significantly improved hippocampal volume, cortical density, and regulated the release of neurotransmitters like monoamines and neuropeptides in patients with MDD.

Additionally, the research suggests that explosive interval training has the most significant effect on reducing depression levels in patients, while continuous endurance training has the highest frequency of use and clinical acceptability. Furthermore, mind–body training has the best adherence. Lastly, resistance strength training may have a similar or slightly smaller effect than explosive interval training. However, the effects of exercise combined with pharmacological interventions may be the best possible treatment.

Research shows that physical activity improves depressive symptoms, cognitive function, and sleep status in patients with MDD. The types, durations, and intensities of physical activity are less understood, and thus require further study to understand the differences in the effects of these interventions on MDD. To ensure the best outcomes of physical activity in MDD intervention, this study suggests that the dosage characteristics of physical activity in different MDD populations should be emphasized before developing exercise prescriptions. In summary, physical activity may be used as an adjunctive tool in future research and clinical treatment of MDD.

Reference

Guan J, Sun Y, Fan Y, et al. Effects and neural mechanisms of different physical activity on major depressive disorder based on cerebral multimodality monitoring. Front Hum Neurosci. 2024;18:1406670.

Sex and Age in the Differential Efficacy of 10 Hz and Intermittent Theta-Burst Repetitive Transcranial Magnetic Stimulation

Recent research examined whether there are sex- and age-dependent differences in outcomes with intermittent theta burst stimulation (iTBS) and 10 Hz repetitive transcranial magnetic stimulation (rTMS). Investigators found that 10 Hz appears more efficacious in females than in males, whileiTBS appears less efficacious in females than in males.Overall, rTMS appears more efficacious in patients older than 50, particularly females older than 50. This was the first report of a differential response to 2 different rTMS protocols based upon sex.

Investigators evaluated the relationship between biological sex, age, and treatment outcomes among 414 participants with MDD who were treated with 10 Hz or iTBS rTMS. Investigators used linear mixed-effects modeling to examine the association between treatment and change in the 30-item Inventory of Depressive Symptomatology Self-Report (IDS-SR30) score from baseline to treatments 10 and 30, with biological sex (M/F), protocol (iTBS/10 Hz), age (≥/<50 years old), and time (treatment 1/10/30) as fixed effects.

There was a significant 3-way sex-protocol-time interaction at treatments 10 (P = 0.016) and 30 (P = 0.031). Males showed significantly greater improvement with iTBS than females at treatments 10 (P = 0.041) and 30 (P = 0.035), whereas females showed numerically greater improvement with 10 Hz treatment. While there was not a significant 3-way age-protocol-time interaction, there was a significant interaction between age (≥50 years old) and time at treatments 10 (P = 0.007) and 30 (P = 0.042), and among age, sex, and time at treatment 30 (P = 0.028).

Reference

Slan AR, Citrenbaum C, Corlier J, et al. The role of sex and age in the differential efficacy of 10 Hz and intermittent Theta-burst (iTBS) repetitive transcranial magnetic stimulation (rTMS) treatment of major depressive disorder (MDD). J Affect Disord. 2024:S0165-0327(24)01358-2.

Brain Stimulation That Has Been Personalized Significantly Decreases Depression Symptoms

Flavio Frohlich, PhD, professor of psychiatry at the UNC School of Medicine, has pioneered methods for investigating how brain overactivity can be brought into balance and help alleviate depression symptoms.

Frohlich et al have successfully developed and tested a closed-loop system that can measure a patient’s individual alpha frequencies and stimulate the brain with a low-level alternating electrical current to bring balance to alpha oscillations in participants with MDD. The data shows that 80% of 15 patients experienced marked improvement in their depression symptoms immediately and throughout the following 2 weeks, according to standard clinical tests and self-reporting.

In this pilot study, participants were given hour-long sessions for 5 consecutive days, and the closed-loop system allowed the investigators to continually measure alpha waves and mete out low levels of electricity to help the brain bring its alpha oscillations back into synchronicity. Notably, there was no placebo group; however, the investigators have secured funding from the National Institute of Mental Health to do a further randomized double-blinded control study of the new closed-loop system.

“Today’s stimulation paradigms mostly focus on specific neuronal networks across brain regions and are not designed to target the structure of large-scale electrical brain activity, which can be measured as rhythmic patterns we refer to as network oscillations,” said Frohlich, professor of psychiatry at the UNC School of Medicine and director of the Carolina Center for Neurostimulation. “We already knew, through our research and others’, that brain stimulation can improve depression symptoms, but current paradigms use 6 weeks of treatments. We showed dramatic improvement after 5 days. Our work shows that low-energy electric brain stimulation has potential for safe, rapid relief without medication.”

Reference

Schwippel T, Pupillo F, Feldman Z, et al. Closed-loop transcranial alternating current stimulation for the treatment of major depressive disorder: an open-label pilot study. Am J Psychiatry. 2024:appiajp20230838.

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