Project Grant R01MH143749

The National Institute of Mental Health awarded The McLean Hospital Corporation $771,937 on September 1, 2026, under the Mental Health Research Grants program (CFDA 93.242) to investigate the synaptic mechanisms underlying intermittent theta burst stimulation (ITBS) as a treatment for major depressive disorder.

The research examines whether ITBS, an FDA-cleared patterned form of transcranial magnetic stimulation delivered clinically to the dorsolateral prefrontal cortex, works by enhancing synaptic plasticity through N-methyl-D-aspartate receptor (NMDAR) activation. The project proposes two aims: blocking NMDAR function during ITBS in depressed patients (Aim 1) and activating it (Aim 2) to assess long-term potentiation-associated changes using EEG-based TMS-evoked potentials. The study will compare 40 depressed patients to 40 healthy controls. This work validates a theory that pharmacologic augmentation with D-cycloserine combined with ITBS enhances clinical outcomes through synaptic plasticity mechanisms, with results intended to guide optimization of plasticity-promoting treatments for depression and other disorders.

The project period runs through July 31, 2031, with performance at McLean Hospital in Belmont, Massachusetts. McLean Hospital, a nonprofit psychiatric teaching hospital affiliated with Harvard Medical School, serves as the recipient organization.