Does habitual caffeine consumption moderate the effect of dorsomedial intermittent theta-burst stimulation on functional brain activity? A resting state connectivity analysis in depressive patients.

Depression is one of the leading causes of disability around the world. Even though different treatments are considered relatively effective, the response rates of the current therapies are still too elevated. Previous studies have shown that repetitive transcranial magnetic stimulation (rTMS) using intermittent theta-burst stimulation (iTBS) has been found to be effective in depressive patients resistant to pharmacological or psychotherapeutic treatments. In a recent follow-up study (Frick et al., 2021) researchers have demonstrated that habitual caffeine consumption moderated the antidepressant effect of dorsomedial prefrontal (dmPFC) iTBS. Given the purported dopaminergic effects of dmPFC stimulation, it has been suggested that caffeine could interact with dmPFC and iTBS to augment dopaminergic signaling and increase antidepressant effects. In this study, the potentiating effect of caffeine is investigated through a functional magnetic resonance imaging (fMRI) resting-state analysis. Forty-two participants with current depressive episodes were randomized to active iTBS or sham treatment delivered two times per day for 10-15 weekdays. Neuronavigated stimulation was applied to the dorsomedial prefrontal cortex. Patients were scanned before and after TMS treatment. Symptom improvement was measured using change in self-reported Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pretreatment habitual caffeine consumption was quantified using self-reports of number of cups of coffee and energy drinks consumed the two days before the treatment starts. The resting state analysis has been performed with Conn Toolbox. In conclusion, habitual caffeine consumption does not appear to have any effect in moderating TMS on functional brain connectivity.