Longer depressive episode duration negatively influences HF-rTMS treatment response: a cerebellar metabolic deficiency?

Repetitive transcranial magnetic stimulation (rTMS) is an evidence based neurostimulation modality used to treat patients with Major Depressive Disorder (MDD). In spite that the duration of current a depressive episode has been put forward as a negative predictor for clinical outcome, little is known about the underlying neurobiological mechanisms of this phenomenon. To address this important issue, in a sample of 43 melancholic stage III treatment resistant antidepressant-free refractory MDD patients, we reanalysed regional cerebral glucose metabolism (CMRglc) before high frequency (HF)-rTMS treatment, applied to the left dorsolateral prefrontal cortex (DLPFC). Besides that a lower baseline cerebellar metabolic activity indicated negative clinical response, a longer duration of the depressive episode was a negative indicator for recovery and negatively influenced cerebellar CMRglc. This exploratory 18FDG PET study is the first to demonstrate that the clinical response of HF-rTMS treatment in TRD patients may depend on the metabolic state of the cerebellum. Our observations could imply that for left DLPFC HF-rTMS non-responders other brain localisations for stimulation, more specifically the cerebellum, may be warranted.