Neuroendocrinology and rTMS An important aspect of the physiology of rTMS could be related to the endocrinological response of the HPA axis.46,47 Keck48 proposed that rTMS
influences occur at the hypothalamic level, suggesting that the (dorsolateral) prefrontal cortex participates in the rTMS-induced blunted response of HPA activity. HF-rTMS would inhibit cortisol-releasing hormone synthesis and release (Figure 2).. Some studies have examined this hypothesis in depressed patients.47 For instance, in a sample of severely Inhibitors,research,lifescience,medical depressed patients, salivary cortisol concentrations Gamma-secretase inhibitor Notch decreased immediately after one active left DLPFC HF-rTMS session and not after sham rTMS.48 Pridmore50 observed normalization of the dexamethasone suppression Inhibitors,research,lifescience,medical test in a small sample of medicated depressed subjects after multiple sessions of HF-rTMS. Figure2. Visualization of a theoretical working mechanism of HF-rTMS applied to the DLPFC on the HPA-system in unipolar major depression. In the left hand corner a figure-of-eight shaped repetitive transcranial magnetic stimulation (rTMS) coil is depicted. rTMS … In addition, in a sham-controlled left prefrontal HFrTMS trial, Szuba et al51 found acute mood Inhibitors,research,lifescience,medical and serum thyroid-stimulating hormone elevations in drug-free depressed patients after each active stimulation session. Mood improvement
was only observed after active HFrTMS. These observations could imply that the clinical effects of Inhibitors,research,lifescience,medical rTMS act in a similar way to pharmacological interventions: clinical improvement after antidepressant treatment has been associated with a normalization of HPA system
function and different antidepressants may act in the same way in attenuating the HPA axis.52,53 Inhibitors,research,lifescience,medical However, it has to be noted that in depressed patients HPA system abnormalities are not consistently observed.47 Neurotransmitter systems and rTMS Only a few studies have examined the rTMS effects on neurotransmitter systems in major depression. Nature Immunology Because rTMS treatment resulted in psychomotor symptom improvement, such as a reduction in motor slowness in bodily movement and speech, increased voice volume, and facial inexpressivity, some authors suggested that a possible working mechanism of action could be by activating the dopaminergic system.54,55 Indeed, several brain imaging studies using dopaminergic ligands point to an rTMS-related release in endogenous dopamine when stimulating prefrontal cortical areas,56,57 although others found no impact on the dopaminergic system at all.58,59 In major depression, the serotonergic system has been extensively investigated, and serotonin (5-HT) is an important excitatory transmitter involved in HPAsystem regulation.