Gold, McDonald Horne, Christine Kotila, Pedro Martinez, Kate Musallam, Terry M. Phillips, James. C. Reynolds, Nancy G. Sebring, Esther Sternberg, and Sara Torvik (Associate Investigators). I wish to thank: all the subjects participating in this study; Ms Kate Musallam, nurse manager, and all the other NIMH nurses who supported these studies. The informatics support for this study was provided by Mr Frank Pierce from ®Esprit Health. Selected abbreviations and acronyms BMD Bone mineral density CRP C-reactive protein Inhibitors,research,lifescience,medical HPA hypothalamic-pituitary-adrenal

MDD major depressive disorder PAI-1 plasminogen activator inhibitor
Unipolar major depression is one of the most common mental diseases worldwide.1,2 Unfortunately, not all patients respond to the available pharmacological treatment algorithms and refractory depression

is not uncommon.3 Furthermore, the underlying Inhibitors,research,lifescience,medical pathophysiological mechanisms of this affective disorder are still under debate.4 In spite of these neurobiological uncertainties, we are in need of alternative treatment options.5 Repetitive transcranial magnetic stimulation (rTMS; a type of TMS that occurs in a rhythmic and repetitive form) has been put forward as a new technique to treat this debilitating illness.6 Current evidence suggests that rTMS applied to the dorsolateral prefrontal click here cortex (DLPFC) is a promising treatment strategy for Inhibitors,research,lifescience,medical depression, but not all patients Inhibitors,research,lifescience,medical show a positive outcome.7,8 Current clinical outcome studies report rather modest

superiority compared with placebo (sham).9-11 To date, it remains unclear which TMS parameters, such as stimulation duration and intensity, can produce the most benefits.6,8,9,12 Moreover, there is no consensus of the exact brain localization for individual coil placement.13 Inhibitors,research,lifescience,medical To answer these important questions, it would be important to gain more insight in the underlying neurobiological working mechanisms of rTMS. To date, no clear theoretical framework has yet emerged as to why rTMS treatment could result in a “normalization” of mood in depressed Rebamipide patients.14,15 rTMS, the dorsolateral prefrontal cortex, and unipolar depression The majority of rTMS treatment studies target the DLPFC15,17 The (dorsolateral) prefrontal cortex is implicated in regulating affective states, providing cognitive control over stress and emotion responsiveness.18 A variety of studies has shown that a series of daily sessions of high frequency ( HF)-rTMS delivered to the left DLPFC or low frequency (LF)-rTMS applied to the right DLPFC are effective in reducing symptoms in clinically depressed populations.10,11,15 rTMS can either activate or suppress motor, sensory, or cognitive functions, depending on the brain location and parameters of its delivery: LF-rTMS (<1Hz) is considered to “inhibit” cortical regional activity, while HF-rTMS (>1Hz) “activates” cortical areas.