21 The impact of depression on health and wellbeing is not confined to the patients themselves, but frequently extends to their human networks, negatively affecting social, familial, and occupational relationships.22 Depression is presently managed with psychological, pharmacological, or physical

interventions or their combination. However, all present treatment options have limitations, such as medication side effects, nonresponse (including a high Inhibitors,research,lifescience,medical proportion of treatment-refractory patients who do not respond to any therapy),23 and frequent relapse. Even patients who have responded to antidepressant treatment are often reluctant to take medication in the long term and thus experience an increased relapse risk.24 Together these complex challenges underscore the need for better, and more effective, treatment and relapse prevention

options for depression, and for solutions that are to be designed through interaction between researchers, clinicians, and the patients themselves. A Inhibitors,research,lifescience,medical functional Selleck Gefitinib imaging approach Inhibitors,research,lifescience,medical (in the broad sense, incorporating both fMRI and electrophysiological techniques) to elucidating the circuits underlying the symptom complexes of depression, but also of those involved in their remediation, can be useful in this new therapeutic endeavor in several respects. Firstly, it may allow researchers to identify Inhibitors,research,lifescience,medical correlates of individual symptoms or symptom groups, for example, altered activation of frontostriatal circuits during period of apathy and fatigue. If these imaging-based state markers can be shown to be reliable and diagnostic, they may become new targets

for self-regulation training through neurofeedback (or other neuromodulatory interventions). Inhibitors,research,lifescience,medical With further refinement of functional imaging methods and higher signal-to-noise ratio obtained through higher field strengths, there mayeven be scope for a detailed functional mapping of brain stem nuclei that may reveal information about the underlying chemical imbalances, thus possibly giving rise to new pharmacological strategies. Even if this combination of advanced functional (and structural) neuroimaging and a symptom cluster-based approach to depression does not produce clear, individually- targetable state markers, the knowledge of the functional systems involved new can still inform new treatment approaches, notably in neuromodulation. I have argued15 that the biological correlates of the mechanisms that help to overcome a mental illness, such as emotion regulation or fear extinction,25 may be more consistent than those of the original illness. Thus, if we can apply functional imaging to reveal the neural correlates of successful treatment26-29 (see also the article by Beauregard in this issue, p 75), we can subsequently apply neuromodulation techniques to target these neural networks directly.