The results of her work suggest, that FHPI metabolism in certain brain areas, as measured by PET, may serve as a mediator of response to the SSRIs. Specifically, she found an increase in brain stem and dorsal cortical metabolism (prefrontal, parietal, anterior cingulatc, and posterior cingulate), and a decrease in limbic and striatum metabolism (subgenual cingulate, hippocampus, insula, and palladium) from week 1 to week 6 of treatment among fluoxetine responders. Fluoxetine nonrcsponders did not demonstrate changes in these areas during the same treatment period (weeks 1-6). Similarly, Tosifescu et al123 established a relationship between normalization in measures

Inhibitors,research,lifescience,medical of brain Inhibitors,research,lifescience,medical biocnergetic metabolism among patients with SSRI-resistant MDD who experienced symptom improvement (clinical response) following T3 augmentation of their SSRI treatment, regimen. In a recent work, Mayberg et al121 reviewed earlier studies examining the relationship between regional metabolic changes and symptom improvement during the treatment of MDD with antidepressants, and concluded that a significant correlation between

normalization of frontal hypometabolism and clinical improvement was the best-replicated finding. However, a similar Inhibitors,research,lifescience,medical relationship (ie, between an increase in frontal metabolism and symptom improvement) was also reported Inhibitors,research,lifescience,medical during placebo treatment.121 The results of the latter study suggest that such changes, at least as detected by the technology available at the time, appear to be related to nonspecific (placebo) rather than specific (drug) treatment effects and, therefore, may not serve as robust differential treatment mediators. Little et al,124 for instance, Inhibitors,research,lifescience,medical examined whether there are differences in the relationship between brain metabolism at baseline (predictor or moderator) and symptom improvement between two antidepressants of different class (the NDRI bupropion versus the SNRI venlafaxine). For the most part, similar findings predicted symptom improvement

for both agents (frontal and left temporal hypometabolism), although some differences emerged (compared with control subjects, bupropion responders (n = 6) also had cerebellar hypermetabolism, whereas venlafaxine responders showed bilateral Thiamine-diphosphate kinase temporal and basal ganglia hypometabolism). This study has yet to be replicated, either with regards to baseline brain metabolism (ie, moderator of response), or changes in baseline brain metabolism (ie, mediator of response). Quantitative EEG Quantitative electroencephalography (QEEG) involves the use of computer software analysis to deconstruct, electroencephalographic (EEG) tracings and quantify parameters including frequency and amplitudes (traditional EEG involves manual readings).