Pretreatment regional brain glucose uptake in the midbrain on PET may predict remission from a major depressive episode after three months of treatment.

In order to test the hypotheses that pretreatment metabolic activity in the midbrain and the rostral anterior cingulate may predict remission in response to medications enhancing monoaminergic transmission, we compared relative regional cerebral metabolic rate of glucose (rCMRglu) using positron emission tomography (PET) in medication-free patients with major depression who remitted after 3 months of monoaminergic medication, with non-remitters on the same treatment. [(18)F]-FDG PET was conducted in a group of 33 drug-free DSM-IV major depression subjects prior to antidepressant treatment. Patients were prescribed paroxetine initially (61%) unless they had failed paroxetine previously. Treatment was then managed by the subjects' own physician with 91% receiving a selective serotonin reuptake inhibitor and 78% another non-selective monoamine reuptake inhibitor during the 3 months of treatment. Voxel-based parametric brain maps of remitters were compared with maps of non-remitters using SPM2. Remission was defined as a >50% decrease in and a final score of <or=10 on the 24-item Hamilton Depression Rating Scale. We found that treatment remitters have lower activity in a single contiguous brain region (with global maxima in the midbrain, cluster level P=0.013, corrected for multiple comparison (CMC)), prior to treatment, compared with non-remitters to 3 months of community-based monoaminergic antidepressant treatment. Degree of improvement correlated with pretreatment midbrain activity. Pretreatment clinical picture and intensity of treatment did not distinguish remitters. No other area of the brain showed a significant difference between remitters and non-remitters even with CMC completely disabled. Lower relative regional brain activity in the region of monoaminergic nuclei prior to treatment predicts remission in response to 3 months of antidepressant treatment, despite no clinical differences at baseline and no difference in treatment intensity. Brain imaging is a potential objective laboratory technique that may guide treatment selection where clinical methods have not shown promise. Prospective studies are needed to replicate these findings and determine whether outcome prediction is limited to a specific class of antidepressants.