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Six subjects with DSM-III defined unipolar major depressive disorder had positron emission tomography scans using 18F-2-fluoro-2-deoxy-D-glucose (2FDG) before and after treatment with imipramine. Their 12 scans were compared to the scans of six controls matched for age. Significant reductions in metabolism for subjects in the depressed group were found on scans for both the anterior and right frontal regions. Significant reductions in metabolism occurred more often in the right hemisphere than the left. No significant changes in metabolism could be attributed to imipramine. In addition, absolute metabolic rates were not related to the degree of depression pre- and post-treatment. The findings suggest that hypometabolism in the frontal cortex and right hemisphere may occur in major depressive disorders.

To the Editor: We read with interest the paper by Eidelberg et ai. (1993), in which the authors state that they ana­ lyzed the scans according to our method. Unfortu­ nately, they did not. We used elliptical striatal regions of interest (ROIs) in our original paper and found a clear aging effect (Martin et aI., 1989). Eidelberg et ai. used rectangular ROIs in their attempt to replicate our method. The difference may be critical, as rectan­ gular ROIs would necessarily include more ventri­ cle, where there is no background activity, than el­ liptical ROIs; the error introduced by this may ob­ scure any aging effect. Eidelberg et ai. concede in their article that their failure to demonstrate an ef­ fect of age may be explained by excess variability. The issue is important, as the Eidelberg et ai. paper attempts to resolve disparate findings of an age re­ lationship in fluorodopa uptake using different ROIs (Martin et aI., 1989; Sawle et aI., 1990). We have recently shown in a new data set that using total striatal ROIs reveals an aging effect in fluorodopa uptake, while using small (8.8-mm­ diameter) ROIs does not (Vingerhoets et aI., 1994). These findings reconcile the differing conclusions of Martin et ai. (1989) (who used total striatal ROIs and found an age effect) and Sawle et ai. (1990) (who used small ROIs and did not). The difference between the methods does not relate just to the size of the ROIs; large ROIs measure the total striatal fluorodopa uptake, while small ROIs measure the concentration of fluorodopa uptake per milliliter of striatum. Eidelberg et ai. are confused by this point when they state that the total striatal ROI method is sensitive to the known age-related striatal atrophy (Murphy et aI., 1992). In fact, the opposite is true, because dopaminergic neurons make up a minimal part of the volume of the striatum. Any atrophy of the nondopaminergic elements would alter the con­ centration of fluorodopa uptake but not the total uptake, which is therefore the true measure of ni­ grostriatal dopaminergic function. Eidelberg et ai. could have contributed to the dis­ cussion by applying the methods of both Martin et ai. and Sawle et ai. to the same data set. U nfortu­ nately they did not replicate the methods, and

This article describes and partially validates a method for predicting whether an observed regional metabolic value is consistent with the observed value of another region, A regression equation was generated from a set of normal metabolic values, and then this equation was applied to patients with symptomatic Huntington's disease and patients at risk for this disorder. The results of the regression method were consistent with observations of the absolute rate for the normal subjects and Huntington's patients. For the at-risk patients, 6 of 18 were found to have reduced caudate metabolism relative to observed thalamic values. Since the initial scan, one of these identified at-risk individuals has developed symptomatic Huntington's disease. The method may be appropriate for other disorders where there are potential subgroups (e.g., schizophrenia) within a diagnostic category.