Several studies report that GH treatment of GH deficient adults improves quality of life (QOL). It is unclear whether improved QOL is an indirect result of the metabolic effects of GH producing increased lean body mass and reduced body fat, or whether it might be a direct effect of GH on the central nervous system. While one might expect that the short stature present in GH deficient children is associated with psychological distress, there is scant evidence that short children have such problems or that GH treatment improves them. Thus, this study of 41 children (30 boys) from Japan with isolated GH deficiency is of significant interest. Patients completed a self-rating depression scale for children before and after 6 months or longer of GH treatment. The depression score improved from 9.7 +/-6.1 before to 6.9 +/-4.6 on GH treatment (Wilcoxon’s signed ranks test difference p=.00013). Six patients scored >16, consistent with a “depressive tendency”. The depressive tendency resolved in 5/6 with GH treatment; these patients showed a decrease of 8.5 points on the depression scale, greater than in the overall group. Although one might predict that the improvement in the depression score would be correlated with height gain, this was not the case. Could the changes be due to a direct effect of GH on the brain? The findings in this study are limited by lack of a control group. It is possible that medical attention to the issue, regardless of outcome, produced a positive effect. Regardless, the important finding is that a subgroup of children with GHD are at risk for significant depression, which improves with GH treatment. Steve LaFranchi, MD