PROJECT SUMMARY Adolescence is most strikingly characterized by the pubertal growth spurt. It is also a time when the prevalence of depressive and anxiety disorders increases dramatically, a fact reflected in the widespread use of antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs). In fact, antidepressants comprise the second to third most commonly prescribed medication class in this age group. We and others have found that SSRIs are associated with height growth suppression in adolescents. This was particularly true in boys undergoing puberty. To build on these findings, we recently completed another study (R21HD097776) of children and adolescents undergoing puberty and starting treatment with one of two commonly prescribed SSRIs, sertraline and fluoxetine. We again found that, over the 6-month follow-up period, the higher the SSRI dose, the more significant height growth suppression was. In fact, SSRI use reduced growth by about 50% of that observed in unmedicated participants. Notably, sertraline was associated with the most significant deleterious effect on height. Moreover, the higher the SSRI dose, the lower the serum concentration level of insulin growth factor 1 (IGF-1), the principal marker of growth hormone (GH) neurosecretory function. To better characterize the clinical implications of these findings, we now propose to 1) determine whether the suppression of height growth and IGF-1 plateaus or continues unabated over the course of a 2-year follow- up, 2) whether differences between the 4 most prescribed SSRIs (sertraline, fluoxetine, citalopram, and escitalopram) exist, and 3) whether SSRI treatment merely slows growth down or, rather, stunts it, thus reducing anticipated adult height. The latter will be evaluated using serial assessments of bone age. In sum, the proposed study will be the first to investigate the magnitude of height growth suppression induced by SSRIs, its clinical predictors, and its long-term sequelae, shedding light on a currently little-recognized side effect of a widely and increasingly used medication class. The information will be critical to informing clinical decision making.