Increased Amygdala: Hippocampal Volume Ratios Associated with Severity of Anxiety in Pediatric Major Depression Shauna MacMillan, B.S., 1 Philip R. Szeszko, Ph.D., 2 Gregory J. Moore, Ph.D., 1,3 Rachel Madden, B.A., 1 Elisa Lorch, M.A., 1 Jennifer Ivey, B.S., 1 S. Preeya Banerjee, M.A., 1 and David R. Rosenberg, M.D. 1,4 ABSTRACT Background: Neurobiologic abnormalities in the temporal lobe, particularly medial temporo- limbic circuits, have been implicated in the pathogenesis of major depressive disorder (MDD). Although MDD commonly emerges during childhood and adolescence, to our knowledge, no prior study has examined temporal lobe anatomy in pediatric patients with MDD near the onset of illness before treatment. Methods: Volumetric magnetic resonance imaging scans were conducted in 23 psychotropic drug-naïve pediatric patients with MDD, aged 8–17 years, and 23 case-matched healthy com- parison subjects. Results: Pediatric patients with MDD had significantly larger left (14%) and right (11%) amygdala:hippocampal volume ratios than controls. Increased left and right amygdala:hip- pocampal volume ratios were associated with increased severity of anxiety but not increased severity of depression or duration of illness. Conclusion: These results suggest that alterations in amygdala:hippocampal volume ratios in pediatric MDD may more reflect severity of associated anxiety than depression. These re- sults underscore the importance of assessment for comorbidity in the study of MDD. 65 JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY Volume 13, Number 1, 2003 © Mary Ann Liebert, Inc. Pp. 65–73 Departments of 1 Psychiatry, 3 Radiology, and 4 Pediatrics, Wayne State University School of Medicine, Detroit, Michigan. 2 Department of Psychiatry Research, Hillside Hospital, Glen Oaks, New York. INTRODUCTION P EDIATRIC MAJOR DEPRESSIVE DISORDER (MDD) is a common and often chronic illness that is continuous with adult MDD (Birmaher et al. 1996a, 1996b; Harrington et al. 1990; Kovacs et al. 1984; Lewinsohn et al. 1986, 1993, 2000; Rao et al. 1993, 1995, 1996; Ryan et al. 1987, 1992, 1994; Williamson et al. 1995). Consistent with rates reported in adult patients with MDD, the lifetime prevalence of pediatric MDD is ap- proximately 15–20% (Kessler et al. 1994; Lewinsohn et al. 1986, 1993). Epidemiologic studies indicate that 1 in 40 children and 1 in 12 adolescents are affected by mood disorders at any point in time (Coyle 2001). Investiga- tions of pediatric patients with MDD near ill- ness onset are, therefore, critical to examine