| Depression is a devastating, debilitating disorder that is one of the leading causes of social impairment and economic hardship in the world today. Although long considered a fundamentally adult disorder, depression is quite prevalent in children and adolescents, and there is evidence that early-onset mood disorders are more severe and have worse lifetime prognoses. Despite this situation, very little is known about the neural correlates of depression, especially in pediatric populations. Female adolescents are particularly at risk, suffering from depression at twice the rate of males. A further level of complexity is rooted in the similarity of depressive episodes that originate from different underlying mood disorders, specifically major depressive disorder (MDD) and bipolar disorder (BD). The similar symptomatology of depression associated with MDD and BD often leads to misdiagnosis, improper treatment, and illness exacerbation. This thesis studies the underlying neural signature of depression in female adolescents, and the experiments presented here investigate the potential of functional brain imaging to differentiate depressive episodes engendered by MDD versus BD.;The second study (Chapter 4) investigates the phenomenon of affective interference. It has previously been demonstrated in depressed patients that emotional stimuli can interfere with a subsequent cognitive-based task. To study this phenomenon, we designed another fMRI task using emotional faces and basic math. Our findings confirm the affective interference phenomenon, and describe how this phenomenon manifests differently within the studied groups.;We conclude with a review of the literature on the biology of emotion, examining the anatomy, function, and connectivity of associated brain regions in healthy humans and patients with mood disorders (Chapter 5). After the discussion, interpretations of this dissertation's data and future areas of research are presented. Few studies have examined the biological mechanisms of depressive disorders within the adolescent brain or attempted to distinguish the neural circuitry of depression in MDD and BD, but this research is of primary importance.;The background for the study and the overall research methodology are outlined in Chapters 1 and 2. The first study (Chapter 3) uses an original functional magnetic resonance imaging (fMRI) task to characterize the neural responses of healthy and depressed females to emotional stimuli. Then, the functional responses of healthy females, depressed females with a diagnosis of MDD, and depressed females with a diagnosis of BD are directly compared to elucidate between-group differences. Several previous studies have implicated the amygdala, a subcortical nucleus within the limbic system, in the processing of negative emotional stimuli, suggesting exaggerated and sustained activation in this region in depressed patients as compared to controls. However, we found that depressed female adolescents exhibited less activation in the amygdala than healthy controls, and that this was true for both depressive subgroups. In addition, our findings show an inverse relationship between amygdalar activation in response to negative stimuli and depressive symptom severity on the day of scan. |
