Adolescence is a period of high risk for the onset of depression; 15% of adolescents, including a disproportionately high number of females, experience an episode of Major Depressive Disorder (MDD)15-17. Importantly, MDD during adolescence is associated with high rates of recurrence of the disorder18. Although most adolescents do not meet criteria for MDD until after the age of 15, subsyndromal depressive symptoms rise precipitously between ages 10-15, the period coinciding with puberty. Because gonadal hormone receptors are located in brain networks that have been shown to be aberrant in depressed adults and older adolescents19-26, scientists theorize that puberty precipitates the onset of MDD by altering developmental trajectories of brain networks that are relevant to MDD13,27,28. Specifically, puberty is hypothesized to alter the functional connectivity and efficiency of organizational structure in the salience network (SN; implicated in interpreting emotionally salient stimuli), the default mode network (DMN; implicated in self-referential processes, such as rumination), the executive control network (ECN: implicated in emotion regulation)13,27,29. We do not yet understand the nature of the relation between individual variability in trajectories of brain network connectivity and organizational efficiency during puberty and variability in trajectories of depressive symptoms. We also do not know whether or how the timing of pubertal onset interacts with brain development to influence depressive symptom trajectories, a critical issue given that the release of gonadal hormones during puberty interacts with the ongoing development of neural networks. Puberty occurs in a social context; in particular, children's progression through puberty has been found to elicit changes in parenting style, including parental warmth and limit-setting30,31. Furthermore, youth whose parents exhibit higher levels of authoritative parenting (high in both warmth and limit-setting) during puberty exhibit fewer depressive symptoms32-40 and smaller increases in depressive symptoms through puberty38,41. Neuroimaging studies suggest that this relation is mediated by parenting-related variability in brain activation in regions within the SN, DMN, and ECN14,42. Because parenting style is a treatment-relevant and modifiable aspect of adolescents' environments, we propose to examine the contribution of parenting style to individual differences in the trajectories of adolescents' brain networks and in the development of depressive symptoms. We propose to prospectively assess 80 healthy, pre-pubertal 10- and 11-year-old girls annually for five years. We will add three additional resting-state functional neuroimaging and pubertal assessments to a large, ongoing longitudinal study, and we will obtain reports of parenting behaviors at all time points. To study a sample at risk for developing depression, we will limit our sample to low-socioeconomic-status girls43-46. By clarifying which specific aspects of brain development go awry and when, this study will help to focus treatments and provide brain targets that can be used to sensitively monitor treatment efficacy.
Adolescence is a period of high risk for the onset of Major Depressive Disorder (MDD); compared with later-onset MDD, adolescent-onset MDD is associated with longer and more severe depressive episodes that are more refractory to treatment, have higher rates of recurrence, and involve greater engagement in high-risk behaviors that increase morbidity and mortality. In the proposed study, we will longitudinally assess brain network connectivity in high-risk youth as they progress through the puberty in order to characterize how trajectories of brain development may diverge in individuals who go on to develop MDD; we will also examine how positive parenting may buffer against maladaptive trajectories. Findings from the proposed study will yield insights into the brain-based etiology supporting the developmental emergence of adolescent-onset MDD and will inform the design of targeted early interventions.
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