Changes in reward system structure and function are thought to underlie many of the behavioral features, both positive and negative, that characterize adolescence. While increasing striatal response to reward during adolescence putatively supports positive and age typical behaviors such as greater exploration and peer affiliation, blunted striatal response to reward is observed in adolescent Major Depressive Disorder (MDD), maternally defined MDD-risk, and prospective worsening of depressive symptoms. Although it is clear that functional response to reward changes dramatically over normative development, and that blunted reward responding is linked to negative outcomes, it is unclear how depression risk may impact longitudinal trajectories of positive valence system function over adolescence. Understanding how and why maternally defined depression risk may interact with typical developmental processes could lead to a better understanding of the etiopathogenesis of depression and the development of prevention/intervention programs. To investigate these questions the proposed study aims to employ longitudinal functional neuroimaging methods to first examine whether blunted striatal reward responding is a consistent correlate of MDD-risk from childhood through adolescence (i.e. relates to the intercept rather than the slope of striatal reward response) or whether such blunting emerges/strengthens over development (i.e. relates to the rate of change in striatal reward response). Whether maternal neurobiological features, including striatal response to reward and structural integrity of reward-related white matter tracts, mediate relationships between maternal MDD history and offspring function will also be examined. To investigate these questions the proposed study capitalizes on an existing longitudinal data set where neural (fMRI) response to reward feedback was evaluated in a large sample of 8-14 year-old girls, with a second fMRI scan to be collected at a two-year follow up. Functional measures of maternal neural response to reward (fMRI) as well as white matter structural integrity (Diffusion Spectrum Imaging ? DSI) will also be collected at the two-year follow up, and are novel contributions of the proposed study. Analyses will focus on the never-depressed daughters of mothers with either a history of depression or without a history of any Axis I disorder. The proposed study will provide training in advanced neuroimaging techniques (DSI and fMRI), models of risk and developmental psychopathology, as well as advanced statistical techniques for both mediation and longitudinal analyses. This research will provide an enhanced understanding of a core dysfunctional mechanism in depression risk, reward responsiveness, and its trajectory across development.
Major Depressive Disorder (MDD) is a substantial public health concern associated with negative outcomes (e.g., poor academic performance, early pregnancy, and poor social functioning);1,2 given the debilitating nature of MDD and that current treatment options have poor long-term success rates, there has been increasing interest in applying preventative interventions to improve outcomes. Population-level risk for MDD rises rapidly during adolescence,3,4 thus to develop and administer preventative interventions it is vital to investigate how known risk factors for depression, such as maternal depression history,5 interact with ongoing adolescent development of neural processes associated with depression, such as striatal reward response.6 The proposed project will investigate 1) the relationship between maternal depression history and longitudinal trajectories of striatal response to reward in non-depressed daughters (i.e. risk) and whether maternal neurobiological factors (i.e. striatal function and structural integrity of reward-related white matter tracts) may mediate relationships between maternal depression and trajectories of striatal function in non-depressed, high- risk offspring.
|Luking, Katherine R; Nelson, Brady D; Infantolino, Zachary P et al. (2017) Internal Consistency of Functional Magnetic Resonance Imaging and Electroencephalography Measures of Reward in Late Childhood and Early Adolescence. Biol Psychiatry Cogn Neurosci Neuroimaging 2:289-297|