Default Mode and Frontoparietal Network Dynamics: Associations with Familial Risk for Depression and Stress Sensitivity.

Background: Major Depressive Disorder (MDD) is associated with alterations within the default mode (DMN) and frontoparietal (FPN) networks. However, it is unclear whether changes in these networks occur prior to onset in youth at high familial risk for MDD or are a consequence of MDD. Moreover, studies examining premorbid MDD vulnerability markers have focused on static rather than dynamic network properties, which could further elucidate DMN-FPN imbalances linked to MDD risk. Methods: Eighty-nine unaffected 12-14-year-old adolescents both with (n = 27) and without (n = 62) a maternal history of MDD completed a resting state functional magnetic resonance imaging scan and self-report assessments of depressive symptoms and perceived stress at baseline and every three months across a two-year span. A coactivation pattern (CAP) analysis was conducted to examine functional network dynamic properties, including time spent in each CAP (total number of volumes), CAP persistence (number of consecutive volumes in each CAP), and number of transitions between posterior DMN-FPN and canonical DMN CAPs. Multilevel models estimated whether DMN-FPN dynamic properties predicted future depressive symptoms and stress sensitivity. Results: High-risk adolescents spent more time and exhibited a longer persistence in a posterior DMN-FPN CAP. DMN-FPN CAP persistence predicted future perceived stress, but only among high-risk adolescents. High-risk adolescents characterized by high DMN-FPN persistence reported greater future perceived stress, whereas those showing low DMN-FPN persistence had reduced perceived stress over time. Unexpectedly, DMN-FPN dynamics did not predict future depressive symptoms. Conclusions: Altered DMN-FPN CAP properties among high-risk adolescents mirror alterations among individuals with MDD, suggesting that DMN-FPN dynamics may be a risk marker rather than consequence of MDD. Furthermore, longer DMN-FPN CAP persistence increases vulnerability in high-risk adolescents by predicting greater future stress sensitivity, a well-known catalyst for MDD. Replication in a larger sample is warranted.

Reward-Related Neural Circuitry in Depressed and Anxious Adolescents: A Human Connectome Project.

OBJECTIVE: Although depression and anxiety often have distinct etiologies, they frequently co-occur in adolescence. Recent initiatives have underscored the importance of developing new ways of classifying mental illness based on underlying neural dimensions that cut across traditional diagnostic boundaries. Accordingly, the aim of the study was to clarify reward-related neural circuitry that may characterize depressed-anxious youth. METHOD: The Boston Adolescent Neuroimaging of Depression and Anxiety Human Connectome Project tested group differences regarding subcortical volume and nucleus accumbens activation during an incentive processing task among 14- to 17-year-old adolescents presenting with a primary depressive and/or anxiety disorder (n = 129) or no lifetime history of mental disorders (n = 64). In addition, multimodal modeling examined predictors of depression and anxiety symptom change over a 6-month follow-up period. RESULTS: Our findings highlighted considerable convergence. Relative to healthy youth, depressed-anxious adolescents exhibited reduced nucleus accumbens volume and activation following reward receipt. These findings remained when removing all medicated participants (∼59% of depressed-anxious youth). Subgroup analyses comparing anxious-only, depressed-anxious, and healthy youth also were largely consistent. Multimodal modeling showed that only structural alterations predicted depressive symptoms over time. CONCLUSION: Multimodal findings highlight alterations within nucleus accumbens structure and function that characterize depressed-anxious adolescents. In the current hypothesis-driven analyses, however, only reduced nucleus accumbens volume predicted depressive symptoms over time. An important next step will be to clarify why structural alterations have an impact on reward-related processes and associated symptoms.

Reward Functioning Abnormalities in Adolescents at High Familial Risk for Depressive Disorders.

BACKGROUND: A parental history of major depressive disorder (MDD) is an established risk factor for MDD in youth, and clarifying the mechanisms related to familial risk transmission is critical. Aberrant reward processing is a promising biomarker of MDD risk; accordingly, the aim of this study was to test behavioral measures of reward responsiveness and underlying frontostriatal resting activity in healthy adolescents both with (high-risk) and without (low-risk) a maternal history of MDD. METHODS: Low-risk and high-risk 12- to 14-year-old adolescents completed a probabilistic reward task (n = 74 low-risk, n = 27 high-risk) and a resting-state functional magnetic resonance imaging scan (n = 61 low-risk, n = 25 high-risk). Group differences in response bias toward reward and resting ventral striatal and medial prefrontal cortex (mPFC) fractional amplitude of low-frequency fluctuations (fALFFs) were examined. Computational modeling was applied to dissociate reward sensitivity from learning rate. RESULTS: High-risk adolescents showed a blunted response bias compared with low-risk adolescents. Computational modeling analyses revealed that relative to low-risk adolescents, high-risk adolescents exhibited reduced reward sensitivity but similar learning rate. Although there were no group differences in ventral striatal and mPFC fALFFs, groups differed in their relationships between mPFC fALFFs and response bias. Specifically, among high-risk adolescents, higher mPFC fALFFs correlated with a blunted response bias, whereas there was no fALFFs-response bias relationship among low-risk youths. CONCLUSIONS: High-risk adolescents exhibit reward functioning impairments, which are associated with mPFC fALFFs. The blunted response bias-mPFC fALFFs association may reflect an excessive mPFC-mediated suppression of reward-driven behavior, which may potentiate MDD risk.

Delineating the social valuation network in adolescents.

Adolescents strive for peer approval, and an increased sensitivity to peers' opinions is normative. However, among vulnerable adolescents, peer evaluation can be detrimental, contributing to affective disorders. It is, therefore, critical to improve our understanding of neural underpinnings of peer evaluation. Prior research has investigated averaged neural responses to peer acceptance or rejection, neglecting to probe trial-by-trial computations that mirror real-time updating of daily activities. In non-social decision-making, a common neural valuation system centered on the medial prefrontal cortex (mPFC) has emerged, which evaluates different reward types on a common scale to guide choices. However, it is unclear whether the mPFC also tracks complex social scenarios involving peer feedback. To address this gap, we acquired fMRI data from 55 healthy adolescents during the Chatroom Task, which probes peer evaluation, and implemented a computational approach to characterize trial-by-trial social value, thereby allowing us to interrogate the neural correlates of social value. Consistent with our hypothesis, social value signals were encoded in the mPFC. Interestingly, analyses also revealed a wider social-specific valuation network including the precuneus and amygdala. Understanding how adolescents make social decisions and neural markers associated with it, may, ultimately, help us clarify promising targets for intervention.