Multi-Level Models of Internalizing Disorders and Translational Developmental Science: Seeking Etiological Insights that can Inform Early Intervention Strategies

Abstract

This commentary discusses the articles in this special section with an emphasis on the specific utility of multivariate, multi-level models in developmental psychopathology for ultimately contributing to both etiologic insights and translational advances. These issues are considered not only in terms of the specific papers, but also within a larger set of questions regarding the opportunities (and challenges) currently facing the field. We describe why we believe this an exciting time for integrative team-science approaches to tackle these challenges—a time that holds great promise for rapid advances in integrative developmental science that includes a biological level of mechanistic understanding. In order to facilitate this, we outline a range of approaches within both translational neuroscience and translational developmental science that can be used as frameworks for understanding how such research can provide etiologic insights regarding real-world targets at the level of social, behavioral, and affective processes that can be modified during key developmental windows of opportunity. We conclude that a “construct validity” framework, where biological data form a critical, but not privileged, component of key etiological mechanisms, combined with a developmental perspective on key period of sensitivity to intervention effects, is most likely to provide significant translational outcomes.

Uniting adolescent neuroimaging and treatment research: Recommendations in pursuit of improved integration

“…Step 1 is in line with recent recommendations by Allen and Dahl (Allen and Dahl, 2015), wherein the first foundational step in this collaborative is to identify the “modifiable” elements of treatment response that are of interest to the investigative team. Here, the research team must select which factors they believe may be fundamental to an adolescent’s positive treatment response (or lack thereof).…”

Orbitofrontal cortex connectivity as a mechanism of adolescent behavior change

“…Based on advances in the field of translational “bench-to-bedside” science 29,31,78 , there are two different avenues through which these data could inform direct care. One is by evaluating the strength of the role of the OFC network as a predictor of treatment response.…”

Interpersonal life stress, inflammation, and depression in adolescence: Testing Social Signal Transduction Theory of Depression

“…During childhood, only 3% of boys and girls meet criteria for major depressive disorder (MDD) over the past year (Merikangas et al, 2010). Researchers have identified a wide variety of mechanisms that may underlie this dramatic increase in depression risk for adolescent girls, including stress generation, heightened neurocognitive sensitivity to threat, and exaggerated hypothalamicpituitary-adrenal axis reactivity (Allen & Dahl, 2015;Gibb, Beevers, & McGeary, 2013;Gold, 2015;Hammen, 2006;Hankin, 2015;Rudolph, 2008). Researchers have identified a wide variety of mechanisms that may underlie this dramatic increase in depression risk for adolescent girls, including stress generation, heightened neurocognitive sensitivity to threat, and exaggerated hypothalamicpituitary-adrenal axis reactivity (Allen & Dahl, 2015;Gibb, Beevers, & McGeary, 2013;Gold, 2015;Hammen, 2006;Hankin, 2015;Rudolph, 2008).…”

“…Following the pubertal transition, though, depression rates increase nearly fivefold overall and, in addition, girls suddenly become twice as likely to develop MDD on average relative to boys (Avenevoli, Swendsen, He, Burstein, & Merikangas, 2015). Researchers have identified a wide variety of mechanisms that may underlie this dramatic increase in depression risk for adolescent girls, including stress generation, heightened neurocognitive sensitivity to threat, and exaggerated hypothalamicpituitary-adrenal axis reactivity (Allen & Dahl, 2015;Gibb, Beevers, & McGeary, 2013;Gold, 2015;Hammen, 2006;Hankin, 2015;Rudolph, 2008). For the most part, though, this work has examined processes that are not mechanistically capable of directly inducing depressive symptoms.…”