Dispositional negativity, cognition, and anxiety disorders: An integrative translational neuroscience framework

Abstract

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the underlying mechanisms have only recently begun to come into focus. Here, we review new insights into the nature and biological bases of dispositional negativity, a fundamental dimension of childhood temperament and adult personality and a prominent risk factor for the development of pediatric and adult anxiety disorders. Converging lines of epidemiological, neurobiological, and mechanistic evidence suggest that dispositional negativity increases the likelihood of psychopathology via specific neurocognitive mechanisms, including attentional biases to threat and deficits in executive control. Collectively, these observations provide an integrative translational framework for understanding the development and maintenance of anxiety disorders in adults and youth and set the stage for developing improved intervention strategies.

Introduction

Anxiety is a sustained state of elevated apprehension, arousal, and vigilance that occurs in the absence of clear and immediate danger (Davis et al., 2010; Grupe and Nitschke, 2013; LeDoux, 2015; Shackman and Fox, 2016). Anxiety lies on a continuum and, when expressed in extreme ways or in inappropriate contexts, can become debilitating (Conway et al., n.d.; Craske et al., 2017; Salomon et al., 2015; Shackman et al., 2016b). Anxiety disorders are the most prevalent family of mental illnesses (Global Burden of Disease Collaborators, 2016; U.S. Burden of Disease Collaborators, 2018; Wang et al., 2017). They typically emerge early in life, enabling greater cumulative damage, and can contribute to the development of depression, substance abuse, and other adverse outcomes (Bitsko et al., 2018; Fox and Kalin, 2014; Kessler et al., 2007, Kessler et al., 2012; Lee et al., 2014; McGorry et al., 2011; Pratt et al., 2016; Shackman et al., 2016b, Torvik et al., n.d.). Existing treatments are underutilized, inconsistently effective, and, in the case of pharmaceuticals, associated with significant adverse effects (Craske et al., 2017; Gordon and Redish, 2016; Griebel and Holmes, 2013). In short, anxiety disorders impose a staggering burden on public health and the global economy, underscoring the urgency of developing a more complete understanding of the underlying mechanisms (DiLuca and Olesen, 2014; Global Burden of Disease Collaborators, 2016; Roehrig, 2016; U.S. Burden of Disease Collaborators, 2018).

We begin by describing new insights into the nature and the biological bases of dispositional negativity, a central dimension of mammalian temperament that confers elevated risk for the development of anxiety disorders and other stress-sensitive psychiatric diseases. Like anxiety disorders, dispositional negativity is a complex, multidimensional phenotype that encompasses variation in behavior, peripheral physiology, feelings, and cognition (Cavanagh and Shackman, 2015; Grupe and Nitschke, 2013; LeDoux, 2015; Shackman et al., 2016a, Shackman et al., 2016b). A key challenge is to identify the mechanisms underlying these features and discover how they contribute to the etiology of psychiatric disease in adults and youth. Here, we focus on recent advances in our understanding of threat-related^a attentional biases and deficits in executive control. These intermediate cognitive phenotypes are key features of dispositional negativity and there is compelling evidence that each can contribute to the development and course of anxiety disorders. While important strides have been made at delineating the neural underpinnings of attentional biases to threat, much less scientific attention has been devoted to executive deficits. In the final section, we highlight emerging evidence that these intermediate phenotypes can interact when threat-related cues are present but unrelated to on-going goals. While these new observations provide important insights, they also raise a number of interesting questions. We conclude by outlining some of the most important avenues for future research and some strategies for addressing them.