The Neurobiology of Dispositional Negativity and Attentional Biases to Threat: Implications for Understanding Anxiety Disorders in Adults and Youth

Abstract

When extreme, anxiety can become debilitating. Anxiety disorders, which often first emerge early in development, are common and challenging to treat, yet the neurocognitive mechanisms that confer increased risk have only recently begun to come into focus. Here we review recent work highlighting the importance of neural circuits centered on the amygdala. We begin by describing dispositional negativity, a core dimension of childhood temperament and adult personality and an important risk factor for the development of anxiety disorders and other kinds of stress-sensitive psychopathology. Converging lines of epidemiological, neurophysiological, and mechanistic evidence indicate that the amygdala supports stable individual differences in dispositional negativity across the lifespan and contributes to the etiology of anxiety disorders in adults and youth. Hyper-vigilance and attentional biases to threat are prominent features of the anxious phenotype and there is growing evidence that they contribute to the development of psychopathology. Anatomical studies show that the amygdala is a hub, poised to govern attention to threat via projections to sensory cortex and ascending neuromodulatory systems. Imaging and lesion studies demonstrate that the amygdala plays a key role in selecting and prioritizing the processing of threat-related cues. Collectively, these observations provide a neurobiologically-grounded framework for understanding the development and maintenance of anxiety disorders in adults and youth and set the stage for developing improved intervention strategies.

Intrinsic functional connectivity of the central extended amygdala

“…Third, vmPFC lesions have been shown to reduce these defensive responses and imaging research suggests that this anxiolytic effect is likely to be mediated by “downstream” alterations in BST metabolism (Fox et al, ; Kalin, Shelton, & Davidson, ; Motzkin et al, ; Rudebeck, Saunders, Prescott, Chau, & Murray, ). These and other observations (e.g., Grayson et al, ; Kalin et al, ; Meyer et al, ; Mobbs et al, ) motivate the hypothesis that fear and anxiety partially reflect a core neural system encompassing the BST, Ce, vmPFC, anterior hippocampus, and PAG (Fox et al, b; Oler et al, ; Shackman et al, b).…”

“…While imaging research hints at potential functional differences between the two regions (Alvarez et al, ; Fox et al, b; Meyer, Padmala, & Pessoa, ; Shackman et al, ; Somerville et al, ), methodological limitations preclude decisive inferences (Fox & Shackman, in press; Shackman & Fox, ). Importantly, other work suggests that alterations in EAc function likely plays a key role in the development, maintenance, and recurrence of anxiety disorders, depression, and substance abuse (Avery et al, ; Brinkmann et al, , , ; Buff et al, ; Fox & Kalin, ; Kaczkurkin et al, ; Münsterkötter et al, ; Shackman et al, a, b; Stevens et al, ; Williams et al, ; Wise & Koob, ).…”

Dispositional negativity: An integrative psychological and neurobiological perspective.

“…Davis & Whalen, 2001; Freese & Amaral, 2009). Lesion, imaging, and electrophysiological evidence demonstrate that the amygdala can trigger shifts of attention to threat-relevant social cues (e.g., eyes) and that reentrant projections from the basolateral (BL) nucleus of the amygdala to the visual cortex and superior colliculus play a crucial role in prioritizing the processing of threat-relevant cues (Shackman, Kaplan, et al, in press ). The amygdala is also poised to promote non-specific states of vigilance via projections to ascending neurochemical systems (i.e., acetylcholine, dopamine, norepinephrine) in the basal forebrain and brainstem that can modulate the responsiveness of sensory cortex to incoming information (Arnsten, 2009, 2015; M.…”

Dispositional negativity in the wild: Social environment governs momentary emotional experience.

“…Individual differences in dispositional negativity have important consequences for health, wealth, and wellbeing (Shackman, Kaplan, et al, 2016; Shackman, Tromp, et al, 2016). Individuals with a more negative disposition show lower levels of objective socioeconomic attainment (Damian, Su, Shanahan, Trautwein, & Roberts, 2015; Ng, Eby, Sorensen, & Feldman, 2005; Shanahan, Bauldry, Roberts, Macmillan, & Russo, 2014) and experience lower levels of subjective well-being (Steel, Schmidt, & Shultz, 2008).…”