Understanding anxiety symptoms as aberrant defensive responding along the threat imminence continuum

Abstract

Threat-anticipatory defensive responses have evolved to promote survival in a dynamic world. While inherently adaptive, aberrant expression of defensive responses to potential threat could manifest as pathological anxiety, which is prevalent, impairing, and associated with adverse outcomes. Extensive translational neuroscience research indicates that normative defensive responses are organized by threat imminence, such that distinct response patterns are observed in each phase of threat encounter and orchestrated by partially conserved neural circuitry. Anxiety symptoms, such as excessive and pervasive worry, physiological arousal, and avoidance behavior, may reflect aberrant expression of otherwise normative defensive responses, and therefore follow the same imminence-based organization. Here, empirical evidence linking aberrant expression of specific, imminence-dependent defensive responding to distinct anxiety symptoms is reviewed, and plausible contributing neural circuitry is highlighted. Drawing from translational and clinical research, the proposed framework informs our understanding of pathological anxiety by grounding anxiety symptoms in conserved psychobiological mechanisms. Potential implications for research and treatment are discussed.

Keywords: Anxiety; Anxiety disorders; Avoidance; Defensive response; Fear; Physiological responses; Threat imminence; Worry.

Figure 1.

Phases of threat imminence (defined along horizontal axis) are described in terms of magnitude of expression (vertical axis; from low to high magnitude) of cognitive (blue) and physiological (red) defensive responses, the behaviors they drive (green), and how these may be linked to anxiety symptoms and related responses (purple). Note that some symptoms may potentially occur in more than one phase. Solid and dashed lines describe expected intensity for individuals characterized by high and low levels of anxiety, respectively (note that anxiety severity, and magnitude of defensive responses, likely reflects a continuum).

Figure 2.

Brain structures and regions hypothesized to play key roles in defensive responses associated with each phase of threat imminence. Additional structures and regions are likely involved; the subset depicted here has been specifically associated with anxiety. Note: dmPFC = dorsomedial prefrontal cortex; PFC = prefrontal cortex; BNST = bed nucleus of the stria terminalis; Ant. = anterior; Post. = posterior; PAG = periaqueductal gray.

Changes in physiological response by threat imminence in individuals with and without anxiety disorders.

Threat-imminence phases were defined as epochs (demarcated in gray boxes) relative to cue and thermal stimulation onset in which skin conductance was indexed. Data points and lines reflect response to threat (highly painful heat; solid lines) and safety (non-painful heat; dashed line), for the anxiety (red) and no-anxiety comparison (blue) groups. Data presented reflect physiological activation already accounting for individual differences in local tonic (baseline) responding. Distance between X-axis ticks is 2 seconds. Note: *, p<0.05, **, p<0.01, ***, p<0.001. Colored asterisks reflect within-group changes; black asterisks reflect between-group effects. Data adapted from prior work.