Startle potentiation to uncertain threat as a psychophysiological indicator of fear-based psychopathology: An examination across multiple internalizing disorders.

Abstract

Heightened reactivity to uncertain threat (U-threat) is an important individual difference factor that may characterize fear-based internalizing psychopathologies (IPs) and distinguish them from distress/misery IPs. To date, however, the majority of existing research examining reactivity to U-threat has been within individuals with panic disorder and major depressive disorder (MDD) and no prior study has directly tested this hypothesis across multiple IPs. The current study therefore explored whether heightened reactivity to U-threat is a psychophysiological indicator of fear-based psychopathology across five groups: current 1) social anxiety disorder (SAD), 2) specific phobia (SP), 3) generalized anxiety disorder (GAD), 4) MDD, and 5) individuals with no history of psychopathology (controls). All 160 adults completed a well-validated threat-of-shock task designed to probe responses to predictable (P-) and U-threat. Startle eyeblink potentiation was recorded as an index of aversive arousal. Results indicated that individuals with SAD and SP evidenced greater startle potentiation to U-threat, but not P-threat, relative to individuals with GAD, MDD and controls (who did not differ). The current findings, along with the prior panic disorder and MDD literature, suggest that heightened reactivity to U-threat is a psychophysiological indicator of fear-based disorders and could represent a neurobiological organizing principle for internalizing psychopathology. The findings also suggest that individuals with fear disorders generally display a hypersensitivity to uncertain aversive events, which could contribute to their psychopathology.

Neural reactivity to reward and internalizing symptom dimensions

“…Consistent with the RDoC strategy (Kozak & Cuthbert, 2016), individuals were not excluded for comorbid disorders but instead classified by their clinician-determined principal diagnosis, as determined by the most severe and impairing symptoms (see Table 1). Panic disorder (PD), social anxiety disorder (SAD), and post-traumatic stress disorder (PTSD) were coded as ‘fear-based disorders’ whereas major depressive disorder (MDD), dysthymia, and generalized anxiety disorder (GAD) were coded as ‘distress/misery’ disorders consistent with our prior studies (Gorka et al, in press). …”

Preliminary evidence that reactivity to uncertain threat is an endophenotype for alcohol use disorder

“…We also included lifetime history of any mood or anxiety disorder (i.e., panic disorder, social anxiety disorder, specific phobia, generalized anxiety disorder, major depressive disorder, dysthymia, and/or posttraumatic stress disorder; yes/no) as a covariate. Although the groups did not differ in rates of depression or anxiety, internalizing psychopathology is known to influence startle reactivity during the NPU task and adjusting for comorbidity is therefore necessary (Gorka et al, 2017b). Any significant condition x group interaction was followed-up by testing the effect of group at each task condition using separate ANOVAs.…”

“…Converging lines of research indicate that exaggerated reactivity to uncertain threat (U-threat) is a core individual difference factor related to multiple forms of psychopathology (Carleton, 2016; Grupe and Nitschke, 2013; Gorka et al, 2017b). Uncertainty about future threats diminishes one’s ability to avoid danger or prepare for its impact, resulting in a generalized feeling of apprehension and hypervigilance, referred to as anticipatory anxiety (Barlow, 2000; Davis et al, 2010).…”

How many blinks are necessary for a reliable startle response? A test using the NPU-threat task

“…It is noteworthy that reactivity to unpredictable threat may be more reliable than reactivity to predictable threat, as the literature on the relation between startle potentiation to predictable threat and anxiety psychopathology is less consistent (e.g., Shankman et al, 2013; Grillon et al, 2008) than the literature on the relation between startle potentiation to unpredictable threat and anxiety psychopathology (e.g., Gorka et al, 2017; Lieberman et al, 2016; Shankman et al, 2013). That is, mixed findings on the relation between anxiety psychopathology and reactivity to predictable threat may be in part due to the poorer reliability of startle potentiation during the anticipation of predictable threat.…”