Greater sustained anxiety but not phasic fear in women compared to men.

Abstract

Startle reflex studies in rodents indicate that female are more reactive than rats in experimental models of sustained anxiety but not in models of phasic fear (Toufexis, 2007). This study examined evidence for a similar effect in humans. Participants were exposed to three conditions, (1) predictable aversive shocks signaled by a cue, (2) unpredictable shocks, and (3) no shocks. Acoustic startle stimuli were delivered regularly across conditions. Phasic startle potential to the threat cue in the predictable condition was not affected by sex. In contrast, and consistent with basic research, the sustained increase in startle in the predictable and unpredictable conditions was greater in women compared to men. Animal studies suggest that such an effect may be mediated by the effects of sexual dimorphism in limbic structures, including the bed nucleus of the stria terminalis. However, psychosocial factors may also contribute to this effect. Keywords fear; anxiety; sex difference; startle; unpredictability The greater prevalence of mood and anxiety disorders among women compared to men (Kessler et al., 1994) points to a potential sex difference in reactivity to threat. Preclinical studies may provide clues as to the nature of this difference. A recent review focusing on animal models, using the startle reflex as an operational measure of aversive states, compared sex differences in two types of aversive responses, anxiety, a sustained state of distress to uncertain threat, and fear, a phasic defensive response to certain danger (Toufexis, 2007). Contrasting phasic and sustained aversive states was motivated by evidence of a neural differentiation between them, the former relying on the central nucleus of the amygdala (CeA) and the latter on the bed nucleus of the stria terminalis (BNST; Davis, 1998), as well as by an indication of strong sexual dimorphism in the BNST (Allen & Gorski, 1990). Toufexis concluded that BNST-mediated sustained potentiated startle (anxiety), but not cued specific fear-potentiated startle (fear), was increased in female rats compared to males.The present study examined evidence for a similar sex difference in humans, also using startle as a measure of aversive states. We have distinguished phasic fear to a predictable threat signaled by a cue from the more sustained contextual anxiety state during administration of predictable (certain) and unpredictable (uncertain) shocks (Grillon et al., 2006; Grillon, Baas, Lissek, Smith, & Milstein, 2004a). Based on Toufexis's review (Toufexis, 2007), we hypothesized that relative to men, women would show enhanced contextual-potentiated startle but not increased fear-potentiated startle to a threat cue.

Anxiety and Depression Symptom Dimensions Demonstrate Unique Relationships with the Startle Reflex in Anticipation of Unpredictable Threat in 8 to 14 Year-Old Girls

“…Self-reported anxiety during the different threat conditions was also assessed at the end of the task. As previously mentioned, girls, relative to boys, demonstrate increased rates of anxiety (Lewinsohn et al, 1998) and heightened sensitivity to unpredictable threat (Grillon, 2008; Schmitz et al, 2011). Therefore, the present study focused on girls only in order to increase variability in anxiety symptoms and the startle reflex in anticipation of unpredictable threat.…”

“…Throughout the task, the startle eye blink reflex to acoustic probes (e.g., loud white noise) is recorded as an index of defense system activation across experimental conditions. In adults, the startle reflex is potentiated in anticipation of both predictable and unpredictable threat relative to no threat (Grillon et al, 2004; Nelson, Hajcak, & Shankman, 2015), and females, relative to males, exhibit a heightened startle reflex in anticipation of unpredictable threat (Grillon, 2008). Furthermore, relative to non-anxious controls, individuals with panic disorder and posttraumatic stress disorder exhibit a heightened startle reflex in anticipation of unpredictable threat, although the association with predictable threat has been mixed (Grillon, Lissek, et al, 2008; Grillon, Pine, et al, 2009; Shankman et al, 2013).…”

Depressed mood enhances anxiety to unpredictable threat

“…One group underwent a sad mood induction procedure and the other a neutral induction procedure. The threat experiment was similar to that of our previous studies examining responses to predictable and unpredictable shocks (Grillon 2008a; b; Grillon et al 2004). Following attachment of the electrodes, nine startle stimuli (habituation) were delivered every 18–25 sec.…”

Acute Tryptophan Depletion Increases Translational Indices of Anxiety but not Fear: Serotonergic Modulation of the Bed Nucleus of the Stria Terminalis?

“…First, it has been well validated in humans. Anxiety-potentiated startle, but not fear-potentiated startle is increased in panic disorder and posttraumatic stress disorder (Grillon, 2008a;Grillon et al, 2009). Second, the task is translational by design and the procedures and responses have directly comparable rodent counterparts (Davis et al, 2010;Grillon, 2008b).…”