Cognitive inflexibility and heightened error monitoring are related to lower sexual functioning.

Sexual functioning is an important predictor of well-being and relationship satisfaction. Previous research indicates that several aspects of cognitive function are related to sex-related behaviors and functioning among individuals with sex-related disorders, neurological disorders, and in older adults; however, this has been relatively underexamined in younger populations. To examine this, the present study assessed whether behavioral and/or neurophysiological measures of cognitive function are associated with sexual functioning in a community sample of young 489 adults (64 % female) ages 18-30. Cognitive flexibility (n = 460) and inhibition (n = 466) were measured using neuropsychological assessment (D-KEFS), and conflict monitoring and error monitoring were measured by event-related potentials (conflict N2: n = 394; error-related negativity: n = 389). After separately testing relations between the different measures of cognitive function and sexual functioning, we assessed whether results (1) remained after covarying for externalizing and internalizing dimensions (PID-5; n = 489) or (2) varied by gender. Finally, we tested whether any aspects of cognitive function were unique predictors of sexual functioning. Cognitive flexibility and error monitoring (i.e., error-related negativity) were both significantly related to sexual functioning among males and females, such that poorer cognitive flexibility and heightened error monitoring were related to lower sexual functioning. No significant effects emerged for inhibition or conflict monitoring. In a multiple regression model, cognitive flexibility and error monitoring each accounted for a unique portion of variance in sexual functioning beyond other aspects of cognitive function and psychopathology-related traits. Results suggest that cognitive function is a meaningful correlate of sexual functioning in young adulthood, which should be considered further in future research.

Shared and unique neural circuitry underlying temporally unpredictable threat and reward processing.

Temporally unpredictable stimuli influence behavior across species, as previously demonstrated for sequences of simple threats and rewards with fixed or variable onset. Neuroimaging studies have identified a specific frontolimbic circuit that may become engaged during the anticipation of temporally unpredictable threat (U-threat). However, the neural mechanisms underlying processing of temporally unpredictable reward (U-reward) are incompletely understood. It is also unclear whether these processes are mediated by overlapping or distinct neural systems. These knowledge gaps are noteworthy given that disruptions within these neural systems may lead to maladaptive response to uncertainty. Here, using functional magnetic resonance imaging data from a sample of 159 young adults, we showed that anticipation of both U-threat and U-reward elicited activation in the right anterior insula, right ventral anterior nucleus of the thalamus and right inferior frontal gyrus. U-threat also activated the right posterior insula and dorsal anterior cingulate cortex, relative to U-reward. In contrast, U-reward elicited activation in the right fusiform and left middle occipital gyrus, relative to U-threat. Although there is some overlap in the neural circuitry underlying anticipation of U-threat and U-reward, these processes appear to be largely mediated by distinct circuits. Future studies are needed to corroborate and extend these preliminary findings.

How to study the menstrual cycle: Practical tools and recommendations.

Despite decades of research on the physiological and psychological effects of the menstrual cycle, studies have not sufficiently adopted consistent methods for operationalizing the menstrual cycle. This has resulted in substantial confusion in the literature and limited possibilities to conduct systematic reviews and meta-analyses. In order to facilitate more rapid accumulation of knowledge on cycle effects, the present paper offers a set of integrative guidelines and standardized tools for studying the menstrual cycle as an independent variable. We begin with (1) an overview of the menstrual cycle and (2) premenstrual disorders, followed by (3) recommendations and tools regarding data collection in cycle studies. These recommendations address selecting the appropriate study design and sampling strategy, managing demand characteristics, identifying a sample of naturally-cycling individuals, and measuring menstrual bleeding dates, ovarian hormones, and ovulation. We proceed with suggestions for (4) data preparation and coding of cycle day and phases, as well as (5) data visualization, statistical modeling, and interpretation of menstrual cycle associations. We also provide (6) recommendations for using menses start day and ovulation testing to schedule visits in laboratory studies and end with a (7) comprehensive summary and conclusion. Regardless of whether the influence of the menstrual cycle is of central interest in a study or should be controlled to accurately assess the effects of another variable, the use of these recommendations and tools will help make study results more meaningful and replicable.

Heightened reactivity to uncertain threat as a neurobehavioral marker of suicidal ideation in individuals with depression and anxiety.

Identifying neurobehavioral correlates of suicidal ideation can help detect those most vulnerable for suicide among high-risk groups, such as those with internalizing psychopathology. Individuals with elevated sensitivity to uncertain threat (U-threat) have a strong preference for known outcomes relative to unknown outcomes and often experience high levels of chronic distress. We therefore hypothesized that among individuals with internalizing psychopathology, those with heightened reactivity to U-threat would be especially prone to suicidal ideation as a means to escape uncertainty. The present study examined whether in two independent samples suicidal ideation was associated with heightened startle response to U-threat, and whether the effects were specific to responses U-threat relative to predictable threat (P-threat). Study 1 was a sample of treatment-seeking patients (N = 99) and Study 2 was a community sample (N = 102). Participants in both samples met current DSM-5 criteria for an anxiety and/or depressive disorder. In Study 1, current suicidal ideation was positively associated with startle potentiation to U-threat. Similarly, in Study 2, a lifetime history of suicidal ideation was positively associated with startle potentiation to U-threat. The relation between suicidal ideation and startle potentiation to U-threat remained when adjusting for number of internalizing diagnoses. Heightened reactivity to U-threat may therefore characterize those with a propensity for suicidal ideation among individuals with internalizing psychopathology.

The Relation Between Posttraumatic Stress Symptom Severity and Startle Potentiation to Predictable and Unpredictable Threat.

Aberrant threat reactivity has been implicated in the pathophysiology of posttraumatic stress disorder (PTSD); however, the literature on this association is mixed. One factor that may contribute to this inconsistent association is differences in severity of posttraumatic stress symptoms (PTSSs) across studies, but no studies have tested this hypothesis. The relation between PTSD and threat reactivity may also differ between unpredictable threats (U-threats) and predictable threats (P-threats), given burgeoning evidence to support a particular role for aberrant responding to U-threat in PTSD. The present study examined how PTSS severity relates to startle potentiation to U-threat and P-threat in a trauma-exposed community sample (N = 258). There was a negative linear, but not quadratic, relation between PTSS severity and startle potentiation to U-threat, but not P-threat. Blunted defensive responding to U-threat may therefore contribute to higher levels of PTSSs and may represent a novel treatment target for higher levels of PTSSs.

Startle during threat longitudinally predicts functional impairment independent of DSM diagnoses.

Heightened responsivity to unpredictable, and perhaps predictable, threat characterizes some internalizing disorders and may be vulnerability factors for psychopathology as well. However, few studies have directly tested whether individual differences in unpredictable and/or predictable threat responding longitudinally predict symptoms of psychopathology and functional outcomes. Examining functioning is particularly important given that functioning is separable from symptoms of psychopathology. The present study examined whether electromyography startle measures of predictable and/or unpredictable threat responding was associated with interviewer-assessed symptoms of internalizing psychopathology and functional impairment at baseline (n = 409) and one-year follow-up (n = 104). Elevated startle responding to unpredictable and predictable threat longitudinally predicted a worsening of functioning over time and this effect was independent of change of symptoms over time. Importantly, threat responding at baseline predicted functional impairment during the follow-up independent of the effects of DSM-defined fear-based (e.g., panic disorder) or distress-misery (e.g., major depressive disorder) internalizing disorders. These findings provide initial support for the incremental validity of neurobiological vulnerability markers of threat responding over and above DSM disorders and highlight the importance of distinguishing functional outcomes from symptom outcomes.

Error-related neural activity and alcohol use disorder: Differences from risk to remission.

Studies suggest that individuals with alcohol use disorder (AUD) display abnormal neural error-processing, measured via the error-related negativity (ERN). The nature of the error-related abnormalities in AUD is unclear, however, as prior research has yielded discrepant findings. In addition, no study to date has attempted to characterize the dispositional nature of the ERN in AUD and directly test to what extent ERN amplitude reflects a risk factor, disease marker, and/or scar of AUD psychopathology. The current study compared ERN amplitude across 244 adult volunteers in the following five groups: 1) current AUD (n = 39), 2) AUD in remission (n = 60), 3) at-risk for AUD (n = 43), 4) psychiatric controls with comparable rates of internalizing psychopathology as the AUD groups (n = 53), and 5) healthy controls with no lifetime history of psychopathology (n = 49). Risk for AUD was defined as a positive, first-degree family history. All participants completed a well-validated flanker task, designed to robustly elicit the ERN, during continuous electroencephalographic (EEG) data collection. Results indicated that individuals with current AUD displayed smaller ERNs compared with individuals at-risk for AUD, with AUD in remission, psychiatric controls, and healthy controls. There were no differences amongst any of the other groups. This suggests that a blunted ERN may be concomitant with current AUD psychopathology and relatedly, a novel neurobiological AUD treatment target and/or objective marker of AUD disease status.

Individual differences in combat experiences and error-related brain activity in OEF/OIF/OND veterans.

Increased error-related negativity (ERN) has been implicated in the pathophysiology of multiple forms of psychopathology. Although there is increasing evidence that the ERN can be shaped by environment and experience, no studies to date have examined this question in a clinical sample. In the current study, we examined the influence of combat exposure on the ERN using electroencephalogram (EEG) in a sample of military veterans with a high prevalence of psychopathology. Participants included sixty-seven U.S. military veterans from Operations Enduring Freedom, Iraqi Freedom, and New Dawn (OEF/OIF/OND). The degree of combat exposure was assessed using the Deployment Risk and Resilience Inventory-2 (DRRI-2) and Combat Exposure Scale (CES). A well-validated flanker task was used to elicit the ERN during continuous EEG recording. Results revealed that veterans who reported experiencing greater combat exposure exhibited a more enhanced ERN, even when adjusting for broad anxiety and posttraumatic stress disorder (PTSD) symptoms. The association between combat exposure and ERN was not moderated by PTSD symptom severity. The current study demonstrates that greater combat exposure is associated with a more enhanced ERN among OEF/OIF/OND veterans. This enhanced ERN may be one mechanism that places veterans at greater risk for developing psychiatric disorders following exposure to combat. Future longitudinal studies are needed to directly test whether the ERN mediates the relation between level of combat exposure and the development of internalizing disorders.

Distinct responses to predictable and unpredictable threat in anxiety pathologies: effect of panic attack.

BACKGROUND: Delineating specific clinical phenotypes of anxiety disorders is a crucial step toward better classification and understanding of these conditions. The present study sought to identify differential aversive responses to predictable and unpredictable threat of shock in healthy comparisons and in non-medicated anxiety patients with and without a history of panic attacks (PAs). METHOD: 143 adults (72 healthy controls; 71 patients with generalized anxiety disorder (GAD) or/and social anxiety disorder (SAD), 24 with and 47 without PAs) were exposed to three conditions: 1) predictable shocks signaled by a cue, 2) unpredictable shocks, and 3) no shock. Startle magnitude was used to assess aversive responses. RESULTS: Across disorders, a PA history was specifically associated with hypersensitivity to unpredictable threat. By disorder, SAD was associated with hypersensitivity to predictable threat, whereas GAD was associated with exaggerated baseline startle. CONCLUSIONS: These results identified three physiological patterns. The first is hypersensitivity to unpredictable threat in individuals with PAs. The second is hypersensitivity to predictable threat, which characterizes SAD. The third is enhanced baseline startle in GAD, which may reflect propensity for self-generated anxious thoughts in the absence of imminent danger. These results inform current thinking by linking specific clinical features to particular physiology profiles.

Impact of posttraumatic stress symptom dimensions on amygdala reactivity to emotional faces.

Posttraumatic stress disorder (PTSD) is highly prevalent and associated with impairment, even at the subthreshold level. It is therefore important to identify biological processes that contribute to the pathophysiology of posttraumatic stress symptoms (PTSS). Although neuroimaging research has highlighted the importance of heightened amygdala reactivity to aversive stimuli in PTSS, not all studies have yielded evidence of this relationship. Given that PTSS is comprised of four, factor analytically distinct dimensions of symptoms - re-experiencing, avoidance, hyperarousal, and negative cognitions and mood - it is possible that heightened amygdala reactivity to aversive stimuli is specific to certain PTSS clusters. In a sample of 45 trauma-exposed individuals, the present study therefore examined how specific PTSS clusters relate to amygdala responding during functional magnetic resonance imaging (fMRI) to both negative and positive emotional faces during a well-validated social-emotional task, the Emotional Face Assessment Task (EFAT). Results indicated that hyperarousal symptoms were positively associated with left amygdala reactivity across all emotional face conditions. There was no interaction of hyperarousal by condition (i.e., fearful, sad, angry, or happy faces), and other PTSS clusters were not associated with amygdala reactivity. These results indicate that the hyperarousal cluster of PTSS may have a unique relationship with amygdala reactivity to socioemotional information. The results also corroborate a growing literature suggesting that trauma-exposed individuals characterized by high PTSS hyperarousal symptoms may display exaggerated psychophysiological reactivity to appetitive and aversive stimuli.

Impact of posttraumatic stress symptom dimensions on psychophysiological reactivity to threat and reward.

Posttraumatic stress symptoms (PTSS) are associated with significant distress and impairment. Research has therefore focused on identifying neurobehavioral deficits that contribute to the pathophysiology of PTSS. One issue that has contributed to difficulty in identifying these deficits is the highly heterogeneous nature of PTSS. PTSS is comprised of four, factor analytically distinct dimensions of symptoms - re-experiencing, avoidance, hyperarousal, and negative cognitions and mood. It is therefore unlikely that there is one single mechanism that accounts for all of PTSS and elucidating neurobehavioral deficits associated with specific PTSS symptom dimensions may better inform clinical prevention and intervention efforts. Within the broader internalizing disorder literature, two key constructs that contribute to psychopathology are aberrant neural reactivity to threat and reward. However, the literature linking PTSS to these deficits is mixed, suggesting that aberrant neural reactivity to threat or reward may be specific to certain PTSS dimensions. In a sample of 51 trauma-exposed adults with a range PTSS, the present study therefore examined how the four dimensions of PTSS uniquely relate to two well-validated event-related potential (ERP) neural indices of threat and reward reactivity - the error-related negativity (ERN) and reward-related positivity (RewP), respectively. Results indicated that hyperarousal symptoms were associated with enhanced ERN, and enhanced RewP. In contrast, negative cognitions and mood symptoms were uniquely associated with a more blunted RewP. These results indicate that certain PTSS symptom dimensions have unique relations with neural indicators of threat and reward reactivity and may therefore have distinct pathophysiologies.

Association between neural reactivity and startle reactivity to uncertain threat in two independent samples.

Prior studies indicate that anxiety disorders are associated with heightened sensitivity to uncertain threat (U threat). Individual differences in reactivity to U threat have been measured in the laboratory with two methodologies-startle eyeblink potentiation and fMRI. While startle and fMRI are purported to relate to each other, very little research exists on whether individual differences in one measure are associated with individual differences in another and, thus, whether startle and fMRI capture shared mechanisms. Therefore, the current study was designed to investigate if and where in the brain measures of startle potentiation and fMRI BOLD signal correlate during response to U threat across two independent samples. Participants in both studies completed two threat anticipation tasks-once during collection of startle potentiation and once during fMRI. In Study 1 (n = 43), the startle and fMRI tasks both used electric shock as the threat. As an extension, in Study 2 (n = 38), the startle task used electric shock but the fMRI task used aversive images. Despite these methodological differences, greater startle potentiation to U threat was associated with greater dorsal anterior cingulate, caudate, and orbitofrontal cortex reactivity to U threat in both samples. The findings suggest that startle and fMRI measures of responding to U threat overlap, and points toward an integrated brain-behavior profile of aberrant U threat responding.

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

Emotion-modulated startle is a frequently used method in affective science. Although there is a growing literature on the reliability of this measure, it is presently unclear how many startle responses are necessary to obtain a reliable signal. The present study therefore evaluated the reliability of startle responding as a function of number of startle responses (NoS) during a widely used threat-of-shock paradigm, the NPU-threat task, in a clinical (N=205) and non-clinical (N=92) sample. In the clinical sample, internal consistency was also examined independently for healthy controls vs. those with panic disorder and/or major depression and retest reliability was assessed as a function of NoS. Although results varied somewhat by diagnosis and for retest reliability, the overall pattern of results suggested that six startle responses per condition were necessary to obtain acceptable reliability in clinical and non-clinical samples during this threat-of-shock paradigm in the present study.

Impact of Panic on Psychophysiological and Neural Reactivity to Unpredictable Threat in Depression and Anxiety.

Exaggerated anxious responding to unpredictable threat (U-threat) is a core feature of panic disorder (PD). However, it is unknown whether this abnormality is specific to the diagnosis of PD or would manifest along a continuum of panic symptomatology (PS). Additionally, little is known about the neural processes underlying this abnormality among those high in PS. Finally, no studies have tested whether startle potentiation and limbic neural reactivity - commonly used indices of U-threat responsivity - are associated and therefore reflect common abnormalities. These questions were investigated in 42 adults with a range of PS. U-threat responding was measured twice during threat-of-shock - once with startle and once with functional magnetic resonance imaging (fMRI). As hypothesized, PS positively predicted startle potentiation and dACC reactivity to U-threat. Startle potentiation and dACC activation to U-threat were positively associated. These results suggest a biobehavioral profile of aberrant responding to U-threat associated with PS.

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

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 5 groups: current (a) social anxiety disorder (SAD); (b) specific phobia (SP); (c) generalized anxiety disorder (GAD); (d) MDD; and (c) 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. (PsycINFO Database Record

Using a cultural and RDoC framework to conceptualize anxiety in Asian Americans.

Asian Americans are one of the fastest growing minority groups in the United States; however, mental health within this population segment, particularly anxiety disorders, remains significantly understudied. Both the heterogeneity within the Asian American population and the multidimensional nature of anxiety contribute to difficulties in understanding anxiety in this population. The present paper reviewed two sources of heterogeneity within anxiety in Asian Americans: (1) cultural variables and (2) mechanisms or components of anxiety. Specifically, we examined four cultural variables most commonly found in research related to anxiety in Asian Americans: acculturation, loss of face, affect valuation, and individualism-collectivism. We also discussed ways to parse anxiety through a Research Domain Criteria (RDoC) framework, specifically focusing on sensitivity to acute and potential threat, constructs within the Negative Valence System. Previously unpublished preliminary data were presented to illustrate one way of examining ethnic differences in anxiety using an RDoC framework. Finally, this paper offered recommendations for future work in this area.

Comparing the validity of informant and self-reports of personality using laboratory indices of emotional responding as criterion variables.

Personality traits relate to risk for psychopathology and can inform predictions about treatment outcome. In an effort to obtain a comprehensive index of personality, informant reports of personality are sometimes obtained in addition to self-reports of personality. However, there is limited research comparing the validity of self- and informant reports of personality, particularly among those with internalizing psychopathology. This is important given that informants may provide an additional (and perhaps different) perspective on individuals' personality. The present study therefore compared how both reports of positive affectivity (PA) and negative affectivity (NA) relate to psychophysiological and subjective measures of emotional responding to positive and negative stimuli. Given that our sample (n = 117) included individuals with no history of psychopathology, as well as individuals with major depressive disorder (MDD) and/or panic disorder (PD), we were also able to explore whether these internalizing diagnoses moderated the association between personality reports and measures of emotional responding. Informant-reported PA predicted physiological responses to positive stimuli (but not negative). Informant-reported NA predicted physiological responses to negative stimuli (but not positive). Self-reported personality did not predict physiological responding, but did predict subjectively measured emotional responding (NA for negative responding, PA for positive responding). Diagnoses of internalizing psychopathology (PD or MDD) did not moderate these associations. Results suggest self- and informant reports of personality may each provide valid indices of an individual's emotional response tendencies, but predict different aspects of those tendencies.

Association between problematic alcohol use and reactivity to uncertain threat in two independent samples.

BACKGROUND: Recent laboratory studies have shown that acute alcohol intoxication selectively and effectively dampens aversive responding to uncertain threat. An emerging hypothesis is that individuals who exhibit heightened reactivity to uncertain threat may be especially motivated to use alcohol to dampen their distress, setting the stage for negative reinforcement processes to drive excessive alcohol use. However, no study to date has directly examined whether current problematic drinkers exhibit heightened reactivity to uncertain threat as would be expected. METHODS: The present study was therefore designed to examine the association between current problematic alcohol use and reactivity to uncertain threat during sobriety in two, independent samples. In Study 1 (n=221) and Study 2 (n=74), adult participants completed the same well-validated threat-of-shock task which separately probes responses to temporally predictable and unpredictable threat. Startle potentiation was measured as an index of aversive responding. Problematic alcohol use was defined as number of binge episodes within the past 30days in Study 1 and total scores on a self-report measure of hazardous drinking in Study 2. RESULTS: As hypothesized, across both studies greater levels of problematic drinking were associated with greater startle potentiation to unpredictable threat. In Study 2, hazardous drinking scores were also positively associated with startle potentiation to predictable threat. CONCLUSIONS: The findings are notably consistent with the notion that heightened reactivity to uncertain threat is an important individual difference factor associated with the onset and/or maintenance of problematic drinking behaviors and may therefore be a novel prevention and intervention target.

Induced-anxiety differentially disrupts working memory in generalized anxiety disorder.

BACKGROUND: Anxiety is characterized by a bias towards threatening information, anxious apprehension, and disrupted concentration. Previous research in healthy subjects suggests that working memory (WM) is disrupted by induced anxiety, but that increased task-demand reduces anxiety and WM is preserved. However, it is unknown if patients with generalized anxiety disorder (GAD) can similarly normalize their performance on difficult WM tasks while reducing their anxiety. Increased threat-related bias and impoverished top-down control in trait anxiety suggests that patients may not reap the same cognitive and emotional benefits from demanding tasks that those low in anxiety. Here we examine this possibility using a WM task of varying difficulty. METHODS: GAD patients (N = 30) and healthy controls (N = 30) performed an n-back task (no-load, 1-back, 2-back, and 3-back) while at risk for shock (threat) or safe from shock (safe). Anxiety was measured via startle reflex and self-report. RESULTS: As predicted, healthy controls' performance was impaired under threat during low-load tasks and facilitated during high-load tasks. In contrast, GAD patients' performance was impaired under threat regardless of WM load. Anxiety was reduced as cognitive load increased in both groups. CONCLUSIONS: The divergence of emotion regulation (reduction) and performance (persistent impairment) in the patient but not the control group, suggests that different top-down mechanisms may be operating to reduce anxiety. Continued WM disruption in patients indicates that attentional resources are allocated to emotion regulation instead of goal-directed behavior. Implications for our understanding of cognitive disruption in patients, and related therapeutic interventions are discussed.

Cognitive flexibility mediates the relation between intolerance of uncertainty and safety signal responding in those with panic disorder.

There is a growing literature associating anxiety disorders with an inability to inhibit defensive responding during safety conditions of threatening tasks. However, investigations on the relation between panic disorder (PD) and defensive responding to safety have yielded mixed results. A recent study from our laboratory revealed that intolerance of uncertainty (IU) moderates this association, such that only individuals with PD and a high IU exhibit heightened startle potentiation during safety. The mechanism underlying this relationship is unknown. Given that safety conditions typically alternate with periods of threat, cognitive flexibility (i.e., the ability to adjust one's habitual responding to a situation, given the input of new information) may be involved in the ongoing reappraisal of danger and adjustment of defensive responding. Thus, the present study sought to investigate whether deficits in cognitive flexibility mediate the association between IU and defensive responding to safety among a sample of 71 adults diagnosed with PD. As hypothesised, cognitive flexibility mediated the relationship between IU and heightened startle potentiation during safety conditions. This finding suggests that within this subgroup, a failure to inhibit defensive responding during safety conditions may be due to deficits in cognitive flexibility.