Sleep quality impacts the link between reactivity to uncertain threat and anxiety and alcohol use in youth.

Individual differences in reactivity to unpredictable threat (U-threat) have repeatedly been linked to symptoms of anxiety and drinking behavior. An emerging theory is that individuals who are hyper-reactive to U-threat experience chronic anticipatory anxiety, hyperarousal, and are vulnerable to excessive alcohol use via negative reinforcement processes. Notably, anxiety and alcohol use commonly relate to disruptions in sleep behavior and recent findings suggest that sleep quality may impact the link between reactivity to U-threat and psychiatric symptoms and behaviors. The aim of the current study was to examine the unique and interactive effects of reactivity to U-threat and sleep quality on anxiety symptoms and drinking behavior in a cohort of youth, ages 16-19 years. Participants (N = 112) completed a well-validated threat-of-shock task designed to probe individual differences in reactivity to U-threat and predictable threat (P-threat). Startle eyeblink potentiation was recorded during the task as an index of aversive reactivity. Participants also completed well-validated self-report measures of anxiety and depression symptoms, lifetime alcohol use, and current sleep quality. Results revealed significant startle reactivity to U-threat by sleep quality interactions on anxiety symptoms and lifetime drinking behavior. At high levels of sleep disturbance (only), greater reactivity to U-threat was associated with greater anxiety symptoms and total number of lifetime alcoholic beverages. These results suggest that sensitivity to uncertainty and chronic hyperarousal increases anxiety symptoms and alcohol use behavior, particularly in the context of poor sleep quality.

Neural reactivity to threat impacts the association between bullying victimization and suicide risk in youth.

Bullying victimization is a risk factor for suicidal ideation, suicide behaviors, and death by suicide in youth. However, not all victims of bullying report suicidal thoughts and behaviors, suggesting that there may be certain subgroups who are at high risk for suicide. Neuroimaging studies suggest that individual differences in neurobiological threat reactivity may contribute to increased vulnerability to suicide, particularly in the context of repeated exposure to bullying. The purpose of the present study was to examine the unique and interactive effects of past-year bullying victimization and neural reactivity to threat on suicide risk in youth. Ninety-one youth (ages 16-19) completed self-report measures of past-year bullying victimization and current suicide risk. Participants also completed a task designed to probe neural reactivity to threat. Specifically, participants passively viewed negative or neutral images during functional magnetic resonance imaging. Bilateral anterior insula (AIC) and amygdala (AMYG) reactivity to threat/negative images (>neutral images) was used to capture threat sensitivity. Greater bullying victimization was associated with increased suicide risk. There was also a bullying by AIC reactivity interaction such that among individuals with high AIC reactivity, greater bullying was associated with increased suicide risk. Among individuals with low AIC reactivity, there was no association between bullying and suicide risk. Results suggest that youth with increased AIC reactivity to threat may be particularly vulnerable to suicide in the context of bullying. These individuals may represent a high-risk group for subsequent suicide behavior and AIC function may be a promising objective prevention target.

Behavioral and brain reactivity to uncertain stress prospectively predicts binge drinking in youth.

Prior studies show that individuals with alcohol use disorder exhibit exaggerated behavioral and brain reactivity to uncertain threats (U-threat). It is posited this brain-based factor emerges early in life and contributes to the onset and escalation of alcohol problems. However, no study to date has tested this theory using a longitudinal within-subjects design. Ninety-five young adults, ages 17-19, with minimal alcohol exposure and established risk factors for alcohol use disorder participated in this multi-session study with a 1-year tracking period. Startle eyeblink potentiation and brain activation were collected at separate baseline sessions during the well-validated No-Predictable-Unpredictable (NPU) threat-of-shock task designed to probe reactivity to U-threat and predictable threat (P-threat). Participants self-reported their drinking behavior over the past 90 days at baseline and one-year later. We fit a series of multilevel hurdle models to model the binary outcome of whether binge drinking occurred and the continuous outcome of number of binge drinking episodes. Zero-inflated binary submodels revealed that greater baseline startle reactivity, bilateral anterior insula (AIC) reactivity, and dorsal anterior cingulate cortex (dACC) reactivity to U-threat were associated with increased probability of binge drinking. There were no other associations between reactivity to U- and P-threat and probability of binge drinking and number of binging episodes. These results demonstrate that exaggerated reactivity to U-threat is a brain-based individual difference factor that connotes risk for problem drinking. These findings also add to a growing literature implicating AIC and dACC dysfunction in the pathophysiology of alcohol use disorder.

Neural and Self-report Measures of Sensitivity to Uncertainty as Predictors of COVID-Related Negative Affect.

The COVID-19 pandemic has been a period of unprecedented uncertainty. Research indicates individuals differ in their response to uncertainty and these differences are mediated by anterior insula (aINS) function. Those most sensitive to uncertainty are likely vulnerable to negative affect in the context of the pandemic. The current study was designed to directly test this question using both neural and self-reported measures of sensitivity to uncertainty. Fifty-nine volunteers completed a task designed to probe neural response to anticipation of predictable (P-) and unpredictable (U-) threat-of-electric-shock during functional magnetic resonance imaging and a self-report measure of intolerance of uncertainty (IU). Approximately two years later, during the peak of the pandemic, participants reported their emotional reactions to the COVID-19 crisis. Multilevel mixed models revealed that greater aINS activation to U-threat and greater self-reported IU were independent predictors of increased COVID-related negative affect. These findings were significant when adjusting for biological sex and depression and anxiety symptom severity. The results add to a growing literature demonstrating that individual differences in response to uncertainty have a robust impact on mood and functioning. Results also highlight that individuals highly sensitive to uncertainty may be at increased risk for poor mental health during the ongoing pandemic.

Impact of Trauma Type on Startle Reactivity to Predictable and Unpredictable Threats.

ABSTRACT: Trauma exposure has been repeatedly linked to psychophysiological threat reactivity, although the directionality of this association has been inconsistent. Several factors likely contribute to inconsistent findings including type of trauma and threat paradigm. The present study therefore examined the impact of trauma type on psychophysiological reactivity to predictable (P-) and unpredictable (U-) threat in young adults (N = 112). Participants were classified into three groups: history of interpersonal or noninterpersonal trauma, or no history of trauma. Startle eyeblink potentiation was recorded during a well-validated threat-of-shock paradigm. Results indicated individuals with interpersonal trauma exposure displayed exaggerated startle reactivity to U-threat (only) compared with both other groups. In contrast, individuals with noninterpersonal trauma exhibited blunted startle reactivity to U-threat (only) compared with both other groups. Findings reveal that trauma and threat type influence threat reactivity and that those with a history of interpersonal trauma may uniquely display exaggerated sensitivity to stressors that are uncertain.

Behavioral and neural sensitivity to uncertain threat in individuals with alcohol use disorder: Associations with drinking behaviors and motives.

A developing theory is that individuals with alcohol use disorder (AUD) display exaggerated reactivity to threats that are uncertain (U-threat), which facilitates excessive drinking as a means of avoidance-based coping. There is a promising initial behavioral evidence supporting this theory; however, the neural bases of reactivity to U-threat in individuals with AUD have not been examined. The extent to which biomarkers of U-threat reactivity map onto drinking behaviors and coping motives for alcohol use is also unknown. The current study therefore examined group differences in behavioral and neural reactivity to U-threat in adults with and without AUD. The study also tested whether behavior and brain responses to U-threat correlate with problematic drinking and coping motivated drinking. Volunteers (n = 65) with and without a history of AUD (38 AUD, 27 controls) were included and completed a well-validated threat-of-shock task to probe responses to U-threat and predictable threat (P-threat) while startle eyeblink potentiation was collected. Individuals also completed a newly designed, analogous version of the task during functional magnetic resonance imaging (fMRI). Results indicated that individuals with AUD displayed greater startle magnitude during U-threat, but not P-threat, and greater right insula and dorsal anterior cingulate cortex (dACC) activation during both forms of threat compared with controls. Startle magnitude and insula activation during U-threat positively correlated with self-reported problem drinking and coping motives for alcohol use. Findings demonstrate that individuals with AUD display exaggerated sensitivity to U-threat at the behavioral and neural level and that these multimethod biomarkers tap into negative reinforcement processes of alcohol abuse.

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.

Developmental changes in resting-state functional networks among individuals with and without internalizing psychopathologies.

BACKGROUND: Three well-established intrinsic connectivity networks (ICNs) involved in cognitive-affective processing include the cognitive control network (CCN), default mode network (DMN), and salience and emotional network (SEN). Despite recent advances in understanding developmental changes in these ICNs, the majority of research has focused on single seeds or networks in isolation with limited age ranges. Additionally, although internalizing psychopathologies (IPs), such as anxiety and depression, are often characterized by maladaptive cognitive-affective processing styles, it is not clear how IP history influences age-related changes in brain networks. METHOD: The current study aimed to characterize the normative development of the CCN, DMN, and SEN across a large age-span (7-29 year olds) of typically developing (TD) individuals (n = 97). We also explore how age may impact differences in network connectivity between TD individuals and patients with IPs (n = 136). RESULTS: Among TD individuals, DMN and CCN connectivity strengthened with age, whereas connectivity between the SEN and ventromedial prefrontal cortex weakened across development. When exploring group (IP vs. TD) differences, the IP group was characterized by greater connectivity between the CCN and cerebellum and between the SEN and caudate from childhood to early adulthood, relative to TD individuals. In addition, patients with IPs, versus TD individuals, exhibited reduced connectivity between the SEN and medial frontal gyrus from adolescence to adulthood. CONCLUSIONS: The current findings shed light on differential age-related changes in brain network patterns among psychiatrically free, TD individuals and those with internalizing disorders, and may provide plausible targets for novel mechanism-based treatments that differ based on developmental stage.