Emotional salience of positive and negative aspects of cannabis use in cannabis use disorder: The development of a novel self-referential processing task using the late positive potential

Background: Cannabis Use Disorder (CUD) is increasingly prevalent in the United States, while perceived addiction risk and treatment-seeking are declining. Emotional salience of cannabis-use-related problems and benefits likely contribute to motivation to change, but measurement of this process has been limited. The present study sought to validate a novel assessment of emotional appraisal of self-referential cannabis-use-related information across subjective and neurophysiological units of analysis. Method: Non-treatment-seeking individuals with DSM-5 severe CUD (N = 42) completed a task that presented auditory self-referential, personalized cannabis-use-related problem and benefit statements, as well as neutral self-referential statements, during electroencephalography recording. The late positive potential (LPP) was used as a neurophysiological measure of emotional salience. Valence/arousal ratings of each statement, along with their motivational importance in sustaining vs. reducing cannabis use, were also obtained. Results: As predicted, valence and arousal ratings significantly differentiated cannabis-use-related problems and benefits from neutral statements. Partially consistent with predictions, the LPP to cannabis-use-related benefits was significantly larger than LPPs to cannabis-use-related problems and neutral statements, which did not differ from each other. Bonferroni-adjusted exploratory correlations revealed that the LPP to cannabis-use-related problems was sensitive to recent cannabis use frequency. Conclusion: These results provide some support for the validity of this novel multi-method assessment of emotional reactivity to personalized cannabis-use-related self-referential information in non-treatment-seeking individuals with severe CUD. The dissociation between subjective and neurophysiological reactivity to self-referential cannabis-related problem statements should be further explored

Thwarted Belongingness Predicts Greater Neural Reactivity to a Novel Social Exclusion Image Set: Evidence From the Late Positive Potential

Introduction: Thwarted belongingness (TB) is among the most well-researched risk factors for suicidal ideation (SI). Yet, there is little research examining neural mechanisms underlying this construct. The present study used a novel social exclusion image set in concert with the late positive potential (LPP) to test the role of neural reactivity social exclusion in TB and SI. Methods: Participants (n = 243) were recruited based on elevated suicide risk and completed an emotional picture viewing task. The LPP was used to index neural reactivity to a novel set of social exclusion images and international affective picture system (IAPS) neutral, positive, and negative images. Results: Greater TB predicted a larger social exclusion ΔLPP (social exclusion LPP relative to neutral LPP) and social exclusion LPP even when accounting for SI, biological sex, age, negative affect, and perceived burdensomeness. Moreover, the social exclusion LPP was uniquely related to TB beyond the LPP to other images. Last, a larger social exclusion LPP predicted greater SI via elevations in TB. Conclusion: Reactivity to social exclusion stimuli may play an important role in SI via elevated TB, but not perceived burdensomeness. Future research should further explore the neural mechanisms underlying other IPT constructs

The Role of Anxiety Sensitivity Cognitive Concern In Suicidal Ideation: A Test of the Depression-Distress Amplification Model in Clinical Outpatients

Suicide constitutes a significant public health burden as global suicide rates continue to increase. Thus, it is crucial to identify malleablesuicide risk factors to develop prevention protocols. Anxiety sensitivity, or a fear of anxiety-related sensations, is a potential malleable risk factor for the development of suicidal ideation. The Depression-Distress Amplification Model (DDAM) posits that the anxiety sensitivity cognitive concerns (ASCC) subfactor interacts with depressive symptoms to amplify the effects of depression and lead to suicidal ideation. The current study tested the DDAM across the two most widely-replicated factors of depressive symptoms (cognitive and affective/somatic) in comparison to a risk factor mediation model where ASCC are related to suicidal ideation via depressive symptoms. Participants included 295 clinical outpatients from a community clinic. The interaction between ASCC and depressive symptoms in the prediction of suicidal ideation was not significant for either cognitive or affective/somatic symptoms of depression. However, results revealed a significant indirect effect of ASCC through cognitive symptoms of depression in the prediction of suicidal ideation. These cross sectional findings are not consistent with the DDAM. Rather, the relationship may be better conceptualized with a model in which ASCC is related to suicidal ideation via cognitive symptoms of depression

Fearlessness About Death is Related to Diminished Late Positive Potential Responses When Viewing Threatening and Mutilation Images in Suicidal Ideators

Background: Very few people who desire death by suicide ever make a suicide attempt, highlighting the importance of determining factors that influence the capability to enact lethal self-harm. One such factor is fearlessness about death, which has been found to be an important predictor of suicide attempts. Recently, longitudinal evidence found that fearlessness about death is positively associated with fluctuations in suicidal ideation. Efforts exploring biophysical mechanisms of suicide have found diminished physiological responses to threat/mutilation-related images in suicide attempters and in individuals who report being less fearful of death. These studies suggest that an individual with greater fearlessness about death may demonstrate a blunted response to threat/mutilation stimuli; however, this hypothesis has yet to be directly tested. Methods: This study used an electroencephalography/event-related potential paradigm to examine late positive potential (LPP) amplitude differences in an adult community sample (N = 280), as well as a subsample with current suicidal ideation (n = 62), with a high rate of psychopathology (90.1%). It was hypothesized that participants with higher fearlessness about death would show diminished responses (smaller LPP amplitude) when viewing threat/mutilation images. Results: Results indicated that participants with suicidal ideation and elevated fearlessness about death demonstrated a blunted emotional response to threat/mutilation images but similar reactions to rewarding pleasant stimuli. Conclusions: These results suggest blunted LPP responses to threat/mutilation stimuli may be a potential biophysical mechanism for fearless about death

Interactive Effects of Traumatic Brain Injury and Anxiety Sensitivity Cognitive Concerns on Post-traumatic Stress Among Active Duty Soldiers

Traumatic brain injury (TBI) history has been repeatedly linked with heightened risk for post-traumatic stress (PTS) among active duty soldiers. Yet, no research to date has examined the relationship between TBI and PTS in the context of anxiety sensitivity cognitive concerns (ASCC), a well-established cognitive-affective risk factor for PTS that may intensify the effects of TBI on PTS via the amplification of TBI-related symptoms of cognitive dyscontrol. The present study tested the moderating effects of ASCC on the relationship between the number of lifetime probable TBIs and PTS among a sample of 89 trauma-exposed active duty soldiers. Results demonstrated that high ASCC potentiated the relationship between number of probable TBIs and PTS while low ASCC muted this association. Interestingly, ASCC was more closely related to PTS among those with a greater number of probable TBIs compared to those with zero past TBIs. These results underscore the importance of ASCC in the association of TBI and PTS

Differentiating Suicide Attempts and Suicidal Ideation Using Neural Markers of Emotion Regulation

Background: Theories of suicide posit distinct etiological pathways for suicide attempts (SA) and suicidal ideation (SI) that are marked, in part, by disruptions in the ability to regulate reactions to threat/mutilation and interpersonally-relevant emotional stimuli. However, little research has specifically tested these associations. To address this gap, the present study extracted the Late Positive Potential (LPP) during an emotion regulation task to evaluate the independent associations that SA history and SI share with initial responsivity to, and regulation of, these distinct emotional contents. Methods: A clinical sample (N = 257) were recruited based on elevations in suicide risk factors. Participants completed a picture viewing and regulation task that included threat/mutilation, reward, and neutral images from the International Affective Picture System. Immediately prior to picture onset, participants were instructed to passively view the image, increase their emotional reaction to the image, or decrease their emotional reaction to the image. Results: Differential patterns of LPP amplitudes only emerged in the context of attempts to regulate emotional responses such that SA history predicted a superior ability to volitionally mitigate responses to threat/mutilation while SI was related to a worse ability to increase responses to reward. Effect sizes were in the small and small-to-medium range. Limitations: The present data were cross-sectional and included low trial counts. Conclusions: Taken together, these findings support existing theories of suicide suggesting that distinct mechanisms underlie suicidal thoughts and behaviors. Future research should seek to determine if these mechanisms may serve as a viable intervention targets

IL-6, but not TNF-α, response to alcohol cues and acute consumption associated with neural cue reactivity, craving, and future drinking in binge drinkers

Objective and design: Preclinical studies suggest learned immune system responses to alcohol cues and consumption may contribute to alcohol's pharmacodynamic properties and/or Alcohol Use Disorder (AUD) pathogenesis. Mechanistically, these immune alterations may be associated with increased craving and alcohol consumption, both acutely and over time. We sought to characterize this relationship in a randomized, counter-balanced, crossover neuroimaging experiment which took place between June 2020–November 2021. Methods: Thirty-three binge drinkers (BD) and 31 non-binge, social drinkers (SD), matched for demographic and psychological variables, were exposed to alcohol cues and water cues in two separate 7 T functional magnetic resonance imaging (fMRI) scans. Each scan was followed by the Alcohol Taste Test (ATT) of implicit motivation for acute alcohol. Craving measures and blood cytokine levels were collected repeatedly during and after scanning to examine the effects of alcohol cues and alcohol consumption on craving levels, Tumor necrosis factor alpha (TNF-α), and Interleukin 6 (IL-6) levels. A post-experiment one-month prospective measurement of participants’ “real world” drinking behavior was performed to approximate chronic effects. Results: BD demonstrated significantly higher peak craving and IL-6 levels than SD in response to alcohol cues and relative to water cues. Ventromedial Prefrontal Cortex (VmPFC) signal change in the alcohol-water contrast positively related to alcohol cue condition craving and IL-6 levels, relative to water cue condition craving and IL-6 levels, in BD only. Additionally, peak craving and IL-6 levels were each independently related to ATT alcohol consumption and the number of drinks consumed in the next month for BD, again after controlling for craving and IL-6 repones to water cues. However, TNF-α release in the alcohol cue condition was not related to craving, neural activation, IL-6 levels, immediate and future alcohol consumption in either group after controlling for water cue condition responses. Conclusions: In sum, BD show greater craving and IL-6 release in the alcohol cue condition than SD, both of which were associated with prefrontal cue reactivity, immediate alcohol consumption, and future alcohol consumption over the subsequent 30 days. Alcohol associated immune changes and craving effects on drinking behavior may be independent of one another or may be indicative of a common pathway by which immune changes in BD could influence motivation to consume alcohol. Trial registration: Clinical Trials NCT04412824