Daniel E. Bradford

How Bad Could It Be? Alcohol Dampens Stress Responses to Threat of Uncertain Intensity

Stress response dampening is an important motive for alcohol use. However, stress reduction via alcohol (alcohol SRD) is observed inconsistently in the laboratory, and this has raised questions about the precise mechanisms and boundary conditions for these effects. Emerging evidence indicates that alcohol SRD may be observed selectively during uncertain but not certain threats. In a final sample of 89 participants, we measured stress response via potentiation of defensive startle reflex in response to threat of shock in blocks with certain (low and high) and uncertain shock intensity. Our alcohol-administration procedure produced blood alcohol concentrations (BACs) across a broad range (0.00%–0.12%) across participants. Increasing BACs were associated with linearly decreasing startle potentiation and self-reported anxiety. This SRD effect was greater during uncertain than certain threat. More broadly, these results suggest that distinct mechanisms are involved in response to threats of uncertain intensity and threats of certain intensity.

Psychometric properties of startle and corrugator response in NPU, affective picture viewing, and resting state tasks.

The current study provides a comprehensive evaluation of critical psychometric properties of commonly used psychophysiology laboratory tasks/measures within the NIMH RDoC. Participants (N = 128) completed the no-shock, predictable shock, unpredictable shock (NPU) task, affective picture viewing task, and resting state task at two study visits separated by 1 week. We examined potentiation/modulation scores in NPU (predictable or unpredictable shock vs. no-shock) and affective picture viewing tasks (pleasant or unpleasant vs. neutral pictures) for startle and corrugator responses with two commonly used quantification methods. We quantified startle potentiation/modulation scores with raw and standardized responses. We quantified corrugator potentiation/modulation in the time and frequency domains. We quantified general startle reactivity in the resting state task as the mean raw startle response during the task. For these three tasks, two measures, and two quantification methods, we evaluated effect size robustness and stability, internal consistency (i.e., split-half reliability), and 1-week temporal stability. The psychometric properties of startle potentiation in the NPU task were good, but concerns were noted for corrugator potentiation in this task. Some concerns also were noted for the psychometric properties of both startle and corrugator modulation in the affective picture viewing task, in particular, for pleasant picture modulation. Psychometric properties of general startle reactivity in the resting state task were good. Some salient differences in the psychometric properties of the NPU and affective picture viewing tasks were observed within and across quantification methods.

Role-Playing and Real-Time Strategy Games Associated with Greater Probability of Internet Gaming Disorder

Research indicates that a small subset of those who routinely play video games show signs of pathological habits, with side effects ranging from mild (e.g., being late) to quite severe (e.g., losing a job). However, it is still not clear whether individual types, or genres, of games are most strongly associated with Internet gaming disorder (IGD). A sample of 4,744 University of Wisconsin-Madison undergraduates (Mage=18.9 years; SD=1.9 years; 60.5% female) completed questionnaires on general video game playing habits and on symptoms of IGD. Consistent with previous reports: 5.9-10.8% (depending on classification criteria) of individuals who played video games show signs of pathological play. Furthermore, real-time strategy and role-playing video games were more strongly associated with pathological play, compared with action and other games (e.g., phone games). The current investigation adds support to the idea that not all video games are equal. Instead, certain genres of video games, specifically real-time strategy and role-playing/fantasy games, are disproportionately associated with IGD symptoms.

Empirically based comparisons of the reliability and validity of common quantification approaches for eyeblink startle potentiation in humans

Abstract Startle potentiation is a well‐validated translational measure of negative affect. Startle potentiation is widely used in clinical and affective science, and there are multiple approaches for its quantification. The three most commonly used approaches quantify startle potentiation as the increase in startle response from a neutral to threat condition based on (1) raw potentiation, (2) standardized potentiation, or (3) percent‐change potentiation. These three quantification approaches may yield qualitatively different conclusions about effects of independent variables (IVs) on affect when within‐ or between‐group differences exist for startle response in the neutral condition. Accordingly, we directly compared these quantification approaches in a shock‐threat task using four IVs known to influence startle response in the no‐threat condition: probe intensity, time (i.e., habituation), alcohol administration, and individual differences in general startle reactivity measured at baseline. We confirmed the expected effects of time, alcohol, and general startle reactivity on affect using self‐reported fear/anxiety as a criterion. The percent‐change approach displayed apparent artifact across all four IVs, which raises substantial concerns about its validity. Both raw and standardized potentiation approaches were stable across probe intensity and time, which supports their validity. However, only raw potentiation displayed effects that were consistent with a priori specifications and/or the self‐report criterion for the effects of alcohol and general startle reactivity. Supplemental analyses of reliability and validity for each approach provided additional evidence in support of raw potentiation.

Not just noise: Individual differences in general startle reactivity predict startle response to uncertain and certain threat

General startle reactivity reflects defensive reactivity independent of affective foreground. We examined the relationship between general startle reactivity and startle response to threat in three tasks with distinct manipulations of threat uncertainty. General startle reactivity was a stronger predictor of startle response during threat (vs. no threat) and uncertain (vs. certain threat). These results confirm that including general startle reactivity in our analyses can increase the power and/or precision to test effects of other focal experimental manipulations or grouping variables. Moreover, this suggests that individual differences in defensive reactivity moderate responding to threats of various types in our environment. As such, individual differences in general startle reactivity may index important psychological attributes related to trait affectivity, premorbid vulnerability for psychopathology, and manifest psychopathology.

Justify your alpha

In response to recommendations to redefine statistical significance to P ≤ 0.005, we propose that researchers should transparently report and justify all choices they make when designing a study, including the alpha level.

The Role of Game Genres and the Development of Internet Gaming Disorder in School- Aged Children

Background and Objectives: Internet Gaming Disorder (IGD) is characterized by a pattern of video game playing that results in significant issues with daily life (e.g. problems with inter-personal relationships or poor academic/job performance), and where the gaming persists despite these negative outcomes. Here we tested the hypothesis that the prevalence of IGD depends on the types of games a child plays. Methods: A sample of 2,982 children from Singaporean primary and secondary schools were recruited for the current study. They filled out questionnaires related to IGD symptoms, general video game play habits, as well as other measures of daily life function. Games were categorized into five genres (Role-playing, Strategy, Action, Puzzle, Music) and the prevalence of IGD was examined as a function of each individual’s favorite genre of game. Results: Not all genres were equally associated with IGD. The highest rates of IGD were associated with players of Role-playing games followed by players of Action, Music, Strategy, and Puzzle games, respectively. However, this pattern was only found in secondary school-age children with primary school-aged children showing no differentiation by genre. Conclusion: Consistent with previous work, respondents’ favorite game genres predicted differential probabilities of IGD. However, this was only true in older children, not in younger children. Future work is needed to determine if this is because young children are not susceptible to the differential influence of various genres or because the games that young children play within these genres lack the critical ingredients that exist in these game types played by older children and adults.

Increased startle potentiation to unpredictable stressors in alcohol dependence: Possible stress neuroadaptation in humans.

Stress plays a key role in addiction etiology and relapse. Rodent models posit that following repeated periods of alcohol and other drug intoxication, compensatory allostatic changes occur in the central nervous system (CNS) circuits involved in behavioral and emotional response to stressors. We examine a predicted manifestation of this neuroadaptation in recently abstinent alcohol-dependent humans. Participants completed a translational laboratory task that uses startle potentiation to unpredictable (vs. predictable) stressors implicated in the putative CNS mechanisms that mediate this neuroadaptation. Alcohol-dependent participants displayed significantly greater startle potentiation to unpredictable than predictable stressors relative to nonalcoholic controls. The size of this effect covaried with alcohol-related problems and degree of withdrawal syndrome. This supports the rodent model thesis of a sensitized stress response in abstinent alcoholics. However, this effect could also represent premorbid risk or mark more severe and/or comorbid psychopathology. Regardless, pharmacotherapy and psychological interventions may target unpredictable stressor response to reduce stress-induced relapse.

The need for precise answers for the goals of precision medicine in alcohol dependence to succeed

Dear Editor, We read the study by Mann et al. [1] with great interest. Clinical trials of pharmacotherapies for alcohol use disorder have yielded inconsistent or suboptimal outcomes, but it may be that drinker characteristics moderate pharmacotherapy efficacy. To begin to answer the important clinical question of “which medication will work best for which patient,” Mann et al. [1] grouped drinkers by whether they drank for alcohol’s positive and/or negative reinforcing qualities. This yielded: ‘reward drinkers’ (high-reward and low-relief), ‘relief drinkers’ (low-reward and high-relief), ‘all high drinkers’ (high-reward and high-relief) and ‘all low drinkers’ (low-reward and low-relief). The authors sought “to test differential efficacy of naltrexone and acamprosate based on individual differences in neurotransmitter dysfunction” putatively expected across these subgroups. They predicted “individuals with primarily reward drinking tendencies [reward drinkers w/opioidergic dysfunction] would respond better to naltrexone ... whereas individuals with primarily relief drinking tendencies [relief drinkers w/glutamatergic dysfunction] would respond better to acamprosate” [1]. The study takes a novel precision medicine approach within a rigorously designed clinical trial and a mechanistic focus. It offers immediate potential to address longstanding shortcomings in treatment efficacy and efficiency. We were surprised, however, to find that the reported analyses never directly tested the differential efficacy of naltrexone versus acamprosate in any subgroups as proposed. Instead, the authors compared the effects of each drug (vs. placebo) for each of the reward and relief drinkers relative to the effects of the same drug (vs. placebo) for all low drinkers. The key finding was a 2 (naltrexone vs. placebo) × 2 (reward drinkers vs. all low drinkers) interaction, which indicated the differential efficacy of naltrexone vs. placebo was improved in reward drinkers relative to all low drinkers (means displayed in Fig. 1a). This finding in a welldesigned study such as this one is perhaps itself worth publication. Its clinical implications for precision medicine, however, are limited as it only implies clinicians should choose naltrexone over placebo to treat reward drinkers. It does not speak to whether clinicians should choose naltrexone over acamprosate to treat reward drinkers. The results of their analyses thereby fail to address the proposed research question: “which medication will work best for which patients (i.e. precision medicine)” [1]. To rigorously test the differential efficacy of naltrexone vs. acamprosate for reward drinkers, the authors could have tested the 2 (naltrexone vs. acamprosate) × 2 (reward drinkers vs. all low drinkers) interaction (Fig. 1b). Unfortunately, the observed pattern of means provides no evidence that clinicians should choose naltrexone over acamprosate when they treat reward drinkers specifically. It also does not demonstrate any match between selective drug mechanisms and putative subgroup dysfunction that serves as the foundation for this precision medicine study. Although this correspondence focuses only on one recent paper, these analytic concerns and related issues remain rampant in clinical research [2, 3]. As the rigor of research increases through open science practices, such as preregistration of analyses,

Alcohol’s effects on emotionally motivated attention, defensive reactivity, and subjective anxiety during uncertain threats

Abstract Developing a better understanding of how and under what circumstances alcohol affects the emotions, cognitions and neural functions that precede and contribute to dangerous behaviors during intoxication may help to reduce their occurrence. Alcohol intoxication has recently been shown to reduce defensive reactivity and anxiety more during uncertain vs certain threat. However, alcohol’s effects on emotionally motivated attention to these threats are unknown. Alcohol may disrupt both affective response to and attentional processing of uncertain threats making intoxicated individuals less able to avoid dangerous and costly behaviors. To test this possibility, we examined the effects of a broad range of blood alcohol concentrations on 96 participants’ sub-cortically mediated defensive reactivity (startle potentiation), retrospective subjective anxiety (self-report) and cortically assessed emotionally motivated attention (probe P3 event related potential) while they experienced visually cued uncertain and certain location electric shock threat. As predicted, alcohol decreased defensive reactivity and subjective anxiety more during uncertain vs certain threat. In a novel finding, alcohol dampened emotionally motivated attention during uncertain but not certain threat. This effect appeared independent of alcohol’s effects on defensive reactivity and subjective anxiety. These results suggest that alcohol intoxication dampens processing of uncertain threats while leaving processing of certain threats intact.