Topiramate Versus Naltrexone for Alcohol Use Disorder: A Genotype-Stratified Double-Blind Randomized Controlled Trial.

OBJECTIVE: There have been no well-controlled and well-powered comparative trials of topiramate with other pharmacotherapies for alcohol use disorder (AUD), such as naltrexone. Moreover, the literature is mixed on the effects of two polymorphisms-rs2832407 (in GRIK1) and rs1799971 (in OPRM1)-on response to topiramate and naltrexone, respectively. The authors sought to examine the comparative effectiveness of topiramate and naltrexone in improving outcomes in AUD and to examine the role of the rs2832407 and rs1799971 polymorphisms, respectively, on response to these medications. METHODS: In a 12-week, double-blind, placebo-controlled, randomized, multisite, genotype-stratified (rs2832407 and rs1799971) clinical trial comparing topiramate and naltrexone in treating AUD, 147 patients with AUD were randomly assigned to treatment with topiramate or naltrexone, stratified by genotype (rs2832407*CC and *AC/AA genotypes and rs1799971*AA and *AG/GG genotypes). The predefined primary outcome was number of heavy drinking days per week. Predefined secondary outcomes included standard drinks per drinking day per week, body mass index (BMI), craving, markers of liver injury, mood, and adverse events. RESULTS: For the number of heavy drinking days per week, there was a near-significant time-by-treatment interaction. For the number of standard drinks per drinking day per week, there was a significant time-by-treatment interaction, which favored topiramate. There were significant time-by-treatment effects, with greater reductions observed with topiramate than naltrexone for BMI, craving, and gamma-glutamyltransferase level. Withdrawal due to side effects occurred in 8% and 5% of the topiramate and naltrexone groups, respectively. Neither polymorphism showed an effect on treatment response. CONCLUSIONS: Topiramate is at least as effective and safe as the first-line medication, naltrexone, in reducing heavy alcohol consumption, and superior in reducing some clinical outcomes. Neither rs2832407 nor rs1799971 had effects on topiramate and naltrexone treatments, respectively.

Impact of personalized alcohol intake and cognitive feedback on alcohol use behavior in hazardous drinkers: A quasi-randomized trial.

BACKGROUND: Worldwide, alcohol use is a major contributor to the burden of disease and mortality. A sizeable literature suggests that brief web-based interventions that incorporate personalized normative and/or health consequences feedback are effective at reducing alcohol intake. The relative efficacy of an intervention that also includes individualized feedback about brain health has not been examined, nor has the utility of integrating a smartphone app component. METHOD: Participants (N = 436, Mage = 21.27) completed baseline protocols (n = 178 recorded alcohol use via an app for 14 days) and were then assigned to one of three feedback conditions using randomized block allocation with stratification based on the total number of standard drinks consumed. Control participants received no feedback; Alcohol Intake Feedback (Alc) participants received personalized information about their alcohol use; Alcohol Intake plus Cognitive Feedback (AlcCog) participants received personalized details about alcohol use plus individualized brain-health information related to impulsivity. The impact of feedback on alcohol consumption behavior was examined as a function of feedback condition and hazardous/non-harmful drinking status (as defined by the World Health Organization) at an 8-week follow-up. RESULTS: Hazardous drinkers in both the Alc and AlcCog conditions reduced their alcohol intake by 31% to 50% more than those in the Control condition. Reductions were not related to whether participants completed web- plus app-based components or web-only components of the intervention. There was no change in the alcohol intake of non-harmful drinkers. CONCLUSIONS: This proof-of-concept study showed that hazardous drinkers respond well to brief electronic interventions that incorporate personalized normative and/or health consequences feedback. Further research is required to determine how best to make impulsivity-related brain-health consequences of drinking manifest and how to maximize the potential of smartphones apps.

Chronic cannabis use and error awareness: The effect on learning from errors.

BACKGROUND: Cannabis is the third most commonly used drug worldwide, with studies suggesting a deleterious effect on some aspects of performance monitoring. It is unknown, however, whether diminished error awareness influences adaptive behaviour in cannabis users. Therefore, this study examined the effect of error awareness on learning from errors in cannabis users. METHODS: Thirty-six chronic cannabis users (Mage = 23.81 years; female, 36%) and 34 controls (Mage = 21.53 years; female, 76%) completed a Go/No-Go task that allowed participants to learn from errors and adapt their behaviour. Multilevel models were specified to determine whether the effect of error awareness on learning from errors differs between cannabis users and controls, and whether cannabis-use measures predict error correction while accounting for error awareness. RESULTS: While error awareness and correction rates did not differ between the groups, there was a significant effect of age of use onset on error correction in cannabis users. Further, the effect of error awareness was dependent on age of onset, and cannabis use-related frequency and harm. That is, cannabis users reporting an earlier age of regular use or scoring higher on the cannabis use index were less likely to perform correctly following an aware error. CONCLUSION: It appears overall cannabis use might not be tightly coupled to behavioural indices of performance monitoring. There is evidence, however, that aspects of cannabis use predict impairments in learning from errors that may be associated with treatment outcomes.

The role of impulsivity in the relationship between affect and alcohol consumption in young adults.

BACKGROUND: Theoretical models of alcohol use posit that individuals consume alcohol to ameliorate negative affect or to heighten positive affect. It is important, however, to consider the influence of factors that may determine an individual's tendency to consume excessive amounts of alcohol under positive and negative circumstances. Thus, the current study examined a large sample of young adults to clarify whether positive and negative affect predict total alcohol consumption on drinking days and whether facets of impulsivity moderate these relationships. METHODS: Six-hundred ninety-three young adults (Mage = 19.71 years, SD = 2.04; female = 62.9%) completed the Behavioral Inhibition System/Behavioral Activation System (BIS/BAS) scales at baseline followed by daily measures of positive and negative affect and self-reported alcohol use for 13 days. Generalized linear mixed models were specified to assess the role of pre-consumption affect on total drinks consumed across drinking days and to determine the moderating effect of each BIS/BAS subscale. RESULTS: Participants were significantly more likely to drink in greater quantities on occasions preceded by higher positive affect but not negative affect. While fun-seeking positively predicted total drinks consumed, there were no significant interaction effects between the BIS/BAS subscales and affect on total drinks consumed. CONCLUSIONS: These findings challenge existing affect regulation models and have implications for ecological momentary interventions aimed at addressing hazardous drinking behaviors.

Evaluating untimed and timed abridged versions of Raven's Advanced Progressive Matrices.

INTRODUCTION: Raven's Advanced Progressive Matrices (APM) are frequently utilized in clinical and experimental settings to index intellectual capacity. As the APM is a relatively long assessment, abridged versions of the test have been proposed. The psychometric properties of an untimed 12-item APM have received some consideration in the literature, but validity explorations have been limited. Moreover, both reliability and validity of a timed 12-item APM have not previously been examined. METHOD: We considered the psychometric properties of untimed (Study 1; N = 608; Mage = 27.89, SD = 11.68) and timed (Study 2; N = 479; Mage = 20.93, SD = 3.12) versions of a brief online 12-item form of the APM. RESULTS: Confirmatory factor analyses established both versions of the tests are unidimensional. Item response theory analyses revealed that, in each case, the 12 items are characterized by distinct differences in difficulty, discrimination, and guessing. Differential item functioning showed few male/female or native English/non-native English performance differences. Test-retest reliability was .65 (Study 1) to .69 (Study 2). Both tests had medium-to-large correlations with the Wechsler Abbreviated Scale of Intelligence (2nd ed.) Perceptual Reasoning Index (r = .50, Study 1; r = .56, Study 2) and Full-Scale IQ (r = .34, Study 1; r = .41, Study 2). CONCLUSION: In sum, results suggest both untimed and timed online versions of the brief APM are psychometrically sound. As test duration was found to be highly variable for the untimed version, the timed form might be a more suitable choice when it is likely to form part of a longer battery of tests. Nonetheless, classical test and item response theory analyses, plus validity considerations, suggest the untimed version might be the superior abridged form.

Web-Based Independent Versus Laboratory-Based Stop-Signal Task Performance: Within-Subjects Counterbalanced Comparison Study.

BACKGROUND: Considered a facet of behavioral impulsivity, response inhibition facilitates adaptive and goal-directed behavior. It is often assessed using the Stop-Signal Task (SST), which is presented on stand-alone computers under controlled laboratory conditions. Sample size may consequently be a function of cost or time and sample diversity constrained to those willing or able to attend the laboratory. Statistical power and generalizability of results might, in turn, be impacted. Such limitations may potentially be overcome via the implementation of web-based testing. OBJECTIVE: The aim of this study was to investigate if there were differences between variables derived from a web-based SST when it was undertaken independently-that is, outside the laboratory, on any computer, and in the absence of researchers-versus when it was performed under laboratory conditions. METHODS: We programmed a web-based SST in HTML and JavaScript and employed a counterbalanced design. A total of 166 individuals (mean age 19.72, SD 1.85, range 18-36 years; 146/166, 88% female) were recruited. Of them, 79 undertook the independent task prior to visiting the laboratory and 78 completed the independent task following their laboratory visit. The average time between SST testing was 3.72 (SD 2.86) days. Dependent samples and Bayesian paired samples t tests were used to examine differences between laboratory-based and independent SST variables. Correlational analyses were conducted on stop-signal reaction times (SSRT). RESULTS: After exclusions, 123 participants (mean age 19.73, SD 1.97 years) completed the SST both in the laboratory and independently. While participants were less accurate on go trials and exhibited reduced inhibitory control when undertaking the independent-compared to the laboratory-based-SST, there was a positive association between the SSRT of each condition (r=.48; P<.001; 95% CI 0.33-0.61). CONCLUSIONS: Findings suggest a web-based SST, which participants undertake on any computer, at any location, and in the absence of the researcher, is a suitable measure of response inhibition.

Examining the neural correlates of error awareness in a large fMRI study.

Goal-directed behavior is dependent upon the ability to detect errors and implement appropriate posterror adjustments. Accordingly, several studies have explored the neural activity underlying error-monitoring processes, identifying the insula cortex as crucial for error awareness and reporting mixed findings with respect to the anterior cingulate cortex (ACC). Variable patterns of activation have previously been attributed to insufficient statistical power. We therefore sought to clarify the neural correlates of error awareness in a large event-related functional magnetic resonance imaging (fMRI) study. Four hundred and two healthy participants undertook the error awareness task, a motor Go/No-Go response inhibition paradigm in which participants were required to indicate their awareness of commission errors. Compared to unaware errors, aware errors were accompanied by significantly greater activity in a network of regions, including the insula cortex, supramarginal gyrus (SMG), and midline structures, such as the ACC and supplementary motor area (SMA). Error awareness activity was related to indices of task performance and dimensional measures of psychopathology in selected regions, including the insula, SMG, and SMA. Taken together, we identified a robust and reliable neural network associated with error awareness.

Error awareness and post-error slowing: The effect of manipulating trial intervals.

Post-error slowing is often considered to be an error-related process that relies upon conscious error recognition, however evidence regarding this relationship is mixed. These inconsistent findings may be explained by the influence of task demands on post-error slowing. The current set of experiments aimed to investigate the role of error awareness in post-error slowing in an error awareness task with up to three dynamic conditions. In each condition, we manipulated the interval between lure trials (infrequent trials that require a different response to target trials) such that they were presented either randomly (standard condition), closely spaced (proximal condition) or widely spaced (distal condition) among target trials. This design attempted to clarify if the relationship between error awareness and post-error slowing is contingent upon task constraints such as trial timing and whether it persists over several trials. Our experiments demonstrate that under dynamic lure interval conditions, error awareness and post-error slowing are only weakly related. Further, post-error slowing was greatest in the standard condition which randomly presented lure trials, while accuracy was lowest in this condition across both experiments. Exclusion of the first post-error trial from both experiments eliminated all effects, indicating that there were only transient differences in post-error reaction time adjustments that were exclusive to the first post-error trial. Our findings thus align with non-functional accounts of post-error slowing and support the notion that post-error slowing and cognitive control can be separate processes that are largely not dependent on error awareness.

Adaptation following errors: Error awareness predicts future performance.

The ability to detect an error in performance is critical to ongoing and future goal-directed behaviour. Diminished awareness of errors has been associated with a loss of insight and poor functional recovery in several clinical disorders (e.g., attention-deficit/hyperactivity disorder, addiction, schizophrenia). Despite the clear imperative to understand and remediate such deficits, error awareness and its instantiation in corrective behaviour remains to be fully elucidated. The present study investigated the relationship between error awareness and future performance in order to determine whether conscious recognition of errors facilitates adaptive behaviour. Fifty-one healthy participants completed a motor Go/No-Go error awareness task that afforded the opportunity to learn from errors. A mixed-effects model was specified wherein awareness of an error was used to predict inhibitory performance on the following No-Go trial. The model revealed a significant predictive effect of error awareness on future performance, such that aware errors were more frequently followed by correct inhibitory performance. Notably, improvement in performance accuracy was not due to a temporary increase in conservatism of responding, but appeared to be a context-specific adaptation. These results highlight the adaptive role of error awareness and the relationship between error awareness and learning from errors that has the potential to contribute to clinical symptomatology.

Early psychological interventions for posttraumatic stress, depression and anxiety after traumatic injury: A systematic review and meta-analysis.

The psychological impacts of injury have significant long-term implications on injury recovery. This review examined the effectiveness of interventions delivered within three months of injury on reducing the severity of posttraumatic stress disorder (PTSD), anxiety and depression symptoms. A systematic search of seven databases (PsycINFO, Medline, Web of Science, CINAHL, Embase, Scopus and Cochrane Library) identified 15,224 records. 212 full-text articles were retrieved, 26 studies were included in narrative synthesis, and 12 studies with lower risk of bias were included in meta-analyses. Prolonged exposure, and cognitive and behavioural interventions elicited improvements in PTSD, anxiety and depression symptoms; multidisciplinary interventions improved PTSD and depression symptoms; and education-based interventions had little impact on any psychological symptoms. Studies comprising risk stratified or stepped care methods showed markedly greater population impact through better reach, implementation and adoption. Meta-analyses revealed small-medium reductions in PTSD symptoms over the first 12 months postinjury (SMD = 0.32 to 0.49) with clinically meaningful effects in 64% of studies; reduced depression symptoms at 0-3 (small effect; SMD = 0.34) and 6-12 months postinjury (medium effect; SMD = 0.60), with clinically meaningful effects in 40% of studies; but no pooled effects on anxiety symptoms at any time. Altogether, exposure- and CBT-based psychological interventions had the greatest impact on PTSD and depression symptoms postinjury when delivered within three months of injury, with risk-stratified, stepped care having the greatest population impact potential.