Neural correlates of increased alcohol demand following alcohol cue exposure in adult heavy drinkers.

Alcohol use disorder is associated with overvaluation of alcohol relative to other rewards, in part due to dynamic increases in value in response to alcohol-related cues. In a neuroeconomic framework, alcohol cues increase behavioral economic demand for alcohol, but the neural correlates these cue effects are unknown. This functional magnetic resonance imaging study combined a neuroeconomic alcohol purchase task with an alcohol cue exposure in 72 heavy drinkers with established sensitivity to alcohol cues (51 % female; mean age=33.74). Participants reported how many drinks they would consume from $0-$80/drink following exposure to neutral and alcohol images in a fixed order. Participants purchased significantly more drinks in the alcohol compared to the neutral condition, which was also evident for demand indices (i.e., intensity, breakpoint, Omax, elasticity; ps<0.001; ds=0.46-0.92). Alcohol purchase decisions were associated with activation in rostral middle and medial frontal gyri, anterior insula, posterior parietal cortex, and dorsal striatum, among other regions. Activation was lower across regions in the alcohol relative to neutral cue condition, potentially due to greater automaticity of choices in the presence of alcohol cues or attenuation of responses due to fixed cue order. These results contribute to growing literature using neuroeconomics to understand alcohol misuse and provide a foundation for future research investigating decision-making effects of environmental alcohol triggers.

Resting state functional connectivity as a predictor of brief intervention response in adults with alcohol use disorder: A preliminary study.

BACKGROUND: Brief interventions for alcohol use disorder (AUD) are generally efficacious, albeit with variability in response. Resting state functional connectivity (rsFC) may characterize neurobiological indicators that predict the response to brief interventions and is the focus of the current investigation. MATERIALS AND METHODS: Forty-six individuals with AUD (65.2% female) completed a resting state functional magnetic resonance imaging (fMRI) scan immediately followed by a brief intervention aimed at reducing alcohol consumption. Positive clinical response was defined as a reduction in alcohol consumption by at least one World Health Organization (WHO) risk drinking level at 3-month follow-up. rsFC was analyzed using seed-to-voxel analysis with seed regions from four networks: salience network, reward network, frontoparietal network, and default mode network. RESULTS: At baseline, responders had greater rsFC between the following seed regions in relation to voxel-based clusters than non-responders: (i) anterior cingulate cortex (ACC) in relation to left postcentral gyrus and right supramarginal gyrus (salience network); (ii) right posterior parietal cortex in relation to right ventral ACC (salience network); (iii) right interior frontal gyrus (IFG) pars opercularis in relation to right cerebellum and right occipital fusiform gyrus (frontoparietal); and (iv) right primary motor cortex in relation to left thalamus (default mode). Lower rsFC in responders vs. nonresponders was seen between the (i) right rostral prefrontal cortex in relation to left IFG pars triangularis (frontoparietal); (ii) right IFG pars triangularis in relation to right cerebellum (frontoparietal); (iii) right IFG pars triangularis in relation to right frontal eye fields and right angular gyrus (frontoparietal); and (iv) right nucleus accumbens in relation to right orbital frontal cortex and right insula (reward). CONCLUSIONS: Resting state functional connectivity in the frontoparietal, salience, and reward networks predicts the response to a brief intervention in individuals with AUD and could reflect greater receptivity or motivation for behavior change.

Clinical Efficacy of Deep Transcranial Magnetic Stimulation in Psychiatric and Cognitive Disorders: Protocol for a Systematic Review.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a widely used noninvasive brain stimulation technique for psychiatric and cognitive disorders. In recent years, deep TMS (dTMS) has shown promise as an enhanced form of TMS able to stimulate deeper brain structures and target broader networks. Various magnetic Hesed-coil (H-coil) designs-a novel feature of dTMS-have been used to stimulate brain regions implicated in the pathophysiology of specific psychiatric and cognitive disorders, thereby producing therapeutic effects. Given the novelty of dTMS in psychiatry, little is known about the clinical efficacy of dTMS across psychiatric and cognitive disorders-that is, whether dTMS performs superiorly to sham or control. OBJECTIVE: In this paper, we outline a protocol for a systematic review investigating the clinical efficacy of dTMS. The primary objective is to conduct a systematic review of the literature on dTMS for psychiatric and cognitive disorders and, if feasible, a meta-analysis to compare the efficacy of active dTMS versus sham/control for psychiatric disorders. Dementia and related cognitive disorders will also be examined. A secondary objective will be to examine subgroup differences (by age, sex, H-coil design, and dTMS parameters [ie, pulses per session, percentage of motor threshold, etc]) to evaluate whether dTMS differentially influences clinical outcomes based on these factors. METHODS: A comprehensive search of the APA PsycINFO, Embase, MEDLINE, and PubMed databases will be conducted using keywords such as "H-coil" and "dTMS." Two authors (AD and MD) will be responsible for screening relevant articles, assessing article eligibility (according to predetermined inclusion and exclusion criteria), and data extraction. All included articles will undergo a quality and risk of bias assessment. Data from included articles will be summarized qualitatively in a systematic review. If a sufficient number of equivalent studies are available, a meta-analysis will be performed to (1) determine the effect of active versus sham dTMS (or another control arm) across psychiatric and cognitive disorders, and (2) examine subgroup effects of clinical outcomes. RESULTS: The preliminary search rendered a total of 1134 articles from the APA PsycINFO, Embase, and MEDLINE databases. After full-text screening, 21 eligible articles remained. One additional article was identified from the references section of an existing systematic review. In total, 22 eligible articles were included. Data extraction and quality of assessment procedures are ongoing. CONCLUSIONS: We will outline the evidence relating to the clinical efficacy of dTMS in various psychiatric and cognitive disorders. The results of the prospective systematic review will provide clinicians with valuable insight into the clinical (ie, participant age, sex, psychiatric or cognitive disorder, etc) and methodological factors (ie, H-coil design, dTMS parameters, etc) which may contribute to dTMS efficacy, and thereby may assist clinicians in their decision to prescribe dTMS for specific psychiatric and cognitive disorders. TRIAL REGISTRATION: PROSPERO CRD42022360066; https://tinyurl.com/5ev6byrn. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/45213.

The Impact of Recreational Cannabis Legalization on Cannabis Use and Associated Outcomes: A Systematic Review.

Background: Recreational cannabis legalization has become more prevalent over the past decade, increasing the need to understand its impact on downstream health-related outcomes. Although prior reviews have broadly summarized research on cannabis liberalization policies (including decriminalization and medical legalization), directed efforts are needed to synthesize the more recent research that focuses on recreational cannabis legalization specifically. Thus, the current review summarizes existing studies using longitudinal designs to evaluate impacts of recreational cannabis legalization on cannabis use and related outcomes. Method: A comprehensive bibliographic search strategy revealed 61 studies published from 2016 to 2022 that met criteria for inclusion. The studies were predominantly from the United States (66.2%) and primarily utilized self-report data (for cannabis use and attitudes) or administrative data (for health-related, driving, and crime outcomes). Results: Five main categories of outcomes were identified through the review: cannabis and other substance use, attitudes toward cannabis, health-care utilization, driving-related outcomes, and crime-related outcomes. The extant literature revealed mixed findings, including some evidence of negative consequences of legalization (such as increased young adult use, cannabis-related healthcare visits, and impaired driving) and some evidence for minimal impacts (such as little change in adolescent cannabis use rates, substance use rates, and mixed evidence for changes in cannabis-related attitudes). Conclusions: Overall, the existing literature reveals a number of negative consequences of legalization, although the findings are mixed and generally do not suggest large magnitude short-term impacts. The review highlights the need for more systematic investigation, particularly across a greater diversity of geographic regions.

Alcohol cues increase behavioral economic demand and craving for alcohol in nontreatment-seeking and treatment-seeking heavy drinkers.

BACKGROUND: Behavioral economic research has revealed significant increases in alcohol demand following exposure to alcohol-related cues. Prior research has focused exclusively on nontreatment-seeking heavy drinkers, included only male participants, or used heterogeneous methods. The current studies sought to replicate and extend existing findings in treatment-seeking and nontreatment-seeking heavy drinkers while also examining sex effects and moderation by alcohol use disorder (AUD) severity. METHODS: Study 1 included 117 nontreatment-seeking heavy drinkers (51.5% women; M age 34.69; 56.4% AUD+), and Study 2 included 89 treatment-seeking heavy drinkers with AUD (40.4% women; M age = 41.35). In both studies, alcohol demand was measured using a hypothetical alcohol purchase task (APT), and subjective alcohol craving was measured using visual analog scales. Measures were collected following exposure to neutral (water) cues in a standard room and alcohol cues in a bar lab. RESULTS: Alcohol demand (intensity, Omax , breakpoint, and elasticity) and craving were significantly increased following alcohol cues compared to neutral cues (ps < 0.005) with effect sizes ranging from small to large (ηp 2 = 0.074-0.480). Participants with AUD (Study 1) or with higher AUD severity (Study 2) reported higher craving and higher demand for most indices (i.e., main effects; ps < 0.032, ηp 2 = 0.043-0.239). A larger alcohol cue increase in Omax was found for AUD+ participants in Study 1 compared to non-AUD participants (p = 0.028, ηp 2 = 0.041) but not for any other indices in Study 1 or Study 2. There were no significant sex effects. CONCLUSIONS: These findings replicate and extend prior research by offering additional insight into alcohol cue effects on the reinforcing value of alcohol and subjective motivation to drink. The results also suggest that sex and AUD severity do not meaningfully impact cue effects across most indices of demand.

Delay Discounting as a Transdiagnostic Process in Psychiatric Disorders: A Meta-analysis.

Importance: Delay discounting is a behavioral economic index of impulsive preferences for smaller-immediate or larger-delayed rewards that is argued to be a transdiagnostic process across health conditions. Studies suggest some psychiatric disorders are associated with differences in discounting compared with controls, but null findings have also been reported. Objective: To conduct a meta-analysis of the published literature on delay discounting in people with psychiatric disorders. Data Sources: PubMed, MEDLINE, PsycInfo, Embase, and Web of Science databases were searched through December 10, 2018. The psychiatric keywords used were based on DSM-IV or DSM-5 diagnostic categories. Collected data were analyzed from December 10, 2018, through June 1, 2019. Study Selection: Following a preregistered Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) protocol, 2 independent raters reviewed titles, abstracts, and full-text articles. English-language articles comparing monetary delay discounting between participants with psychiatric disorders and controls were included. Data Extraction and Synthesis: Hedges g effect sizes were computed and random-effects models were used for all analyses. Heterogeneity statistics, one-study-removed analyses, and publication bias indices were also examined. Main Outcomes and Measures: Categorical comparisons of delay discounting between a psychiatric group and a control group. Results: The sample included 57 effect sizes from 43 studies across 8 diagnostic categories. Significantly steeper discounting for individuals with a psychiatric disorder compared with controls was observed for major depressive disorder (Hedges g = 0.37; P = .002; k = 7), schizophrenia (Hedges g = 0.46; P = .004; k = 12), borderline personality disorder (Hedges g = 0.60; P < .001; k = 8), bipolar disorder (Hedges g = 0.68; P < .001; k = 4), bulimia nervosa (Hedges g = 0.41; P = .001; k = 4), and binge-eating disorder (Hedges g = 0.34; P = .001; k = 7). In contrast, anorexia nervosa exhibited statistically significantly shallower discounting (Hedges g = -0.30; P < .001; k = 10). Modest evidence of publication bias was indicated by a statistically significant Egger test for schizophrenia and at the aggregate level across studies. Conclusions and Relevance: Results of this study appear to provide empirical support for delay discounting as a transdiagnostic process across most of the psychiatric disorders examined; the literature search also revealed limited studies in some disorders, notably posttraumatic stress disorder, which is a priority area for research.

Identity development in cultural context: The role of deviating from master narratives.

OBJECTIVE: The great majority of research on identity and personality development has focused on individual processes of development, to the relative neglect of the cultural context of development. We employ a recently articulated framework for the examination of identity development in context, centered on the construct of master narratives, or culturally shared stories. METHOD: Across four studies, we asked emerging and midlife adults (N = 512) to narrate personal experiences of deviations from these master narratives. RESULTS: Across three quantitative studies, we show that (a) those who elaborated their deviation experiences were more likely to be in structurally marginalized positions in society (e.g., ethnic or sexual minorities); (b) those who elaborated an empowering alternative to the master narrative were more likely to be engaged in identity processes; and (c) master narratives maintain their rigidity by the frequency of their use. In study 4, using qualitative analyses, we illustrate the rigidity of master narratives, as well as the degree to which they take shape in social and group experiences. CONCLUSIONS: These studies emphasize the importance of cultural context in considering personality and identity development.

Fluorogenic Substrates for In Situ Monitoring of Caspase-3 Activity in Live Cells.

The in situ detection of caspase-3 activity has applications in the imaging and monitoring of multiple pathologies, notably cancer. A series of cell penetrating FRET-based fluorogenic substrates were designed and synthesised for the detection of caspase-3 in live cells. A variety of modifications of the classical caspase-3 and caspase-7 substrate sequence Asp-Glu-Val-Asp were carried out in order to increase caspase-3 affinity and eliminate caspase-7 cross-reactivity. To allow cellular uptake and good solubility, the substrates were conjugated to a cationic peptoid. The most selective fluorogenic substrate 27, FAM-Ahx-Asp-Leu-Pro-Asp-Lys(MR)-Ahx, conjugated to the cell penetrating peptoid at the C-terminus, was able to detect and quantify caspase-3 activity in apoptotic cells without cross-reactivity by caspase-7.