Individuals with problem gambling and obsessive-compulsive disorder learn through distinct reinforcement mechanisms.

Obsessive-compulsive disorder (OCD) and pathological gambling (PG) are accompanied by deficits in behavioural flexibility. In reinforcement learning, this inflexibility can reflect asymmetric learning from outcomes above and below expectations. In alternative frameworks, it reflects perseveration independent of learning. Here, we examine evidence for asymmetric reward-learning in OCD and PG by leveraging model-based functional magnetic resonance imaging (fMRI). Compared with healthy controls (HC), OCD patients exhibited a lower learning rate for worse-than-expected outcomes, which was associated with the attenuated encoding of negative reward prediction errors in the dorsomedial prefrontal cortex and the dorsal striatum. PG patients showed higher and lower learning rates for better- and worse-than-expected outcomes, respectively, accompanied by higher encoding of positive reward prediction errors in the anterior insula than HC. Perseveration did not differ considerably between the patient groups and HC. These findings elucidate the neural computations of reward-learning that are altered in OCD and PG, providing a potential account of behavioural inflexibility in those mental disorders.

IL-33/sST2 signaling pathway in pulmonary thromboembolism: A clinical observational study.

BACKGROUND: Pulmonary thromboembolism (PTE) is a cardiovascular emergency that can result in mortality. In the interleukin-33 (IL-33) /soluble suppression of tumorigenicity 2 (sST2) signaling pathway, increased sST2 is a cardiovascular risk factor. This study aimed to investigate the effectiveness of biomarkers in the IL-33/sST2 signaling pathway in determining PTE diagnosis, clinical severity, and mortality. METHOD: This study was conducted as a single-center, prospective, observational study. Patients admitted to the emergency department and diagnosed with PTE constituted the patient group (n = 112), and healthy volunteers with similar sociodemographic characteristics constituted the control group (n = 62). Biomarkers in the IL-33/sST2 signaling pathway were evaluated for diagnosis, clinical severity, and prognosis. RESULTS: IL-33 was lower in the patient group than in the control group (275.89 versus 403.35 pg/mL), while sST2 levels were higher in the patient group than in the control group (53.16 versus 11.78 ng/mL) (p < 0.001 and p = 0.001; respectively). The AUC of IL-33 to diagnose PTE was 0.656 (95 % CI: 0.580-0.726). The optimal IL-33 cut-off point to diagnose PTE was ≤304.11 pg/mL (56.2 % sensitivity, 79 % specificity). The AUC of sST2 to diagnose PTE was 0.818 (95 % CI: 0.752-0.872). The optimal sST2 cut-off point to diagnose PTE was >14.48 ng/mL (83 % sensitivity, 71 % specificity). IL-33 levels were lower in patients with mortality (169.85 versus 332.04 pg/mL) compared to patients without mortality, whereas sST2 levels were higher in patients with mortality (118.32 versus 28.07 ng/mL) compared to patients without mortality (p > 0.001 for both). The AUC of IL-33 to predict the mortality of PTE was 0.801 (95 % CI: 0.715-0.870). The optimal IL-33 cut-off point to predict the mortality of PTE was ≤212.05 pg/mL (75 % sensitivity, 79.5 % specificity). The AUC of sST2 to predict the mortality of PTE was 0.824 (95 % CI: 0.740-0.889). The optimal sST2 cut-off point to predict the mortality of PTE was >81 ng/mL (95.8 % sensitivity, 78.4 % specificity). CONCLUSION: In the IL-33/ST2 signaling pathway, decreased IL-33 and increased sST2 are valuable biomarkers for diagnosis and prediction of mortality in patients with PTE.

Losses disguised as wins evoke the reward positivity event-related potential in a simulated machine gambling task.

Electronic gambling machines include a suite of design characteristics that may contribute to gambling-related harms and require more careful attention of regulators and policymakers. One strategy that has contributed to these concerns is the presentation of "losses disguised as wins" (LDWs), a type of salient losing outcome in which a gambling payout is less than the amount wagered (i.e., a net loss), but is nonetheless accompanied by the celebratory audio-visual stimuli that typically accompany a genuine win. These events could thereby be mistaken for gains, or otherwise act as a reward signal, reinforcing persistent gambling, despite being a loss. This study aimed to determine whether LDWs evoke a reward positivity component in a task modeled on slot machine gambling. A prominent account of the reward positivity event-related potential suggests that it is evoked during the positive appraisal of task-related feedback, relative to neutral or negative events, or that it is evoked by neural systems that implement the computation of a positive reward prediction error. We recruited 32 individuals from university recruitment pools and asked them to engage in a simple gambling task designed to mimic key features of a slot machine design. The reward positivity was identified using temporospatial principal components analysis. Results indicated a more positive reward positivity following LDWs relative to clear losses, consistent with the theory that LDWs contribute to positive reinforcement of continued gambling, despite being net losses.

The acceptability of lifestyle medicine for the treatment of mental illness: perspectives of people with and without lived experience of mental illness.

OBJECTIVE: While lifestyle medicine can be highly effective for treating a range of mental illnesses these approaches are grossly underutilised and have not been systematically implemented into health care systems. Understanding the acceptability of lifestyle medicine is a critical first step to remediate this. This study evaluated the acceptability of lifestyle medicine relative to pharmacotherapy and psychotherapy, and explore perspectives of people with and without lived experience of mental illness. METHODS: Six hundred and forty-nine adult Australian residents (62.6% female; 53.6% with a lifetime diagnosis of mental illness) completed an online survey based on the Theoretical Framework of Acceptability assessing the acceptability of lifestyle medicine, pharmacotherapy and psychotherapy for treating mental illness. RESULTS: Most participants felt positive about lifestyle medicine (76.9%) and felt that such approaches aligned with their personal values (74.9%). They understood how lifestyle medicine worked (86.4%) and believed it would be effective (69.6%). Lived experience of mental illness was associated with greater perceived burden and lower self-efficacy to engage in lifestyle medicine activities (both p < 0.001). While there was a clear preference for psychotherapy and lifestyle medicine over pharmacotherapy, pharmacotherapy was perceived as least effortful (p < .001) and participants were least confident in their ability to engage in lifestyle medicine (p < 0.05). CONCLUSION: The findings indicate strong acceptability of lifestyle medicine for mental illness, a preference for non-pharmacological treatment approaches, and an understanding of the challenges associated with making long-term healthy lifestyle modifications amongst people who have lived experience of mental illness.

Key influences on university students' physical activity: a systematic review using the Theoretical Domains Framework and the COM-B model of human behaviour.

BACKGROUND: Physical activity is important for all aspects of health, yet most university students are not active enough to reap these benefits. Understanding the factors that influence physical activity in the context of behaviour change theory is valuable to inform the development of effective evidence-based interventions to increase university students' physical activity. The current systematic review a) identified barriers and facilitators to university students' physical activity, b) mapped these factors to the Theoretical Domains Framework (TDF) and COM-B model, and c) ranked the relative importance of TDF domains. METHODS: Data synthesis included qualitative, quantitative, and mixed-methods research published between 01.01.2010-15.03.2023. Four databases (MEDLINE, PsycINFO, SPORTDiscus, and Scopus) were searched to identify publications on the barriers/facilitators to university students' physical activity. Data regarding study design and key findings (i.e., participant quotes, qualitative theme descriptions, and survey results) were extracted. Framework analysis was used to code barriers/facilitators to the TDF and COM-B model. Within each TDF domain, thematic analysis was used to group similar barriers/facilitators into descriptive theme labels. TDF domains were ranked by relative importance based on frequency, elaboration, and evidence of mixed barriers/facilitators. RESULTS: Thirty-nine studies involving 17,771 participants met the inclusion criteria. Fifty-six barriers and facilitators mapping to twelve TDF domains and the COM-B model were identified as relevant to students' physical activity. Three TDF domains, environmental context and resources (e.g., time constraints), social influences (e.g., exercising with others), and goals (e.g., prioritisation of physical activity) were judged to be of greatest relative importance (identified in > 50% of studies). TDF domains of lower relative importance were intentions, reinforcement, emotion, beliefs about consequences, knowledge, physical skills, beliefs about capabilities, cognitive and interpersonal skills, social/professional role and identity, and behavioural regulation. No barriers/facilitators relating to the TDF domains of memory, attention and decision process, or optimism were identified. CONCLUSIONS: The current findings provide a foundation to enhance the development of theory and evidence informed interventions to support university students' engagement in physical activity. Interventions that include a focus on the TDF domains 'environmental context and resources,' 'social influences,' and 'goals,' hold particular promise for promoting active student lifestyles. TRIAL REGISTRATION: Prospero ID-CRD42021242170.

Developing the PEAK mood, mind, and marks program to support university students' mental and cognitive health through physical exercise: a qualitative study using the Behaviour Change Wheel.

BACKGROUND: Concerns about mental and cognitive health are common among university students. Engaging in regular physical exercise has been shown to enhance both mental health and cognitive performance, yet most students are not participating in the level of exercise required to obtain these benefits. The Behaviour Change Wheel (BCW) provides a framework for developing behavioural interventions that are informed by theory, evidence, and stakeholder perspectives. The current study aimed to apply the BCW to develop the PEAK Mood, Mind, and Marks program (i.e., PEAK), a behaviour change intervention designed to increase university students' exercise engagement for the benefit of their mental and cognitive health. METHODS: PEAK was developed across three stages of the BCW: (1) understand the target behaviour, (2) identify intervention options, and (3) identify intervention content and delivery mode. Development was informed by triangulated data from a systematic literature review, co-design consultations with key stakeholders, and knowledge of relevant experts. Consultations with stakeholders involved focus groups with 25 university students and individual interviews with 10 university leaders and staff to identify barriers and facilitators to students' exercise engagement and the adoption and implementation of PEAK by universities. Template analysis was used to code transcripts to the capability, opportunity, and motivation (COM-B) model of behaviour. The BCW was applied to identify the most appropriate intervention types and behaviour change techniques (BCTs). RESULTS: Thirty-one barriers and facilitators were identified and mapped to seven intervention types (Education; Modelling; Persuasion; Environmental Restructuring; Incentivisation; Training; and Enablement) and 26 BCTs, which were delivered across digital channels and in-person. The final intervention consisted of multiple components targeting students' capability (e.g., increasing knowledge about the mental and cognitive health benefits of exercise), opportunity (e.g., providing a flexible range of accessible exercise options and social support), and motivation (e.g., increasing the perceived importance of exercise) to exercise. CONCLUSIONS: University students and staff describe a need and appetite for more empowering, scalable solutions to support students' mental and cognitive health. Exercise-based approaches that are informed by behaviour change frameworks, evidence, and stakeholder perspectives, such as PEAK, have the potential to address this need. Current findings will inform a pilot of PEAK to evaluate its efficacy and implementation.

Three Contrasting Accounts of Electronic Gambling Machine Related Harm: Impacts on Community Views Towards Gambling Policy and Responsibility.

This study investigated whether there was community support for prominent gambling harm reduction policies, as well as perceived responsibility for electronic gambling machine (EGM) related harm in an Australian sample (n = 906). Using a randomised experimental design, we also explored whether these outcomes were influenced by three alternative explanations for EGM-related harm: a brain-based account of gambling addiction, an account that highlighted the intentional design of the gambling environment focused on the "losses disguised as wins" (LDWs), and a media release advocating against further government intervention in the gambling sector. We observed clear majority support for most policies presented, including mandatory pre-commitment, self-exclusion, and a $1 limit on EGM bets. A substantial majority of participants agreed that individuals, governments, and industry should be held responsible for EGM-related harm. Participants presented with the explanation of LDWs attributed greater responsibility for gambling-related harm to industry and government, less agreement that electronic gambling machines are fair, and more agreement that EGMs are likely to mislead or deceive consumers. There was some limited evidence of greater support for policy intervention in this group, including a blanket ban of EGMs, clinical treatment funded by gambling taxes, mass media campaigns, and mandatory pre-commitment for EGMs. We found no evidence that a brain-based account of gambling addiction substantially undermined support for policy intervention. We predicted that the information about LDWs and the brain-based account of EGM related harm would soften attributions of personal responsibility for gambling harm. Our results did not support either of these predictions.

A Rare Cause of Coagulopathy in the Emergency Department: Cefoperazone Use.

Cefoperazone (CPZ) is an antibiotic widely used for moderate to severe infections, especially in countries where resources are difficult to access. This case report aimed to draw attention to coagulopathy, a potential side effect of CPZ. This side effect can cause high mortality and morbidity in patients. In the mechanism of CPZ causing coagulopathy, it is reported that effects such as binding to vitamin K, disrupting vitamin K metabolism, and preventing platelet aggregation are responsible. In this presentation, a case who came to the emergency department with the complaint of hematuria caused by coagulopathy after the use of CPZ-containing antibiotics (CPZ + sulbactam) is presented.

Brain volumes in alcohol use disorder: Do females and males differ? A whole-brain magnetic resonance imaging mega-analysis.

Emerging evidence suggests distinct neurobiological correlates of alcohol use disorder (AUD) between sexes, which however remain largely unexplored. This work from ENIGMA Addiction Working Group aimed to characterize the sex differences in gray matter (GM) and white matter (WM) correlates of AUD using a whole-brain, voxel-based, multi-tissue mega-analytic approach, thereby extending our recent surface-based region of interest findings on a nearly matching sample using a complementary methodological approach. T1-weighted magnetic resonance imaging (MRI) data from 653 people with AUD and 326 controls was analyzed using voxel-based morphometry. The effects of group, sex, group-by-sex, and substance use severity in AUD on brain volumes were assessed using General Linear Models. Individuals with AUD relative to controls had lower GM volume in striatal, thalamic, cerebellar, and widespread cortical clusters. Group-by-sex effects were found in cerebellar GM and WM volumes, which were more affected by AUD in females than males. Smaller group-by-sex effects were also found in frontotemporal WM tracts, which were more affected in AUD females, and in temporo-occipital and midcingulate GM volumes, which were more affected in AUD males. AUD females but not males showed a negative association between monthly drinks and precentral GM volume. Our results suggest that AUD is associated with both shared and distinct widespread effects on GM and WM volumes in females and males. This evidence advances our previous region of interest knowledge, supporting the usefulness of adopting an exploratory perspective and the need to include sex as a relevant moderator variable in AUD.

Using event-related potentials to characterize inhibitory control and self-monitoring across impulsive and compulsive phenotypes: a dimensional approach to OCD.

OBJECTIVE: "Subsyndromal" obsessive-compulsive disorder symptoms (OCDSs) are common and cause impaired psychosocial functioning. OCDSs are better captured by dimensional models of psychopathology, as opposed to categorical diagnoses. However, such dimensional approaches require a deep understanding of the underlying neurocognitive drivers and impulsive and compulsive traits (ie, neurocognitive phenotypes) across symptoms. This study investigated inhibitory control and self-monitoring across impulsivity, compulsivity, and their interaction in individuals (n = 40) experiencing mild-moderate OCDSs. METHODS: EEG recording concurrent with the stop-signal task was used to elicit event-related potentials (ERPs) indexing inhibitory control (ie, N2 and P3) and self-monitoring (ie, error-related negativity and correct-related negativity (CRN): negativity following erroneous or correct responses, respectively). RESULTS: During unsuccessful stopping, individuals high in both impulsivity and compulsivity displayed enhanced N2 amplitude, indicative of conflict between the urge to respond and need to stop (F(3, 33) = 1.48, P < .05, 95% Cl [-0.01, 0.001]). Individuals high in compulsivity and low in impulsivity showed reduced P3 amplitude, consistent with impairments in monitoring failed inhibitory control (F(3, 24) = 2.033, P < .05, 95% CI [-0.002, 0.045]). Following successful stopping, high compulsivity (independent of impulsivity) was associated with lower CRN amplitude, reflecting hypo-monitoring of correct responses (F(4, 32) = 4.76, P < .05, 95% CI [0.01, 0.02]), and with greater OCDS severity (F(3, 36) = 3.32, P < .05, 95% CI [0.03, 0.19]). CONCLUSION: The current findings provide evidence for differential, ERP-indexed inhibitory control and self-monitoring profiles across impulsive and compulsive phenotypes in OCDSs.

Conceptualising compulsivity through network analysis: A two-sample study.

Compulsivity is a transdiagnostic construct crucial to understanding multiple psychiatric conditions and problematic repetitive behaviours. Despite being identified as a clinical- and research-relevant construct, there are limited insights into the internal conceptual structure of compulsivity. To provide a more nuanced understanding of compulsivity, the current study estimated the structure of compulsivity (indexed using the previously validated Cambridge-Chicago Compulsivity Trait Scale, CHI-T) among two large-scale and geographically distinct samples using the network estimation method. The samples consisted of a United Kingdom cohort (n = 122,346, 51.4% female, Mean age = 43.7, SD = 16.5, range = 9-86 years) and a South Africa cohort (n = 2674, 65.6% female, Mean age = 24.6, SD = 8.6, range = 18-65 years). Network community analysis demonstrated that compulsivity was constituted of three interrelated dimensions, namely: perfectionism, cognitive rigidity and reward drive. Further, 'Completion leads to soothing' and 'Difficulty moving from task to task' were identified as core (central nodes) to compulsivity. The dimensional structure and central nodes of compulsivity networks were consistent across the two samples. These findings facilitate the conceptualisation and measurement of compulsivity and may contribute to the early detection and treatment of compulsivity-related disorders.

Internet severity and activities addiction questionnaire (ISAAQ): Psychometrics of item response theory and clustering of online activities.

BACKGROUND: Problematic usage of the internet (PUI) is an umbrella term, referring to a variety of maladaptive online behaviors linked to functional impairment. There is ongoing need for the development of instruments capturing not only PUI severity, but also the online activity types. The Internet Severity and Activities Questionnaire (ISAAQ), previously developed to address this need, required further refinement and validation. METHODS: Cross-sectional data was gathered in two separate samples (South Africa n = 3275, USA-UK n = 943) using the Internet Severity and Activities Addiction Questionnaire (ISAAQ). Item Response Theory (IRT) was used to examine the properties of the scale (Part A of the ISAAQ) and differential item functioning against demographic parameters. The severity scale of the ISAAQ was optimized by eliminating the poorest performing items using an iterative approach and examining validity metrics. Cluster analyses was used to examine internet activities and commonalities across samples (Part B of the ISAAQ). RESULTS: Optimization of ISAAQ using IRT yielded a refined 10-item version (ISAAQ-10), with less differential item functioning and a robust unidimensional factor structure. The ISAAQ-10 severity score correlated strongly with established measures of internet addiction (Compulsive Internet Use Scale [Person's r = 0.86] and the Internet Addiction Test-10 [r = 0.75]). Combined with gaming activity score it correlated moderately strongly with the established Internet Gaming Disorder Test (r = 0.65). Exploratory cluster analyses in both samples identified two groups, one of "low-PUI" [98.1-98.5%], and one of "high-PUI" [1.5-1.9%]. Multiple facets of internet activity appeared elevated in the high-PUI cluster. DISCUSSION: The ISAAQ-10 supersedes the earlier longer version of the ISAAQ, and provides a useful, psychometrically robust measure of PUI severity (Part A), and captures the extent of engagement in a wide gamut of online specific internet activities (Part B). ISAAQ-10 constitutes a valuable objective measurement tool for future studies.

Can lactate levels and lactate kinetics predict mortality in patients with COVID-19 with using qCSI scoring system?

INTRODUCTION: In this study, we aimed to investigate the relationship between blood lactate levels and lactate kinetics (lactate clearance and Δ lactate) for predicting mortality in patients with COVID-19 admitted to the emergency department. METHODS: This study was performed as a retrospective study that included patients admitted to the emergency department between March 1st, 2020, and January 1st, 2022. Lactate levels were recorded at the first admission (0 h lactate) and the highest blood lactate levels in the first 24 h of follow-up (2nd highest lactate). Lactate kinetics were calculated. Clinical severity was determined according to the quick COVID Severity Index (qCSI). RESULTS: 300 patients were included in the study. Lactate levels at admission were similar in groups with or without mortality, but 2nd highest lactate levels were found to be significantly higher in the group with mortality (p < 0.001). Lactate clearance and ∆ lactate levels were also found to be lower in the mortality group (p < 0.001). Lactate kinetics in patients in the clinically low severity group were lower in the mortality group (p = 0.02 and p = 0.039, respectively). In the low-intermediate and high-intermediate groups, 0-h lactate and 2nd highest lactate levels were found to be higher in the mortality group, and lactate kinetics were similar in the groups with and without mortality. In the group with high clinical severity, 2nd highest lactate levels were found to be higher in the group with mortality (p = 0.010). Lactate kinetics were also found to be significantly lower in the mortality group (p < 0.001). In the high qCSI group, based on ROC analysis, the AUC for 2nd highest lactate levels predicting mortality was 0.642 (95% CI: 0.548-0.728). The optimal cut-off value for mortality was greater than >2.4 mmol/L (60.6% sensitivity, 67.4% specificity). The AUC for lactate clearance was 0.748 (95% CI: 0.659-0.824). The lactate clearance cut-off value was ≤ -177.78% (49.3% sensitivity, 100% specificity). The AUC for ∆ lactate was 0.707 (95% CI: 0.616-0.787). The optimal ∆ lactate cut-off was ≤ -2 mmol/L (45.1% sensitivity, 93.5% specificity). CONCLUSION: In COVID-19, 2nd highest blood lactate and lactate kinetics were found to be prognostic indicators of the disease. High 2nd highest lactate levels and low lactate kinetics in patients with high clinical severity were guiding physicians regarding the outcome of the disease.

Lifestyle risk factors for obsessive-compulsive symptoms and related phenomena: What should lifestyle interventions target?

OBJECTIVE: Understanding the impact of lifestyle on mental illness symptoms is important for informing psycho-education and developing interventions which target mental and physical comorbidities. Obsessive-compulsive and related disorders can have a significant impact on health-related quality of life and physical health. However, our understanding of the impact of lifestyle on obsessive-compulsive symptoms and broader compulsive and impulsive problematic repetitive behaviours is limited. AIMS: We investigated whether lifestyle factors predicted change in obsessive-compulsive symptoms and problematic repetitive behaviours in a general population sample over a 3-month period. METHODS: Eight hundred thirty-five participants completed an online questionnaire battery assessing lifestyle and mental health. Of these, 538 participants completed the same battery 3 months later. We conducted negative binomial regressions to analyse the association of lifestyle factors at baseline with future (1) obsessive-compulsive symptoms, (2) compulsive problematic repetitive behaviours and (3) impulsive problematic repetitive behaviours, adjusting for baseline obsessive-compulsive symptoms and problematic repetitive behaviours. RESULTS: Lower vegetable (p = 0.020) and oily fish (p = 0.040) intake and lower moderate intensity physical activity (p = 0.008) predicted higher obsessive-compulsive symptoms at follow-up. Higher intake of high-fat foods (p < 0.001) predicted higher compulsive problematic repetitive behaviours at follow-up. No lifestyle factors significantly predicted impulsive problematic repetitive behaviours at follow-up. CONCLUSION: Our results speak to the potential importance of lifestyle quality screening, education and lifestyle interventions (e.g. an anti-inflammatory diet) for individuals experiencing compulsivity-related behaviours and/or symptoms. Further research into potential mechanisms of action will allow for more targeted approaches to lifestyle interventions for transdiagnostic compulsive behaviours.

The effect of phone and video counselling given to participants living with obesity on weight loss and quality of life during the COVID-19 pandemic: a randomised controlled trial.

BACKGROUND: Although remote dietary counselling practices have increased in the COVID-19 pandemic, it is not known which method is more effective. This study aimed to determine the effect of diet counselling by phone or video on weight loss and to compare it with the traditional follow-up method. METHODS: Forty-six participants living with obesity were randomised into the phone counselling (n = 15), video counselling (n = 15), and traditional follow-up groups (n = 16), and were followed for 10 weeks. The anthropometric measurements, quality-of-life questionnaire (SF-36) scores and total calorie/macronutrient intakes were recorded and compared at baseline and at the end of the study. RESULTS: In the phone counselling, video counselling and traditional follow-up groups body weight (-4.8 ± 0.9, -5.7 ± 1.8 and -3.3 ± 0.8 kg, respectively) and SF-36 general health scores (14.2 ± 4.2, 15.9 ± 3.6 and 10.2 ± 3.7, respectively) of the participants changed significantly compared to baseline (group × time interaction, p < 0.05). The change in the body weight and SF-36 general health score was more in the phone counselling and video counselling groups relative to the traditional follow-up group (group × time interaction, p < 0.01). The highest decrease in total calorie (-301.4 ± 112.2 kcal) and carbohydrate (-26.6 ± 11.2 g) intake was in the video counselling group compared to the other groups (group × time interaction, p < 0.01). CONCLUSION: Video counselling and phone counselling were effective in weight loss in the COVID-19 pandemic. It is important to maintain remote dietary counselling practices to support weight management when face-to-face meetings are not possible.

A Novel, Expert-Endorsed, Neurocognitive Digital Assessment Tool for Addictive Disorders: Development and Validation Study.

BACKGROUND: Many people with harmful addictive behaviors may not meet formal diagnostic thresholds for a disorder. A dimensional approach, by contrast, including clinical and community samples, is potentially key to early detection, prevention, and intervention. Importantly, while neurocognitive dysfunction underpins addictive behaviors, established assessment tools for neurocognitive assessment are lengthy and unengaging, difficult to administer at scale, and not suited to clinical or community needs. The BrainPark Assessment of Cognition (BrainPAC) Project sought to develop and validate an engaging and user-friendly digital assessment tool purpose-built to comprehensively assess the main consensus-driven constructs underpinning addictive behaviors. OBJECTIVE: The purpose of this study was to psychometrically validate a gamified battery of consensus-based neurocognitive tasks against standard laboratory paradigms, ascertain test-retest reliability, and determine their sensitivity to addictive behaviors (eg, alcohol use) and other risk factors (eg, trait impulsivity). METHODS: Gold standard laboratory paradigms were selected to measure key neurocognitive constructs (Balloon Analogue Risk Task [BART], Stop Signal Task [SST], Delay Discounting Task [DDT], Value-Modulated Attentional Capture [VMAC] Task, and Sequential Decision-Making Task [SDT]), as endorsed by an international panel of addiction experts; namely, response selection and inhibition, reward valuation, action selection, reward learning, expectancy and reward prediction error, habit, and compulsivity. Working with game developers, BrainPAC tasks were developed and validated in 3 successive cohorts (total N=600) and a separate test-retest cohort (N=50) via Mechanical Turk using a cross-sectional design. RESULTS: BrainPAC tasks were significantly correlated with the original laboratory paradigms on most metrics (r=0.18-0.63, P<.05). With the exception of the DDT k function and VMAC total points, all other task metrics across the 5 tasks did not differ between the gamified and nongamified versions (P>.05). Out of 5 tasks, 4 demonstrated adequate to excellent test-retest reliability (intraclass correlation coefficient 0.72-0.91, P<.001; except SDT). Gamified metrics were significantly associated with addictive behaviors on behavioral inventories, though largely independent of trait-based scales known to predict addiction risk. CONCLUSIONS: A purpose-built battery of digitally gamified tasks is sufficiently valid for the scalable assessment of key neurocognitive processes underpinning addictive behaviors. This validation provides evidence that a novel approach, purported to enhance task engagement, in the assessment of addiction-related neurocognition is feasible and empirically defensible. These findings have significant implications for risk detection and the successful deployment of next-generation assessment tools for substance use or misuse and other mental disorders characterized by neurocognitive anomalies related to motivation and self-regulation. Future development and validation of the BrainPAC tool should consider further enhancing convergence with established measures as well as collecting population-representative data to use clinically as normative comparisons.

Using the Theoretical Domains Framework to Inform the Implementation of Therapeutic Virtual Reality into Mental Healthcare.

Evidence supporting the efficacy of therapeutic virtual reality (VR) for mental health conditions is rapidly growing. However, little is known about how best to implement VR, or the challenges perceived by treatment providers. This study aimed to (1) synthesis perspectives of staff working in private mental healthcare and (2) use the Theoretical Domains Framework (TDF) and Behaviour Change Wheel (BCW) to identify mechanisms of change targets and intervention functions to facilitate its clinical implementation. Semi-structured interviews were conducted with clinicians (n = 14) and service managers (n = 5) working in a major private mental health hospital in Victoria, Australia. Transcripts were coded using framework analysis to identify relevant TDF domains. Specific belief statements were generated and coded as a barrier and/or facilitator and thematically organised within domains. Domains were ranked for importance based on frequency, elaboration, and evidence of conflicting beliefs. Using the BCW, domains were mapped to their respective COM-B components and indicated intervention functions. A total of 11 TDF domains were identified as relevant to early-stage implementation of therapeutic VR. Three domains were judged as highly important (beliefs about consequences; environmental context and resources; knowledge), while seven domains were judged as moderately important (social/professional role and identity; emotions; skills; memory, attention, and decision processes; intentions; beliefs about capabilities; social influences). Based on current data, we propose a theory-informed roadmap to promote VR uptake in mental healthcare services. A priority for intervention development should be addressing knowledge gaps and attitudinal barriers (e.g., safety concerns) with education and training.

Regular aerobic exercise is positively associated with hippocampal structure and function in young and middle-aged adults.

Regular exercise has numerous benefits for brain health, including the structure and function of the hippocampus. The hippocampus plays a critical role in memory function, and is altered in a number of psychiatric disorders associated with memory impairments (e.g., depression and schizophrenia), as well as healthy aging. While many studies have focused on how regular exercise may improve hippocampal integrity in older individuals, less is known about these effects in young to middle-aged adults. Therefore, we assessed the associations of regular exercise and cardiorespiratory fitness with hippocampal structure and function in these age groups. We recruited 40 healthy young to middle-aged adults, comprised of two groups (n = 20) who self-reported either high or low levels of exercise, according to World Health Organization guidelines. We assessed cardiorespiratory fitness using a graded exercise test (VO2 max) and hippocampal structure via manual tracing of T1-weighted magnetic resonance images. We also assessed hippocampal function using magnetic resonance spectroscopy to derive estimates of N-acetyl-aspartate concentration and hippocampal-dependent associative memory and pattern separation tasks. We observed evidence of increased N-acetyl-aspartate concentration and associative memory performance in individuals engaging in high levels of exercise. However, no differences in hippocampal volume or pattern separation capacity were observed between groups. Cardiorespiratory fitness was positively associated with left and right hippocampal volume and N-acetyl-aspartate concentration. However, no associations were observed between cardiorespiratory fitness and associative memory or pattern separation. Therefore, we provide evidence that higher levels of exercise and cardiorespiratory fitness are associated with improved hippocampal structure and function. Exercise may provide a low-risk, effective method of improving hippocampal integrity in an early-to-mid-life stage.

How do substance use disorders compare to other psychiatric conditions on structural brain abnormalities? A cross-disorder meta-analytic comparison using the ENIGMA consortium findings.

Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with brain alterations particularly involving fronto-cerebellar and meso-cortico-limbic circuitry. However, such abnormalities have additionally been reported in other psychiatric conditions, and until recently there has been few large-scale investigations to compare such findings. The current study uses the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) consortium method of standardising structural brain measures to quantify case-control differences and to compare brain-correlates of substance use disorders with those published in relation to other psychiatric disorders. Using the ENIGMA protocols, we report effect sizes derived from a meta-analysis of alcohol (seven studies, N = 798, 54% are cases) and cannabis (seven studies, N = 447, 45% are cases) dependent cases and age- and sex-matched controls. We conduct linear analyses using harmonised methods to process and parcellate brain data identical to those reported in the literature for ENIGMA case-control studies of major depression disorder (MDD), schizophrenia (SCZ) and bipolar disorder so that effect sizes are optimally comparable across disorders. R elationships between substance use disorder diagnosis and subcortical grey matter volumes and cortical thickness were assessed with intracranial volume, age and sex as co-variates . After correcting for multiple comparisons, AUD case-control meta-analysis of subcortical regions indicated significant differences in the thalamus, hippocampus, amygdala and accumbens, with effect sizes (0.23) generally equivalent to, or larger than |0.23| those previously reported for other psychiatric disorders (except for the pallidum and putamen). On measures of cortical thickness, AUD was associated with significant differences bilaterally in the fusiform gyrus, inferior temporal gyrus, temporal pole, superior frontal gyrus, and rostral and caudal anterior cingulate gyri. Meta-analysis of CUD case-control studies indicated reliable reductions in amygdala, accumbens and hippocampus volumes, with the former effect size comparable to, and the latter effect size around half of that reported for alcohol and SCZ. CUD was associated with lower cortical thickness in the frontal regions, particularly the medial orbitofrontal region, but this effect was not significant after correcting for multiple testing. This study allowed for an unbiased cross-disorder comparison of brain correlates of substance use disorders and showed alcohol-related brain anomalies equivalent in effect size to that found in SCZ in several subcortical and cortical regions and significantly greater alterations than those found in MDD in several subcortical and cortical regions. Although modest, CUD results overlapped with findings reported for AUD and other psychiatric conditions, but appear to be most robustly related to reduce thickness of the medial orbitofrontal cortex.

Predicting alcohol dependence from multi-site brain structural measures.

To identify neuroimaging biomarkers of alcohol dependence (AD) from structural magnetic resonance imaging, it may be useful to develop classification models that are explicitly generalizable to unseen sites and populations. This problem was explored in a mega-analysis of previously published datasets from 2,034 AD and comparison participants spanning 27 sites curated by the ENIGMA Addiction Working Group. Data were grouped into a training set used for internal validation including 1,652 participants (692 AD, 24 sites), and a test set used for external validation with 382 participants (146 AD, 3 sites). An exploratory data analysis was first conducted, followed by an evolutionary search based feature selection to site generalizable and high performing subsets of brain measurements. Exploratory data analysis revealed that inclusion of case- and control-only sites led to the inadvertent learning of site-effects. Cross validation methods that do not properly account for site can drastically overestimate results. Evolutionary-based feature selection leveraging leave-one-site-out cross-validation, to combat unintentional learning, identified cortical thickness in the left superior frontal gyrus and right lateral orbitofrontal cortex, cortical surface area in the right transverse temporal gyrus, and left putamen volume as final features. Ridge regression restricted to these features yielded a test-set area under the receiver operating characteristic curve of 0.768. These findings evaluate strategies for handling multi-site data with varied underlying class distributions and identify potential biomarkers for individuals with current AD.