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Background: Patient interest in the use of cannabis-based medicines (CBMs) has increased in Australia. While recent policy and legislative changes have enabled health practitioners to prescribe CBMs for their patients, many patients still struggle to access CBMs. This paper employed a thematic analysis to submissions made to a 2019 Australian government inquiry into current barriers of patient access to medical cannabis. Methods: We identified 121 submissions from patients or family members (n = 63), government bodies (n = 5), non-government organisations (i.e., professional health bodies, charities, consumer organisations or advocacy groups; n = 25), medical cannabis and pharmaceutical industry (n = 16), and individual health professionals, academics, or research centres (n = 12). Data were coded using NVivo 12 software and thematically analysed. The findings were presented narratively using a modified Levesque's patient-centred access to care framework which includes: i) appropriateness; ii) availability and geographic accessibility; iii) acceptability; and iv) affordability. Results: Submissions from government agencies and professional health bodies consistently supported maintaining the current regulatory frameworks and access pathways, whereas an overwhelming majority of patients, advocacy groups and the medical cannabis industry described the current regulatory and access models as 'not fit for purpose'. These differing views seem to arise from divergent persepctives on (i) what and how much evidence is needed for policy and practice, and (ii) how patients should be given access to medical cannabis products amidst empirical uncertainty. Notwithstanding these differences, there were commonalities among some stakeholders regarding the various supply, regulatory, legislative, financial, and dispensing challenges that hindered timely access to CBMs. Conclusions: Progress in addressing the fundamental barriers that determine if and how a patient accesses and uses CBMs needs i) a 'system-level' reform that gives due consideration to the geographic disparity in access to prescribers and medical cannabis, and ii) reframing societal and health professional's views of CBMs by decoupling recreational vs medical cannabis. [ABSTRACT FROM AUTHOR]

Rationale: Mismatch negativity (MMN) is a candidate endophenotype for schizophrenia subserved by N-methyl-D-aspartate receptor (NMDAR) function and there is increasing evidence that prolonged cannabis use adversely affects MMN generation. Few human studies have investigated the acute effects of cannabinoids on brain-based biomarkers of NMDAR function and synaptic plasticity. Objectives: The current study investigated the acute effects of Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone and in combination on the mismatch negativity (MMN). Methods: In a randomised, double-blind, crossover placebo-controlled study, 18 frequent and 18 less-frequent cannabis users underwent 5 randomised drug sessions administered via vaporiser: (1) placebo; (2) THC 8 mg; (3) CBD 400 mg; (4) THC 8 mg + CBD 4 mg [THC + CBDlow]; (5) THC 12 mg + CBD 400 mg [THC + CBDhigh]. Participants completed a multifeature MMN auditory oddball paradigm with duration, frequency and intensity deviants (6% each). Results: Relative to placebo, both THC and CBD were observed to increase duration and intensity MMN amplitude in less-frequent users, and THC also increased frequency MMN in this group. The addition of low-dose CBD added to THC attenuated the effect of THC on duration and intensity MMN amplitude in less-frequent users. The same pattern of effects was observed following high-dose CBD added to THC on duration and frequency MMN in frequent users. Conclusions: The pattern of effects following CBD combined with THC on MMN may be subserved by different underlying neurobiological interactions within the endocannabinoid system that vary as a function of prior cannabis exposure. These results highlight the complex interplay between the acute effects of exogenous cannabinoids and NMDAR function. Further research is needed to determine how this process normalises after the acute effects dissipate and following repeated acute exposure. [ABSTRACT FROM AUTHOR]

Background: Limited studies of multiple sclerosis (MS) exist whereby magnetic resonance imaging (MRI) of the brain with consistent imaging protocols occurs at the same time points as collection of healthy lifestyle measures. The aim of this study was to test the feasibility, acceptability and preliminary efficacy of acquiring MRI data as an objective, diagnostic and prognostic marker of MS, at the same time point as brain-healthy lifestyle measures including diet. Methods: Participants living with relapsing remitting MS partook in one structural MRI scanning session of the brain, completed two online 24-hour dietary recalls and demographic and self-reported lifestyle questionnaires (e.g. self-reported disability, comorbidities, physical activity, smoking status, body mass index (BMI), stress). Measures of central tenancy and level of dispersion were calculated for feasibility and acceptability of the research protocols. Lesion count was determined by one radiologist and volumetric analyses by a data analysis pipeline based on FreeSurfer software suite. Correlations between white matter lesion count, whole brain volume analyses and lifestyle measures were assessed using Spearman's rank-order correlation coefficient. Results: Thirteen female participants were included in the study: eligibility rate 90.6% (29/32), recruitment rate 46.9% (15/32) and compliance rate 87% (13/15). The mean time to complete all required tasks, including MRI acquisition was 115.86 minutes ( ± 23.04), over 4 days. Conversion to usual dietary intake was limited by the small sample. There was one strong, negative correlation between BMI and brain volume (rs = −0.643, p = 0.018) and one strong, positive correlation between physical activity and brain volume (rs = 0.670, p = 0.012) that were both statistically significant. Conclusions: Acquiring MRI brain scans at the same time point as lifestyle profiles in adults with MS is both feasible and accepted among adult females living with MS. Quantification of volumetric MRI data support further investigations using semi-automated pipelines among people living with MS, with pre-processing steps identified to increase automated feasibility. This protocol may be used to determine relationships between elements of a brain-healthy lifestyle, including dietary intake, and measures of disease burden and brain health, as assessed by T1-weighted and T2-weighted lesion count and whole brain volume, in an adequately powered sample. Trial registration: The study protocol was retrospectively registered in the Australia New Zealand Clinical Trials Registry (ACTRN12624000296538). [ABSTRACT FROM AUTHOR]

Depression is associated with an increased risk of cardiometabolic disease linked to weight gain driven by complex interactions between multiple risk factors, including overeating behaviours. However, risk factors that mediate the relationship between depressive symptoms and weight gain remain to be fully elucidated. This study examined food addiction symptoms as a potential mediator on the relationship between depressive symptom severity and adiposity as measured by body mass index (BMI), and evaluated whether this relationship was contingent on appetite symptom profile and sex. In a sample of 628 adults, depressive symptom severity was assessed using the Centre for Epidemiological Studies Depression Scale (CES-D), and food addiction symptoms were measured using the Yale Food Addiction Scale (YFAS, version 2). Participant demographics, including BMI, appetite presentations and sex, were assessed using self-report questions. Mediation and moderated mediation analyses were performed to determine relationships between variables. The prevalence of depressogenic food addiction in the present sample was 21.7%. After accounting for age and averaged amount of exercise, food addiction symptoms fully mediated the relationship between depressive symptom severity and BMI. Appetite symptom profile was a significant moderator of this relationship, with effects more pronounced in those with increased appetite compared to decreased or unchanged appetite. While sex was not a significant moderator, being male or female was associated with higher food addiction scores. This study supports food addiction symptoms as an important behavioural risk factor for increased adiposity linked to greater depressive symptom severity, particularly in those experiencing increased appetite during a depressive episode. Assessment and monitoring of food addiction symptoms may have utility in reducing the risk of increased BMI and adverse health outcomes in those experiencing more severe depressive symptoms. [ABSTRACT FROM AUTHOR]

During slot machine gambling, near-miss outcomes occur when the final winning icon lands one position off the pay-line. To understand how near-misses promote gambling behaviour in healthy populations, autonomic arousal is often used to index outcome response valence. Findings remain equivocal, possibly owing to the limited ecological validity of computer simulations. Relevant psychological traits, such as impulsivity, which increase the risk of problem gambling, are often not examined. Here, we used immersive virtual reality (VR) to investigate near-miss-induced changes in physiological arousal and VR gambling behaviour. Sixty adult participants with no history of problem gambling were immersed in a VR casino-bar where they engaged with a self-selected slot machine. Real-time heart rate (HR) data were acquired during immersion. Within-subjects analyses were conducted on HR and post-reinforcement pauses (PRPs; i.e., time taken to initiate next-spin) across wins, losses and near-misses. Significant HR acceleration occurred for both near-misses and losses compared to wins, indexing an initial orientation response. Both types of losses were associated with faster next-spin responses. Near-misses did not apparently have unique HR or PRP profiles from losses, although this may reflect our loss control condition, which in itself may have been a subtler near-miss outcome. Impulsivity measured by the SUPPS-P was not associated with near-miss responses. Losses may encourage gambling as participants experience more immediate HR acceleration (indexing arousal unique to losing) and initiate faster responses. Future studies should clarify this effect by investigating problem gambling cohorts and develop VR paradigms taking into consideration the current findings and limitations. [ABSTRACT FROM AUTHOR]

Aims: We assessed the mental health effects of Australia's 2019–2020 bushfires 12–18 months later, predicting psychological distress and positive psychological outcomes from bushfire exposure and a range of demographic variables, and seeking insights to enhance disaster preparedness and resilience planning for different profiles of people. Methods: We surveyed 3083 bushfire-affected and non-affected Australian residents about their experiences of bushfire, COVID-19, psychological distress (depression, anxiety, stress, post-traumatic stress disorder) and positive psychological outcomes (resilient coping, wellbeing). Results: We found high rates of distress across all participants, exacerbated by severity of bushfire exposure. For people who were bushfire-affected, being older, having less financial stress, and having no or fewer pre-existing mental disorders predicted both lower distress and higher positive outcomes. Being male or having less income loss also predicted positive outcomes. Severity of exposure, higher education and higher COVID-19-related stressors predicted both higher distress and higher positive outcomes. Pre-existing physical health diagnosis and previous bushfire experience did not significantly predict distress or positive outcomes. Recommendations: To promote disaster resilience, we recommend investment in mental health, particularly for younger adults and for those in rural and remote areas. We also recommend investment in mechanisms to protect against financial distress and the development of a broader definition of bushfire-related impacts than is currently used to capture brushfires' far-reaching effects. [ABSTRACT FROM AUTHOR]

The N1, Tb, and P2 components of the event‐related potential (ERP) are thought to reflect the sequential processing of auditory stimuli in the human brain. Despite their extensive use in biological, cognitive, and clinical neuroscience, there are no guidelines for how to appropriately power ERP studies using these components. In the present study, we investigated how the number of trials, number of participants, effect magnitude, and study design influenced statistical power. Using Monte Carlo simulations of ERP data from a passive listening task, we determined the probability of finding a statistically significant effect in 58,900 experiments repeated 1,000 times each. We found that as the number of trials, number of participants, and effect magnitude increased, so did statistical power. We also found that increasing the number of trials had a bigger effect on statistical power for within‐subject designs than for between‐subject designs, and that within‐subject designs required a smaller number of trials and participants to provide the same level of statistical power for a given effect magnitude than between‐subject designs. These results show that it is important to carefully consider these factors when designing ERP studies, rather than relying on tradition or anecdotal evidence. To improve the robustness and reproducibility of ERP research, we have built an online statistical power calculator (https://bradleynjack.shinyapps.io/ErpPowerCalculator), which we hope will allow researchers to estimate the statistical power of previous studies, as well as help them design appropriately‐powered studies in the future. Using Monte Carlo simulations of ERP data from a passive listening task, we found that the number of trials, number of participants, effect magnitude, and study design interacted to influence statistical power for the N1, Tb, and P2 components. We hope that these results will improve the robustness and reproducibility of ERP research. [ABSTRACT FROM AUTHOR]

Glycine increases N-methyl-d-aspartate receptor (NMDAR) mediated glutamatergic function. Mismatch negativity (MMN) is a proposed biomarker of glutamate-induced improvements in clinical symptoms, however, the effect of glycine-mediated NMDAR activation on MMN in schizophrenia is not well understood. This study aimed to determine the effects of acute and 6-week chronic glycine administration on MMN in schizophrenia patients. MMN amplitude was compared at baseline between 22 patients (schizophrenia or schizoaffective disorder; receiving stable antipsychotic medication; multi-centre recruitment) and 21 age- and gender-matched controls. Patients underwent a randomised, double-blind, placebo-controlled clinical trial with glycine added to their regular antipsychotic medication (placebo, n=10; glycine, n=12). MMN was reassessed post-45-minutes of first dose (0.2g/kg) and post-6-weeks treatment (incremented to 0.6g/kg/day). Clinical symptoms were assessed at baseline and post-6-weeks treatment. At baseline, duration MMN was smaller in schizophrenia compared to controls. Acute glycine increased duration MMN (compared to placebo), whilst this difference was absent post-6-weeks treatment. Six weeks of chronic glycine administration improved PANSS-Total, PANSS-Negative and PANSS-General symptoms compared to placebo. Smaller baseline duration MMN was associated with greater PANSS-Negative symptoms and predicted (at trend level) PANSS-Negative symptom improvement post-6-weeks glycine treatment (not placebo). These findings support the benefits of chronic glycine administration and demonstrate, for the first time, that acute glycine improves duration MMN in schizophrenia. This result, together with smaller baseline duration MMN predicting greater clinical treatment response, suggests the potential for duration MMN as a biomarker of glycine-induced improvements in negative symptoms in schizophrenia. [ABSTRACT FROM AUTHOR]

Prolonged heavy exposure to cannabis is associated with impaired cognition and brain functional and structural alterations. We recently reported attenuated mismatch negativity (MMN) and altered P50 sensory gating in chronic cannabis users. This study investigated the extent of brain functional recovery (indexed by MMN and P50) in chronic users after cessation of use. Eighteen ex-users (median 13.5 years prior regular use; median 3.5 years abstinence) and 18 nonusers completed (1) a multifeature oddball task with duration, frequency, and intensity deviants and (2) a P50 paired-click paradigm. Trend level smaller duration MMN amplitude and larger P50 ratios (indicative of poorer sensory gating) were observed in ex-users compared to controls. Poorer P50 gating correlated with prior duration of cannabis use. Duration of abstinence was positively correlated with duration MMN amplitude, even after controlling for age and duration of cannabis use. Impaired sensory gating and attenuated MMN amplitude tended to persist in ex-users after prolonged cessation of use, suggesting a lack of full recovery. An association with prolonged duration of prior cannabis use may indicate persistent cannabis-related alterations to P50 sensory gating. Greater reductions in MMN amplitude with increasing abstinence (positive correlation) may be related to either self-medication or an accelerated aging process. [ABSTRACT FROM AUTHOR]

Background: Cannabis use is associated with the development of psychotic symptoms and increased risk for schizophrenia. The mismatch negativity (MMN) is a brain event-related potential marker of change detection thought to index glutamatergic N-methyl-D-aspartate receptor-mediated neurotransmission, which is known to be deficient in schizophrenia. This study examined auditory MMN in otherwise healthy chronic cannabis users compared with nonuser control subjects. Methods: Forty-two chronic cannabis users and 44 nonuser healthy control subjects completed a multi-feature MMN paradigm, which included duration, frequency, and intensity deviants (deviants 6%; standards 82%). The MMN was compared between users and control subjects as well as between long- and short-term users and age- and gender-matched control subjects. Associations between MMN, cannabis use measures, and symptoms were examined. Results: The MMN amplitude was significantly reduced to frequency but not duration or intensity deviants in overall cannabis users relative to control subjects. Frequency MMN was similarly attenuated in short- and long-term users relative to control subjects. Long-term users also exhibited reduced duration MMN relative to control subjects and short-term users and this was correlated with increased duration of exposure to cannabis and increased psychotic-like experiences during intoxication. In short-term users, a younger age of onset of regular cannabis use and greater frequency of use were associated with greater psychotic-like experiences and symptomatic distress. Conclusions: These results suggest impaired sensory memory that might reflect N-methyl-D-aspartate receptor dysfunction in chronic cannabis users. The pattern of MMN alterations in cannabis users differed from that typically observed in patients with schizophrenia, indicating overlapping but distinct underlying pathology. [ABSTRACT FROM AUTHOR]

Abstract: Chronic cannabis use has been associated with neurocognitive deficits, alterations in brain structure and function, and with psychosis. This study investigated the effects of chronic cannabis use on P50 sensory-gating in regular users, and explored the association between sensory gating, cannabis use history and the development of psychotic-like symptoms. Twenty controls and 21 regular cannabis users completed a P50 paired-click (S1 and S2) paradigm with an inter-pair interval of 9s. The groups were compared on P50 amplitude to S1 and S2, P50 ratio (S2/S1) and P50 difference score (S1–S2). While cannabis users overall did not differ from controls on P50 measures, prolonged duration of regular use was associated with greater impairment in sensory gating as indexed by both P50 ratio and difference scores (including after controlling for tobacco use). Long-term cannabis users were found to have worse sensory gating ratios and difference scores compared to short-term users and controls. P50 metrics did not correlate significantly with any measure of psychotic-like symptoms in cannabis users. These results suggest that prolonged exposure to cannabis results in impaired P50 sensory-gating in long-term cannabis users. While it is possible that these deficits may have pre-dated cannabis use and reflect a vulnerability to cannabis use, their association with increasing years of cannabis use suggests that this is not the case. Impaired P50 sensory-gating ratios have also been reported in patients with schizophrenia and may indicate a similar underlying pathology. [Copyright &y& Elsevier]

Purpose: As environmental disasters become more common and severe due to climate change, there is a growing need for strategies to bolster recovery that are proactive, cost-effective, and which mobilise community resources. Aims: We propose that building social group connections is a particularly promising strategy for supporting mental health in communities affected by environmental disasters. Methods: We tested the social identity model of identity change in a disaster context among 627 people substantially affected by the 2019–2020 Australian fires. Results: We found high levels of post-traumatic stress, strongly related to severity of disaster exposure, but also evidence of psychological resilience. Distress and resilience were weakly positively correlated. Having stronger social group connections pre-disaster was associated with less distress and more resilience 12–18 months after the disaster, via three pathways: greater social identification with the disaster-affected community, greater continuity of social group ties, and greater formation of new social group ties. New group ties were a mixed blessing, positively predicting both resilience and distress. Conclusions: We conclude that investment in social resources is key to supporting mental health outcomes, not just reactively in the aftermath of disasters, but also proactively in communities most at risk. [ABSTRACT FROM AUTHOR]

Rationale: Regular cannabis use has been associated with brain functional alterations within frontal, temporal, and striatal pathways assessed during various cognitive tasks. Whether such alterations are consistently reported in the absence of overt task performance needs to be elucidated to uncover the core neurobiological mechanisms of regular cannabis use. Objectives: We aim to systematically review findings from studies that examine spontaneous fluctuations of brain function using functional Magnetic Resonance Imaging (fMRI) resting-state functional connectivity (rsFC) in cannabis users versus controls, and the association between rsFC and cannabis use chronicity, mental health symptoms, and cognitive performance. Methods: We conducted a PROSPERO registered systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and searched eight databases. Results: Twenty-one studies were included for review. Samples comprised 1396 participants aged 16 to 42 years, of which 737 were cannabis users and 659 were controls. Most studies found greater positive rsFC in cannabis users compared to controls between frontal-frontal, fronto-striatal, and fronto-temporal region pairings. The same region pairings were found to be preliminarily associated with varying measures of cannabis exposure. Conclusions: The evidence to date shows that regular cannabis exposure is consistently associated with alteration of spontaneous changes in Blood Oxygenation Level-Dependent signal without any explicit cognitive input or output. These findings have implications for interpreting results from task-based fMRI studies of cannabis users, which may additionally tax overlapping networks. Future longitudinal rsFC fMRI studies are required to determine the clinical relevance of the findings and their link to the chronicity of use, mental health, and cognitive performance. [ABSTRACT FROM AUTHOR]

Rationale: Regular cannabis use (i.e. ≥ monthly) is highly prevalent, with past year use being reported by ~ 200 million people globally.High reactivity to cannabis cues is a key feature of regular cannabis use and has been ascribed to greater cannabis exposure and craving, but the underlying neurobiology is yet to be systematically integrated. Objectives: We aim to systematically summarise the findings from fMRI studies which examined brain function in cannabis users while exposed to cannabis vs neutral stimuli during a cue-reactivity fMRI task. Methods: A systematic search of PsycINFO, PubMed and Scopus databases was pre-registered in PROSPERO (CRD42020171750) and conducted following PRISMA guidelines. Eighteen studies met inclusion/exclusion criteria. Samples comprised 918 participants (340 female) aged 16–38 years. Of these, 603 were regular cannabis users, and 315 were controls. Results: The literature consistently reported greater brain activity in cannabis users while exposed to cannabis vs neutral stimuli in three key brain areas: the striatum, the prefrontal (anterior cingulate, middle frontal) and the parietal cortex (posterior cingulate/precuneus) and additional brain regions (hippocampus, amygdala, thalamus, occipital cortex). Preliminary correlations emerged between cannabis craving and the function of partially overlapping regions (amygdala, striatum, orbitofrontal cortex). Conclusions: Exposure to cannabis-cues may elicit greater brain function and thus trigger cravings in regular cannabis users and thus trigger cannabis craving. Standardised and longitudinal assessments of cannabis use and related problems are required to profile with greater precision the neurobiology of cannabis cue-reactivity, and its role in predicting cravings and relapse. [ABSTRACT FROM AUTHOR]

Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are both psychoactive, but only THC is considered intoxicating. There is significant interest in potential therapeutic properties of these cannabinoids and of CBD in particular. Some research has suggested that CBD may ameliorate adverse effects of THC, but this may be dose dependent as other evidence suggests possible potentiating effects of THC by low doses of CBD. We conducted a randomised placebo controlled trial to examine the acute effects of these compounds alone and in combination when administered by vaporisation to frequent and infrequent cannabis users. Participants (n = 36; 31 male) completed 5 drug conditions spaced one week apart, with the following planned contrasts: placebo vs CBD alone (400 mg); THC alone (8 mg) vs THC combined with low (4 mg) or high (400 mg) doses of CBD. Objective (blind observer ratings) and subjective (self-rated) measures of intoxication were the primary outcomes, with additional indices of intoxication examined. CBD showed some intoxicating properties relative to placebo. Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC. The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users and was consistent across objective and subjective measures. Most effects were significant at p < .0001. These findings are important to consider in terms of recommended proportions of THC and CBD in cannabis plant matter whether used medicinally or recreationally and have implications for novice or less experienced cannabis users.Trial registration: ISRCTN Registry Identifier: ISRCTN24109245. [ABSTRACT FROM AUTHOR]

Amidst growing global acceptance of medicinal cannabinoids as a potential therapeutic interest in cannabidiol (CBD) is increasing. In Australia in 2020, a government inquiry examined the barriers that the public are experiencing in accessing medicinal cannabis. A number of recommendations to improve access were made. In response to these recommendations, the Australian therapeutics regulatory authority down-scheduled CBD from Prescription Only (Schedule 4) to Pharmacist Only (Schedule 3). As a group of early to mid-career researchers of the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), we propose some considerations in relation to over-the-counter availability of CBD and opportunities to improve knowledge about its potential therapeutic benefits alongside its increased uptake. [ABSTRACT FROM AUTHOR]

Background: The most important two medicinal cannabinoids are Δ9‐tetrahydrocannabinol (THC) and cannabidiol (CBD). Vaporised administration is superior due to its higher systemic availability, lower individual variability and faster drug delivery. Although it is common THC is co‐administered with CBD, the influence of CBD on the pharmacokinetics, especially the systemic availability of THC after vaporised administration, is unknown. Aims: To investigate the influence of different doses of co‐administered CBD on the systemic availability of THC, and to compare the availability of THC and CBD in a sample of frequent and infrequent cannabis users. Methods: The study used a randomised, double‐blind, crossover placebo‐controlled design. THC and/or CBD in ethanol was vaporised and inhaled. Plasma concentrations of THC and CBD were analysed. The THC data created in this study were pooled together with published THC pharmacokinetic data in order to cover all the phases of THC disposition. Population pharmacokinetic model of THC was developed based on the pooled data. The model of CBD was developed based on the data created in this study. Results: Population pharmacokinetic models of THC and CBD were developed. With concomitant inhalation of high‐dose CBD, the systemic availability of THC decreased significantly. Frequent cannabis users appeared to have higher systemic availability of THC and CBD when high‐dose CBD was administered. Conclusions: The results observed in this study are useful for guiding future pharmacokinetic studies of medicinal cannabinoids, and for development of dosing guidelines for medical use of cannabis in the 'real‐world' setting. [ABSTRACT FROM AUTHOR]

Schizophrenia may be conceptualised using a dimensional approach to examine trait-like expression such as schizotypy within non-clinical populations to better understand pathophysiology. A candidate psychosis-risk marker, the auditory mismatch negativity (MMN) is thought to index the functionality of glutamatergic NMDA receptor mediated neurotransmission. Although the MMN is robustly reduced in patients with schizophrenia, the association between MMN and schizotypy in the general population is under-investigated. Thirty-five healthy participants completed the Schizotypal Personality Questionnaire (SPQ) and a multi-feature MMN paradigm (standards 82%, 50 ms, 1000 Hz, 80 dB) with duration (100 ms), frequency (1200 Hz) and intensity (90 dB) deviants (6% each). Spearman's correlations were used to explore the association between schizotypal personality traits and MMN amplitude. Few associations were identified between schizotypal traits and MMN. Higher Suspiciousness subscale scores tended to be correlated with larger frequency MMN amplitude. A median-split comparison of the sample on Suspiciousness scores showed larger MMN (irrespective of deviant condition) in the High compared to the Low Suspiciousness group. The trend-level association between MMN and Suspiciousness is in contrast to the robustly attenuated MMN amplitude observed in schizophrenia. Reductions in MMN may reflect a schizophrenia-disease state, whereas non-clinical schizotypy may not be subserved by similar neuropathology. [ABSTRACT FROM AUTHOR]

Compulsivity is recognized as a transdiagnostic phenotype, underlying a variety of addictive and obsessive-compulsive behaviors. However, current understanding of how it should be operationalized and the processes contributing to its development and maintenance is limited. The present study investigated if there was a relationship between the affective process Experiential Avoidance (EA), an unwillingness to tolerate negative internal experiences, and the frequency and severity of transdiagnostic compulsive behaviors. A large sample of adults (N = 469) completed online questionnaires measuring EA, psychological distress and the severity of seven obsessive-compulsive and addiction-related behaviors. Using structural equation modelling, results indicated a one-factor model of compulsivity was superior to the two-factor model (addictive- vs OCD-related behaviors). The effect of EA on compulsivity was fully mediated by psychological distress, which in turn had a strong direct effect on compulsivity. This suggests distress is a key mechanism in explaining why people with high EA are more prone to compulsive behaviors. The final model explained 41% of the variance in compulsivity, underscoring the importance of these constructs as likely risk and maintenance factors for compulsive behavior. Implications for designing effective psychological interventions for compulsivity are discussed. [ABSTRACT FROM AUTHOR]