Role of adenosine A2A receptors in hot and cold cognition: Effects of single-dose istradefylline in healthy volunteers.

The role of the adenosine neurochemical system in human cognition is under-studied, despite such receptors being distributed throughout the brain. The aim of this study was to shed light on the role of the adenosine A2A receptors in human cognition using single-dose istradefylline. Twenty healthy male participants, aged 19-49, received 20 mg istradefylline and placebo, in a randomized, double-blind, placebo-controlled cross-over design. Cognition was assessed using computerized cognitive tests, covering both cold (non-emotional) and hot (emotion-laden) domains. Cardiovascular data were recorded serially. Cognitive effects of istradefylline were explored using repeated measures analysis of variance and paired t-tests as appropriate. On the EMOTICOM battery, there was a significant effect of istradefylline versus placebo on the Social Information Preference task (t = 2.50, p = 0.02, d=-0.59), indicating that subjects on istradefylline interpreted social situations more positively. No other significant effects were observed on other cognitive tasks, nor in terms of cardiovascular measures (pulse and blood pressure). De-briefing indicated that blinding was successful, both for participants and the research team. Further exploration of the role of adenosine A2A receptors in emotional processing may be valuable, given that abnormalities in related cognitive functions are implicated in neuropsychiatric disorders. The role of adenosine systems in human cognition requires further clarification, including with different doses of istradefylline and over different schedules of administration.

Why Is Non-suicidal Self-injury More Common in Women? Mediation and Moderation Analyses of Psychological Distress, Emotion Dysregulation, and Impulsivity.

OBJECTIVE: Non-suicidal self-injury (NSSI) appears to be more common among women than men, though the underlying reasons for this remain unclear. In a community sample of young adults (N = 996, aged 18-33) assessed during the COVID-19 pandemic, we investigated alternative explanation for the NSSI prevalence gap: are women more likely to experience the feelings which lead to NSSI as a coping strategy, or does this prevalence gap result from differences in how men and women respond to distress? METHODS: Cross-sectional mediation and moderation analyses tested how self-reported psychological distress (K10), emotion dysregulation (DERS), and impulsivity (UPPS-P) may contribute to a higher prevalence of NSSI among women. RESULTS: Women were twice as likely as men to report past-year NSSI (14.47% versus 7.78%, OR = 2.00, 95% CI [1.29, 3.13]). Women reported significantly higher psychological distress and significantly lower sensation seeking and positive urgency than men. Psychological distress partially statistically mediated the relationship between gender and past-year NSSI. Gender did not significantly moderate associations between psychological distress, emotion dysregulation, or impulsivity and past-year NSSI. Past-year NSSI prevalence did not significantly decrease with age and we found no significant age by gender interaction. CONCLUSIONS: Greater levels of NSSI in young women are partly explained by their greater levels of psychological distress, but not by differences in how men and women respond to this distress. Given similar levels of psychological distress, emotion dysregulation, and impulsivity, women and men are similarly likely to experience NSSI. HighlightsWomen aged 18-33 were significantly more likely to report past-year NSSI than menWomen's greater psychological distress contributed to their higher NSSI prevalenceVariables investigated here were similarly associated with NSSI in men and women.

The impact of the initial COVID-19 outbreak on young adults' mental health: a longitudinal study of risk and resilience factors.

Few studies assessing the effects of COVID-19 on mental health include prospective markers of risk and resilience necessary to understand and mitigate the combined impacts of the pandemic, lockdowns, and other societal responses. This population-based study of young adults includes individuals from the Neuroscience in Psychiatry Network (n = 2403) recruited from English primary care services and schools in 2012-2013 when aged 14-24. Participants were followed up three times thereafter, most recently during the initial outbreak of the COVID-19 outbreak when they were aged between 19 and 34. Repeated measures of psychological distress (K6) and mental wellbeing (SWEMWBS) were supplemented at the latest assessment by clinical measures of depression (PHQ-9) and anxiety (GAD-7). A total of 1000 participants, 42% of the original cohort, returned to take part in the COVID-19 follow-up; 737 completed all four assessments [mean age (SD), 25.6 (3.2) years; 65.4% female; 79.1% White]. Our findings show that the pandemic led to pronounced deviations from existing mental health-related trajectories compared to expected levels over approximately seven years. About three-in-ten young adults reported clinically significant depression (28.8%) or anxiety (27.6%) under current NHS guidelines; two-in-ten met clinical cut-offs for both. About 9% reported levels of psychological distress likely to be associated with serious functional impairments that substantially interfere with major life activities; an increase by 3% compared to pre-pandemic levels. Deviations from personal trajectories were not necessarily restricted to conventional risk factors; however, individuals with pre-existing health conditions suffered disproportionately during the initial outbreak of the COVID-19 pandemic. Resilience factors known to support mental health, particularly in response to adverse events, were at best mildly protective of individual psychological responses to the pandemic. Our findings underline the importance of monitoring the long-term effects of the ongoing pandemic on young adults' mental health, an age group at particular risk for the emergence of psychopathologies. Our findings further suggest that maintaining access to mental health care services during future waves, or potential new pandemics, is particularly crucial for those with pre-existing health conditions. Even though resilience factors known to support mental health were only mildly protective during the initial outbreak of the COVID-19 pandemic, it remains to be seen whether these factors facilitate mental health in the long term.

Associations between COVID-19 pandemic impact, dimensions of behavior and eating disorders: A longitudinal UK-based study.

BACKGROUND: There is growing concern about how people with eating disorders are impacted by the widespread societal restructuring during the COVID-19 crisis. AIMS: We aimed to examine how factors relating to the impact of the pandemic associate with eating disorders and quantify this relationship while adjusting for concurrent and longitudinal parameters of risk. METHODS: We gathered demographic, behavioral and clinical data pre- and mid-pandemic as well as childhood trauma history from a longitudinal online survey of 489 adults (mean age 23.4 years) recruited from the Neuroscience in Psychiatry Network (NSPN). Using pre-pandemic (T1) and concurrent (T2) data we aimed to predict eating disorders at mid-pandemic (T2). We deployed hierarchical generalized logistic regression to ascertain the strength of longitudinal and concurrent associations. RESULTS: Pre-pandemic eating disorder scores strongly associated with concurrent eating disorder (z = 5.93). More conflict at home mid-pandemic (z = 2.03), pre- (lower sensation seeking z = -2.58) and mid-pandemic (higher lack of perseverance z = 2.33) impulsivity traits also associated with mid-pandemic eating disorder. CONCLUSION: Conflict at home mid-pandemic and specific aspects of impulsiveness significantly associated with concurrent eating disorder when adjusted for pre-pandemic eating disorder symptoms, baseline demographics, behavioral traits, history of traumatic experiences and concurrent psychopathology. These results provide insight into the struggles of those suffering with eating disorders during the COVID-19 pandemic and highlight the importance of impulsiveness traits and the immediate family environment in their experience of illness during the pandemic.

Cortical dopamine reduces the impact of motivational biases governing automated behaviour.

Motivations shape our behaviour: the promise of reward invigorates, while in the face of punishment, we hold back. Abnormalities of motivational processing are implicated in clinical disorders characterised by excessive habits and loss of top-down control, notably substance and behavioural addictions. Striatal and frontal dopamine have been hypothesised to play complementary roles in the respective generation and control of these motivational biases. However, while dopaminergic interventions have indeed been found to modulate motivational biases, these previous pharmacological studies used regionally non-selective pharmacological agents. Here, we tested the hypothesis that frontal dopamine controls the balance between Pavlovian, bias-driven automated responding and instrumentally learned action values. Specifically, we examined whether selective enhancement of cortical dopamine either (i) enables adaptive suppression of Pavlovian control when biases are maladaptive; or (ii) non-specifically modulates the degree of bias-driven automated responding. Healthy individuals (n = 35) received the catechol-o-methyltransferase (COMT) inhibitor tolcapone in a randomised, double-blind, placebo-controlled cross-over design, and completed a motivational Go NoGo task known to elicit motivational biases. In support of hypothesis (ii), tolcapone globally decreased motivational bias. Specifically, tolcapone improved performance on trials where the bias was unhelpful, but impaired performance in bias-congruent conditions. These results indicate a non-selective role for cortical dopamine in the regulation of motivational processes underpinning top-down control over automated behaviour. The findings have direct relevance to understanding neurobiological mechanisms underpinning addiction and obsessive-compulsive disorders, as well as highlighting a potential trans-diagnostic novel mechanism to address such symptoms.

Gambling disorder in the UK: key research priorities and the urgent need for independent research funding.

Gambling in the modern era is pervasive owing to the variety of gambling opportunities available, including those that use technology (eg, online applications on smartphones). Although many people gamble recreationally without undue negative effects, a sizeable subset of individuals develop disordered gambling, which is associated with marked functional impairment including other mental health problems, relationship problems, bankruptcy, suicidality, and criminality. The National UK Research Network for Behavioural Addictions (NUK-BA) was established to promote understanding of, research into, and treatments for behavioural addictions including gambling disorder, which is the only formally recognised behavioural addiction. In this Health Policy paper, we outline the status of research and treatment for disordered gambling in the UK (including funding issues) and key research that should be conducted to establish the magnitude of the problem, vulnerability and resilience factors, the underlying neurobiology, long-term consequences, and treatment opportunities. In particular, we emphasise the need to: (1) conduct independent longitudinal research into the prevalence of disordered gambling (including gambling disorder and at-risk gambling), and gambling harms, including in vulnerable and minoritised groups; (2) select and refine the most suitable pragmatic measurement tools; (3) identify predictors (eg, vulnerability and resilience markers) of disordered gambling in people who gamble recreationally, including in vulnerable and minoritised groups; (4) conduct randomised controlled trials on psychological interventions and pharmacotherapy for gambling disorder; (5) improve understanding of the neurobiological basis of gambling disorder, including impulsivity and compulsivity, genetics, and biomarkers; and (6) develop clinical guidelines based on the best contemporary research evidence to guide effective clinical interventions. We also highlight the need to consider what can be learnt from approaches towards mitigating gambling-related harm in other countries.

Structural gray matter differences in Problematic Usage of the Internet: a systematic review and meta-analysis.

Problematic Usage of the Internet (PUI) has been linked to diverse structural gray matter changes in individual data studies. However, no quantitative synthesis across studies has been conducted. We aimed to identify gray matter regions showing significant spatial convergence across neuroimaging studies in PUI. We searched PubMed and PsycINFO up to 10/03/2021 and included original, cross-sectional comparative studies that examined structural gray matter imaging in PUI versus control groups; reported a whole-brain analysis; and provided peak coordinates for gray matter differences. From a total of 624 potentially relevant studies, 15 (including 355 individuals with PUI and 363 controls) were included in a meta-analysis of voxel-based morphometry studies. Anatomical likelihood estimation (ALE) meta-analysis was performed using extracted coordinates and identified significant spatial convergence in the medial/superior frontal gyri, the left anterior cingulate cortex/cingulate gyrus, and the left middle frontal/precentral gyri. Datasets contributing to these findings all indicated reduced gray matter in cases compared to controls. In conclusion, voxel-based morphometric studies indicate replicable gray matter reductions in the dorsolateral prefrontal cortex and anterior cingulate cortex in PUI, regions implicated in reward processing and top-down inhibitory control. Further studies are required to understand the nature of gray matter differences across PUI behaviors, as well as the contribution of particular mental health disorders, and the influence of variation in study and sample characteristics.

Cognitive Inflexibility in OCD and Related Disorders.

Cognitive inflexibility is suggested by the hallmark symptoms of obsessive-compulsive disorder (OCD), namely the occurrence of repetitive thoughts and/or behaviours that persist despite being functionally impairing and egodystonic to the individual. As well as being implied by the top-level symptoms, cognitive inflexibility in OCD, and some related conditions, has also been objectively quantified in case-control studies using computerised cognitive tasks. This chapter begins by considering the objective measurement of different aspects of cognitive flexibility using neuropsychological paradigms, with a focus on neural and neurochemical substrates. It moves on to conduct a systematic review and meta-analysis of findings from a widely deployed flexibility task: the Intra-Dimensional/Extra-Dimensional Set-Shift Task (IDED). By pooling data from 11 studies (335 OCD patients and 311 controls), we show that Extra-Dimensional (ED) shift deficits are a robust and reproducible finding (effect size medium-large) in OCD across the literature, and that this deficit is not attributable to group differences in age or IQ. The OCD ED deficit is then discussed in terms of dysfunction of fronto-striatal pathways (as exemplified, for example, by functional connectivity data), and the putative role of different neurotransmitters. We consider evidence that impaired ED shifting constitutes a candidate vulnerability marker (or 'endophenotype') for OCD. The available literature is then surveyed as to ED findings in other obsessive-compulsive (OC) related disorders (e.g. hoarding, body-dysmorphic disorder, and trichotillomania), as well as in non-OC disorders (schizophrenia and anxiety symptoms in general). Lastly, we consider more recent, emerging developments in the quantification of compulsivity using cognitive tasks and questionnaires, as well as key directions for future research, including the need to refine compulsivity and its composite cognitive processes.

Brain micro-architecture and disinhibition: a latent phenotyping study across 33 impulsive and compulsive behaviours.

Impulsive and compulsive symptoms are common, tend to co-occur, and collectively account for a substantive global disease burden. Latent phenotyping offers a promising approach to elucidate common neural mechanisms conferring vulnerability to such symptoms in the general population. We utilised the Neuroscience in Psychiatry Network (NSPN), a cohort of young people (aged 18-29 years) in the United Kingdom, who provided questionnaire data and Magnetic Resonance Imaging scans. Partial Least Squares was used to identify brain regions in which intra-cortical myelination (measured using Magnetisation Transfer, MT) was significantly associated with a disinhibition phenotype, derived from bi-factor modelling of 33 impulsive and compulsive problem behaviours. The neuroimaging sample comprised 126 participants, mean 22.8 (2.7 SD) years old, being 61.1% female. Disinhibition scores were significantly and positively associated with higher MT in the bilateral frontal and parietal lobes. 1279 genes associated with disinhibition-related brain regions were identified, which were significantly enriched for functional biological interactions reflecting receptor signalling pathways. This study indicates common microstructural brain abnormalities contributing to a multitude of related, prevalent, problem behaviours characterised by disinhibition. Such a latent phenotyping approach provides insights into common neurobiological pathways, which may help to improve disease models and treatment approaches. Now that this latent phenotyping model has been validated in a general population sample, it can be extended into patient settings.

Trans-diagnostic measurement of impulsivity and compulsivity: A review of self-report tools.

INTRODUCTION: Impulsivity and compulsivity are important constructs, relevant to understanding behaviour in the general population, as well as in particular mental disorders (e.g. attention deficit hyperactivity disorder, obsessive-compulsive disorder). The current paper provides a narrative review of self-report impulsivity and compulsivity scales. METHODS: A literature search was conducted using the following terms: ("impulsivity" OR "compulsivity") AND ("self-report" OR "questionnaire" OR "psychometric" OR "scale"). RESULTS: 25 impulsive and 11 compulsive scales were identified, which varied considerably in psychometric properties, convenience, and validity. For impulsivity, the most commonly used scales were the BIS and the UPPS-P, whilst for compulsivity, the Padua Inventory was commonly used. The majority of compulsivity scales measured OCD symptoms (obsessions and compulsions) rather than being trans-diagnostic or specific to compulsivity (as opposed to obsessions). Scales capable of overcoming these limitations were highlighted. DISCUSSION: This review provides clarity regarding relative advantages and disadvantages of different scales relevant to the measurement of impulsivity and compulsivity in many contexts. Areas for further research and refinement are highlighted.

Eating disorders with over-exercise: A cross-sectional analysis of the mediational role of problematic usage of the internet in young people.

Eating disorders are widespread illnesses with significant global impact. There is growing concern about how young people overuse online resources leading to mental health sequelae. We gathered data from 639 individuals from a population cohort. Participants were all young adults at the point of contact and were grouped as having probable eating disorder with excessive exercise (n = 37) or controls (n = 602). We measured obsessionality, compulsivity, impulsivity, and problematic internet use. Group differences in these domains were evaluated; and structural equation modelling (SEM) was used to assess structural relationships between variables. Cases had higher scores of obsessional thoughts of threat (Cohen's d = 0.94, p < 0.001), intolerance towards uncertainty (Cohen's d = 0.72; p < 0.001), thoughts of importance and control (Cohen's d = 0.65, p < 0.01), compulsivity (Cohen's d = 0.72; p < 0.001), negative urgency (Cohen's d = 0.75, p < 0.001), and higher problematic usage of the internet (Cohen's d = 0.73; p-corrected <0.001). Our SEM showed significant partial mediation of problematic internet use on both the effect of obsessionality latent factor on cases (z-value = 2.52, p < 0.05), as well as of sensation seeking latent factor on cases (z-value = 2.09, p < 0.05). Youth with eating disorder and heightened exercise levels have increased obsessive thoughts of threat, compulsivity traits and sensation seeking impulsivity. The association between obsessive thoughts and eating disorders, as well as sensation seeking and eating disorders were partially mediated by problematic internet use. Problematic internet use may be playing a role in the development or maintenance of eating disorder symptoms in the background of obsessional thoughts and sensation seeking impulsive traits.